Multicenter Study of Hyperpolarized Xenon Magnetic Resonance Imaging in Children with Cystic Fibrosis Following Initiation of Cystic Fibrosis Transmembrane Regulator Modulator Therapy (HyPOINT)
Bibliographic record
Abstract
Abstract Rationale Elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved lung function in people with cystic fibrosis (CF), prompting the need for outcome measures that can detect mild disease. In this new era of CFTR (CF transmembrane regulator) modulator therapy, more sensitive endpoints are required to evaluate the progression of early lung disease and to determine the efficacy of new CF therapies. Before the availability of highly effective therapies, xenon-129 magnetic resonance imaging (MRI) was shown to be more sensitive to regional ventilation changes compared with spirometry. Objectives To evaluate the longitudinal changes in pulmonary function and Xe MRI outcomes after treatment with ETI in children and young people with CF. Methods Lung function was assessed longitudinally at baseline and 1, 6, and 12 months after ETI treatment initiation in children and young people with CF between the ages of 6 and 18 years at four study sites. Ventilation defect percentage (VDP), reader defect percentage (RDP), lung clearance index (LCI) and forced expiratory volume in 1 second (FEV1) were reported. Results A total of 28 participants were enrolled; 25 completed at least baseline and one-month measurements. All four measures (RDP, VDP, LCI, and FEV1) improved at one month after ETI initiation, with mean (standard deviation) absolute changes of −1.2 (1.7) in LCI, 6.9 (12.3) in FEV1 % predicted, −4.3 (4.8) in VDP, and −7.8 (9.6) in RDP. Xe MRI outcomes (RDP and VDP) showed the largest relative treatment effects, with mean relative improvements of 43% and 72%, respectively. One-third of participants (8 of 25) had improvements in VDP and RDP but did not show improvements in FEV1. Conclusions Xe MRI captures sustained ventilation improvements after ETI initiation. Xe MRI metrics may provide a suitable endpoint for future interventional trials, particularly for people with CF with mild lung disease.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".