Innate dysregulation and growth failure in Pediatric Crohn Disease
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».