Faculty Bibliography

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing intestinal neoplasia-particularly colorectal neoplasia, including dysplasia and colorectal cancer (CRC)-as a primary consequence of chronic inflammation. While the current incidence of CRC in IBD is lower compared with prior decades, due, in large part, to more effective therapies and improved colonoscopic technologies, CRC still accounts for a significant proportion of IBD-related deaths. The focus of this review is on the pathogenesis; epidemiology, including disease- and patient-related risk factors; diagnosis; surveillance; and management of IBD-associated neoplasia.

Background/UNASSIGNED:The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization. Methods/UNASSIGNED:In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization. Results/UNASSIGNED:We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034). Conclusion/UNASSIGNED:Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.

INTRODUCTION: Diarrhea is a common complication of HIV/AIDS. Although non-infectious enteropathy may be attributed to HIV infection, enteric pathogens are frequently detected in episodes of diarrhea. The objective of this study was to investigate the relationship between CD4 count and enteric infection as detected by multiplex gastrointestinal PCR stool testing in HIV/AIDS patients.
METHOD(S): We performed a cross-sectional analysis of adult inpatients and outpatients who underwent stool testing with a FilmArray multiplex gastrointestinal pathogen PCR panel (GI PCR panel) during an acute episode of diarrhea from December 2015 to February 2019. Our primary endpoint was the detection of any enteric pathogen. Patients were stratified by the presence of HIV infection and CD4 count at time of stool testing.
RESULT(S): Of 80 HIV+patients who underwent a GI PCR panel, 45 (56%) tested positive for an enteric pathogen (Table 1). HIV+patients with CD4 counts >500 (n=26) were more likely to have a pathogen detected (19, 73%) compared to patients with a CD4 count <200 (n=30) consistent with AIDS (12, 40%; P=0.03; Figure). Patients with a CD4 count between 201 and 499 (n=24) had a positivity rate that was in between that of patients with low and high CD4 counts (14, 58%). Of 30 AIDS patients, 9 (30%) had a GI infection not detected by GI PCR including CMV, HSV, LGV, MAI, and syphilis. Among this subset of 9 AIDS patients, 4 (44%) tested negative on GI PCR. AIDS patients were less likely to be adherent to antiretroviral therapy, and more likely to be on opportunistic infection prophylaxis compared to HIV+patients with CD4 counts >200 (P=0.03 and P=0.002 respectively.) Compared to patients with CD4 counts >200, those with AIDS were more likely to receive empiric antimicrobial therapy at stool testing (P<0.001), and in the 30 days following stool testing, as likely to visit an emergency room (P=0.24), require hospitalization (P=0.31), or undergo endoscopic procedures for continued GI symptoms (P=0.67).
CONCLUSION(S): Enteric infections were common in HIV+patients who underwent a GI PCR panel for an episode of diarrhea, with the highest proportion of positive results in patients with CD4 counts >500. Based on historical data, this rate of positivity is considerably higher than in the general population of patients with an episode of diarrhea. These data suggest that AIDS patients may be more likely to have a pathogen not included on the GI PCR panel, or a chronic cause of diarrhea such as HIV-enteropathy

INTRODUCTION: Diarrhea is a common sequela of solid organ transplantation. Post-transplant diarrhea may be attributed to non-infectious causes including medications, however the contribution of infectious etiology is unclear. The objective of our study was to evaluate the relationship between post-transplant immunosuppression and enteric infection as detected by multiplex gastrointestinal PCR stool testing in solid organ transplant (SOT) recipients.
METHOD(S): We performed a multicenter cross-sectional analysis of inpatient and outpatient SOT recipients who underwent stool testing with a FilmArray multiplex gastrointestinal pathogen PCR panel (GI PCR panel) during an acute episode of diarrhea from April 2016 to May 2019. The primary endpoint was the detection of any enteric pathogen. Patients were stratified by the number of major classes of immunosuppressive agents, including calcineurin inhibitors, anti-proliferative agents, and corticosteroids, at time of stool testing.
RESULT(S): We identified 232 SOT patients who underwent a GI PCR panel comprising 52 (23%) lung, 84 (36%) kidney, 41 (18%) heart, and 55 (24%) liver transplants. 92 (40%) tested positive for an enteric pathogen. Patients whose immunosuppressive regimen included 3 medications (n = 139) were more likely to have a gastrointestinal pathogen detected (63, 45%) compared to patients on 2 immunosuppressive medications (P = 0.02; Figure 1) Renal transplant patients were more likely to have an enteric pathogen detected (60%; P < 0.0001) compared to other organ types, and more likely to be on 3 immunosuppressive medications (P < 0.01). Viruses, specifically norovirus and sapovirus, and bacteria, including C. difficile and E. coli subtypes, were common in transplant recipients on 2 immunosuppressive agents (Table 1). Of 139 patients on 3 immunosuppressive agents, 89 (59%) were more likely to be on opportunistic infection prophylaxis for CMV and P. jiroveciipneumonia compared to those patients on 2 drugs (P < 0.001). In the 30 days following stool testing, all SOT recipients, regardless of the number of immunosuppressive drugs, were as likely to visit an emergency room (P = 0.57), require hospitalization (P = 0.66), or undergo endoscopic procedures for persistent GI symptoms (P = 0.78).
CONCLUSION(S): Gastrointestinal infections, particularly enteric viruses, were common in SOT recipients who underwent a GI PCR panel for an episode of post-transplant diarrhea, with the highest proportion of positive results in patients maintained on 3 or more immunosuppressive agents

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)