NIMBUS study protocol: a single-centre feasibility study of non-invasive monitoring with bowel ultrasound in paediatric inflammatory bowel disease.

INTRODUCTION: Incidence of inflammatory bowel disease (IBD) is increasing in childhood and treatment increasingly targets mucosal healing. Monitoring bowel inflammation requires endoscopy or MRI enterography which are invasive, expensive and have long waiting lists.We aim to examine the feasibility of a non-invasive monitoring tool-bowel ultrasound (BUS)-in children with IBD and explore correlations with inflammatory markers and disease activity measures. Some BUS criteria have been found to correlate with these markers; however, this has not been validated in children.We aim to examine the feasibility of BUS for monitoring inflammation in this population; highlighting useful parameters for this purpose. We aim to inform a larger scale randomised controlled trial using BUS. METHODS AND ANALYSIS: This prospective observational feasibility study will be carried out over 24 months at the Noah's Ark Children's Hospital for Wales, Cardiff; with the endpoint recruitment of 50 participants. Children aged 2-18 years with a modified Porto criteria diagnosis of IBD will be included.Patients without IBD or who have previously undergone IBD-related surgery will be excluded; as will families unable to give informed consent.Ultrasound scan images and reports will be collected, as well as laboratory results and clinical outcomes.The primary aim will assess the feasibility of targeted BUS for disease monitoring; including recruitment statistics. The secondary aims will involve data collection and correlation analysis for targeted ultrasound parameters, biomarkers, disease activity scores and prediction of changes in treatment. The statistical methods will include: feasibility metrics, descriptive statistics, cross-tabulation and χ2 analysis, correlation analysis, regression analysis. ETHICS AND DISSEMINATION: Ethical approval is granted by NHS Research Ethics Committee. The sponsor is Cardiff and Vale University Health Board. We will publish the results in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT05673278.

The Pediatric Crohn Disease Morbidity Index (PCD-MI): Development of a Tool to Assess Long-Term Disease Burden Using a Data-Driven Approach.

BACKGROUND/OBJECTIVE: Heterogeneity and chronicity of Crohn disease (CD) make prediction of outcomes difficult. To date, no longitudinal measure can quantify burden over a patient's disease course, preventing assessment and integration into predictive modeling. Here, we aimed to demonstrate the feasibility of constructing a data driven, longitudinal disease burden score. METHODS: Literature was reviewed for tools used in assessment of CD activity. Themes were identified to construct a pediatric CD morbidity index (PCD-MI). Scores were assigned to variables. Data were extracted automatically from the electronic patient records at Southampton Children's Hospital, diagnosed from 2012 to 2019 (inclusive). PCD-MI scores were calculated, adjusted for duration of follow up and assessed for variation (ANOVA) and distribution (Kolmogorov-Smirnov). RESULTS: Nineteen clinical/biological features across five themes were included in the PCD-MI including blood/fecal/radiological/endoscopic results, medication usage, surgery, growth parameters, and extraintestinal manifestations. Maximal score was 100 after accounting for follow-up duration. PCD-MI was assessed in 66 patients, mean age 12.5 years. Following quality filtering, 9528 blood/fecal test results and 1309 growth measures were included. Mean PCD-MI score was 14.95 (range 2.2-32.5); data were normally distributed ( P = 0.2) with 25% of patients having a PCD-MI < 10. There was no difference in the mean PCD-MI when split by year of diagnosis, F -statistic 1.625, P = 0.147. CONCLUSIONS: PCD-MI is a calculatable measure for a cohort of patients diagnosed over an 8-year period, integrating a wide-range of data with potential to determine high or low disease burden. Future iterations of the PCD-MI require refinement of included features, optimized scores, and validation on external cohorts.

Factors Affecting Delayed Gastric Emptying and Long-Term Outcomes of Children With Gastric Emptying.

OBJECTIVES: Our study attempted to identify what factors best predict for delayed gastric emptying (DGE) and whether children respond to treatment. METHODS: Children aged between 0 and 18 were included who had a gastric emptying scintigraphy (GES) study performed between 2009 and 2018. Baseline clinical details were recorded from clinic visit records regarding symptoms, medication, and past medical history. Results were analyzed using multivariate regression analysis and coefficient analysis. Children were followed up at 2 years to assess their symptoms and medication usage. RESULTS: Two hundred and eighty-five children were included in the study of which 174 demonstrated DGE. All children had symptoms prior to GES, the most common symptom being that of vomiting and reflux symptoms which were present in over 90% of patients; other common symptoms like abdominal pain and nausea were seen commonly in around 30%. A genetic disorder and prior surgery were more common in children with DGE but there was no difference in presenting symptoms between normal and DGE groups. Regression analysis showed prior surgery and particularly prior abdominal surgery predicted for DGE and additionally predicted for those with highly DGE. Improvement in symptoms and reduction in medication usage was seen after 2 years. CONCLUSIONS: This study provides one of the largest data sets looking at DGE in children. Prior surgery was found to be a key factor in predicting for highly DGE. Symptoms and medication usage did significantly reduce substantially after 2 years.

