Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( qCD+S ) vs. without persistent GI symptoms ( qCD-S ). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur-metabolic pathways in qCD+S. Methods: We performed a multi-center observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD ( aCD ) and non-IBD diarrhea-predominant irritable bowel syndrome ( IBS-D ) were included as controls. Results: Thirty-nine patients with qCD+S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD+S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD+S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD+S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H 2 S signaling. Multi-omic integration demonstrated that enriched microbes in qCD+S were associated with important sulfur-metabolic pathways. Bacterial sulfur-metabolic genes, including CTH , isfD , sarD , and asrC , were dysregulated in qCD+S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting presence of qCD+S. Discussion: Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD+S, which implicate H 2 S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H 2 S pathways results in improved quality of life in qCD+S. Key Messages: What is Already Known Even in the absence of inflammation, persistent gastrointestinal symptoms are common in Crohn's disease.The microbiome is altered in quiescent Crohn's disease patients with persistent symptoms, but the functional significance of these changes is unknown. What is New Here Sulfur metabolites and sulfur metabolic pathways were enriched in stool in quiescent Crohn's disease patients with persistent symptoms.Multi-omic integration showed enriched microbes were associated with important sulfur metabolic pathways in quiescent Crohn's disease patients with persistent symptoms. How Can This Study Help Patient Care Strategies to decrease sulfidogenic microbes and associated sulfur metabolic pathways could represent a novel strategy to improve quality of life in quiescent Crohn's disease with persistent GI symptoms.

NCCN Guidelines® Insights: Colorectal Cancer Screening, Version 1.2024.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.

Understanding the Perspectives and Experiences of Patients with Acute Severe Ulcerative Colitis in the Hospital: A Qualitative Analysis.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a life-treating presentation of ulcerative colitis (UC) that requires prompt initiation of treatment to avoid complication. Unfortunately, outcomes for ASUC are suboptimal, with as many as 20-30% of patients requiring colectomy. This can be challenging for patients and highlights the need to understand patient experiences and perspectives navigating ASUC. METHODS: A qualitative descriptive study utilizing semi-structured interviews was conducted to understand perspectives and experiences of patients navigating ASUC. Adult patients hospitalized for ASUC between January 2017 and March 2024 were eligible. Interviews were conducted both retrospectively among patients with a recent hospitalization and prospectively among patients within 24 h of hospitalization for ASUC. Interviews were analyzed using a well-established hybrid inductive-deductive approach. RESULTS: Thirty-four patients (44.2% response rate) hospitalized for ASUC were interviewed. Hybrid thematic analysis uncovered five major themes: (1) the pervasive impact of UC on QoL and mental health, (2) challenges associated with navigating uncertainty, (3) prioritizing colon preservation, (4) bridging the divide between outpatient expectations and inpatient realities, and (5) balancing rapid symptom improvement with steroid safety. Our findings advocate for transparent approach to care, emphasizing the need for effective communication, education, and better alignment with patient values and expectations. CONCLUSION: Five key themes were identified, each with significant implications for developing a more patient-centered approach to ASUC care. These themes captured meaningful insight into patient perceptions and experiences, identifying multiple areas for actionable interventions to improve care.

The Microbiome in Quiescent Crohn's Disease With Persistent Symptoms Show Disruptions in Microbial Sulfur and Tryptophan Pathways.

Background and Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and worsen quality of life. Amongst patients without inflammation (quiescent CD), we hypothesized that microbial community structure and function, including tryptophan metabolism, would differ between patients with persistent symptoms (qCD + S) and without persistent symptoms (qCD-S). Methods: We performed a multicenter observational study nested within the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by Crohn's Disease Patient-Reported Outcome-2. Active CD, diarrhea-predominant irritable bowel syndrome, and healthy controls were included as controls. Stool samples underwent whole-genome shotgun metagenomic sequencing. Results: Thirty-nine patients with qCD + S, 274 qCD-S, 21 active CD, 40 diarrhea-predominant irritable bowel syndrome, and 50 healthy controls were included for analysis. Patients with qCD + S had a less-diverse microbiome. Furthermore, patients with qCD + S showed significant enrichment of bacterial species that are normal inhabitants of the oral microbiome (eg Rothia dentocariosa, Fusobacterium nucleatum) and sulfidogenic microbes (eg Prevotella copri, Bilophila spp.). Depletion of important butyrate and indole producers (eg Eubacterium rectale, Faecalibacterium prausnitzii) was also noted in qCD + S. Potential metagenome-related functional changes in cysteine and methionine metabolism, ATP transport, and redox reactions were disturbed in qCD + S, also suggestive of altered sulfur metabolism. Finally, qCD + S showed significant reductions in bacterial tnaA genes, which mediate tryptophan metabolism to indole, and significant tnaA allelic variation compared with qCD-S. Conclusion: The microbiome in qCD + S showed significant differences in sulfidogenesis, butyrate producers, and typically oral microbes compared to qCD-S and active CD. These results suggest that inflammation may lead to durable microbiome alterations which may mediate persistent symptoms through testable mechanisms.

