Dynamic changes in extracellular vesicle-associated miRNAs elicited by ultrasound in inflammatory bowel disease patients.

Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood. 26 patients with IBD were included in the prospective clinical study. Serum samples were collected before and 30 min after diagnostic transabdominal ultrasound. Differential miRNA expression was analyzed by sequencing. Candidate inducible EV-miRNAs were functionally assessed in vitro by transfection of miRNA mimics and qPCR of predicted target genes. Serum EV-miRNA concentration at baseline correlated with disease severity, as determined by clinical activity scores and sonographic findings. Three miRNAs (miR-942-5p, mir-5588, mir-3195) were significantly induced by sonography. Among the significantly regulated EV-miRNAs, miR-942-5p was strongly induced in higher grade intestinal inflammation and correlated with clinical activity in Crohn's disease. Prediction of target regulation and transfection of miRNA mimics inferred a role of this EV-miRNA in regulating barrier function in inflammation. Induction of mir-5588 and mir-3195 did not correlate with inflammation grade. This proof-of-concept trial highlights the principle of induced molecular shifts in EVs from inflamed tissue through transabdominal ultrasound. These inducible EVs and their molecular cargo like miRNA could become novel biomarkers for intestinal inflammation in IBD.

Prevalence of spondyloarthritis in inflammatory bowel disease according ASAS and ultrassonography and its correlation with plasma calprotectin.

BACKGROUND: Enteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels. METHODS: This was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant. RESULTS: A total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of enteropathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041). CONCLUSIONS: A total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria.

BODY FAT COMPOSITION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A COMPARATIVE STUDY BETWEEN SKINFOLDS AND ULTRASONOGRAPHY.

BACKGROUND: Inflammatory bowel diseases (IBD) are associated with important changes in nutritional status. OBJECTIVE: The aim of the study was to compare body fat composition between two anthropometric methods: skinfolds and ultrasonography, in patients with IBD. METHODS: Single-center cross-sectional study with IBD patients in remission or active disease. For the agreement analysis between the body fat assessment methods, the Bland Altman method was used. RESULTS: A total of 101 patients with IBD were included, 75 with Crohn's disease and 26 with ulcerative colitis. Approximately 56% of the patients with Crohn's disease and 65.4% of those with ulcerative colitis had a body fat composition above normal levels, with no significant difference between the diseases (P=0.63). The Bland-Altman concordance analysis showed that the methods for assessing the percentage of fat by the adipometer and ultrasound were not in full agreement (P=0.001), despite both presented good correlation (CC 0.961; P=0.000). CONCLUSION: The analysis of body fat percentage in patients with IBD was different between the skinfolds and ultrasound. Both methods can be used to assess the of body fat percentage of patients with IBD. However, monitoring of body fat sequentially and longitudinally should always be performed using the same method throughout the disease course. Prospective longitudinal studies are warranted to precisely define the role of these two methods of measuring body composition in patients with IBD. BACKGROUND: • Inflammatory bowel diseases are associated with changes in nutritional status. BACKGROUND: • Skinfolds measurements and ultrasound are valid methods for assessing body composition and body fat. BACKGROUND: • These methods despite comparable are not identical and are useful in clinical nutritional practices in IBD.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

Substantial cost savings of ultrasound-based management over magnetic resonance imaging-based management in an inflammatory bowel disease service.

BACKGROUND: Imaging is used to monitor disease activity in small bowel Crohn's disease (CD). Magnetic Resonance Enterography is often employed as a first modality in the United Kingdom for assessment and monitoring; however, waiting times, cost, patient burden and limited access are significant. It is as yet uncertain if small bowel intestinal ultrasound (IUS) may be a quicker, more acceptable, and cheaper alternative for monitoring patients with CD. METHODS: A clinical service evaluation of imaging pathways was undertaken at a single NHS site in England, United Kingdom. Data were collected about patients who were referred and underwent an imaging analysis for their IBD. Only patients who underwent a therapy change were included in the analysis. Data were collected from care episodes between 01 January 2021-30 March 2022. RESULTS: A combined total of 193 patient care episodes were reviewed, 107 from the IUS pathway and 86 from the MRE pathway. Estimated costs per patient in the IUS pathway was £78.86, and £375.35 per patient in the MRE pathway. The MRE pathway had an average time from referral to treatment initiation of 91 days (SD= ±61) with patients in the IUS pathway waiting an average of 46 days (SD= ±17). CONCLUSIONS: Findings from this work indicate that IUS is a potential cost-saving option when compared to MRE when used in the management of CD. This is in addition to the cost difference of the radiological modalities. A large, multicentre, prospective study is needed to validate these initial findings.

