Glucocorticoid bioactivity does not predict response to steroid therapy in severe pediatric ulcerative colitis
Bibliographic record
Abstract
BACKGROUND: The pathophysiological basis for corticosteroid (CS) failure in ulcerative colitis (UC) is unknown. A transactivation glucocorticoid bioassay (GBA) was developed to measure the biological activity of CS by quantifying glucocorticoid response elements. This approach eliminates differences in bioavailability, chemistry, affinity, and other potential differences between the various steroids regarding their ability to activate the glucocorticoid receptor. In this multicenter prospective study, we aimed to evaluate whether CS bioavailability plays a role in CS refractoriness in severe pediatric UC. METHODS: GBA (using COS-1 transfected cells) was measured in the serum of 50 children (52% males, age 13.4 +/- 3.5 years) admitted for acute severe UC on the third day of CS treatment. Demographic, clinical, and laboratory data were prospectively recorded. RESULTS: Of the children enrolled, 16 (32%) failed CS therapy and required infliximab (n = 14) or colectomy (n = 2) within a median of 10 days (interquartile range [IQR] 6.5-14.5). Reflecting internal validity of the assay, GBA was highly correlated with the last CS dose and the time interval to bloodletting (r = -0.41 and r = -0.54, respectively; P < 0.001). There was no statistically significant difference in the GBA levels between responders and nonresponders (249 nM versus 200 nM cortisol equivalent, P = 0.18). In a multivariate regression model adjusted for time elapsed from CS and the administered dose, GBA did not predict response to CS (P = 0.34). CONCLUSIONS: The lack of correlation of GBA level and treatment outcome lends support to the hypothesis that the bioavailability, type, and dosing of intravenous CS are not associated with response or failure to the drug.
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 | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".