Faculty Bibliography

BACKGROUND/UNASSIGNED:The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. OBJECTIVES/UNASSIGNED:We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. DESIGN/UNASSIGNED:We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. METHODS/UNASSIGNED:Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. RESULTS/UNASSIGNED: = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. CONCLUSION/UNASSIGNED:telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.

The human immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we utilize multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after BNT162b2 immunization. Our data reveal distinct subpopulations of CD8 ⁺ T cells which reliably appear 28 days after prime vaccination (7 days post boost). Using a suite of cross-modality integration tools, we define their transcriptome, accessible chromatin landscape, and immunophenotype, and identify unique biomarkers within each modality. By leveraging DNA-oligo-tagged peptide-MHC multimers and T cell receptor sequencing, we demonstrate that this vaccine-induced population is SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we also identify these CD8 ⁺ populations in scRNA-seq datasets from COVID-19 patients and find that their relative frequency and differentiation outcomes are predictive of subsequent clinical outcomes. Our work contributes to our understanding of T cell immunity, and highlights the potential for integrative and multimodal analysis to characterize rare cell populations.

BACKGROUND & AIMS:Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS:We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS:In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS:In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Patients with chronic ulcerative and Crohn's colitis are at increased risk for colorectal neoplasia(CRN [dysplasia and cancer]) compared to the general population. Risk factors for CRN include extent of colitis, cumulative inflammatory burden, family history of colorectal cancer, and primary sclerosing cholangitis. Best practices to prevent CRN include control of colonic inflammation, high quality surveillance colonoscopy with or without enhanced imaging techniques, resection of visible dysplasia if possible, and colectomy in patients with unresectable dysplasia, invisible multifocal low grade dysplasia, or invisible high grade dysplasia. Cessation of dysplasia surveillance is individualized and should involve shared decision making based on factors including but not limited to chronologic age, frailty, co-morbid conditions, life expectancy, results of prior surveillance exams, and risk factors for CRN.

INTRODUCTION/BACKGROUND:Enteric infection with Clostridioides difficile , Escherichia coli subtypes, and norovirus is commonly detected in flares of inflammatory bowel disease (IBD). We associated the gut microbiome during flare complicated by a gastrointestinal pathogen with outcomes of IBD. METHODS:We performed a cross-sectional study of 260 patients (92 IBD and 168 non-IBD) with a gastrointestinal polymerase chain reaction panel positive for C. difficile, E. coli , or norovirus, or negative during an episode of diarrhea from 2018 to 2020, and 25 healthy controls. Clinical variables, IBD status, and 2-year outcomes were collected. Using 16S rRNA sequencing, we measured the effect size of the gut microbiome on IBD characteristics and outcomes. RESULTS:There were major differences in the gut microbiome between patients with and without a pathogen and IBD. In IBD, a higher proportion of patients without a pathogen required hospitalization and IBD therapies at flare and within the 2 years after flare, driven by a milder disease course in flares complicated by an E. coli subtype or norovirus. Examining the contribution of clinical covariates, the presence of IBD, and C-reactive protein, C. difficile had a greater relative influence on the gut microbiome compared with the presence of an E. coli subtype or norovirus. In patients with C. difficile or no pathogen, lower microbiome diversity at flare was associated with adverse IBD outcomes over 2 years. DISCUSSION/CONCLUSIONS:Distinctive pathogen-specific gut microbiomes were associated with subsequent IBD outcomes. These findings may have direct implications for the management of IBD flares complicated by enteric pathogens.

BACKGROUND:The prognostic significance of histology in ileal pouch-anal anastomosis (IPAA) remains unclear. The aim of this study was to evaluate if histologic variables are predictive of IPAA clinical outcomes and healthcare utilization. METHODS:This was a retrospective cohort study of patients with IPAA undergoing surveillance pouchoscopy at a tertiary care institution. Pouch body biopsies were reviewed by gastrointestinal pathologists, who were blinded to clinical outcomes, for histologic features of acute or chronic inflammation. Charts were reviewed for clinical outcomes including development of acute pouchitis, chronic pouchitis, biologic or small molecule initiation, hospitalizations, and surgery. Predictors of outcomes were analyzed using univariable and multivariable logistic and Cox regression. RESULTS:A total of 167 patients undergoing surveillance pouchoscopy were included. Polymorphonuclear leukocytes (odds ratio [OR], 1.67), ulceration and erosion (OR, 2.44), chronic inflammation (OR, 1.97), and crypt distortion (OR, 1.89) were associated with future biologic or small molecule initiation for chronic pouchitis. Loss of goblet cells was associated with development of chronic pouchitis (OR, 4.65). Pyloric gland metaplasia was associated with hospitalizations (OR, 5.24). No histologic variables were predictive of development of acute pouchitis or surgery. In an exploratory subgroup analysis of new IPAA (<1 year), loss of goblet cells was associated with acute pouchitis (OR, 14.86) and chronic pouchitis (OR, 12.56). Pyloric gland metaplasia was again associated with hospitalizations (OR, 13.99). CONCLUSIONS:Histologic findings may be predictive of IPAA outcomes. Pathologists should incorporate key histologic variables into pouchoscopy pathology reports. Clinicians may need to more closely monitor IPAA patients with significant histologic findings.

