Innate dysregulation and growth failure in Pediatric Crohn Disease
Bibliographic record
Abstract
Recent studies have shown that growth delay persists in many pediatric CD patients with current therapeutic approaches. In the current study, we have tested the following hypotheses: a) growth during therapy will be influenced by anti-TNF therapy, and b) patients with dysregulated innate immune function due to NOD2 mutations and Granulocyte-Macrophage Colony Stimulating Factor auto-antibodies (GM-CSF Ab) will exhibit the most significant growth retardation. We have enrolled a cohort of 215 children with CD, UC, or IBD-U at Tanner stage I or II of puberty at three sites, and have completed two year prospective follow-up. To estimate the effect of IBD upon growth relative to genetic potential, we have determined a standardized height deficit score (dHTz) based upon mid-parental height. The mean(SD) predicted HTz for CD patients based upon mid-parental heights was -0.01(0.9). The mean(SD) dHTz in CD patients was equal to -0.5(1.23) at entry, and -0.55(1.15) at year 2. The median (IQR) abbreviated PCDAI at entry was equal to 5(0,15), indicating that most patients were in remission or had mild activity. However, the median(IQR) serum lipopolysaccharide binding protein (LBP) concentration was equal to 29(20,30) mcg/mL in the IBD patients, compared to 14(10,17) mcg/mL in healthy controls (p<0.001), demonstrating activation of systemic inflammation. The median(IQR) fecal S100A12 concentration at study entry was equal to 585(145,1030) mcg/kg, confirming active mucosal inflammation in most subjects. An increase in HTz at year 2 was noted in those who received anti-TNF therapy (mean(SD) change in HTz: +0.1(0.6)), compared to patients not exposed to anti-TNF (mean(SD) change in HTz: -0.2(0.6)). CD patients with both GM-CSF Ab and NOD2 mutations (NOD2+GMAb+) exhibited the greatest degree of growth retardation, with a mean(SD) dHTz of -0.69(1.6), compared to -0.41(1.2) in CD patients with one or neither factor. The frequency of CD patients with HTz ≤ -1 increased from 27% to 53% in the NOD2+GMAb+ group. Disease location did not differ between these groups. Moreover, neither mean(SD) protein (2(0.6) gm/kg/day vs. 2(0.8) gm/kg/day) nor caloric (62(15) kcal/kg/day vs. 56(21) kcal/kg/day) intake differed between the NOD2+GMAb+ group and disease controls. However, mean(SD) weight z score was reduced, from -0.4(1.3) in disease controls to -1.1(1.2) in the NOD2+GMAb+ group. Neither serum LBP nor fecal S100A12 differed between the NOD2+GMAb+ group and the other CD patients. This suggests a relative increase in protein/calorie requirements to maintain normal weight in the NOD2+GMAb+ group. Growth retardation relative to both genetic potential and norms for age and gender was observed in CD patients at diagnosis and during the first two years of therapy. Dysregulated innate immunity, in the absence of a difference in nutritional intake or disease location, was associated with the most significant reductions in weight and linear growth.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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) | 0.001 | 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".