Morning light treatment for inflammatory bowel disease: a clinical trial.

BACKGROUND: Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD. METHODS: We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex. DISCUSSION: Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.

A step closer to understanding how a diet high in simple carbohydrates may cause dysbiosis.

The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens. Disease-associated gut dysbiosis has been characterized by blooms of pathobionts, which are bacterial species that can drive disease under certain conditions. Pathobionts like Enterobacteriaceae often bloom during flares of inflammatory bowel disease (IBD) and are causally linked with IBD in murine models. In this issue of the JCI, Hecht and colleagues investigated how simple carbohydrates are causally linked to the bloom of the gut pathobiont Klebsiella pneumoniae, which belong to the Enterobacteriaceae family. Notably, the presence of fiber reduced the dissemination of K. pneumoniae into the blood and liver in a colitis model. Their findings provide a diet-related mechanism for gut dysbiosis, which has implications in the management of IBD and other conditions in which gut dysbiosis is an underlying factor.

Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease.

BACKGROUND: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS: We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 µg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES: Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Using Computer Vision to Improve Endoscopic Disease Quantification in Therapeutic Clinical Trials of Ulcerative Colitis.

BACKGROUND & AIMS: Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients. METHODS: Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance. RESULTS: Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g = 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI. CONCLUSIONS: As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.

Use of Upadacitinib in 16 Tofacitinib-refractory Ulcerative Colitis Patients: A Single-center Case 2Series.

We present a case series of 16 patients with ulcerative colitis who received upadacitinib after failing tofacitinib. Five patients (36%) achieved steroid-free clinical remission. Five (62%) demonstrated endoscopic response, while 2 patients (25%) achieved endoscopic remission. Adverse events were low.

The Fecal Microbiome in Quiescent Crohn's Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers.

Background and Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and negatively impact quality of life. We aimed to determine whether quiescent CD patients with persistent symptoms ( qCD+symptoms ) have changes in microbial structure and functional potential compared to those without symptoms ( qCD-symptoms ). Methods: We performed a prospective multi-center observational study nested within the SPARC IBD study. CD patients were included if they had evidence of quiescent disease as defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by the CD-PRO2 questionnaire. Active CD ( aCD ), diarrhea-predominant irritable bowel syndrome ( IBS-D ), and healthy controls ( HC ) were included as controls. Stool samples underwent whole genome shotgun metagenomic sequencing. Results: A total of 424 patients were analyzed, including 39 qCD+symptoms, 274 qCD-symptoms, 21 aCD, 40 IBS-D, and 50 HC. Patients with qCD+symptoms had a less diverse microbiome, including significant reductions in Shannon diversity ( P <.001) and significant differences in microbial community structure ( P <.0001), compared with qCD-symptoms, IBS-D, and HC. Further, patients with qCD+symptoms showed significant enrichment of bacterial species that are normal inhabitants of the oral microbiome, including Klebsiella pneumoniae (q=.003) as well as depletion of important butyrate and indole producers, such as Eubacterium rectale (q=.001), Lachnospiraceae spp . (q<.0001), and Faecalibacterium prausnitzii (q<.0001), compared with qCD-symptoms. Finally, qCD+symptoms showed significant reductions in bacterial tnaA genes, which mediate tryptophan metabolism, as well as significant tnaA allelic variation, compared with qCD-symptoms. Conclusion: The microbiome in patients with qCD+symptoms show significant changes in diversity, community profile, and composition compared with qCD-symptoms. Future studies will focus on the functional significance of these changes. What You Need to Know: Background: Persistent symptoms in quiescent Crohn's disease (CD) are prevalent and lead to worse outcomes. While changes in the microbial community have been implicated, the mechanisms by which altered microbiota may lead to qCD+symptoms remain unclear.Findings: Quiescent CD patients with persistent symptoms demonstrated significant differences in microbial diversity and composition compared to those without persistent symptoms. Specifically, quiescent CD patients with persistent symptoms were enriched in bacterial species that are normal inhabitants of the oral microbiome but depleted in important butyrate and indole producers compared to those without persistent symptoms.Implications for Patient Care: Alterations in the gut microbiome may be a potential mediator of persistent symptoms in quiescent CD. Future studies will determine whether targeting these microbial changes may improve symptoms in quiescent CD.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

BACKGROUND: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. RESULTS: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. CONCLUSION: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

Identifying the Presence, Activity, and Status of Extraintestinal Manifestations of Inflammatory Bowel Disease Using Natural Language Processing of Clinical Notes.

