Faculty Bibliography

INTRODUCTION: Rapid, highly sensitive and specific multiplex polymerase chain reaction-based stool assays for gastrointestinal pathogens (GI PCR) are increasingly being used alternatively to conventional stool culture. We investigated the concordance between simultaneous GI PCR and stool culture with an ova and parasite (O&P) exam in outpatients presenting with symptoms of infectious gastroenteritis.
METHOD(S): We performed a cross-sectional study of outpatients who received a FilmArray GI PCR test for acute diarrhea at an academic medical center from September 2015 to February 2019 to identify patients who had a concomitant stool culture with an ova and parasite exam (conventional testing) at the same time, on the same stool sample. The primary outcome was detection of an infection on GI PCR or conventional stool testing. Correlation was evaluated using McNemar's test for pathogens detected on both tests. Other categorical variables were compared with Chi-square analysis.
RESULT(S): We identified 150 outpatients who received GI PCR and stool culture with an ova and parasite exam for an episode of acute gastroenteritis. 106 (71%) patients had a pathogen isolated on GI PCR for 144 total pathogens including 128 (88%) bacteria, 13 (9%) viruses, and 3 (2%) parasites; 21 (14%) patients had a pathogen isolated on conventional testing for 18 total pathogens including 9 (50%) bacteria and 9 (50%) parasites (Table 1). Multiple pathogens were found in 38 (26%) GI PCR tests. PCR testing most commonly identified Enteropathogenic Escherichia coli (EPEC), representing 42 (33%) positive PCR tests. Conventional testing most commonly identified Campylobacter jejuni with 13 (54%) positive tests. Of 28 total C. jejuni infections, 15 (54%) were positive only on PCR, 3 (10%) only on conventional testing, and 10 (36%) on both modalities, showing that conventional testing missed 54% of all infections (P=0.008). Conventional testing missed 4/6 (67%, P=0.125) Salmonella infections and 9/14 (64%, P=0.0215) Yersinia infections, nor did it detect any viral or diarrheagenic E. coli infections. Overall, PCR detected 144 of 191 (75%) of possible pathogens whereas conventional testing detected 47 of 179 possible pathogens (26%).
CONCLUSION(S): GI PCR testing identified multiple pathogens unidentified by conventional testing, such as enteric viruses and pathogenic strains of E. coli. Conventional testing missed 88% of enteric bacteria showing poor concordance between simultaneous GI PCR testing and stool culture with an ova and parasite exam. (Table Presented)

INTRODUCTION: Relapse of Crohn's disease (CD) is common after surgical resection. Prior data have demonstrated that postoperative tumor necrosis factor antagonists (anti-TNF) may reduce recurrence, although little is known about the efficacy of other biologic therapies. The aim of this study was to compare biologics for preventing postoperative objective recurrence in adult CD patients.
METHOD(S): We performed a retrospective chart review of CD patients who underwent intestinal resection from 2012 to 2018. Demographics, IBD history, pre- and postoperative course were obtained from the electronic medical record. The primary outcome was postoperative recurrence during follow up, defined as a composite of endoscopic (Rutgeerts grade > i2), biochemical (increase in CRP >5 mg/dL), or radiographic (presence of active inflammation) disease recurrence stratified by postoperative biologic exposure, including anti-TNF, vedolizumab (VDZ), ustekinumab (UST), and no therapy. Student's t-test, Pearson's chi-squared, logistic and Cox regression analyses were used to detect differences in the composite and components of the outcome among these groups.
RESULT(S): 123 patients were included. CD recurrence occurred in 36.6% of patients (13.0% biochemically, 24.4% endoscopically, 16.3% radiographically) at a median of 6.9 months (IQR 3.3-14.1) from surgery (Table 1). The number of patients in the anti-TNF, VDZ, UST, and no therapy groups were 57 (46.7%), 6 (4.9%), 13 (10.7%), and 46 (37.7%), respectively. Biologic therapy was initiated after ileostomy reversal within 3 months for 55 patients (72.4%), between 3-6 months for 11 patients (14.5%), and between 6-12 months for 10 patients (13.2%). Adjusting for prior resection and anti- TNF exposure, any biologic initiation within 6 months of surgery was superior to initiation after 6 months for preventing postoperative endoscopic recurrence (OR 0.24, 0.06-0.92), but not for the composite outcome. There were statistically significant differences among biologics for recurrence (Figure 1). Adjusting for prior resection and anti-TNF exposure, less patients relapsed under anti- TNF exposure compared to UST (HR 3.46, 1.45-8.23) for the composite outcome, and compared to UST (HR 3.95, 1.43-10.9) and VDZ (HR 4.42, 1.02-19.1) for endoscopic recurrence (Figure 2).
CONCLUSION(S): Among CD patients, initiation of biologics within 6 months and anti-TNF agents were superior in preventing postoperative recurrence compared to other management strategies. (Figure Presented)

