PONE-D-21-37187Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in diabetic foot infection patients with severe renal impairment: a retrospective cross-sectional studyPLOS ONE

Dear Dr. Que,

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.

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Kanhaiya Singh, Ph.D

Academic Editor

PLOS ONE

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Additional Editor Comments:

Although reviewers have found this study interesting, they have raised some significant concerns. Please address the novelty and study concerns as mentioned by Reviewer 1. Also, please discuss in details about the excluded subjects.

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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: Partly

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: N/A

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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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: Ref: PONE-D-21-37187

In the present article entitled “Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in

diabetic foot infection patients with severe renal impairment: a retrospective cross-sectional

study” Que et al., have attempted to investigate the accuracy of erythrocyte sedimentation rate (ESR) in

diagnosing diabetic foot osteomyelitis (DFO) in diabetic foot infection (DFI) patients

with and without severe renal impairment (SRI). Although the manuscript contains extensive amount of work, I have several concerns about study design, data presentation and interpretation. Here are the specific comments.

Abstract: The starting paragraph is not scientifically developed. If there is already plethora of studies, why authors want to study this? There is no gap of knowledge is shown.

1. Inclusion criteria: The authors have studied patients with severe renal impairment: No mention has been made of patients receiving Hemodialysis/ peritoneal dialysis for the diabetic nephropathy. As noted in a previous study

by Alisomali MI et al (ref no 29): Post-dialysis the ESR was raised in most of the stable patients on regular HD and was significantly higher than the pre-dialysis ESR (by, on average, 5.8 mm/h).

2. Novelty concern and Study Design concerns: The same study (ref no 29) and several other studies (cited below) have mentioned that 'high ESR may be limited diagnostic utility in patients with Chronic kidney disease'. Making the entire diagnostic value in patients specifically having Diabetic foot infection and osteomyelitis redundant.

Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40. https://www.ncbi.nlm.nih.gov/pubmed/3605082

Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801. http://annals.org/aim/fullarticle/700910

Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224. https://www.ncbi.nlm.nih.gov/pubmed/11015011

Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248. https://www.karger.com/Article/PDF/186266

As the authors mention later in study limitations, the diagnosis of Diabetic foot osteomyelitis has not been established by bone biopsy in majority which is a gold standard.(line 251)

Fig 2 'The difference in ESR between DFI patients with and without SRI': Individual data points could be shown in the Box- Whisker plot to compare two variables. Also the legend does not mention the type of graph or analysis used (Kruksal - Wallis H test)

Fig 3: more could have been done with the present data if authors could find the Positive and negative predictive value using ROC curves and prevalence of disease in population.

To conclude ESR is inherently a very non-specific inflammatory marker to begin with which can be raised in diabetes mellitus and its several associated complications.

Best regards,

Reviewer #2: The role of ESR in making a diagnosis of osteomyelitis in diabetic foot ulcers is complimentary to other investigations including imaging and bone scan. This is an interesting study stating that the adjunctive value of ESR in diagnosing osteomyelitis diminishes in patients with severe renal impairment. ESR may therefore be used as a screening test for making a presumptive diagnosis of osteomyelitis in patients with diabetic foot infections without renal impairment

Reviewer #3: 1. In line number 71, authors mentioned there is a high chance of diabetic patients to suffer from kidney diseases. But Fig. 1 shows out of 364 DFI patients only 44 are having SRI. Also, HbA1c% of patients with SRI is lower than patients who do not have SRI, as indicated in Table 1. Both these data are contradicting to the statement made in line number 7.

2. Conclusion part should be rewritten for clarity (refer to line 257). In line 264, no need to write the values in bracket as it is already mentioned.

3. Some graphs/diagrams corresponding to the statistical data table should be great to visualize the important parameters.

4. A list of abbreviations will be helpful for the readers, as there are too many abbreviations used.

5. As the authors declare, "a prospective study with a priori calculated sample size is needed to verify the reliability of our conclusions" - it should be justified the relevance of study with the present data set with a future scope of research.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-21-37187R1Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in diabetic foot infection patients with severe renal impairment: a retrospective cross-sectional studyPLOS ONE

Dear Dr. Que,

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.

Please submit your revised manuscript by Apr 04 2022 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: https://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,

Kanhaiya Singh, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Please address the comment raised by Reviewer 1.

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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 #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

**********

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

Reviewer #1: N/A

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

**********

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: Authors have answered all the previous questions raised during the first review.

Minor issues that need to be addressed:

Legends: lines 234-239: the authors may add some interpretations of the graph along with the methods used

Figure 4: the font needs to be unbolded so the image is easier to interpret

Reviewer #3: (No Response)

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Reviewer #1: No

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.]

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Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in diabetic foot infection patients with severe renal impairment: a retrospective cross-sectional study

PONE-D-21-37187R2

Dear Dr. Que,

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,

Kanhaiya Singh, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

**********

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

**********

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

Reviewer #1: N/A

**********

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

**********

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

**********

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: (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