P244 The first step to IBD prevention exploring rate of pre-clinical inflammation in subset of asymptomatic subjects at risk of IBD: screening stage of the PIONIR trial
Bibliographic record
Abstract
Abstract Background With the increasing prevalence of inflammatory bowel diseases (IBD) globally, it is necessary to start focusing efforts on prevention of the diseases. The Genetic, Environmental, Microbial (GEM) study identified biological signatures predictive of developing IBD in first degree relatives (FDR) of patients with Crohn’s disease (CD). The ongoing PIONIR (Preventing IBD ONset in Individuals at Risk) study is a randomized controlled trial aimed to explore whether the Tasty & Healthy diet can change the CD-risk associated biomarkers of healthy FDRs who are particularly high risk of developing CD, originally followed in the GEM cohort. We report here the rate of IBD and pre-IBD inflammation in a subset cohort. Methods Subjects, 6-35 years of age from the GEM cohort who were identified by a combination of predictors at recruitment to GEM to have an increased risk for persistently elevated fecal calprotectin (FC) (i.e. Microbiome Risk Score (MRS), increased gut permeability and/or multiplex family of CD) were approached to perform a new FC test. Subjects who had FC>70µg/g, confirmed by a second sample, were offered a panenteric video capsule endoscopy (VCE), but some elected to proceed to ileocolonoscopy instead. Results For the PIONIR recruitment, a total of 450 subjects were approached from 7 sites in Israel and Canada, of whom 183 consented and provided a stool sample for FC (Figure). FC was elevated in 57 (31%) subjects, confirmed by re-testing in 36 (20%); 25/36 underwent VCE/ileocolonoscopy (Figure). In total, 8 (4.4% of the screened cohort) had normal-appearing mucosa, in 10 (5.5%) there were non-specific mucosal changes (e.g. several erosions or erythema), 6 (3.3%) had ulcers compatible with CD and 1 (0.6%) was inconclusive. The median FC of those eventually diagnosed with CD (816 [IQR 361-1123) was higher than the remaining 30 without IBD with elevated FC (175 [111-281], p=0.003). FC>275µg/g was highly predictive of CD in the entire cohort (AUROC 0.97 (95%CI 0.93-0.99); sensitivity 83%, specificity 94%). Conclusion Preclinical mucosal inflammation in VCE/ileocolonoscopy was found in 18 of 183 (9.8%) screened subjects (i.e. elevated FC with either normal or nonspecific mucosal findings), 134 (73%) had normal FC and 11 (6%) with elevated FC had missing VCE/ileocolonoscopy data. Six had CD (3.3%, or 17% of the 36 with elevated FC). Detecting subjects at risk at their preclinical stages, possibly with FC>275µg/g, is the first necessary step in developing preventive strategies for IBD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".