Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 5 appraisals
Cell reports. Medicine
Toward generalizable prediction of cancer signal using a cell-free DNA language model.
Cell-free DNA can be used for early cancer detection, minimal residual disease monitoring, and post-treatment risk stratification. However, current assays are often designed for a single purpose and rely on deep or broad sequencing panels that capture only a small fraction of tumor-derived signals, limiting transferability, increasing cost, and reducing scalability. Fragmentia-AI is an artificial intelligence language model that learns fragment-level sequence patterns in tumor-derived cell-free DNA. Instead of focusing on mutations, it uses the structure of cell-free DNA to detect cancer signals in a partially panel-agnostic manner from ultra-low sequencing input, approximately 0.1%-1% of conventional depth. The model performs well across cancer types and clinical settings, including monitoring after surgery or immunotherapy, and in samples with low variant allele frequencies or no detected mutations. Fragment-level analyses identify shorter fragments and tumor-derived sequence patterns across panels of different sizes and ultra-low-pass whole-genome sequencing in multiple cohorts.
23 July 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Mucoactive agents in bronchiectasis: a systematic review and meta-analysis
BACKGROUND: Mucoactive agents aim to improve mucociliary clearance in bronchiectasis, disrupting the cycle of impaired clearance, infection and inflammation. Registry data show 28% of patients use these agents, but prescribing varies due to limited evidence. We aimed to update evidence on mucoactive agents' effects in adults with bronchiectasis. METHODS: We conducted a systematic review and meta-analysis, searching Medline, Embase, CENTRAL and trial registries to 1 October 2025. Eligible studies included adults with bronchiectasis, evaluating any mucoactive agent versus placebo or control. Cystic fibrosis and paediatric studies were excluded. The primary outcome was exacerbation frequency; secondary outcomes included lung function, quality of life and adverse events. FINDINGS: From 1512 records, 24 studies (20 randomised, four observational: n=7051) evaluated eight mucoactive agents (ambroxol, bromhexine, carbocisteine, erdosteine, hypertonic saline, mannitol, N-acetylcysteine, rhDNase). Most trials had high or some risk of bias. Seven randomised studies (n=1259) reported exacerbations; pooled analysis did not demonstrate a statistically significant difference in annualised exacerbation incidence (mean difference -0.40 per patient per year, 95% CI -1.04-0.24; p=0.22; I2=91%; very low certainty). Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV1 % pred), showing a small mean increase of 3.23% (95% CI 0.31-6.15; p=0.03; I2=69.9%; very low certainty). Pooled analyses did not demonstrate significant differences for other spirometry measures, quality of life or adverse events. INTERPRETATION: Pooled evidence did not show a reduction in exacerbations and FEV1 % pred improvements were small. Evidence certainty was low/very low, meaning overall clinical benefit remains uncertain, highlighting the need for targeted trials of specific agents and subgroups.
25 June 2026
Read appraisal →Journal of bronchology & interventional pulmonology
AIBAN-AI Bronchial Detection and Airway Navigation System
BACKGROUND: Accurate navigation within the lungs is critical for bronchoscopy procedures but remains challenging due to the complex airway anatomy. Artificial intelligence (AI) integrating real-time landmark detection and navigation guidance may enhance precision and safety. METHODS: We developed an AI Bronchial detection and Airway Navigation system (AIBAN) for bronchoscopy, combining airway lumen detection, anatomic localization, and navigation guidance. A YOLOv8-based detection module was used to identify 34 airway landmarks in real time. Next, an airway-level localization module estimated the bronchoscope's position using a hierarchical anatomic graph, identifying the deepest branch compatible with all coherent detections in each frame. A navigation module then recommended the next airway to follow along predefined anatomic paths, providing directional cues to perform a complete and systematic bronchoscopy. RESULTS: AIBAN was developed on a data set of 18 bronchoscopy videos, using 15 for training and 3 for validation. In validation, the framework correctly identified the bronchoscope's location in 91.1% of the frames. In addition, 92.6% of predictions were within one airway branch of the true location, and 94.5% were within 2 branches. The navigation guidance performance was also promising, with the system following the correct anatomic pathway in 96.2% of test videos, demonstrating reliable guidance through the lungs. CONCLUSION: AIBAN enables accurate airway detection, localization, and navigation guidance in a simulation-based setting. It can provide reliable guidance along predefined paths and precise spatial positioning and is a promising tool for medical training and has potential for future clinical implementation.