INTRODUCTION: Gut microbial dysbiosis and impaired mucosal immunity play a major role in the pathogenesis of inflammatory bowel disease (IBD). Previous research has shown that IBD patients experience greater disease burden from gastrointestinal infections. The increasing availability of gastrointestinal multiplex polymerase chain reaction stool panels (GI PCR) has allowed for the rapid and accurate identification of viral, bacterial, and parasitic pathogens not readily diagnosable with conventional stool testing. We aimed to characterize the burden and risk factors for gastrointestinal infections on outpatients with and without inflammatory bowel disease presenting with symptoms of acute gastroenteritis.
METHOD(S): We performed a cross-sectional review of outpatients presenting with gastroenteritis to an academic medical center from September 2015 to March 2019 who received a FilmArray GI PCR. Baseline demographics, presence of IBD and disease characteristics, risk factors including travel history, sexual activity, HIV status, and symptoms on initial presentation were recorded. The primary outcome was the detection of an enteric pathogen. Secondary outcomes include the class of pathogen detected, i.e., viral, bacterial, parasitic. T-test and Chi-square analysis were used to compare outcomes between groups.
RESULT(S): We reviewed 815 outpatients who received GI PCR testing, of whom 94 (12%) were diagnosed with IBD. Patients with IBD were more likely to present to the initial visit with bloody diarrhea (46% vs. 8%, P < 0.001), hematochezia (15% vs. 6%, P = 0.001), and fever (23% vs. 9%, P < 0.001; Table 1). Of outpatients with IBD, 33 (35%) had a gastrointestinal pathogen detected compared to 216 (30%, P = 0.190) of non-IBD outpatients. Patients with IBD were more likely to have viral (28% vs. 18%, P = 0.044) or multiple pathogens (11% vs. 6%, P = 0.028) and less likely to have bacterial (61% vs. 73%, P = 0.920) and parasitic infections (0 vs. 6%, P = 0.382) on GI PCR (Table 2). There were no statistically significant differences in gender, race, travel history, sexual activity, HIV status, or rate of pathogen detection between patients with and without IBD.
CONCLUSION(S): Enteric infections were common in outpatients with and without IBD. IBD patients presented with more viral and multiple pathogens on GI PCR testing compared to non-IBD controls. Further studies are needed to investigate the impact of these different enteric pathogens on clinical management and disease burden. (Figure Presented)

INTRODUCTION: Patients with inflammatory bowel disease (IBD) frequently receive stool testing for exacerbations in gastrointestinal symptoms. Multiplex polymerase chain reaction-based gastrointestinal pathogen panels (GI PCR) offer significant benefits in sensitivity over conventional tests such as culture and ova and parasites exam. However, it is unclear how additional pathogen positive findings by GI PCR affect further clinical management. In this study we compared the downstream healthcare utilization of IBD patients who received GI PCR to conventional stool testing.
METHOD(S): We reviewed outpatients presenting to an academic medical center with an acute episode of diarrhea from September 2015 to February 2019 to identify patients with IBD who received stool testing with a FilmArray GI PCR or stool culture and ova and parasite exam (conventional testing). All patients received isolated PCR testing for Clostridium difficile. Each GI PCR patient was randomly matched with a conventional testing patient based on age, sex, and date of testing. Post-visit endoscopy, abdominal radiology, antibiotic therapy, and escalation in IBD medical therapy defined as an increase in the dose of a prior medication or prescription of a new medication were recorded. Long-term outcomes including emergency room (ER) visits, hospitalizations, and abdominal surgery were recorded as well. Ttest and Chi-square analysis were used to compare outcomes between groups.
RESULT(S): Among 1,104 patients receiving stool testing, we identified 120 outpatients with IBD, of whom 26 (22%) received conventional stool testing and 94 (78%) GI PCR testing. Of 26 patients with conventional testing, 1 (4%) had a pathogen identified on testing while 36 (38%) of 94 GI PCR patients had positive tests (Table 2). There were no significant differences in demographics, IBD characteristics, rates of C. difficile infection, and behavioral risk factors between groups (P > 0.05). GI PCR patients were less likely to receive any endoscopic exam in the 30-day period after their initial visit (20% vs. 42%, P = 0.021). There were no significant differences in exposure to radiology, antibiotics, escalation of IBD therapy, or long-term IBD outcomes (P > 0.05).
CONCLUSION(S): Testing with GI PCR was associated with lower rates of post-visit endoscopywith no differences in long-term outcomes in outpatients with IBD. This study suggests that in certain populations of patients, GI PCR testing has the potential to reduce downstream healthcare utilization andmanagement burden