Prediction of Crohn's Disease Stricturing Phenotype Using a NOD2-derived Genomic Biomarker.

BACKGROUND: Crohn's disease (CD) is highly heterogenous and may be complicated by stricturing behavior. Personalized prediction of stricturing will inform management. We aimed to create a stricturing risk stratification model using genomic/clinical data. METHODS: Exome sequencing was performed on CD patients, and phenotype data retrieved. Biallelic variants in NOD2 were identified. NOD2 was converted into a per-patient deleteriousness metric ("GenePy"). Using training data, patients were stratified into risk groups for fibrotic stricturing using NOD2. Findings were validated in a testing data set. Models were modified to include disease location at diagnosis. Cox proportional hazards assessed performance. RESULTS: Six hundred forty-five patients were included (373 children and 272 adults); 48 patients fulfilled criteria for monogenic NOD2-related disease (7.4%), 24 of whom had strictures. NOD2 GenePy scores stratified patients in training data into 2 risk groups. Within testing data, 30 of 161 patients (18.6%) were classified as high-risk based on the NOD2 biomarker, with stricturing in 17 of 30 (56.7%). In the low-risk group, 28 of 131 (21.4%) had stricturing behavior. Cox proportional hazards using the NOD2 risk groups demonstrated a hazard ratio (HR) of 2.092 (P = 2.4 × 10-5), between risk groups. Limiting analysis to patients diagnosed aged < 18-years improved performance (HR-3.164, P = 1 × 10-6). Models were modified to include disease location, such as terminal ileal (TI) disease or not. Inclusion of NOD2 risk groups added significant additional utility to prediction models. High-risk group pediatric patients presenting with TI disease had a HR of 4.89 (P = 2.3 × 10-5) compared with the low-risk group patients without TI disease. CONCLUSIONS: A NOD2 genomic biomarker predicts stricturing risk, with prognostic power improved in pediatric-onset CD. Implementation into a clinical setting can help personalize management.

NOD2 is a well-established risk gene for development of Crohn's disease and stricturing behavior. Here we demonstrate NOD2 can be utilized as a genomic biomarker, stratifying patients into 2 stricturing risk groups. Further refinement using disease location at diagnosis improved risk stratification.

NOD2 in Crohn's Disease-Unfinished Business.

Studies of Crohn's disease have consistently implicated NOD2 as the most important gene in disease pathogenesis since first being identified in 2001. Thereafter, genome-wide association, next-generation sequencing and functional analyses have all confirmed a key role for NOD2, but despite this, NOD2 also has significant unresolved complexity. More recent studies have reinvigorated an early hypothesis that NOD2 may be a single-gene cause of disease, and the distinct ileal stricturing phenotype seen with NOD2-related disease presents an opportunity for personalized diagnosis, disease prediction and targeted therapy. The genomics of NOD2 has much that remains unknown, including the role of rare variation, phasing of variants across the haplotype block and the role of variation in the NOD2-regulatory regions. Here, we discuss the evidence and the unmet needs of NOD2 research, based on recently published evidence, and suggest methods that may meet these requirements.

A scoping review: urinary markers of metabolic maturation in infants with CHD and the relationship to growth.

BACKGROUND: Growth failure in infants born with CHD is a persistent problem, even in those provided with adequate nutrition. OBJECTIVE: To summarise the published data describing the change in urinary metabolites during metabolic maturation in infants with CHD and identify pathways amenable to therapeutic intervention. DESIGN: Scoping review. ELIGIBILITY CRITERIA: Studies using qualitative or quantitative methods to describe urinary metabolites pre- and post-cardiac surgery and the relationship with growth in infants with CHD. SOURCES OF EVIDENCE: NICE Healthcare Databases website was used as a tool for multiple searches. RESULTS: 347 records were identified, of which 37 were duplicates. Following the removal of duplicate records, 310 record abstracts and titles were screened for inclusion. The full texts of eight articles were reviewed for eligibility, of which only two related to infants with CHD. The studies included in the scoping review described urinary metabolites in 42 infants. A content analysis identified two overarching themes of metabolic variation predictive of neurodevelopmental abnormalities associated with anaerobic metabolism and metabolic signature associated with the impact on gut microbiota, inflammation, energy, and lipid digestion. CONCLUSION: The results of this scoping review suggest that there are considerable gaps in our knowledge relating to metabolic maturation of infants with CHD, especially with respect to growth. Surgery is a key early life feature for CHD infants and has an impact on the developing biochemical phenotype with implications for metabolic pathways involved in immunomodulation, energy, gut microbial, and lipid metabolism. These early life fingerprints may predict those individuals at risk for neurodevelopmental abnormalities.