11 May 2026
Read appraisal →PloS one
Biomarkers of mitochondrial dynamics in idiopathic pulmonary fibrosis: Identification and validation through transcriptomic and single-cell analyses
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has increasingly been associated with dysregulated mitochondrial quality control and dynamics. However, the molecular mechanisms underlying these alterations remain incompletely understood. This study aimed to systematically identify and validate candidate biomarkers related to mitochondrial dynamics in IPF and to characterize their cell-type specificity and putative regulatory relationships. METHODS: We integrated bulk transcriptomic datasets from the Gene Expression Omnibus (GEO), single-cell RNA sequencing (scRNA-seq) data, and literature-derived mitochondrial dynamics gene sets. Candidate genes were identified through differential expression analysis and consensus clustering, followed by functional enrichment and protein-protein interaction (PPI) network analyses. A total of 101 machine-learning model combinations-including random forest, LASSO, and support vector machine-were constructed to select optimal feature genes. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and further evaluated with artificial neural network (ANN) modeling. Additional analyses included chromosomal localization, immune infiltration profiling, multilayer regulatory network construction (transcription factors, lncRNAs, circRNAs), molecular docking prediction, and single-cell expression and pseudotime trajectory analysis. Key biomarkers were further evaluated by RT-qPCR in an independent clinical cohort. RESULTS: Integrated multi-omics and machine-learning analyses identified CD247, IL7R, and RETN as candidate biomarkers related to mitochondrial dynamics-associated pathways in IPF. Across independent transcriptomic datasets, RETN was upregulated, whereas CD247 and IL7R were downregulated, and each showed diagnostic value (single-gene AUC > 0.7). The ANN model based on these genes achieved encouraging discriminative performance (training AUC = 0.91; validation AUC = 0.82), and expression differences were confirmed by RT-qPCR in a modest independent cohort. Enrichment analyses indicated convergence on spliceosome-related pathways, and regulatory-network analysis highlighted interactions involving transcription factors and non-coding RNAs, including circRNA CDR1as. Molecular docking suggested putative interactions with selected compounds. Single-cell analyses suggested that dysregulation was most evident in monocyte-associated compartments in one publicly available scRNA-seq dataset, and pseudotime analysis indicated dynamic expression patterns, with early transient increases in CD247 and IL7R and progressive elevation of RETN. CONCLUSION: Through multi-omics integration and machine-learning approaches, we identified and preliminarily validated CD247, IL7R, and RETN as candidate biomarkers related to mitochondrial dynamics-associated pathways in IPF. These findings provide transcriptomic and cell-type-specific evidence suggesting potential immune-mitochondrial associations in IPF and may inform future biomarker validation and mechanistic hypothesis generation.
26 Apr 2026
Read appraisal →Pulmonology
Comparative diagnostic performance of advanced endoscopic techniques in suspected sarcoidosis: A systematic review and network meta-analysis
BACKGROUND: While various endoscopic techniques are used for minimally invasive tissue sampling in suspected sarcoidosis, comprehensive evidence comparing their diagnostic efficacy is limited, and the optimal approach remains unclear. RESEARCH QUESTION: Which endoscopic technique provides the greatest diagnostic advantage for sarcoidosis? STUDY DESIGN AND METHODS: We systematically searched 3 databases for studies published up to 22 April 2025. A network meta-analysis was conducted within a Bayesian framework, with diagnostic yield as the primary outcome. RESULTS: A total of 35 studies were included. Compared to TBLB, both EBUS-guided intranodal forceps biopsy (EBUS-IFB) (RR 3.50, 2.14-5.84) and EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) (RR 3.52, 1.97-6.48) showed higher diagnostic yield. SUCRA rankings placed EBUS-IFB (0.912) and EBUS-TMC (0.910) at the top, followed by EBUS-guided core needle biopsy (EBUS-CNB) (0.587), EUS-FNA (0.582), and EBUS-TBNA (0.560), EUS-B-FNA (0.498). Conventional techniques, including cTBNA (0.279), TBLB (0.168), and EBB (0.001), ranked lowest. All procedures had a favourable safety profile. CONCLUSIONS: In centres with appropriate expertise, EBUS-IFB and EBUS-TMC may offer superior diagnostic performance for sarcoidosis. However, given the low certainty of evidence, these conclusions should be interpreted with caution. Clinical decisions should be individualised, considering the patient's condition when determining the final diagnostic strategy.
8 Apr 2026
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