Peripheral Blood Monocytosis Is Associated With Long-Term Disease Severity in Pediatric-Onset Inflammatory Bowel Disease.

OBJECTIVES: Peripheral blood monocytosis (PBM) is a marker of increased disease severity in adults with inflammatory bowel diseases (IBDs). We sought to determine whether PBM serves as a prognostic biomarker in patients with pediatric-onset IBD for a more aggressive long-term disease course when followed into adulthood. METHODS: Patients with pediatric-onset inflammatory bowel disease were identified within an adult tertiary care center, within a consented, prospectively collected natural history disease registry, to compare clinical outcomes between patients with and without PBM from the years 2009 to 2019. Patients demonstrating elevation in PBM at any time defined membership and long-term clinical trajectories were compared with pediatric-onset patients without PBM. RESULTS: A total of 581 patients with IBD, diagnosed by 18 years of age, were identified for inclusion, of which 440 patients were diagnosed with Crohn disease and 141 with ulcerative colitis. Monocytosis was detected by complete blood cell counts in 40.1% of patients. PBM was associated with steroid and biologic exposure, number of IBD-related surgeries, and increased health care utilization. Multivariate logistic regression analyses, accounting for elevation of inflammatory markers and other values associated with acute disease activity as well as steroid use, showed persistently increased odds of biologic exposure, emergency department visits, and hospitalizations, but not surgeries, after detection of monocytosis. CONCLUSIONS: Within patients with pediatric-onset IBD, the sub-cohort with PBM had associated worse clinical outcomes and other markers of increased disease severity.

Predictors of Suicidal Ideation Among IBD Outpatients.

BACKGROUND: Suicidal ideation (SI) is understudied in inflammatory bowel diseases (IBD). We aim to determine SI rates among IBD outpatients and to evaluate predictors of SI. MATERIALS AND METHODS: This is a prospective observational study of consecutive adult IBD outpatients over 18 months. Patients were screened for depression and SI using patient health questionnaire (PHQ-9). Demographic data were obtained from electronic medical record. Regression modeling was used for predictor analyses. RESULTS: In total, 71 of consecutive 1352 IBD outpatients had SI. Significant correlations between SI and depression severity, tricyclic antidepressants (TCA), IBD-related quality of life, and low vitamin D levels were seen. Univariate regression showed that depression severity, TCA use, and quality of life predicted SI. Multivariate regression showed depression severity (ß=0.46; P=0.002) and TCA use (ß=0.31; P=0.012) made unique contributions. CONCLUSIONS: SI is associated with depressive severity and less directly with IBD activity. Low-dose TCA, often used for chronic abdominal pain, is also a risk factor. Identifying the subset of IBD patients most vulnerable to SI can facilitate proper referrals to behavioral services and prevent progression to completed suicides.

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.

Quality of Sleep and Coexistent Psychopathology Have Significant Impact on Fatigue Burden in Patients With Inflammatory Bowel Disease.

BACKGROUND: Fatigue is common in inflammatory bowel disease (IBD) patients and is associated with factors such as psychopathology, sleep quality, and disease activity. GOAL: To investigate the combined role of all the above factors in the burden of fatigue among IBD patients. STUDY: We conducted an observational study of adult patients enrolled in an IBD clinical research registry at a tertiary care clinic. Fatigue burden was defined by Item 1 of the Short-form IBD Questionnaire (SIBDQ), which is scored on a 7-point Likert scale. Crohn's disease (CD) and ulcerative colitis (UC) disease activity were measured with the Harvey-Bradshaw Index or the UC Activity Index, respectively. Labs were obtained to assess anemia, vitamin deficiencies, and inflammatory markers. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Use of psychotropic medications and narcotics was used as proxy measure of psychopathology and pain. RESULTS: Among 685 IBD patients enrolled in the registry, 631 (238 UC, 393 CD) had a complete SIBDQ. High fatigue burden was found in 57.5% of patients (64.4% CD, 46.2% UC). Fatigue burden was significantly associated with sleep disturbance (PSQI), SIBDQ, and disease activity. CD patients had more fatigue burden than UC patients. Multivariate regression showed that poor quality of life, sleep disturbance, and being on a psychotropic medication are significantly associated with fatigue burden for both UC and CD. CONCLUSION: Because fatigue is common in IBD patients, these findings suggest that attention to quality of sleep and psychopathology is as important as medical disease management.

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.

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.

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.

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.

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.

Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization. METHODS: We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type. RESULTS: A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05). CONCLUSIONS: Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.

The Impact of Cholecystectomy on Long-Term Disease Outcomes and Quality of Life in Patients with Crohn's Disease.

