Faculty Bibliography

Background: Ozanimod, a sphingosine, 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in multiple countries for the treatment of relapsing multiple sclerosis and in the United States for the treatment of moderately to severely active Ulcerative Colitis (UC). A treat-to-target strategy for Inflammatory Bowel Disease (IBD) has been outlined in the Selecting Therapeutic Targets in IBD (STRIDE-II) consensus recommendations. Mucosal healing was identified as an important treatment target and may be associated with improved patient (pt) outcomes. Here we assess the relationship between early mucosal healing at week (wk), 10 and clinical outcomes at wk, 52 in ozanimod-treated pts with moderately to severely active UC in the phase, 3 True North trial (NCT02435992).
Method(s): A subset of pts in True North were randomised to and/or received oral ozanimod, 0.92 mg (equivalent to ozanimod HCl, 1 mg) during the, 10-wk induction period, achieved clinical response at wk, 10 and continued ozanimod during the maintenance period. For this post hoc analysis, we examined clinical remission, corticosteroid (CS)-free remission, and mucosal healing at wk, 52 in pts with versus without mucosal healing at wk, 10. Clinical remission was defined as rectal bleeding subscore = 0, stool frequency subscore <=1 (and >=1-point reduction from baseline), and mucosal endoscopy subscore (MES) <=1 without friability. CS-free remission was defined as remission with no CS use for >=12 wk. Mucosal healing was defined as MES <=1 without friability and a Geboes score <2.0.
Result(s): Demographics and disease characteristics were generally well balanced between ozanimod-treated pts with (n=44) and without (n=186) mucosal healing at wk, 10, albeit a higher proportion of pts without mucosal healing had prior biologic exposure. Higher proportions of ozanimod-treated pts who achieved mucosal healing at wk, 10 had clinical remission, CS-free remission, and mucosal healing at wk, 52 versus pts who did not achieve mucosal healing at wk, 10 (Figure). Among the ozanimod-treated pts who did not achieve mucosal healing at wk, 10, 24.2% went on to achieve mucosal healing at wk 52.
Conclusion(s): Using a novel, stringent definition for mucosal healing, which requires endoscopic improvement and histologic remission (Geboes <2.0), ozanimod-treated pts who achieved mucosal healing at wk, 10 had improved clinical, endoscopic, and histologic outcomes at wk, 52. A proportion of pts who did not reach mucosal healing at wk, 10 benefited from longer ozanimod treatment, achieving mucosal healing at wk 52. (Figure Presented)

BACKGROUND AND AIMS/OBJECTIVE: METHODS:L on the soonest peripheral blood drawn within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of 3 large, unaffiliated hospital networks, tested positive for CDI by stool polymerase chain reaction, and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. RESULTS:There were 4518 unique hospitalized adults with CDI included (2142 in the derivation cohort and 2376 in the validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts. In the validation cohort, the factors most strongly associated with death were eosinopenia (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.77-3.50), albumin <3 g/dL (aOR 3.26, 95% CI 2.13-3.49), and creatinine >1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A 6-variable clinical prediction model was developed that improved on existing classification schemes for CDI severity (area under the receiver operating characteristic curve of 0.75 vs 0.68). CONCLUSION/CONCLUSIONS:Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

Background/UNASSIGNED:Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. Objectives/UNASSIGNED:We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. Design/UNASSIGNED:We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Methods/UNASSIGNED:Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. Results/UNASSIGNED: = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). Conclusion/UNASSIGNED:In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

Introduction/UNASSIGNED:Diarrhea is common in persons living with HIV (PLWH)/AIDS. With the increasing utilization of multiplex gastrointestinal PCR panel (GI panel) testing, we aimed to characterize the roles of CD4 count and hospitalization in GI panel assessments of PLWH with acute diarrhea. Methods/UNASSIGNED:We performed a cross-sectional study of adult PLWH with acute diarrhea who underwent GI panel testing at two urban academic centers. Demographic, HIV disease, GI panel result, and hospitalization data were collected, and patients were cohorted by CD4 count (CD4 < 200, CD4 200-499, CD4 > = 500). The primary outcome was enteric infection as detected by GI panel, and hospitalization. Results/UNASSIGNED:, giardiasis, and multiple pathogens. MSM status independently predicted enteric infection (aOR 1.93, 95% CI: 1.02-3.67). Conclusions/UNASSIGNED:GI panel results vary by HIV disease severity and hospitalization in PLWH. Clinicians - especially in the inpatient setting - should carefully consider these factors when interpreting GI panel results. Further characterization of diarrheal etiology in PLWH with a negative GI panel is needed. Plain Language Summary/UNASSIGNED:

BACKGROUND:There is wide variation in the quality of care of hospitalized patients with inflammatory bowel disease (IBD). Prior studies have demonstrated that a specialized inpatient IBD service improves short-term outcomes. In this study, we assessed the impact of a dedicated IBD service on the quality of care and long-term outcomes. METHODS:This retrospective cohort study included adult patients admitted for a complication of IBD between March 2017 and February 2019 to a tertiary referral center. In March 2018, a dedicated inpatient IBD service co-managed by IBD gastroenterologists and colorectal surgeons was implemented. Quality of care outcomes included C. difficile stool testing, confirmed VTE prophylaxis administration and opiate avoidance. Long-term outcomes were clinical remission, IBD-related surgery, ED visits, and hospital readmissions at 90 days and 12 months. RESULTS:In total, 143 patients were included; 66 pre- and 77 post-implementation of the IBD service. Fifty-two percent had ulcerative colitis and 48% had Crohn's disease. After implementation, there was improvement in C.difficile testing (90% vs. 76%, P = 0.04), early VTE prophylaxis (92% vs. 77%, P = 0.01) and decreases in narcotic use (14% vs. 30%, P = 0.02), IBD-related ED visits at 90 days (7% vs 18%, P = 0.03) and 12 months (16% vs 30%, P = 0.04), and IBD readmissions at 90 days (16% vs. 30%, P = 0.04). There were no differences in rates of clinical remission or surgery. CONCLUSIONS:The creation of a dedicated inpatient IBD service improved quality of IBD care and reduced post-discharge ED visits and readmissions and broader implementation of this strategy may help optimize care of hospitalized IBD patients.

BACKGROUND:Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compare the impact of PCR stool testing to conventional stool testing in outpatients presenting with relapse of IBD. METHODS:In a retrospective cohort study of outpatients with IBD presenting to NYU Langone Health with flare from September 2015 to April 2019, we compared patients who underwent stool testing with GI PCR to age-, sex-, and IBD-subtype-matched patients who underwent culture and ova and parasite exam (conventional testing). The primary outcome was IBD therapy escalation after testing. Secondary outcomes included rates of posttesting endoscopy, abdominal radiography, antibiotics, and IBD-related emergency department visits, hospitalizations, and abdominal surgeries. RESULTS:We identified 134 patients who underwent GI PCR matched to 134 patients who underwent conventional testing. Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01). We found that GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes. On multivariate analysis, testing with GI PCR was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; P = 0.02) for escalation of IBD therapies. CONCLUSIONS:Testing with GI PCR was associated with higher rates of pathogen detection and lower rates of IBD therapy escalation and endoscopy in the outpatient setting. These changes in management were not associated with a difference in IBD outcomes.