What is already known on this topic ­ Ultrasound is a quick and accurate imaging investigation for patients living with Crohn's disease. Its effect on the cost utility of an Inflammatory Bowel Disease service is unknown.What this study adds ­ This work provides initial data suggesting that an ultrasound-based service may provide significant cost savings when compared to a magnetic resonance imaging-based service.How this study might affect research, practice, or policy ­ This work is part of a larger programme of work to investigate the barriers to wider ultrasound implementation in UK IBD services. This work will contribute to the design of an implementation and training package for intestinal ultrasound in the UK.

Intestinal ultrasound in inflammatory bowel disease.

Intestinal ultrasound (IUS) is non-invasive, fast, cheap, and well-tolerated and requires no preparation and is thus applicable as a point-of-care monitoring tool of inflammatory bowel disease (IBD). Evidence suggests that IUS is comparable to other standard monitoring modalities, i.e., endoscopy, MRI, calprotectin, and C-reactive protein and might be more accurate in predicting response to treatment at an early stage consequently allowing for timely optimised treatment. This review finds that integrating IUS as the standard of care in every IBD outpatient clinic and as the primary outcome in future medical trials seems inevitable.

Bone health screening practices with dual-energy X-ray absorptiometry and prediction of abnormal results in pediatric inflammatory bowel disease.

OBJECTIVES: Pediatric patients diagnosed with inflammatory bowel disease (IBD) are at risk of suboptimal peak bone mass attainment. This study aimed to understand rates of bone health screening adherence, describe factors associated with dual-energy X-ray absorptiometry (DXA) acquisition, and identify factors associated with abnormal DXA. METHODS: We performed a retrospective cohort study of pediatric IBD patients over a 10-year time frame. We included IBD patients (2-20 years of age) enrolled in ImproveCareNow and excluded patients with primary metabolic bone disease. Time-to-event methods and multivariable logistic regression were employed to identify factors associated with DXA acquisition and abnormal DXA. RESULTS: In 676 patients, 464 (68.63%) pediatric patients with IBD had a risk factor for low bone mineral density (BMD); 137 (29.53%) underwent an initial DXA scan. Quiescent disease was significantly associated with a reduced likelihood of DXA (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97), while weight z-score <-2 was significantly associated with DXA performance (HR: 2.07; 95% CI: 1.08-3.98). Abnormal DXA results (BMD z-score ≤-1) occurred in 59 (35.54%) individuals. After adjusting for visit diagnosis, delayed puberty, severe disease course, 6 months or greater of steroid exposure, and history of fracture, BMI z-score <-1 (odds ratio: 5.45; 95% CI: 2.41-12.33) was associated with abnormal DXA. CONCLUSIONS: DXA screening occurred in less than one-third of eligible pediatric IBD patients. Compliance was more common in patients with a weight z-score <-2 and less common in those with quiescent disease. BMI strongly predicted abnormal DXA results when adjusting for risk factors for abnormal BMD.

Artificial intelligence image-based prediction models in IBD exhibit high risk of bias: A systematic review.

BACKGROUND: There has been an increase in the development of both machine learning (ML) and deep learning (DL) prediction models in Inflammatory Bowel Disease. We aim in this systematic review to assess the methodological quality and risk of bias of ML and DL IBD image-based prediction studies. METHODS: We searched three databases, PubMed, Scopus and Embase, to identify ML and DL diagnostic or prognostic predictive models using imaging data in IBD, to Dec 31, 2022. We restricted our search to include studies that primarily used conventional imaging data, were undertaken in human participants, and published in English. Two reviewers independently reviewed the abstracts. The methodological quality of the studies was determined, and risk of bias evaluated using the prediction risk of bias assessment tool (PROBAST). RESULTS: Forty studies were included, thirty-nine developed diagnostic models. Seven studies utilized ML approaches, six were retrospective and none used multicenter data for model development. Thirty-three studies utilized DL approaches, ten were prospective, and twelve multicenter studies. Overall, all studies demonstrated high risk of bias. ML studies were evaluated in 4 domains all rated as high risk of bias: participants (6/7), predictors (1/7), outcome (3/7), and analysis (7/7), and DL studies evaluated in 3 domains: participants (24/33), outcome (10/33), and analysis (18/33). The majority of image-based studies used colonoscopy images. CONCLUSION: The risk of bias was high in AI IBD image-based prediction models, owing to insufficient sample size, unreported missingness and lack of an external validation cohort. Models with a high risk of bias are unlikely to be generalizable and suitable for clinical implementation.

A radiomics nomogram based on MSCT and clinical factors can stratify fibrosis in inflammatory bowel disease.

