PONE-D-20-40304

Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients

PLOS ONE

Dear Dr. Ma,

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.

According to reviewer's comments (see below) please try to refine statistical analysis and to improve English language

Please submit your revised manuscript by May 24 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

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Michele Provenzano

Academic Editor

PLOS ONE

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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

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

Reviewer #1: No

Reviewer #2: 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: Yes

Reviewer #2: 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: No

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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: Wang and colleagues carried-out a Research article testing the association between serum sodium quartile and in hospital mortality in patients with acute aortic dissection. The topis seems of interest. Please see below my criticisms:

- In abstract, serum sodium has been splitted into quartiles according to distribution. Was Q1 considered the reference in che cox model ? please specify this information since it has been stated that hazard ratio in Q3 and Q4 was increased but it was not reported the reference category. Please remember that the hazard ratio is a measure of relative risk (in time-to-event analyses)

- Methods: how variables have been added to the model 2 ? based on the plausibility of their association with short term mortality ? please clarify

- Methods: usually the variable sodium has a biphasic association with risk (U-shaped). This means that risk increases for both low and high sodium values. Was the linearity of effect of sodium on the endpoint tested?

- Following the previous point, I would suggest Authors to do a sensitivity analysis by replacing the category Q1 with Q2 as reference for the Cox model

- I am not fully sure that Cox model is appropriate for such analysis with short-term follow-up (of some days). It seems that the event occurs almost in the same period of sodium measurement. Can Authors provide one or more references which may clarify this point?

Reviewer #2: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. The authors indicated that the admission serum sodium was an independent risk factor for postoperative hospital death of AAD patients. I would suggest

1. an English language editing;

2; to review fig n. 2 (low quality image)

3. to write the small cohort of patients in the study limitations

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Reviewer #1: No

Reviewer #2: Yes: GIUSEPPE FILIBERTO SERRAINO

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PONE-D-20-40304R1

Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients

PLOS ONE

Dear Dr. Ma,

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:

The Statistical Referee raised major concerns about the methodolgy used in this article. Please try to revise the manuscript in accordance to the comments reported below

==============================

Please submit your revised manuscript by Aug 29 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Michele Provenzano

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Please note that the present manuscript has not yet sufficiently improved. In fact, several methodological flaws still persist. Please see the comments below

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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 #3: (No Response)

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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 #3: No

**********

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

Reviewer #3: No

**********

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 #3: Yes

**********

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 #3: No

**********

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 #3: In this manuscript, Huang et al examined the association of serum sodium level on admission with postoperative in-hospital mortality in 415 acute aortic dissection patients enrolled in the Fourth Hospital of Hebei Medical University. The authors found the serum sodium was significantly associated with in-hospital mortality risk. However, there are several concerns about the study.

1. One major concern is the proportional hazards assumption. There is huge difference between patients who survived and those who died (14 days vs 2 days). The authors should formally test the assumption before using the Cox model.

2. Another concern is that this is an association study. There is no way to derive causality effect. Please remove any implication of causality.

3. Please clarify how the variables were determined. For example, for the smoking, is it current smoker or past smoker? For drinking, how many drinks were used to determine the drinker status?

4. The exclusion criteria included the serious lack of clinical data. How is it defined? What about other variables with a moderate missing rate? Were they excluded or imputed?

5. Did any patient die before the operation? If so, will it affect the association? What is the time interval between admission and the operation?

6. It seems that the variation of sodium levels is very small (SD=4.8). All four quartiles included some participants with normal sodium levels (Q1 : ≤ 136 mmol/L, Q2 : 137 – 138 mmol/L, Q3: 139 -140 mmol/L, Q4 : ≥141 mmol/L). What would be measurement variability?

7. Can authors comment on the possible reasons why Q2 was not significant, but Q3 and Q4 were significant?

8. In Figure 2, please indicate the number of events under the x-axis. Also it is unclear why there was a big drop of survival probability in Day 40 for Q4, especially given the median of 2 days in the non-survival group.

9. In Figure 3, given that there is no direct connection between quarters, a barplot would be more appropriate.

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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 #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients

PONE-D-20-40304R2

Dear Dr. Ma,

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.

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Kind regards,

Michele Provenzano

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The manuscript is nicely improved. Thank you for your work

Reviewers' comments: