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.

BACKGROUND:Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE:We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS:The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. RESULTS:We anticipate starting recruitment in December 2022. CONCLUSIONS:Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:PRR1-10.2196/40382.

BACKGROUND:There is little data regarding the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a prior history of cancer who are exposed to ustekinumab or vedolizumab. We assessed the risk of subsequent cancer in patients exposed to these agents. METHODS:We performed a retrospective cohort study of patients with IBD and a history of cancer at an academic medical center between January 2013 and December 2020. We collected data on demographics, IBD and cancer disease characteristics, and drug exposures. The primary exposure was immunosuppressive therapy after diagnosis of cancer. The primary outcome was interval development of new or recurrent cancer. RESULTS:Of 390 patients with IBD and a previous history of cancer, 37 were exposed to vedolizumab, 14 ustekinumab, 41 antitumor necrosis factor (anti-TNF), and 31 immunomodulator; and 267 were not exposed to immunosuppression following cancer diagnosis. During a total median follow-up time of 52 months, 81 (20%) patients developed subsequent cancer: 6 (16%) were exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to immunomodulators, 12 (29%) to anti-TNF, and 56 (21%) with no immunosuppression (P = .41). In a multivariable Cox model adjusting for age, IBD subtype, smoking, cancer recurrence risk, and cancer stage, there was no increase in subsequent cancer with vedolizumab (adjusted hazard ratio, 1.36; 95% CI, 0.27-7.01) or ustekinumab (adjusted hazard ratio, 0.96; 95% CI, 0.17-5.41). Patients with more than 1 biologic exposure also did not have an increased risk of subsequent cancer. CONCLUSIONS:Exposure to ustekinumab or vedolizumab in patients with IBD and a prior history of cancer does not appear to be associated with an increased risk of subsequent new or recurrent cancer.

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

BACKGROUND/UNASSIGNED:Inflammatory bowel disease (IBD) has been linked to adverse pregnancy outcomes, but it is unclear how risks vary by histological activity. METHODS/UNASSIGNED:We performed a nationwide study of Swedish women diagnosed with IBD 1990-2016 and a pre-pregnancy (<12 months) colorectal biopsy with vs. without histological inflammation (1223 and 630 births, respectively). We also examined pregnancy outcomes in 2007-2016 of women with vs. without clinically active IBD (i.e., IBD-related hospitalization, surgery, or medication escalation) <12 months before pregnancy (2110 and 4993 births, respectively). Accounting for smoking, socio-demographics, and comorbidities, generalized linear models estimated adjusted risk ratios (aRRs) for preterm birth (<37 gestational weeks) and small-for-gestational age (SGA, <10th percentile weight for age). FINDINGS/UNASSIGNED:Of infants to women with vs. without histological inflammation, 9.6% (n = 117) and 6.5% (n = 41) were preterm, respectively (aRR = 1.46; 95%CI = 1.03-2.06). Histological inflammation was associated with preterm birth in ulcerative colitis (UC) (aRR = 1.64; 95%CI = 1.07-2.52), especially extensive colitis (aRR = 2.37; 95%CI = 1.12-5.02), but not in Crohn's disease (aRR = 0.99; 95%CI = 0.55-1.78). Of infants to women with vs. without histological inflammation, 116 (9.6%) and 56 (8.9%), respectively, were SGA (aRR = 1.09; 95%CI = 0.81-1.47). Clinically active disease before pregnancy was linked to preterm birth (aRR = 1.42; 95%CI = 1.20-1.69), but not to SGA birth (aRR = 1.13; 95%CI = 0.96-1.32). Finally, of infants to women without clinical activity, histological inflammation was not significantly associated with preterm birth (aRR = 1.20; 95%CI = 0.68-2.13). INTERPRETATION/UNASSIGNED:Histological and clinical activity in IBD, especially in UC, were risk factors for preterm birth. Further research is needed to determine the importance of pre-pregnancy histological activity in women without clinically-defined disease activity. FUNDING/UNASSIGNED:The Swedish Society of Medicine.

Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia.

Introduction: Patients with IBD have a high degree of sexual dysfunction (SD) which has been correlated with depression, disease activity, and past medication use such as steroids and biologic therapy. We aimed to track SD longitudinally and assess the impact of biologic therapy, using IBD-specific scales.
Method(s): Patients with Crohn's disease (CD) and ulcerative colitis (UC) starting a new biologic therapy (anti-TNF, anti-integrin, anti-IL12/23, JAK inhibitor) were surveyed at start of induction therapy and at 6-months. Surveys included the IBD- FSDS and MSDS, PROMIS Brief Sexual Function and Satisfaction Profile, clinical disease activity indices [Harvey-Bradshaw index (HBI), partial Mayo (pMayo) score] and scales that assessed depression [Patient Health Questionnaire-9 (PHQ-9)], and quality of life [Short IBD Questionnaire (SIBDQ)]. Clinical data included inflammatory markers and prior IBD therapies. Therapy response was defined as a reduction in HBI, pMayo, SCCAI >=3 or total HBI <= 4, pMayo < 2, SCCAI <=2 at 6 months.
Result(s): 158 patients (86 males and 72 females) completed surveys at induction, and 101 completed at 6 months. The median age was 31 years, 58% had CD, 42% had UC, and 32% were non-white. At induction, the median MSDS score was 5.5 out of 40 (IQR 2-13) and FSDS was 12 out of 60 (3-27; Table). SD correlated with the SIBDQ (r=0.56, p< 0.001), and PHQ-9 (r=0.51, p< 0.001). MSDS and FSDS scores strongly correlated with PROMIS scores (r= 0.70, p< 0.001), and moderately correlated with the HBI (r=0.49, p=0.002), pMayo and SCCAI score (0.44, p=0.02). SD did not correlate with markers of inflammation. MSDS scores significantly improved at 6 months among all participants (p= 0.048). FSDS and PROMIS scores numerically improved among all participants, but did not reach significance. Both MSDS and FSDS scores significantly improved among therapy responders (p=0.004 and p= 0.042, respectively) as did PROMIS scores. Both patients with prior biologic use and biologic naive patients experienced improvement in sexual function among therapy responders (p=0.02, 0.04).
Conclusion(s): There was a strong correlation between SD, disease activity, depression, and quality of life indices. Biologic therapy improves sexual function in therapy responders, which is again evidenced in this updated cohort. Despite prior data correlating prior biologic use with SD, our new findings in this longitudinal study show improvement in SD in patients who are both biologic naive and those with prior use. (Table Presented)

Introduction: Inflammatory bowel disease (IBD), comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD), is caused by a combination of environmental factors, immune dysregulation, and genetic susceptibility. Other immune-mediated phenomena, like hypothyroidism, have also been observed in this population. Thus, we sought to explore clinical characteristics and outcomes among IBD patients with hypothyroidism compared to IBD patients without hypothyroidism.
Method(s): In a retrospective chart review from a large, tertiary, academic medical center, baseline demographics and clinical data were extracted for patients diagnosed with either UC or CD and having at least one thyroid stimulating hormone (TSH) measurement from prior to 2016. Based on the presence of a documented hypothyroidism ICD-10 code, patients were then divided into two groups, those with IBD alone and those with both IBD and hypothyroidism, as described in Figure. Individual charts were then further examined for disease characteristics, biomarkers, healthcare utilization, medication use, and other comorbidities from 2016 to 2022. Demographic and clinical variables were then compared between the two groups, as seen in Table.
Result(s): We identified 166 adult IBD patients (CD 53%, UC 47%). The mean age was 62.9 years. Among these patients, 116 patients (69.9%) had IBD and hypothyroidism. The most common causes of hypothyroidism were Hashimoto, subclinical, and acquired hypothyroidism. No differences were noted in race, smoking status, or BMI. IBD disease location, behavior, and prevalence of extra-intestinal manifestations did not significantly differ between the two study groups. Both groups had similar number of colonoscopies, hospitalizations, as well as comparable medication use (SSRI/SNRI, steroids, 5-ASA, immunomodulators, biologics). However, patients with IBD and hypothyroidism had higher rates of anemia (p=0.03), hypoalbuminemia (p=0.007), and CRP elevations (p=0.002). Furthermore, patients with both IBD and hypothyroidism had a greater median number of emergency department visits (p=0.039) and axial radiography (p=0.002).
Conclusion(s): IBD patients with hypothyroidism experience a more severe disease course with higher biomarkers of inflammation and healthcare utilization than those without hypothyroidism despite similar IBD phenotype and therapy exposures. This highlights a potential subgroup of IBD patients who may be at risk for increased disease severity and associated poor outcomes. (Table Presented)

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

Loss of Paneth cells and their antimicrobial granules compromises the intestinal epithelial barrier and is associated with Crohn's disease, a major type of inflammatory bowel disease^1-7. Non-classical lymphoid cells, broadly referred to as intraepithelial lymphocytes (IELs), intercalate the intestinal epithelium^8,9. This anatomical position has implicated them as first-line defenders in resistance to infections, but their role in inflammatory disease pathogenesis requires clarification. The identification of mediators that coordinate crosstalk between specific IEL and epithelial subsets could provide insight into intestinal barrier mechanisms in health and disease. Here we show that the subset of IELs that express γ and δ T cell receptor subunits (γδ IELs) promotes the viability of Paneth cells deficient in the Crohn's disease susceptibility gene ATG16L1. Using an ex vivo lymphocyte-epithelium co-culture system, we identified apoptosis inhibitor 5 (API5) as a Paneth cell-protective factor secreted by γδ IELs. In the Atg16l1-mutant mouse model, viral infection induced a loss of Paneth cells and enhanced susceptibility to intestinal injury by inhibiting the secretion of API5 from γδ IELs. Therapeutic administration of recombinant API5 protected Paneth cells in vivo in mice and ex vivo in human organoids with the ATG16L1 risk allele. Thus, we identify API5 as a protective γδ IEL effector that masks genetic susceptibility to Paneth cell death.