Evidence of a genetically driven metabolomic signature in actively inflamed Crohn's disease.

Crohn's disease (CD) is characterised by chronic inflammation. We aimed to identify a relationship between plasma inflammatory metabolomic signature and genomic data in CD using blood plasma metabolic profiles. Proton NMR spectroscopy were achieved for 228 paediatric CD patients. Regression (OPLS) modelling and machine learning (ML) approaches were independently applied to establish the metabolic inflammatory signature, which was correlated against gene-level pathogenicity scores generated for all patients and functional enrichment was analysed. OPLS modelling of metabolomic spectra from unfasted patients revealed distinctive shifts in plasma metabolites corresponding to regions of the spectrum assigned to N-acetyl glycoprotein, glycerol and phenylalanine that were highly correlated (R2 = 0.62) with C-reactive protein levels. The same metabolomic signature was independently identified using ML to predict patient inflammation status. Correlation of the individual peaks comprising this metabolomic signature of inflammation with pathogenic burden across 15,854 unselected genes identified significant enrichment for genes functioning within 'intrinsic component of membrane' (p = 0.003) and 'inflammatory bowel disease (IBD)' (p = 0.003). The seven genes contributing IBD enrichment are critical regulators of pro-inflammatory signaling. Overall, a metabolomic signature of inflammation can be detected from blood plasma in CD. This signal is correlated with pathogenic mutation in pro-inflammatory immune response genes.

Incidence and Prevalence of Paediatric Inflammatory Bowel Disease Continues to Increase in the South of England.

OBJECTIVE: The incidence of paediatric inflammatory bowel disease (IBD) has been increasing over 25 years; however, contemporary trends are not established and the impact of COVID-19 on case rates is unclear. METHODS: Data from Southampton Children's hospital prospective IBD database were retrieved for 2002-2021. Incidence rates were calculated based on referral area populations and temporal trends analysed. Disease prevalence for those aged <18 years was calculated for 2017-2021. Monoclonal prescriptions were reported. RESULTS: In total, 1150 patients were included (mean age at diagnosis 12.63 years, 40.5% female). An estimated 704 patients had Crohn's disease (61.2%), 385 had ulcerative colitis (33.5%), and 61 had IBD unclassified (5.3%). Overall IBD incidence increased, ß = 0.843, P = 3 × 10 -6 , driven by Crohn's disease, ß = 0.732, P = 0.00024 and ulcerative colitis, ß = 0.816, P = 0.000011. There was no change in IBDU incidence, ß = 0.230, P = 0.33. From 2002-2021, 51 patients were diagnosed <6 years of age, 160 patients aged 6 to <10 years and 939 patients aged 10 to <18 years of age. Increased incidence was observed in patients aged 10 to <18 years of age (ß = 0.888, P = 1.8 × 10 -7 ). There was no significant change in incidence of IBD in <6 years (ß = 0.124, P = 0.57), or 6 to <10 years (ß = 0.146, P = 0.54). IBD prevalence increased by an average of 1.71%/year from 2017 to 2021, ß = 0.979, P = 0.004. The number of new monoclonal prescriptions increased from 6 in 2007 to 111 in 2021. CONCLUSIONS: IBD incidence continues to increase in Southern England. Compounding prevalence and increased monoclonal usage has implications for service provision.

The Influence of the Introduction of Biologic Agents on Surgical Intervention in Paediatric Inflammatory Bowel Disease.

OBJECTIVES: To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at a population level. METHODS: Hospital Episode Statistics data were obtained for all admissions within England (1997-2015), in children aged 0-18 years, with an ICD-10 code for diagnosis of Crohn disease (CD), ulcerative colitis (UC), or inflammatory bowel disease-unclassified (IBD-U). Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range). RESULTS: In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7604 (34%) had UC, and 1319 (5.8%) cases had IBD-U. Biological therapy was used in 4054 (17.9%) cases. Surgical resection was undertaken in 3212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, P < 0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2-28.2) months in CD and 8.2 (0.8-21.3) months in UC. As the time-frame of the dataset progressed, there was a decreased rate of surgical intervention ( P = 0.04) and an increased use of biological therapy ( P < 0.0001). Additionally, the number of new diagnoses of PIBD increased. CONCLUSIONS: The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.