Introduction: Traveler's diarrhea is the most common travel related illness and is often encountered in the outpatient setting. Most pathogens that cause traveler's diarrhea are poorly characterized by conventional stool testing such as stool culture and ova and parasite exam. Multiplex polymerase chainreaction based gastrointestinal pathogen panels (GI PCR) offer advantages in sensitivity and turnaround time, however their impact on clinical management is unclear. Our aim was to evaluate the clinical impact of GI PCR testing in outpatients presenting with traveler's diarrhea.
Method(s): We performed a retrospective study comparing outpatients presenting with acute gastrointestinal symptoms at an academic medical center who received stool testing with GI PCR from September 2015 to April 2019, to patients who presented with similar symptoms from February 2009 to April 2012, when GI PCR was unavailable, and received stool culture and ova and parasite exam ("conventional testing"). Patients who received GI PCR were matched by age and sex to patients who received conventional testing. We recorded pathogens isolated, demographic data, history of travel within 30 days of presentation, presenting symptoms and rates of antibiotic therapy.
Result(s): We identified 1,018 outpatients who received GI PCR or conventional stool testing. (n5509 each). There were 70 patients in the conventional cohort and 78 in the GI PCR cohort, respectively, with traveler's diarrhea. In patients who received GI PCR, we observed higher diagnostic yield in patients with traveler's diarrhea who received GI PCR, compared to patients without a history of recent travel (54 vs. 39%, p50.01, Table 1). There was no difference in diagnostic yield in patients who received conventional stool testing (9 vs 10%, p50.74). Patients with travelers' diarrhea were more likely to have pathogenic species of Escherichia coli (E. coli) identified on testing (45 vs. 22%, p, 0.01, Table 2), particularly Enteroaggregative E. coli (23 vs. 6%, p, 0.01). Patients with traveler's diarrhea were more likely to receive antibiotics whether they received GI PCR (38 vs. 27%, p50.04) or conventional testing (35 vs. 25%, p50.06).
Conclusion(s): GI PCR was associated with a higher diagnostic yield in patients presenting with travelers' diarrhea. Patients with travelers' diarrhea were significantly more likely to have pathogenic E. coli species identified on PCR testing, with up to 45% of patients testing positive

Introduction: Previous clinical trials and societal guidelines have established preoperative risk factors for postoperative recurrence (POR) of Crohn's disease (CD). However, in patients who are in endoscopic remission at time of their index postoperative ileocolonoscopy, risk factors for later development of POR is unknown. This study aimed to assess the relative risk of POR after initial endoscopic remission.
Method(s): Retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between the years of 2009-2020. Patients with bowel continuity restoration and index postoperative ileocolonoscopy with modified Rutgeerts' score of <= i2a disease were included. Postoperative ileocolonoscopies were assessed by retrospective application of Rutgeerts' score. The primary outcome was a composite outcome of objective recurrence including radiologic (active disease on cross-sectional enterography), endoscopic (Rutgeerts score >= i2b), and surgical (repeat ICR) POR after initial endoscopic remission.
Result(s): 232 CD patients (median age 35 years, 45.2% stricturing, 15.5% >=2 prior ICR) with initial endoscopic remission (98 i0, 49 i1, 85 i2a disease) were included in the study. The median time to index postoperative colonoscopy was 334 days. 131 (56.5%; 46.9% i0, 53.1% i1,69.4% i2a) patients went on to develop composite POR at median interval of 2.84 years. Risk of composite POR was associated with index Rutgeerts' score (p=0.008; 41.4% endoscopic POR, 38.3% radiologic POR, 14.2% surgical POR). On multivariable Cox proportional hazard regression, patients with i1 disease (aHR: 1.76 95% CI [1.04-2.99]; p=0.036) or i2a disease (aHR; 2.24 [1.49-3.36]; p<0.001) at initial postoperative colonoscopy were at increased risk for composite POR relative to patients with i0 disease (Figure 1; Table 1). Additionally, patients that were exposed to biologics prior to ICR were at increased risk for late POR relative to biologic-naive patients (aHR: 1.84 [1.15-2.95]; p=0.012). Patients with i2a disease was independently associated with decreased time to radiologic (aHR: 1.66 [1.04-2.65]; p=0.033), endoscopic (aHR:2.85 [1.76-4.59]; p<0.001 ), and surgical (aHR: 2.42 [1.11-5.29]; p=0.027) POR (Table 1).
Conclusion(s): Postoperative CD recurrence following early endoscopic remission is common. Early mild ileal or anastomotic inflammation confers increased risk for late recurrence. Future studies to determine surveillance strategies for patients in initial endoscopic remission are needed

Introduction: The impact of isolated postoperative anastomotic lesions on future Crohn's disease (CD) progression is controversial. This study aimed to evaluate the risk of severe disease progression in postoperative CD patients with isolated anastomotic disease.
Method(s): Retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between the years 2009-2020. Patients with bowel continuity restoration, a postoperative colonoscopy <= 18 months from surgery, and >= 1 subsequent colonoscopy were included. Disease activity was assessed utilizing retrospective application of modified Rutgeerts' score (RS) by a centralized reader. Primary outcome was severe endoscopic progression, defined as i3 or i4 disease. Secondary outcome was surgical recurrence defines as repeat ICR.
Result(s): 199 CD patients (median age 34 years, 47.7% stricturing, 33.2% >=1 prior ICR) with index postoperative colonoscopy RS of i0-i2b were included. Study population RS distribution was 28.8% (n=69) i0, 13.3% (n=32) i1, 20.4% (n=49) i2a, 20.4% (n=49) i2b. Median time from ICR to index colonoscopy (260 days [195,377.5]; p=0.83) and time to follow up endoscopy (441 days [335,746.5]; p=0.65) did not differ by index RS. Overall, 26.1% of patients experienced severe endoscopic disease progression and was associated with index RS (p<0.001) (Figure 1). During entire follow up, adjusting for index RS, tobacco use, >=2 prior ICR, and initiation of biologics after index ileocolonoscopy, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR: 5.53 95% CI [2.50-12.76]; p<0.001) and i2a disease (aOR: 2.63 [1.12-6.4];p=0.03). Conversely, i2a disease did not confer increased risk compared to patients in endoscopic remission (2.11 [0.89-4.97]; p=0.087) (Table 1). On multivariable Cox proportional hazard model, adjusting for risk factors, i2b disease was associated with decrease time to severe endoscopic disease progression relative to i0 or i1 disease (aHR: 4.68 [2.42-9.02]; p<0.001) and i2a (aHR: 3.02 [1.50-6.09]; p=0.002). i2a was not associated with decreased time to endoscopic progression relative to i0 or i1 (p=0.25) (Table 1). Surgical recurrence was not associated with index RS (p=0.86).
Conclusion(s): Mild ileal postoperative recurrence, not isolated anastomotic lesions, is associated with increased risk for severe endoscopic disease progression. Prospective studies are needed to further elucidate impact of isolated anastomotic inflammation

Introduction: Postoperative prophylaxis with biologics following ileocecal resection (ICR) for Crohn's disease (CD) reduces endoscopic postoperative recurrence (POR) rates. However, there is limited data regarding optimal treatment strategies of endoscopic POR. We aimed to assess the outcomes of various therapeutic regimens to treat endoscopic POR despite biologic prophylaxis.
Method(s): Retrospective cohort study of adult CD patients who underwent ICR between 2009-2020 at single referral institution. Patients with bowel continuity restoration, first detection of endoscopic POR whilst on a biologic, and >=1 postoperative colonoscopy were included. Modified Rutgeerts' score assessed disease activity and endoscopic POR was defined as Rutgeerts' >=i2b. Treatment changes after POR detection were categorized as therapy optimization (steroids, immunomodulators, dose intensification of biologic, new biologic within class) or new biologic class. The primary outcome of the study was treatment failure defined as endoscopic POR at immediate follow up colonoscopy or surgical POR prior to subsequent colonoscopy. Secondary outcome was endoscopic healing at follow up endoscopy.
Result(s): 81 CD patients with endoscopic POR (54.6% i2b, 22.2% i3, and 22.2% i4) despite biologic prophylaxis were included. A majority (85.4%) were on anti-TNF, 8.6% vedolizumab, and 4.9% were on ustekinumab at time of POR. The predominant intervention was therapy optimization (76.3%, n=61) while 24.7% (n=20) were started on a new biologic class. 60 patients, comprised of 48 (78.7%) therapy optimization and 12 (60.0%) new biologic class, experienced treatment failure (84.6% endoscopic, 15.4% surgical) (P=0.08). On multivariable modeling, initiation of new biologic class was associated with reduced risk for treatment failure compared to therapy optimization (aOR: 0.26 [0.07-0.93]; p=0.04) (Table 1). In patients without surgical POR (n=68), 28 patients, comprised of 18 (35.3%) therapy optimization and 10 (58.9%) of new biologic class, had endoscopic healing at time of follow up endoscopy. On modeling adjusting for endoscopic severity, initiation of new biologic class was associated with endoscopic healing relative to therapy optimization (aOR: 3.3 [1.0-11.92]; p=0.05).
Conclusion(s): In CD patients who experience POR despite biologic prophylaxis, changing mechanism of action may promote greater endoscopic healing than therapy optimization. Larger studies assessing factors associated with response and prospective trials are needed to confirm results