INTRODUCTION: Currently, endoscopic remission in ulcerative colitis (UC) is defined using the Mayo Endoscopic subscore (MES), with a score of 0 (normal mucosa) or 1 (erythema, decreased vascular pattern, mild friability) representing mucosal healing. However, it is not clear if clinical outcomes differ between patients with a MES of 0 and 1. The aim of our study was to evaluate differences in relapse rates between patients with MES of 0 and 1.
METHOD(S): UC patients who underwent colonoscopy at 2 IBD referral centers from 2012 to 2017 were identified. Inclusion criteria consisted of patients with a MES score of 0 or 1, no prior colectomy, and outpatient follow up for a minimum of 1 year after colonoscopy. Data was collected for demographics, disease characteristics, medications, time from last disease flare and inflammatory biomarkers. The primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and colectomy. Chi Square, Fisher's exact and logistic regression modeling were used in statistical calculations.
RESULT(S): 446 UC patients were identified, with 228 (51%) and 218 (49%) having a MES of 0 and 1 respectively. 78% were Caucasian, 52% were female and mean age was 40 +/- 15 years. 20, 34, and 46% had proctitis, left sided colitis and extensive or pancolitis, respectively. 46% of patients were on either a 5-ASA alone or no medical therapy, while 46% were on biologics and 27% were on biologic therapy with an immune suppressant. Within 1 year from colonoscopy, 97 (22%) had a change in medical therapy and 66 (15%) were prescribed steroids. Only 8 and 4 patients were hospitalized for UC or underwent colectomy, respectively. UC patients with a MES of 1 were more likely to experience a relapse (P < 0.01) (Table 1). After adjusting for race, disease extent, and medication use, a MES of 1 was the only factor associated with an increased the risk of relapse (aOR 2.54, 1.61-4.01) (Table 2).
CONCLUSION(S): Patients with mild endoscopic activity by MES were at increased risk for relapse compared to patients with no endoscopic activity. In this population of UC patients, MES score was the only variable that predicted future relapse. Future studies are needed to classify low and high risk patients with mild endoscopic activity through evaluation of novel biomarkers and histology. Gastroenterologists should consider enhanced monitoring and/or changes in medical therapy based on the presence of even mild inflammation. (Figure Presented)

INTRODUCTION: Previous studies have demonstrated that exposure to anti-TNFalpha and/or immunomodulators for inflammatory bowel disease (IBD) following a diagnosis of cancer was not associated with an increased risk of new or recurrent cancer. There is little data regarding the use of newer biologics, vedolizumab and ustekinumab, after a diagnosis of cancer. We aimed to investigate whether patients with IBD and a history of cancer who were subsequently exposed to vedolizumab or ustekinumab have an increased risk of developing new or recurrent cancer.
METHOD(S): We reviewed the medical records of 5062 patients with IBD and cancer from an academic medical center between January 2013 and November 2018 to identify IBD patients who received vedolizumab or ustekinumab following a diagnosis of cancer. We collected demographic, IBD and cancer-related data. Our primary outcome was the development of new or recurrent cancer. Results were compared to historical data regarding the risk of new or recurrent cancer in patients exposed to anti-TNFalpha, an immunomodulator or no therapy for IBD following a diagnosis of cancer.
RESULT(S): We identified IBD patients who received vedolizumab (n = 59) or ustekinumab (n = 18) monotherapy following a diagnosis of cancer (Table 1). The median age at cancer diagnosis was 51 years (IQR 43-65) for vedolizumab and 57 years (IQR 55-66) for ustekinumab. During a median follow-up of 68 months (IQR 21-132) for vedolizumab and 48 months (IQR 12-96) for ustekinumab, 3 (5%) and 3 (17%) patients developed subsequent cancer, respectively. Compared to historical data, there were differences in subsequent cancer risk between exposure groups (Figure 1; log-rank 0.001). However, when adjusted for stage of prior cancer, compared to no therapy, there was no difference in risk of new or recurrent cancer between patients exposed to vedolizumab (HR 0.01, 0.01-7.58), ustekinumab (HR 0.85, 0.11-6.50), anti-TNFalpha (HR 0.60, 0.34-1.07) or immunomodulators (HR 1.01, 0.58-1.75) following a diagnosis of cancer.
CONCLUSION(S): In this single-center study, exposure to vedolizumab or ustekinumab in patients with IBD and a history of cancer conferred a low risk of new or recurrent cancer. Exposure to vedolizumab or ustekinumab monotherapy was not associated with an increased risk of subsequent cancer compared to historical data of exposure to anti-TNF, immunomodulators or no immunosuppression following a diagnosis of cancer. Larger studies are needed to confirm these findings. (Figure Presented)