BACKGROUND: Cholecystectomy (CCY) is one of the most frequently performed abdominal surgeries. However, the impact of CCY in clinical settings with altered gastrointestinal physiology and anatomy, such as Crohn's disease (CD), has not been fully characterized. We sought to investigate clinical outcomes, disease severity, and quality of life of CD patients after CCY. METHODS: We utilized a prospective, longitudinal registry of consented CD patients followed at a tertiary center. Crohn's disease patients that had or had not undergone CCY formed the 2 study groups. The absence or presence of gallbladder was confirmed with abdominal CT scans obtained during routine care. Multiyear clinical, biochemical, and histologic data were collected and analyzed. RESULTS: Among 834 CD patients, 151 (18%) had undergone CCY. History of CCY was associated with higher disease activity (median Harvey-Bradshaw index; P < 0.001), more years with anemia (P = 0.048), lower albumin (P = 0.001), worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001), chronic abdominal pain (P < 0.001), higher risk for incident colonic dysplasia (P = 0.011), higher rates of annual hospital admissions (P = 0.004), and opioid use (P < 0.001). In multivariate analysis, CCY remained associated with higher disease activity (P < 0.001), lower albumin (P = 0.008), lower quality of life (P < 0.001), and more hospital admissions (P = 0.008), whereas CD patients with diseased ileum had higher risk for colonic dysplasia (P = 0.031). CONCLUSIONS: CCY in CD patients was associated with multiple markers of disease activity and worse quality of life during multiyear follow up. This data suggests that CCY in CD patients may adversely impact the long-term clinical course.

Clinical Characteristics of Inflammatory Bowel Disease Patients Requiring Long-Term Parenteral Support in the Present Era of Highly Effective Biologic Therapy.

BACKGROUND: Despite advances in the medical management of inflammatory bowel disease (IBD), a subset of patients may require extensive surgery, leading to short-bowel syndrome/intestinal failure requiring long-term home parenteral nutrition (PN) or customized intravenous fluid (IVF) support. Our aim was to further define the characteristics of IBD patients requiring home PN/IVF. METHODS: This is an observational study from a prospective IBD research registry. Patients receiving long-term home PN/IVF support during 2009-2015 were identified and compared with remaining IBD patients. Demographics, surgical history, smoking, narcotic use, IBD treatment, healthcare charges, and presence of biomarkers were reviewed. The IBD-PN group was stratified into 3 groups based on median healthcare charges. RESULTS: Of 2359 IBD patients, there were 25 (1%, 24 with Crohn's disease) who required home PN/IVF, and 250 randomly selected IBD patients matched for disease type formed the control population. Median duration of PN use was 27 months (interquartile range, 11-66). PN use was significantly associated with smoking, narcotic use, IBD-related operations, and lower quality-of-life scores. Among IBD-PN patients, 7 of 25 (28%, 3 after use of teduglutide) were able to successfully discontinue this modality. Median healthcare charges in the IBD-PN group were $51,456 annually. Median charges in the controls were $3427. Period prevalence mortality was 11.5% in IBD-PN and 3.8% in controls. CONCLUSIONS: IBD patients requiring long-term home PN/IVF support are a small minority in the present era of immunomodulator/biologic therapy. These refractory patients have a 15-fold increase in annual median healthcare charges compared with control IBD patients.

Serum IgG4 Subclass Deficiency Defines a Distinct, Commonly Encountered, Severe Inflammatory Bowel Disease Subtype.

BACKGROUND: Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. METHODS: We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. RESULTS: We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. CONCLUSIONS: An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.

Disease Characteristics and Severity in Patients With Inflammatory Bowel Disease With Coexistent Diabetes Mellitus.

BACKGROUND: Given the rising prevalence of diabetes mellitus (DM) and the limited data on its effect on the course of inflammatory bowel disease (IBD), we characterized multiyear patterns of disease severity in a cohort of IBD patients with coexistent DM. METHODS: Data of consented IBD patients followed prospectively in a natural history registry at a tertiary center between 2009 and 2017 were analyzed. Patients with ≥3 years of clinical follow-up were included. Patients identified with a diagnosis of DM were compared with 400 consecutive IBD controls without a diagnosis of DM, no laboratory evidence of hyperglycemia, and no history of antihyperglycemic treatment. RESULTS: Out of 2810 IBD patients, 141 (5%) had DM (IBD DM; 44% ulcerative colitis, 56% Crohn's disease, 48.2% female). IBD DM had higher use of 5-aminosalicylic acid (5ASA) agents (P = 0.04), narcotics (P < 0.001), and antibiotics (P = 0.007) but not immunomodulators and/or biologics compared with IBD controls. When analyzing biomarkers of severity, IBD DM demonstrated higher frequencies of elevated C-reactive protein (CRP; P = 0.006), elevated erythrocyte sedimentation rate (ESR; P = 0.001), eosinophilia (P = 0.004), monocytosis (P = 0.02), and hypoalbuminemia (P = 0.001). IBD DM had worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001). IBD DM had increased health care utilization compared with controls (emergency room usage P = 0.008, hospitalizations P < 0.001, gastroenterology clinic visits P < 0.001, and median annual charges P < 0.001). Among IBD DM patients, the use of immunomodulators and/or biologics was not associated with further complications as measured by antibiotic use or hospitalizations. CONCLUSIONS: This study of a large IBD cohort suggests that DM in IBD may be associated with increased disease severity and that there may be room for increasing use of highly effective immunomodulator and/or biologic agents in this group.