Intestinal fibrosis is one of the major complications of inflammatory bowel disease (IBD) and a pathological process that significantly impacts patient prognosis and treatment selection. Although current imaging assessment and clinical markers are widely used for the diagnosis and stratification of fibrosis, these methods suffer from subjectivity and limitations. In this study, we aim to develop a radiomics diagnostic model based on multi-slice computed tomography (MSCT) and clinical factors. MSCT images and relevant clinical data were collected from 218 IBD patients, and a large number of quantitative image features were extracted. Using these features, we constructed a radiomics model and transformed it into a user-friendly diagnostic nomogram. A nomogram was developed to predict fibrosis in IBD by integrating multiple factors. The nomogram exhibited favorable discriminative ability, with an AUC of 0.865 in the validation sets, surpassing both the logistic regression (LR) model (AUC = 0.821) and the clinical model (AUC = 0.602) in the test set. In the train set, the LR model achieved an AUC of 0.975, while the clinical model had an AUC of 0.735. The nomogram demonstrated superior performance with an AUC of 0.971, suggesting its potential as a valuable tool for predicting fibrosis in IBD and improving clinical decision-making. The radiomics nomogram, incorporating MSCT and clinical factors, demonstrates promise in stratifying fibrosis in IBD. The nomogram outperforms traditional clinical models and offers personalized risk assessment. However, further validation and addressing identified limitations are necessary to enhance its applicability.

Sonographic detection of massive colonic pseudopolyposis in inflammatory bowel diseases.

PURPOSE: Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS. METHODS: This case-control study included 12 patients with ulcerative colitis or Crohn's colitis with extensive left colon pseudopolyposis and 18 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition. RESULTS: Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis. The detection of both these findings were able to detect extensive pseudopolyposis a sensitivity of 75% (CI 95%: 42.8-94.5%) and a specificity of 100% (CI 95%: 81.5-100%). CONCLUSION: This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition.

Clinical Application of Intestinal Ultrasound in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Intestinal ultrasound (IUS) is a non-invasive, accurate, and well-tolerated tool that provides real-time assessment of inflammatory bowel disease (IBD) activity and is therefore an ideal monitoring tool. This review describes the evolving role of IUS in each phase of clinical management of IBD. RECENT FINDINGS: Accumulating evidence has demonstrated that IUS is an excellent tool for the assessment of suspected IBD, with a very high negative predictive value. It accurately assesses disease activity, disease complications, and in the pre-treatment phase, provides a benchmark for subsequent follow-up. IUS can detect early therapeutic response and correlates well with other established monitoring modalities with arguably superior predictive capabilities and ability to assess a deeper degree of remission, transmural healing (TH). IUS has a crucial role in the management of IBD and has ushered in a new era of monitoring with more rapid evaluation and the opportunity for early optimization, deeper therapeutic targets, and improved outcomes.

Role of ultra-high definition endoscopy (endomicroscopy and endocytoscopy) and real-time histologic examination in inflammatory bowel disease: Scoping review.

OBJECTIVES: Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined. METHODS: We searched PubMed using keywords ("confocal" OR "CLE" OR "endocytoscopy") AND ("IBD" OR "inflammatory bowel" OR "Crohn*" OR "Crohn's" OR "colitis ulcerosa" OR "ulcerative colitis") between 2005 and March 2023. We identified 52 studies for detailed review. RESULTS: Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn's disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC. EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study. CONCLUSION: Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Dye Chromoendoscopy Outperforms High-Definition White Light Endoscopy in Dysplasia Detection for Patients With Inflammatory Bowel Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. METHODS: A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). RESULTS: Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE). DISCUSSION: Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

The value of whole-body dual-energy x-ray absorptiometry in assessing body composition in patients with inflammatory bowel disease: a prospective study.

OBJECTIVES: Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged. METHODS: Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150 µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks. RESULTS: Total fat mass was higher in 54 patients with IBD (56% Crohn's disease, 61% male) than in 30 controls (median 25.1 vs. 18.7 kg, P  = 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P  = 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% ( P  = 0.004) and BMI by 6.4% ( P  = 0.012) in 9 responders to therapy. CONCLUSION: DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice.

[Modern endoscopy in inflammatory bowel disease].

INTRODUCTION: Endoscopic examinations play a very important role in the diagnosis, progress assessment, and therapy of inflammatory bowel diseases (IBD). This includes not only esophagogastroduodenoscopy, sigmoidoscopy, and ileo-colonoscopy, but also assessment of the small intestine. The work-up of the small intestine is primarily carried out using non-invasive techniques (intestinal ultrasound, magnetic resonance enterography (MRE)). However, if the diagnosis remains unclear, a histological proof is necessary or an endoscopic intervention is required, capsule endoscopy and balloon-assisted enteroscopy are used. Furthermore, endoscopic ultrasound is available to assess perianal fistulizing Crohn's disease, and ERCP (endoscopic retrograde cholangiopancreatography) is used in certain patients with IBD-associated primary sclerosing cholangitis (PSC). Given the high resolution of modern endoscopes and the availability of chromoendoscopy, dysplastic lesions are detected earlier and can often be resected endoscopically. In addition, short strictures/stenoses can be treated using balloon dilatations.

AGA clinical practice guideline on the role of biomarkers for the management of Crohn's Disease

Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.