BACKGROUND:Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS:We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS:We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION/CONCLUSIONS:Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

BACKGROUND:Many patients with Crohn's disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded rectums. METHODS:We reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up. RESULTS:From all the CD patients in the institutions' databases, there were 197 who met all our inclusion criteria. A total of 92 (46.7%) of 197 patients ultimately underwent subsequent proctectomy, while 105 (53.3%) still had retained rectums at time of last follow-up. Among these 105 patients with retained rectums, 50 (47.6%) underwent reanastomosis, while the other 55 (52.4%) retained excluded rectums. Of these 55 patients whose rectums remained excluded, 20 (36.4%) were symptom-free, but the other 35 (63.6%) were symptomatic. Among the 50 patients who had been reconnected, 28 (56%) were symptom-free, while 22(44%) were symptomatic. From our entire cohort of 197 cases, 149 (75.6%) either ultimately lost their rectums or remained symptomatic with retained rectums, while only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems. Four patients developed anorectal dysplasia or cancer. CONCLUSIONS:In this multicenter cohort of patients with CD who had fecal diversion, fewer than 15%, and only 6% with perianal disease, achieved reanastomosis without experiencing disease persistence.

Introduction: Ileocecal resection (ICR) often leads to remission of Crohn's Disease (CD), but relapse is common. Guidelines suggest postoperative biologic prophylaxis in high-risk patients and colonoscopy within 6-12 months of surgery to assess for post-operative recurrence (POR). Guidance on adjunctive disease monitoring modalities such as biomarkers and cross-sectional imaging is lacking. We aimed to describe the real-world surveillance approach for CD patients after ICR in relation to evidence-based guidelines.
Method(s): This was a dual center retrospective study of CD patients who underwent ICR with >=1 year of follow-up. We grouped patients into high- (HR) and low-risk (LR) for POR per guidelines and assessed the use of biomarkers, imaging, and colonoscopy postoperatively. Approaches and recurrence rates in patients who received resection prior to or after 2015, accounting for changing practices with guidelines, were compared. Biomarker, radiographic, and endoscopic POR were defined as high CRP/fecal calprotectin (FC), active inflammation on CT/MRE, and modified Rutgeerts >=i2b, respectively. P-values were calculated using Wilcoxon and Chi squared tests.
Result(s): Of 1026 CD patients who underwent ICR, 798 were HR. For LR patients, median time to first CRP was 244 days (d), FC was 267d, imaging was 579d, and colonoscopy was 392d. For HR patients, median time to first CRP was 183d, FC was 241d, imaging was 460d, and colonoscopy was 352d. 72% of HR patients had at least 1 modality within 1 year compared to 59% of LR. Compared to pre-2015, patients who underwent an ICR in 2015 or later had significantly earlier imaging (543d vs. 379d, p< 0.001) and colonoscopy (404d vs. 292d, p< 0.001). There was no difference in time to first CRP or FC. Timing of ICR was significantly associated with postoperative biologic use and the detection of POR by all methods (p< 0.001).
Conclusion(s): 30% of HR CD patients did not undergo any monitoring within the first year after ICR. Evolving practice patterns suggest earlier disease monitoring with imaging and colonoscopy in more recent years whereas utilization of biomarkers was not changed. These data suggest that while guidelines have changed practice, allowing for the earlier identification of POR and initiation of therapy, many patients remain under-monitored. As earlier monitoring may improve long-term clinical outcomes, additional studies are required to further guide optimal surveillance intervals and use of biomarkers

Introduction: Obesity is associated with an increased risk of colorectal neoplasia, but this relationship has not been studied in patients with inflammatory bowel disease (IBD). Both IBD and obesity induce a chronic inflammatory state, so the combination of the two could have an additive or synergistic effect on risk of colorectal neoplasia. Given the increased baseline incidence of dysplasia among IBD patients, identifying modifiable risk factors, such as obesity, could have a significant impact on long term cancer-related outcomes.
Method(s): We performed a retrospective case-control study of IBD colitis patients at an academic IBD Center between January 2006 and February 2022. Demographic and disease-related data, known risk factors for dysplasia, and median BMI during the follow-up period were obtained. Only patients with at least 5 years of colonoscopy reports were included. A case was defined as any patient with biopsy proven dysplasia-indefinite, low-grade, or high-grade-during the study period. A control was defined as any patient with absence of biopsy-proven dysplasia. Obesity was defined as BMI of 30 or greater. Univariate analysis was performed using T-test for continuous variables and chi-square for categorical variables. Multivariate analysis was performed using logistic regression to model dysplasia risk.
Result(s): 106 cases had biopsy-proven colorectal dysplasia (64 IND, 36 LGD, 10 HGD); 125 controls had no dysplasia. Number of colonoscopies (p < 0.001) IBD subtype ulcerative colitis (p = 0.016), maximum histologic severity (p = 0.127), pseudopolyps (p = 0.162), IBD duration (p = 0.098), sex (p = 0.18), age (p < 0.001), smoking history (p = 0.048), prior dysplasia (p < 0.001), and obesity (p < 0.001) were associated with dysplasia on univariate analysis. On multivariable regression, number of colonoscopies (OR 1.26, 95% CI 1.08 - 1.48, p = 0.004), prior dysplasia (OR 3.98, 95% CI 1.23 - 12.86, p = 0.021), and obesity (OR 2.90, 95% CI 1.21 - 6.95, p = 0.017) were each independently associated with increased dysplasia risk. (Figure)
Conclusion(s): Patients with IBD have an increased risk of colorectal neoplasia, but a variety of comorbid states may exacerbate this risk. Notably, we identified obesity as an independent risk factor for dysplasia. Further research is needed to determine whether this risk functions synergistically with IBD or just as an independent risk factor. Furthermore, targeted weight-loss interventions may reduce the incidence of dysplasia among patients with IBD. (Table Presented)