PONE-D-22-32402­­The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: A nationwide studyPLOS 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: Partly

Reviewer #3: Yes

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

Reviewer #1: I Don't Know

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: Yes

Reviewer #2: Yes

Reviewer #3: No

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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: a well conducted study with a good number of studied patients and very clearly written paper. I think the practical application will be of limited impact on the management of the hospitalized patients regarding both diagnosis and treatment

Reviewer #2: Thank you for the opportunity to review this interesting study. Authors have performed retrospective review of inpatients admitted with infection between 2001-2020 to understand relationship of lactate dehydrogenase in regarding to outcomes in pulmonary and non-pulmonary infections. I have few suggestions listed below to improve the manuscript:

1. In this study, authors have shown pulmonary and nonpulmonary infections in an unadjusted model (table 1) only. Also, baseline characteristics (table 1) suggests that both the populations are inherently non-comparable without adjusted analysis. In the discussion 'We also found that the median serum LDH level among patients with pulmonary infections was higher than that of patients with non-pulmonary infections (418 U/L vs. 385 U/L, p<0.001).' may not be correctly interpretable. Author should emphasize this limitation.

2. In table 2, please explain, if gender was added in the model ?

3. I would encourage authors to add univariate analysis in the supplementary tables for transparency of selection of variables in the multivariate analysis.

4. In the table 2, 3, and 4, authors have added many biomarkers such as Hb, WBC, PLT, and Albumin. And all these biomarkers have significant associations. However, authors have not discussed the potential role/importance of these markers. I would suggest adding more discussion about these biomarkers.

5. In the conclusion section, 'Additionally, patients with pulmonary infections and LDH levels >900 U/L are at particularly increased risk of death within 30 days. The findings presented here suggest LDH testing as a helpful bedside tool to estimate mortality risk in patients with infectious disease.' I would suggest rephrasing these sentences, as this study did not assess risk but 'increase odds of death'.

6. A number of previous studies and reviews have shown that In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. Current data included the year 2020 in the analysis. Author should add a caveat specific diseases such as COVID-19.

7. I will suggest to include more references to support the statements made in the discussion. I will also suggest to review the manuscript for grammar and use same fonts for manuscript and all references.

Reviewer #3: Thorough, intelligible review of elevated LD in sepsis with meaningful, interesting results.

Possibly limited clinical utility given the increased LD in different kind of sepsis only modest and would add little to clinical evaluation and management.

There is a considerable literature in this area, which they only summarise but usefully compare to other biomarkers.

Note that the Editor reserves further comments at later stages of the manuscript evaluation process.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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­­The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: A nationwide study

PONE-D-22-32402R1

Dear Dr. Amit Frenkel,

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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Kind regards,

Riccardo Nevola, MD, PhD

Academic Editor

PLOS ONE

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 #2: 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 #2: Yes

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

Reviewer #2: Yes

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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 #2: No

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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 #2: Yes

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6. Review Comments to the Author

Reviewer #2: Thanks a lot. Authors have incorporated all the suggested changes in the manuscript. No further comments.

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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 #2: Yes: Prabal Chourasia

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