Background/Purpose : Prevalence of sacroiliitis (SI) in Crohn's disease (CD) varies widely (range 4% -39%), depending on criteria utilized to define the disease (e.g. inflammatory back pain, plain radiographs or MRI). Sacroiliitis may remain underdiagnosed in CD patients given lack of association with clinical symptoms of back pain and CD activity. However, patients with CD often undergo magnetic resonance enterography (MRE) to assess extent, severity of small bowel CD and radiographic healing, affording clinicians the opportunity to evaluate for the presence of active and/or chronic SI. We sought to identify the prevalence of sacroiliitis in CD patients utilizing MRE and determine its relationship with CD activity, especially with concurrent biologic therapy. Methods : All CD subjects undergoing MRE between years 2014-2018 at a large IBD referral center were identified. A musculoskeletal radiologist, blinded to clinical data, reviewed all MRE exams for the presence of acute bone marrow edema (BME) lesions and chronic lesions suggestive of acute and chronic SI, respectively. A second radiologist, also blinded, assessed MRE for mucosal CD activity using validated measures. Charts were reviewed for demographics, IBD characteristics, presence of back pain, clinical and endoscopic activity of CD, and Crohn's therapies within 3 months of MRE. Comparisons were made between CD subjects with and without SI using chi-square test. Univariate and multivariate logistic regression were used to determine risk factors of SI. Results : 258 subjects with CD underwent MRE during the study period with a mean age of 35 years old, 53% (n=138) were male, and mean duration of CD at the time of MRE was 9 years. Few reported back pain (8%) and 14% had previously seen a rheumatologist. Overall, 17% (n=45) of patients had MR evidence of sacroiliitis (Table 1). Female gender, presence of back pain, and later age of CD diagnosis were associated with signs of sacroiliitis (p=0.05, p< 0.001, p=0.04 respectively; Table 2). Stricturing phenotype was associated with a lower rate of SI (7% vs. 24%; p=0.018), but inflammatory or penetrating phenotypes were not. CD location, activity as noted by clinical scores, endoscopic disease activity, or radiographic disease activity on MRE, were not associated with sacroiliitis (Table 2). On multivariable analysis, back pain was associated with the presence of sacroiliitis on MRE (OR 3.0, 95% CI 1.1-5.6; p=0.04). Concurrent CD therapy with biologics did not lower the risk of sacroiliitis. Conclusion : Although often underdiagnosed, SI is a common comorbid condition in CD. While recent history of back pain was associated with the presence of sacroiliitis visualized on MRE, no correlations were found with other clinical and endoscopic markers of CD activity. Moreover, concurrent CD therapy, especially biologics, was not associated with a lower risk of sacroiliitis on MRE. With limited clinical clues and CD characteristics to suggest sacroiliitis, gastroenterologists can utilize MRE as a screening tool to detect SI and refer CD patients to rheumatologists. Presence of SI on MRE in CD patients with back pain may help identify a subset of individuals likely to benefit from switching to therapies with proven efficacy in axial SpA

BACKGROUND:Low socioeconomic status has been linked with numerous poor health outcomes, but data are limited regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by IBD patients based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status. METHODS:We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid with all other patients. RESULTS:Of 947 patients with IBD, 221 (23%) had been enrolled in Medicaid. Compared with patients with other insurance types, patients with Medicaid had higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, and ethnicity, patients with Medicaid had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Patients with Medicaid had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001), and after adjusting for the same factors, the odds of requiring steroids in the patients with Medicaid was increased (OR 3.77; 95% CI 2.53-5.62). CONCLUSIONS:Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases that lead to progressive bowel damage including the development of stricturing and penetrating complications. Increasingly, cross-sectional imaging with computed tomography or magnetic resonance scans have emerged as leading tools to: (1) assess disease activity; (2) monitor response to therapy or disease recurrence; and (3) identify disease-related complications. Several validated radiological scoring systems have been developed to quantify cross-sectional and longitudinal inflammatory burden in these diseases and to monitor response to treatment. Bowel ultrasound is also a simple and inexpensive tool but is operator dependent in its performance.

BACKGROUND: Low socioeconomic status has been linked to numerous poor health outcomes, but there is little data regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by patients with IBD based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status.
METHOD(S): We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid to all other patients.
RESULT(S): Of 947 patients with IBD, 221 (23%) ever had Medicaid. Compared to other insurances, Medicaid patients had significantly higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or ever visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, race, and ethnicity, Medicaid patients had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Medicaid patients had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001) and after adjusting for the same factors, the odds of requiring steroids in the Medicaid population was increased (OR 3.77; 95% CI 2.53-5.62). CONCLUSION(S): Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often