Preclinical stages of Crohn’s disease defined by faecal calprotectin in asymptomatic first-degree relatives: screening framework for prevention trials
Bibliographic record
Abstract
BACKGROUND: The PIONIR (Preventing IBD ONset in Individuals at Risk) trial evaluates whether the Tasty&Healthy diet can reduce risk of Crohn's disease (CD) development in first-degree relatives (FDRs). The optimal preclinical stage of CD for enrolling subjects to prevention trials is unknown. OBJECTIVES: We aimed to propose a framework for identifying high-risk participants for prevention trials by reporting the outcomes of the pre-PIONIR screening stage. DESIGN: Faecal calprotectin was measured in asymptomatic FDRs aged 6-38 years; those with persistent elevation, defined as >70 µg/g in at least two separate tests, were offered panenteric video capsule-endoscopy or ileocolonoscopy. RESULTS: Of 950 FDRs approached, 331 (35%) agreed to be screened: 63 (19%) had persistently elevated calprotectin, of whom 42 underwent further evaluation. Nine (2.7%) had endoscopic appearance compatible with presymptomatic CD, 22 (6.6%) had non-specific macroscopic mucosal changes and 11 (3.3%) had normal mucosa despite elevated calprotectin, suggesting probable histological inflammation. The 33 participants in the two latter groups were defined as 'potential pre-CD' (17.9% of all screened after adjusting for missing values). Calprotectin >225 µg/g predicted presymptomatic CD (area under the receiver operating characteristic curve 0.97 (95% CI 0.94 to 1.0; p<0.001; sensitivity 89%, specificity 94%). Of those with a single elevated calprotectin value, 22% normalised on repeat testing with significant variability (intraclass correlation coefficient 0.72 (95% CI 0.57 to 0.82)). CONCLUSION: Approximately one in five asymptomatic FDRs had persistently elevated calprotectin, which was able to differentiate those with presymptomatic CD. The findings highlight calprotectin's utility in identifying at-risk individuals during the potential pre-CD stage for enrolment in prevention trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".