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Thank you for revising your manuscript to address the concerns of the reviewers. Reviewer 1 now recommends acceptance and I am satisfied that the comments of reviewer 2 have been addressed. The manuscript is now ready for publication.
The authors have improved their paper accordingly.
The authors have improved their paper accordingly.
The authors have improved their paper accordingly.
The authors have improved their paper accordingly.
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In the introduction please provide more examples of recent studied that identified serum biomarkers as diagnostic tools for PJI (for e.g. doi: 10.3390/jcm13195716 ).
The methodology section should be better structured in subsections (e.g. Study design, Data collection etc). Please provide the normality check test used for the variables.
The number of figures and Tables provided is sufficient.
The discussion interpret the research results and relate them to other findings from the scientific literature. Limitations are provided at the end, but they can be better defined.
The lack of data on preoperative antibiotic/anticoagulant therapy may confound biomarker levels; this should be addressed as a limitation.
A subgroup analysis should be performed on the type of joint (hip vs. knee) or infection timing (early vs. late) because this limits clinical applicability of the study.
While CRP combined with fibrinogen/PC/MPV improves AUC, the clinical rationale for combining biomarkers (especially PC/MPV, which performed poorly alone) is underdeveloped; please provide mechanistic or pathophysiological justification.
The study highlights inconsistent cutoffs in prior literature but does not discuss how their proposed thresholds (e.g., CRP: 10.95 mg/L) compare to existing guidelines (especially with MSIS criteria).
Please check the keywords in accordance with MeSH.
Minor grammatical errors (e.g., Page 6, Line 35: "aberrantly expressed of fibrinogen").
Figure 4 should be enlarged as it is overcrowded and hard to examine.
Overall, the language is clear and understandable.
Line 29: ‘revision’
Line 63: please revise ‘surgeon’ to ‘surgery’
Line 169: ‘Both’ does not make sense. Please remove.
There are literature references supporting most of the document.
A few specific comments:
Line 30: ‘is expected to increase considerably from 1981 to 2014’? Since we are in 2025, I would recommend an updated search of the literature on volume predictions for TJR and PJI.
While the discussion of the need for diagnosis is generally accurate in Lines 35-44, the introduction should include standard guidance for diagnosis, which they have actually referenced in their methodology (line 60).
The article is self-contained with relevant results.
Overall, the experimental design is moderately strong. Inclusion and exclusion criteria are adequately presented.
A few comments about design:
Was there a specific criterion for ‘heavy smoking’?
Please include what specific methods were used in the determination of the biomarkers. Elisa kits, or any other analytical methods. The manufacturer of different kits and the sensitivity of different methods can make a difference in the result.
While the authors do indicate this as a limitation, I recommend estimating the number of patients in each group that can be valuable and to also explain what stratifying by time can add to the analysis. While this is a point for discussion and in general, PJI studies are limited by the number of patients since it is a relatively rare condition, it would still be good to evaluate what was the power of the calculations.
Overall, I find the findings valid and important to the field. Some specific comments for making the discussion stronger:
The authors address a specific but important aspect of the treatment of periprosthetic joint infections, which are devastating to the patient population. As the authors suggest, the diagnostic markers for PJI are limited in their efficiency and are often used together to increase sensitivity and specificity. They are considering diagnostic value at reimplantation, that is the specific case of determining whether an infection is still present after the initial stages of treatment of PJI by the removal of components and antibiotic administration (for approximately 6 weeks). This is not clear to the general audience, the process of revision and the specific challenges of diagnosis/culture at reimplantation should be mentioned.
The literature support for the justification of using PC/MPV is strong and well presented. Is there also a mechanistic reason for the ratio to be more diagnostic than each factor alone? If there is please include some information as this can be very valuable in further studies.
Because the time period seems exceptionally large, stratifying may be warranted according to time (perhaps a surrogate for ‘low’ vs. ‘high’ virulence of infection?).
While the authors do indicate this as a limitation, I recommend estimating the number of patients in each group that can be valuable and to also explain what stratifying by time can add to the analysis.
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