Feeding children with neurodisability: challenges and practicalities.

Nutritional management for children with neurodisability can be challenging and there are an increasing number of children at risk of malnutrition. Management involves healthcare professionals in community and hospital working together with the family with the aim of optimising nutrition and quality of life. Feeding difficulties can be the result of physical causes like lack of oromotor coordination, discomfort associated with reflux oesophagitis or gastrointestinal dysmotility. Non-physical causes include parental/professional views towards feeding, altered perception of pain and discomfort, extreme sensitivity to certain textures and rigidity of feeding schedule associated with artificial feeding. Estimating nutritional needs can be difficult and is affected by comorbidities including epilepsy and abnormal movements, severity of disability and mobility. Defining malnutrition is difficult as children with neurodisability reflect a wide spectrum with disparate growth patterns and body composition and auxology is less reliable and less reproducible. Management involves selecting the type and method of feeding best suited for the patient. As artificial feeding can place a significant burden of care any decision-making should be, as much as possible, in concurrence with the family. Symptom management sometimes requires pharmacological interventions, but polypharmacy is best avoided. The article aims to discuss the pathways of identifying children at risk of malnutrition and available management options with a strong emphasis on working as a clinical team with the child and family.

Temporal trends in ileoanal pouch surgery for paediatric onset ulcerative colitis in England from 1997 to 2015 using hospital episode statistics.

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC) achieves restoration of intestinal continuity with potential return of continence. It is undertaken relatively infrequently in children. We aimed to investigate the national frequency of IPAA in paediatric UC and report outcomes useful for surgeon/centre benchmarking. METHODS: Hospital Episode Statistics data were obtained for all admissions in England (1997-2015) in children (< 18 years) who underwent IPAA for UC using OPCS-4 procedural codes. Surgeon specialty, readmission, and reoperation rates were identified. Data are median (interquartile range). RESULTS: UC was diagnosed in 7604 children in whom 346 (4.6%) underwent IPAA at age 15 [13-17] years. Laparoscopy was used in 55 (15.9%) cases and in the most recent 10 years more commonly by specialist paediatric surgeons (SPS) than general surgeons (GS) (34.3%vs14.7%, p = 0.001). National frequency of IPAA ranged from 12 to 34 annually. Where specialty was available, 95/342 (57%) cases were undertaken by GS and 147/342 (43%) cases by SPS. The proportion of cases undertaken by SPS increased significantly compared to GS over the study period, p = 0.0003. Post-operative length of stay was 8 [6-11] days. During the index admission, unplanned return to theatre was required in 25/346 (7.2%). Following discharge 58 (16.8%) were readmitted within 30 days. Overall return to theatre rate within 30 days of pouch surgery was 11.0% (38/346). CONCLUSION: IPAA for UC within childhood is undertaken infrequently in England, with a shift towards SPS undertaking surgery. These data can be used by surgeons to benchmark outcomes. LEVEL OF EVIDENCE: IV.

Routine abdominal magnetic resonance imaging can determine psoas muscle area in paediatric Crohn's disease and correlates with bioelectrical impedance spectroscopy measures of lean mass.

BACKGROUND: Paediatric Crohn's disease (CD) has been associated with undernutrition. Accurate and accessible measures of body composition would provide data to personalise nutritional therapy. We assessed feasibility of MRI-derived measures of psoas cross-sectional area (PCSA) in paediatric CD and correlated with anthropometric and bioelectrical impedance spectroscopy (BIS) measures. METHODS: MRI small bowel/pelvis images of patients with CD, aged <18 years, were retrieved. Patients with concurrent anthropometric and BIS measurements were eligible for inclusion. The PCSA at L3 was calculated by two assessors and combined. To assess reproducibility of measures we calculated the coefficient of variation (CoV). Age, height-Z-scores, weight-Z-scores and BIS measures were correlated with PCSA. Using normal paediatric data from CT-scans we derived psoas area Z-scores for our cohort. RESULTS: 10 patients were included. Mean age at MRI scan was 14.6 years (11.7-16.3). PCSA was calculated for all MRI scans. There was high reproducibility between measurers, mean CoV 0.099. There was a significant positive correlation between PCSA and BIA-derived fat free mass, Pearson correlation coefficient (PCC) 0.831, p = 0.003. Correlation coefficients for PCSA and Height-for-age Z-score, weight-for-age -Z-score and age were PCC 0.343- p = 0.33, PCC = 0.222- p = 0.54, and PCC 0.6034- p = 0.065, respectively. The mean PCSA Z-score was -1.81, with 70% of the patients having a Z-score < -2.0. CONCLUSIONS: These data demonstrate the feasibility of deriving measures of body composition from routine MRI imagine. There was significant positive correlation between PCSA and BIS-derived lean mass. Further studies are required to confirm applicability of normal ranges prior to routine clinical implementation.

