PONE-D-24-40066Efficacy and safety of creatine phosphate sodium in the treatment of viral myocarditis：A systematic review and meta-analysisPLOS ONE

Dear Dr. Zhang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Academic editor comments to authors:This systematic review and meta-analysis idea is very interesting, however there are many issues that must be clarified: - The authors ignored the historical role of IVIG in the management of viral myocarditis.... - No comparative studies were mentioned regarding the role of IVIG and other new modalities like interferon or creatine phosphate sodium... - The discussion section is deficient and need to be re-written again.. there is many typo errors that need to be revised precisely

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Hany Mahmoud Abo-Haded, MD

Academic Editor

PLOS ONE

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Additional Editor Comments:

This systematic review and meta-analysis idea is very interesting, however there are many issues that must be clarified:

- The authors ignored the historical role of IVIG in the management of viral myocarditis....

- No comparative studies were mentioned regarding the role of IVIG and other new modalities like interferon or creatine phosphate sodium...

- The discussion section is deficient and need to be re-written again..

there is many typo errors that need to be revised precisely

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors has explored the efficacy and safety of CPS use in viral myocarditis by performing metaanalysis. It is interesting research. However, several points require additional clarifications

- In introduction, It was mentioned in the current clinical treatment interferon at first although it is not a standard in management and immunoglobulin are more frequently used although authors did not mention it at all

- In result section under clinical efficacy paragraph, A total of 9 studies is included; however, you cited 10 references (21-24 &26-31) please adjust and remove the extra reference

- I could not find Table 1 among the files available for reviewing, so I could not review the demographics part of the study

- Why data of Meng Wang reference appeared twice in most Forest and Funnel plots figures; please explain.

- The Figure and table legend should be within the main manuscript not in the supporting information section

- Discussion section is limited it would be valuable to discuss how many of the investigated studies used CPS alone and which used CPS in combinations and what was the combinations used.

- Moreover, elaborate on the most recommended dose for CPS as I noticed in inclusion criteria for controls, as authors considered use of low dose CPS to be a control group.

- In discussion, consider writing on the side effects CPS documented in those studies

- Reference 25 has in continuity of it a paragraph of what I think authors roles or conflict of interest part of other paper, please remove it

- Some of references PMID numbers require revision for example references 26,27,28

- It would be valuable to add files detailing the excluded and included studies and additional study data in the Supplementary material section

Reviewer #2: Well written manuscript with proper statistics. The manuscript is technically sound and the well presented . The discussion and the conclusion summarize the important findings. The figures and the statical analysis is appropriate

Reviewer #3: Peer Review of "Creatine Phosphate Sodium in the Treatment of Viral Myocarditis: A Systematic Review and Meta-Analysis"

General Comments

This systematic review and meta-analysis by Wang et al. addresses an important clinical question regarding the efficacy and safety of creatine phosphate sodium (CPS) in the treatment of viral myocarditis (VMC). The authors provide a comprehensive overview of the existing literature and present their findings in a clear, structured manner. However, there are several areas that could benefit from further clarification and refinement to enhance the quality and impact of the manuscript.

Strengths

Relevance: The topic is highly relevant given the increasing recognition of viral myocarditis as a significant health issue. The exploration of alternative treatment options such as CPS is timely and important.

Methodology: The systematic review follows the PRISMA guidelines, and the inclusion of both efficacy and safety outcomes is commendable. The use of established databases for literature search enhances the credibility of the study.

Comprehensive Analysis: The meta-analysis includes a substantial number of patients (1,116), providing a robust data set for analysis. The authors utilize appropriate statistical methods to assess treatment efficacy and safety.

Areas for Improvement

1.Clarity of Results:

While the results are generally well-presented, some sections would benefit from clearer explanations. For example, in the results concerning cardiac troponin I and CK-MB levels, a more detailed description of the clinical significance of the findings would help contextualize the data for readers unfamiliar with these biomarkers.

2.Discussion of Limitations:

The authors acknowledge limitations regarding the sample size and quality of included studies. However, a more in-depth discussion on how these limitations might impact the validity of the conclusions drawn is needed. Specific attention should be given to the potential biases identified in the included studies and how they may affect the reliability of the results.

3.Publication Bias:

The analysis indicates potential publication bias, especially concerning cTnI and CK-MB results. The authors should expand on the implications of this bias and how it may influence the overall conclusions regarding CPS efficacy.

4.Recommendations for Future Research:

While the authors suggest the need for more rigorous studies, they could further detail what specific aspects should be addressed in future research (e.g., study design, patient demographics, dosing strategies).

5.Formatting and Clarity:

Some sections, particularly the methods, could benefit from clearer subheadings to enhance readability. Additionally, the inclusion of flowcharts or diagrams to illustrate the literature selection process could aid comprehension.

Conclusion

Overall, this systematic review and meta-analysis provides valuable insights into the use of CPS for viral myocarditis. With some revisions to enhance clarity, depth of analysis, and discussion of limitations, this manuscript has the potential to make a significant contribution to the field. I recommend acceptance with minor revisions.

Recommendations:

1.Clarify and elaborate on results, particularly in terms of clinical significance.

2.Enhance the discussion of limitations and potential biases.

3.Provide a more detailed outline of future research directions.

4.Improve formatting for better readability.

Thank you for the opportunity to review this manuscript. I look forward to seeing the revised version.

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Reviewer #1: No

Reviewer #2: Yes: Hala Mounir Agha

Reviewer #3: No

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Efficacy and safety of creatine phosphate sodium in the treatment of viral myocarditis：A systematic review and meta-analysis

PONE-D-24-40066R1

Dear Dr. Zhang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Prof. Hany M. Abo-Haded, M.D.Academic Editor PLOS ONEMansoura University, Egypt

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I thank the authors for efficiently and fully addressing all the previously noted comments point by point.

Reviewer #3: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

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