Concordance of Noninvasive Plasma Cell-free DNA With Invasive Diagnostics for Diagnosis of Invasive Fungal Disease
Bibliographic record
Abstract
BACKGROUND: Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) is a promising noninvasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear. METHODS: This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid. RESULTS: Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 bronchoalveolar lavage fluid) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Nonhematologic malignancy and nonneutropenic state were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD. CONCLUSIONS: Noninvasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.
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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 | 0.013 |
| 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 | 0.001 |
| 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".