Short Ileal Microvillus Length Phenotype Associates with Progression from Inflammatory to Complicated Disease Behavior in Pediatric Crohn’s Disease
Bibliographic record
Abstract
BACKGROUND AND AIMS: Our previous studies of adult Crohn's disease (CD) suggested ileal microvillus length (MVL) as a prognostic biomarker for therapy response. We investigated if ileal MVL also differed in pediatric CD versus controls and tested for associations with stricturing or penetrating disease behavior outcomes. METHODS: We determined the average ileal MVL of 412 CD and 88 control H&E-stained ileal histology samples from a subset of the RISK cohort and 2 validation cohorts. The RISK sub-cohort had an average follow-up of >60 months and was used to test for associations between ileal MVL and clinical data, RNA-seq molecular profiles, and histopathological scores. RESULTS: Ileal MVL was shorter in CD relative to control (median of 1.396 µm vs. 1.598 µm, respectively). Ileal MVL generally did not associate with demographics or clinical disease activity indices. However, there was a significant association between shorter ileal MVL and increased risk of development of complicated disease behavior. Furthermore, CD samples with shorter ileal MVL showed a significantly shorter time to development of complicated disease behavior. Ileal MVL positively associated with a gene signature enriched for brush border membrane and negatively associated with a gene signature enriched for extracellular matrix, inflamed macrophages, and fibroblasts. Accordingly, ileal MVL was negatively correlated with histopathological scores. CONCLUSIONS: Short ileal MVL is associated with the development of complicated disease behaviors in pediatric CD, supporting the potential use of this histological phenotype as a biomarker for CD prognosis.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".