PONE-D-24-11769Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysisPLOS ONE

Dear Dr. Gajardo,

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Sonu Bhaskar, MD PhD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Thank you for submitting your work to PLOS One. Based on review of your submission and feedback from reviewers, we would like to invite you to address the points raised and revise your manuscript. We look forward to receiving your revised mansucript.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: No

Reviewer #3: Yes

Reviewer #4: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present a systematic review protocol to assess the association of early high-sensitivity serum troponin levels with short-term mortality in patients admitted to ICU because of sepsis with acute organ dysfunction. Some corrections must be made to the manuscript.

The inclusion of only studies published in English in an era of online translators and artificial intelligence is not justified in a systematic review, since texts in other languages ​​can be translated into English and the authors' native language with good quality. The correct thing to do is not to restrict it by publication language.

Authors should consider in the methodology "The evidence for small-study effects is usually considered on a funnel plot, which shows the study estimates (x axis) against their precision (y axis). A funnel plot is usually recommended if there are 10 or more studies", following the reference https://doi.org/10.1136/bmj.k4597 .

Finally, the authors should try to anticipate in a paragraph possible limitations that could compromise the results of the future systematic review, such as observational studies with small samples, with great heterogeneity and without strict criteria for analyzing troponin levels and diagnosing sepsis.

Reviewer #2: Line 117: Studies will be first analyzed based on their title and abstract. Papers that pass this primary

scrutiny, or whenever it seems insufficient, will be subject to full text assessment by the same reviewers for final selection. (please rephrase how are you going to analyze)

Line 120: Basically, interventional and observational primary studies will be deemed eligible if they reported some form of association between troponin levels and mortality in a general clinical context (how are you going to combine the analysis for different study design).

Reviewer #3: Reviewer’s comments:

The authors are planning to perform a systematic review and meta-analysis examining the prognostic value of early high-sensitivity troponin in predicting short-term mortality in sepsis based on a detailed, comprehensive, and clear protocol that has been registered in PROSPERO (CRD42024468883).

I only have 2 minor comments on the Methods section: Selection criteria.

Page 7, Table 3.

One of the inclusion criteria only limits published articles in English language. To improve the inclusion of more potential articles, the authors may consider not to have any language restrictions.

Page 9. Table 3.

The authors plan to include published studies, conferences, and abstracts. To ensure that the quality of included studies are of higher standards, only published studies in the form of full article should be included in the systematic review and meta-analysis. Please consider excluding abstracts presented in conferences.

I have no further comments.

The end.

Reviewer #4: This study aims to verify the potential association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction.

This protocol will produce a systematic review with meta-analysis which will try to provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients, paving the way for further research in this high-risk population.

The authors have adopted solid methodology and a comprehensive statistical plan for gathering and analyzing data retrieved from available studies.

I don't have specific comments to improve the manuscript further.

My only remark relates to the sentence at line 156 : "Authors will be contacted to request critical missing or not reported data regarding associations of interest. In case of no response, the article will be excluded from this study." I wonder if the authors could find a way to include at least some data from these incomplete articles, if there were any, instead of excluding them a priori.

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Reviewer #1: Yes: Ricardo Ney Cobucci

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis

PONE-D-24-11769R1

Dear Dr. Gajardo,

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,

Sonu Bhaskar, MD PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for submitting the revised version of your manuscript. I am pleased to inform you that it has been accepted for publication.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: No

**********

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 #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have met most of the reviewers' recommendations. The revised manuscript is ready for publication.

Reviewer #2: Dear Authors,

The background is You may change the subheading for literature search to search strategy and explain in a paragraph. You may rephrase this sentence "Subsequently, we will manually scrutinize references of included studies and previous reviews on the topic to retrieve missing pertinent papers".

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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: Yes: Ricardo Ney Cobucci

Reviewer #2: No

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