Immune marker reductions in black and white Americans following sleeve gastrectomy in the short-term phase of surgical weight loss

Charles L. Phillips; Tran T. Le; Seth T. Lirette; Bradley A. Welch; Sarah C. Glover; Adam Dungey; Kenneth D. Vick; Bernadette E. Grayson

doi:10.1371/journal.pone.0288868

Peer Review History

Original SubmissionAugust 25, 2022
31 Jan 2023 Decision Letter - Rasheed Ahmad, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-22-23672Immune marker reductions in black and white Americans following sleeve gastrectomy in the short term phase of surgical weight lossPLOS ONE Dear Dr. Grayson, 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. Major concern with the statistical methods which are not explained well, Kindly, elaborate statistical methods and highlight the importance of the studies. Please submit your revised manuscript by Mar 17 2023 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, Rasheed Ahmad, Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf. 2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files" [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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 ****** 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: No Reviewer #2: Yes ****** 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: The authors of the paper determined if IgG, IgM, IgA, TGFβ, and CRP change similarly in black and white Americans after sleeve gastrectomy. While the rationale of the study seems justified, there are some important problems in the article. Aim, hypothesis, study questions, statistical methods to test these questions, and a logical presentation of the results and discussion unfortunately all seem weak. What was the reason for selecting IgG, IgM, IgA, TGFβ, and CRP, specifically? Introduction: First paragraph. References are missing. The statistical methods are unclear, and it is difficult to follow what is the study question for which each of the tests is performed. For example: ‘In addition to the adjusters listed below’ Please clarify what are these adjusters? Below is mentioned the adjusters for change, as well as for ‘all models were adjusted for…’ ‘Weight change was modeled using ordinary least squares on the difference in weight post-op vs. pre-op. Similar models were used to model immune marker change, additionally adjusting for BMI change, systolic change, and diastolic change.’ It is unclear where these models were used (what is the study question, predictor, outcome). The models are not adjusted for multiple testing. For example, in Table 5, none of the p values would likely remain significant if multiple comparisons were taken into account. The results section is inconsistent. There seems to be no real logic and in every paragraph, the topics jump from one area to another. For example, the first paragraph of the results mixes sex, age and BA/Wa comparison. Row 149- The percentages are unclear regarding total, f/m. BA had no males but 6/34 of WA were males. Was there a difference in immune markers or clinical conditions between the sexes in WA? The next parag (row 157) continues with ‘Pre-operative Characteristics of BA and WA Participants’, but wasn’t there already preop comparisons in the previous parag? The inconsistency continues in the next parag. The text jumps from influence of clinical characteristics to comparisons of BA/WA and back to clinical characteristics. In the text, what test is performed for ‘influence’ or ‘association’. The text also refers to ‘correlation’. What is that test? The immune marker results are drown to the quite expected weight + clinical characteristic text. ‘Plasma IgG varied significantly by race with BA having higher levels of IgG than WA, p<0.001.’ What time point is this referring to? ‘Furthermore, BA had greater reductions in IgG, with an average reduction of 1108 mg/dL as a result of SG in comparison to WA (TABLE 5).’ Is the %change in IgG between BA/WA different. Usually, reductions are greater if the baseline level is higher. Please use exact p values instead of p<0.05 etc. Discussion The discussion lacks focus. For example, there are several paragraphs of ALT, NAFLD, hematocrit, platelet count, although these were not mentioned in the results text and are not relevant for the study question. The discussion also presents new data that is not in the results, like: ‘Participants in the current study showed a reduction in CRP levels at six weeks in both BA and WA, although BA individuals had overall higher CRP levels.’ CRP was not mentioned in the results. After the discussion, the biological or clinical conclusion of the study remains unclear. Table 1, what does Y mean? What do the percentages mean? In Figure 1: What is p(subjects). What time point is meant for p(race)? Figure 1 appears between the tables Reviewer #2: It is recommended to emphasize that bariatric surgery, due to professional ethics, is a treatment for obesity but not first-line, and it is not recommended for patients who have not undergone the first-choice treatments: nutrition and pharmacology, or in those to whom it is necessary to avoid a mortal risk. ****** 6. 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: Yes: Melchor Alpízar-Salazar ******** [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. Attachments Attachment Submitted filename: Immune marker reductions in black and white Americans following sleeve gastrectomy in the short term phase of surgical weight loss.pdf Attachment Submitted filename: Comments (2).docx https://doi.org/10.1371/journal.pone.0288868.r001
Revision 1