BACKGROUND: Extraintestinal manifestations (EIMs) occur commonly in inflammatory bowel disease (IBD), but population-level understanding of EIM behavior is difficult. We present a natural language processing (NLP) system designed to identify both the presence and status of EIMs using clinical notes from patients with IBD. METHODS: In a single-center retrospective study, clinical outpatient electronic documents were collected in patients with IBD. An NLP EIM detection pipeline was designed to determine general and specific symptomatic EIM activity status descriptions using Python 3.6. Accuracy, sensitivity, and specificity, and agreement using Cohen's kappa coefficient were used to compare NLP-inferred EIM status to human documentation labels. RESULTS: The 1240 individuals identified as having at least 1 EIM consisted of 54.4% arthritis, 17.2% ocular, and 17.0% psoriasiform EIMs. Agreement between reviewers on EIM status was very good across all EIMs (κ = 0.74; 95% confidence interval [CI], 0.70-0.78). The automated NLP pipeline determining general EIM activity status had an accuracy, sensitivity, specificity, and agreement of 94.1%, 0.92, 0.95, and κ = 0.76 (95% CI, 0.74-0.79), respectively. Comparatively, prediction of EIM status using administrative codes had a poor sensitivity, specificity, and agreement with human reviewers of 0.32, 0.83, and κ = 0.26 (95% CI, 0.20-0.32), respectively. CONCLUSIONS: NLP methods can both detect and infer the activity status of EIMs using the medical document an information source. Though source document variation and ambiguity present challenges, NLP offers exciting possibilities for population-based research and decision support in IBD.

Extraintestinal manifestations of inflammatory bowel disease impact on patient experience, but are poorly captured by electronic health records. Natural language processing systems are capable of not only detecting extraintestinal manifestations, but also inferring activity information by automated analysis of clinical notes.

Increased rates of brain protein synthesis during [N1,N2] sleep: L-[1-11C]leucine PET studies in human subjects.

During sleep, reduced brain energy demands provide an opportunity for biosynthetic processes like protein synthesis. Sleep is required for some forms of memory consolidation which requires de novo protein synthesis. We measured regional cerebral protein synthesis rates (rCPS) in human subjects to ascertain how rCPS is affected during sleep. Subjects underwent three consecutive L-[1-11C]leucine PET scans with simultaneous polysomnography: 1. rested awake, 2. sleep-deprived awake, 3. sleep. Measured rCPS were similar across the three conditions. Variations in sleep stage times during sleep scans were used to estimate rCPS in sleep stages under the assumption that measured rCPS is the weighted sum of rCPS in each stage, with weights reflecting time and availability of [11C]leucine in that stage. During sleep scans, subjects spent most of the time in N2, N3, and awake and very little time in N1 and REM; rCPS in N1 and REM could not be reliably estimated. When stages N1 and N2 were combined [N1,N2], estimates of rCPS were more robust. In selective regions, estimated rCPS were statistically significantly higher (30-39%) in [N1,N2] compared with N3; estimated rCPS in N3 were similar to values measured in sleep-deprived awake scans. Results indicate increased rates of protein synthesis linked to [N1,N2] sleep.

Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction.

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent-invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the presence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work suggests that the indirect metabolic network between pathobionts and commensal symbionts enables pathobionts to overcome nutritional restriction and thrive in the gut.

The Role of Tissue Biopsy in the Management of Immune Checkpoint Inhibitor Toxicity.

Immune checkpoint inhibitors have revolutionized the treatment of cancer and are now omnipresent. However, immune-related adverse events can present with varying phenotypes and timing, which can pose diagnostic and therapeutic challenges for the treating oncologist as well as subspecialty consultants. Biopsies of affected organs may provide insight into biologic mechanisms as well as potentially guide management in certain circumstances.

The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).

BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.