PONE-D-20-16260

Metabolic Syndrome and Idiopathic Sudden Sensori-Neural Hearing Loss

PLOS ONE

Dear Dr. Quaranta,

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.

The manuscript entitled "Metabolic Syndrome and Idiopathic Sudden Sensori-Neural Hearing Loss" tackles a relevant subject to the ENT scientific community. However, as pointed out by the reviewers, there are some concerns that need to be addressed before this manuscript is considered for publication.

Specifically:

1) NOVELTY: There are other similar studies in the literature, with larger number of patients. Bottomline - what does your study add to the already existing literature?

2) RELEVANCE: What literature gap does this study aim to fill? This matter needs to be explored in-depth in the introduction of the manuscript.

3) FOCUS: Although the authors defined a study design aimed to evaluate the correlations between cardiovascular diseases and ISSNHL, there is an extensive discussion on findings from other authors and speculation on underlying pathophysiological mechanisms. Although important and informative, I recommend including a more in-depth analysis of the authors' own findings.

4) DATA AVAILABILITY: I strongly recommend the authors to make their raw data available as a supplementary material.

Please submit your revised manuscript by Aug 13 2020 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.

Kind regards,

Rafael da Costa Monsanto, M.D.

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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2. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study, including:  a) the date range (month and year) during which patients' medical records were accessed; and b) the source of the medical records analyzed in this work (e.g. hospital, institution or medical center name).

3. We noticed minor instances of text overlap with the following previous publication(s), which need to be addressed:

(1) https://worldwidescience.org/topicpages/m/metabolic+syndrome+involvement.html

(2) https://en.wikipedia.org/wiki/Metabolic_syndrome

The text that needs to be addressed involves the (1) Introduction (lines 53-55), (2) Introduction section (lines 58-64).

In your revision please ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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We will update your Data Availability statement on your behalf to reflect the information you provide.

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: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: 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: I read the manuscript entitled “Metabolic Syndrome and Idiopathic Sudden Sensorineural Hearing Loss” with great interest.

The authors aimed to evaluate the impact of Metabolic Syndrome (MetS) and Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) and the association between the presence of MetS and ISSHL.

Major issues:

Introduction

1. The pathophysiology of ISSHL remains unknown and we have a lot of widely accepted theories. In cases of ISSHL resulting from a known intravascular insult, the loss is permanent. However, the authors describe a high rate of spontaneous recovery suggesting a vascular mechanism at the basis of this disease.

2. The lack of studies on the association between ISSHL and the subsequent risk for stroke prevents from simultaneous contributions of vascular, biochemical and metabolic factors.

Methods

1. Subjects: 39 patients with ISSHL and 44 control– small size sample.

2. What comorbidities did the patients have previously? Have these variables been taken into account?

3. The authors describe that all patients underwent the same treatment protocol (steroids, carbogen inhalation, pentoxifylline, vitamin C and magnesium sulfate. Is that treatment regimen a clinical protocol for treating patients with ISSHL in your hospital?

4. It is know that standard pure tone audiometry not only provides the criteria for diagnosis of ISSHL, characteristics of the initial audiogram have prognostic value. Have these variables been taken into account?

Results

1. There are several studies in the literature who presented similar results, with larges casuistic. For example: Jung SY, Shim HS, Hah YM, Kim SH, Yeo SG. Association of Metabolic Syndrome With Sudden Sensorineural Hearing Loss. JAMA Otolaryngol Head Neck Surg. 2018;144(4):308–314. doi:10.1001/jamaoto.2017.3144.

Discussion

1. Most of the discussion only describe findings from other authors.

Reviewer #2: This manuscript entitled: "Metabolic Syndrome and Idiopathic Sudden Sensorineural Hearing Loss" is well written and addresses a topic that is being widely discussed in the literature. however, we highlight some details that need to be clarified:

1) in the introduction, the authors approach that the pathogenesis of idiopathic sudden hearing loss is controversial, however suggest only a vascular mechanism at the basis of this disease and discussed that ISSHL endothelial dysfunction has been reported "basing all the reasoning for only vascular causes and I think it is important to emphasize that the pathogenesis of ISSHL has multiple other physopathogenic processes involved.

2) The objective is very clear "we evaluated the association between the presence of MetS and ISSHL,." and the study method is all based on a study of association and not a cause and effect relationship. For this reason the statistical tests performed were all for association between two injuries, (sudden idiopathic neurosensory loss and the metabolic syndrome) whose sample is all taken in an association study. The following conclusion is not supported by the results:

"The presence of MetS increased the risk of ISSHL" or "Endothelial dysfunction and microvascular damage could be related to both increased prevalence and poorer recovery". The methodology used in this study as well as the sample size and statistical analysis does not allow us to make these conclusions. We can only conclude that there is an association between ISSHL and metabolic syndrome and that this association is negatively influenced hearing recovery in ISSHL patients.

3) In the abstract the acronym meaning BMI and WHR needs to be scoredin the abstract the acronym meaning BMI and WHR needs to be scored.

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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 #2: No

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Metabolic Syndrome and Idiopathic Sudden Sensori-Neural Hearing Loss

PONE-D-20-16260R1

Dear Dr. Quaranta,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Rafael da Costa Monsanto, M.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

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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 #2: 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

**********

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 would like to acknowledge the time and effort the authors put into writing and answering all the questions. I congratulate the authors for tackling such an important subject.

Reviewer #2: I just had doubts in the study design part that I didn't understand the context of the word “die” in “(prednisone 1 mg / kg die with tapering)”

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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 #2: No