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Evidence-Based Supplement Research
Evidence-Based Supplement Research

High diagnostic value of next-generation sequencing for orthopedic-related infectious diseases: a quantitative analysis of 24 cohort studies.

  • 2025-11-11
  • International journal of surgery (London, England) 112(2)
    • Mingjiang Luo
    • Zubing Mei
    • Min Xu
    • Qing Zhang
    • Ridong Tan
    • Huijie Dai
    • Aoying Li
    • Fuwen Shi
    • Zilong Guo
    • Shiwen Gong
    • Zhiyong Sun
    • Chao Wei
    • Zhihong Xiao

Study Design

Type
Meta-Analysis
Sample size
n = 2,849
Population
orthopedic-related infectious diseases
Methods
systematically searched PubMed, Embase, and Cochrane Library from inception to January 2025; meta-analysis with pooled sensitivity, specificity, PLR, NLR, DOR, SROC curve

Objectives

Identifying pathogenic microorganisms as early as possible is often critical for diagnosing orthopedic-related infectious diseases, but traditional culture methods take a long time to yield results, and they have a high rate of false negatives. Next-generation sequencing (NGS) is an efficient method for microbial diagnosis, but the diagnostic accuracy of NGS in orthopedic-related infectious diseases remains unclear. Therefore, we conducted a meta-analysis to evaluate the diagnostic accuracy of NGS in orthopedic-related infectious diseases.

Methods

From inception to January 2025, we systematically searched the PubMed, Embase, and Cochrane Library databases to identify relevant research reports evaluating the use of NGS in the diagnosis of microbial pathogens for orthopedic-related infectious diseases. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve, which combines sensitivity and specificity across different thresholds, was used to summarize the overall diagnostic accuracy. The area under the SROC curve (AUC) represents the ability of NGS to differentiate between infected and non-infected cases, with values closer to 1 indicating higher diagnostic accuracy. Diagnostic performance was evaluated through the SROC curve with 95% prediction values and confidence interval (CI) contours. Sources of heterogeneity and the stability of results were determined by meta-regression and subgroup analysis, respectively.

Results

Twenty-four studies meeting the inclusion criteria were selected from a total of 2849 citations. The included studies represented a diverse set of cohorts, encompassing a range of orthopedic-related infections across different geographical regions, including North America and Asia. The pooled results of the diagnostic performance of NGS were as follows: sensitivity, 0.88 (95% CI: 0.84-0.92); specificity, 0.94 (95% CI: 0.90-0.96); corresponding to a relatively low missed diagnosis rate of 12% and misdiagnosis rate of 6%; PLR, 14.5 (95% CI: 9.3-22.6); NLR, 0.12 (95% CI: 0.09-0.17); and DOR, 118 (95% CI: 69-201). The area under the SROC curve was 0.97 (95% CI: 0.95-0.98). Deeks' funnel plot showed no obvious evidence of publication bias ( P = 0.24).

Conclusion

In summary, NGS demonstrates high diagnostic accuracy for orthopedic-related infections across various specimen types, sequencing platforms, study designs, and regions. However, significant between-study heterogeneity should be considered when interpreting these results. Future research should focus on large-scale prospective studies to evaluate the impact of sample size, direct comparisons across diverse infection types, and the influence of prior antibiotic exposure on diagnostic performance. Addressing these aspects will facilitate the clinical standardization and broader implementation of NGS, ultimately enhancing its diagnostic and prognostic value.

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