Growth failure is rare in a contemporary cohort of paediatric inflammatory bowel disease patients.

AIM: We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. METHODS: Paediatric inflammatory bowel disease patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011 to 2018. Weight and height standard deviation scores (SDS) were retrieved. Mean SDS values, SDS change and anti-TNF status were analysed at diagnosis and during follow-up. RESULTS: Four hundred and ninety patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5 years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI: 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1 year and remained at the 50th centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (P = .036). Anti-TNF treatment (P = .013) and surgical resection (P = .005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1 year (-0.2 vs -0.01, P = .22), 2-years (-0.27 vs -0.01, P = .07) and 5 years (-0.21 vs 0.25, P = .051). CONCLUSION: Height was generally maintained in Crohn's disease, and impaired linear growth was rare in this cohort.

Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel.

OBJECTIVE: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. DESIGN: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8-10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. CONCLUSION: Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.

Ileal Transcriptomic Analysis in Paediatric Crohn's Disease Reveals IL17- and NOD-signalling Expression Signatures in Treatment-naïve Patients and Identifies Epithelial Cells Driving Differentially Expressed Genes.

BACKGROUND AND AIMS: Crohn's disease [CD] arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD. METHODS: We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted gene co-expression network analysis [WGCNA] was performed and differentially expressed genes [DEGs] were determined. We integrated clinical data to determine co-expression modules associated with outcomes. RESULTS: In all, 27 treatment-naive CD [TN-CD], 26 established CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established CD, nor controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes, including S100A12 and the calprotectin subunit S100A9, were significantly upregulated in TN CD compared with controls [p = 2.61 x 10-15 and p = 9.13 x 10-14, respectively] and established CD [both p = 0.0055]. Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse [correlation-coefficient-0.36, p = 0.07]. Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells. CONCLUSIONS: Ileal tissue from treatment-naïve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.

Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic.

OBJECTIVE: To determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services. METHODS: Internet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020. RESULTS: Respondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4-7.5 and median 3, IQR 2-4) to the point of survey (median 2, IQR 1-4.8 and median 2, IQR 1-3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery. CONCLUSIONS: IBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.

Analysis and Hierarchical Clustering of Blood Results Before Diagnosis in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Pediatric inflammatory bowel disease (PIBD) is associated with a diagnostic delay. Blood tests are a routine part of the work-up in children with chronic abdominal symptoms (pain, diarrhea). Normal blood tests cannot exclude PIBD. We analyzed blood results at diagnosis over a 5-year period. METHODS: Patients diagnosed from 2013 to 2017 were identified from the Southampton-PIBD database. Results were obtained up to 100 days before diagnostic endoscopy. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, hemoglobin, platelets, packed cell volume (PCV), white cell count (WCC), and alanine transferase (ALT) were analyzed. Hierarchical clustering was applied to normalized results. RESULTS: Two hundred fifty-six patients were included (Crohn's disease [CD], 151; ulcerative colitis [UC], 95; IBD-unclassified, 10; median age, 13.48 years; 36.7% female). Hierarchical clustering of patients revealed novel groupings enriched for CD and UC, characterized by specific patterns of results. In PIBD, 9% presented with all normal blood tests, 21.9% with normal CRP and ESR. Abnormal results were seen in all tests (ESR, 56.4% of patients; CRP, 53.4%; albumin, 28%; hemoglobin, 61.9%; platelets, 55.6%; PCV, 64.6%; WCC, 22.7%; and ALT, 7.2%). Normal inflammatory markers were more common in UC compared with CD (UC, 34%; CD, 15.8%; P = 0.0035). UC (14.4% normal) presented with all normal results more frequently than CD (CD, 5.3%; P = 0.02). CRP, ESR, and platelets were significantly higher in CD compared with UC. Albumin and hemoglobin were significantly lower. CONCLUSIONS: Most cases of PIBD present with >1 abnormal blood result, although 1/11 patients presents with normal blood tests and 1/5 present with normal inflammatory markers. Hierarchical clustering offers the potential to produce novel groupings to inform disease categorization and best management.