Circulating TNF-α levels in rheumatoid arthritis: a systematic review and meta-analysis and comparison to TNF-α levels in sepsis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Background: Tumor necrosis factor-alpha (TNF-α) is implicated in the pathogenesis of autoimmune conditions and sepsis. Although anti-TNF-α therapies have demonstrated clinical efficacy in rheumatoid arthritis (RA), there is no established evidence for benefit in patients with sepsis. Objectives: We sought to quantify circulating TNF-α in patients with RA and compare results to TNF-α levels in sepsis. Design: We performed a systematic review and meta-analysis of circulating TNF-α in patients with RA. We searched Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection databases from inception until May 30, 2023. We included randomized controlled studies and observational reports containing more than ten subjects that reported mean serum or plasma TNF-α levels. We used the Newcastle-Ottawa Scale to assess methodological quality of studies. Data sources and methods: Summary data were extracted and analyzed using a random-effects model to estimate the pooled mean circulating TNF-α. Circulating TNF-α in RA was compared to TNF-α levels reported in our systematic review and meta-analysis characterizing cytokine levels in sepsis. Results: We identified and screened 8764 studies, and 104 studies satisfied the inclusion criteria (5399 total participants, including 4419 females). Pooled estimated mean RA TNF-α was 23.1 pg/mL (95% CI 17.8–30.1) in the random-effects model. There was significantly lower TNF-α in RA patients using disease-modifying antirheumatic drugs (DMARDs, p = 0.04) and patients using corticosteroids ( p = 0.01). After adjustment for age and sex, there was no significant difference between TNF-α in RA compared to sepsis. Conclusion: No significant difference between adjusted TNF-α levels in patients with RA versus sepsis was determined. Since TNF-α antagonists show benefit in RA but not sepsis despite comparable circulating concentrations, we conclude TNF-α does not contribute to sepsis pathogenesis. TNF-α concentration may be slightly higher due to study heterogeneity. Trial registration: This investigation was registered in PROSPERO (CRD42023425361).
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.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it