Fibroblast Growth Factor 23 Levels in Pulmonary Involvement Associated With Systemic Sclerosis: A Proof-of-concept Study
Bibliographic record
Abstract
To the Editor:Systemic sclerosis (SSc) is a devastating disease associated with lung involvement, primarily interstitial lung disease (ILD) and pulmonary hypertension (PH). 1 Although computed tomography (CT) and right heart catheterization accurately identify cardiopulmonary injury, 2 their high cost and technical complexity make them inaccessible to most nonspecialized health centers.Thus, the timely detection of lung involvement remains a challenge in real-world settings.A pathogenic link between autoimmunity, inflammation, and vitamin D imbalance is axiomatic in SSc.Closely associated with vitamin D metabolism is fibroblast growth factor 23 (FGF23), a protein secreted by osteocytes and osteoblasts that plays a role in the bone-kidney axis and calcium-phosphorus balance.3 A recent study demonstrated that the endothelin-1 (ET-1) receptor, a critical regulator of vascular tone and endothelial proliferation in the lungs, controls the cellular production of FGF23, positioning this molecule as a potential biomarker of clinical relevance.4 To assess the feasibility of FGF23 as a marker of lung involvement, we conducted a proof-of-concept study in 29 patients with SSc. 1 Evaluation included skin involvement (modified Rodnan skin score [mRSS]), accumulated organ damage (Medsger Disease Severity Scale [MDSS]), and disease activity (Valentini Disease Activity Index [VDAI]).5 Exclusion criteria were pregnancy, cancer, infection, parathyroid disease, chronic kidney disease, autoimmune overlap, and use of bisphosphonates or parathyroid hormone analogs.ILD was diagnosed according to the Canadian Scleroderma Research Group decision rule based on clinical evaluation, chest radiography, and pulmonary function tests, and suspected cases were subsequently confirmed by chest CT. 6 For PH, the European Society of Cardiology/ European Respiratory Society Guidelines echocardiographic-based definition was used: tricuspid regurgitation velocity > 3.4 m/s plus pulmonary artery systolic pressure > 50 mmHg.2 Serum levels of FGF23 (Millipore; range 9.9-2400 pg/mL) and 25-hydroxyvitamin D (IBL International) were measured by ELISA.Sera from 23 healthy individuals (22 women) with a median age of 49 (IQR 44-56) years were studied as controls.This study was approved by the local ethics committee (no.14-888) and conducted in accordance with the Declaration of Helsinki.All individuals gave their consent to participate.Of the 29 patients included, 13 had pulmonary involvement: 4 had isolated ILD (100% with diffuse cutaneous SSc [dcSSc]), 5 isolated PH (100% with limited cutaneous SSc), and 4 concurrent ILD and PH (75% with dcSSc).Table 1 summarizes the
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".