11 May 2023 Author Response PONE-D-22-23672 5.10.23 Please see the updated comment for the Funding and also we changed the name of track changes file. It was all there highlighted. Please look carefully to find it. We ask for expedited re-review of this because of a grant deadline. The PLOSONE emails are going to our quarantine page and take days to identify. Thank you B The authors of the paper determined if IgG, IgM, IgA, TGFβ, and CRP change similarly in black and white Americans after sleeve gastrectomy. While the rationale of the study seems justified, there are some important problems in the article. Aim, hypothesis, study questions, statistical methods to test these questions, and a logical presentation of the results and discussion unfortunately all seem weak. What was the reason for selecting IgG, IgM, IgA, TGFβ, and CRP, specifically? RESPONSE: As demonstrated in paragraph three of the Introduction, BA carry a high burden of Inflammation and as demonstrated in paragraph four, IgG, IgM, IgA, TGFβ, and CRP had been previously reported to be changed In other populations. Further, IgG has been previously shown to be different In BA population. Introduction: First paragraph. References are missing. RESPONSE: References have been added. The statistical methods are unclear, and it is difficult to follow what is the study question for which each of the tests is performed. For example: ‘In addition to the adjusters listed below’ Please clarify what are these adjusters? Below is mentioned the adjusters for change, as well as for ‘all models were adjusted for…’ ‘Weight change was modeled using ordinary least squares on the difference in weight post-op vs. pre-op. Similar models were used to model immune marker change, additionally adjusting for BMI change, systolic change, and diastolic change.’ It is unclear where these models were used (what is the study question, predictor, outcome). RESPONSE: We have updated the Statistical Analysis section of the manuscript to more clearly describe the analyses done. We thank the reviewer for the opportunity to make these clarifications. The models are not adjusted for multiple testing. For example, in Table 5, none of the p values would likely remain significant if multiple comparisons were taken into account. Response: Since this is a hypothesis generating manuscript, as opposed to a hypothesis confirming one, multiple comparisons aren’t of a concern, statistically (ref). While we agree that most of the p-values don’t convey strong results, we would prefer to leave these as-is to assist the reader in making comparisons across the many models that we performed. Andrew Gelman, Jennifer Hill & Masanao Yajima (2012) Why We (Usually) Don't Have to Worry About Multiple Comparisons, Journal of Research on Educational Effectiveness, 5:2, 189-211, DOI: 10.1080/19345747.2011.618213 The results section is inconsistent. There seems to be no real logic and in every paragraph, the topics jump from one area to another. For example, the first paragraph of the results mixes sex, age and BA/Wa comparison. Row 149- The percentages are unclear regarding total, f/m. BA had no males but 6/34 of WA were males. Was there a difference in immune markers or clinical conditions between the sexes in WA? The next parag (row 157) continues with ‘Pre-operative Characteristics of BA and WA Participants’, but wasn’t there already preop comparisons in the previous parag? The inconsistency continues in the next parag. The text jumps from influence of clinical characteristics to comparisons of BA/WA and back to clinical characteristics. RESPONSE: We were moving first through PRE-data and then addressing POST data. But now, we have reformatted and we narrate through each Table and Figure in order. In the text, what test is performed for ‘influence’ or ‘association’. The text also refers to ‘correlation’. What is that test? RESPONSE: We apologize for this wording. We have removed influence and correlation. The logistic regression modelling establishes relationships between factors and we feel that “associate” is a reasonable word to use for this. We refer the reviewer to the updated Statistical Analysis section which should now provide the answers to these questions. The immune marker results are drown to the quite expected weight + clinical characteristic text. RESPONSE: We are not sure what this comment means. ‘Plasma IgG varied significantly by race with BA having higher levels of IgG than WA, p<0.001.’ What time point is this referring to? RESPONSE: This is a main effect of time as well as Student’s t test at pre-op and 6 weeks. ‘Furthermore, BA had greater reductions in IgG, with an average reduction of 1108 mg/dL as a result of SG in comparison to WA (TABLE 5).’ Is the %change in IgG between BA/WA different. Usually, reductions are greater if the baseline level is higher. RESPONSE: As the reviewer suggested, TABLE 3 does show that pre-op levels of IgG were, on average higher in BA than WA. And we agree with the point the reviewer raise about floor effects possibly lower the range that WA IgG values can reduce. To that end, we have added text to the manuscript to address this. Please use exact p values instead of p<0.05 etc. This has been included in the tables. Discussion The discussion lacks focus. For example, there are several paragraphs of ALT, NAFLD, hematocrit, platelet count, although these were not mentioned in the results text and are not relevant for the study question. The discussion also presents new data that is not in the results, like: ‘Participants in the current study showed a reduction in CRP levels at six weeks in both BA and WA, although BA individuals had overall higher CRP levels.’ CRP was not mentioned in the results. RESPONSE: IT is now mentioned in the results. After the discussion, the biological or clinical conclusion of the study remains unclear. Table 1, what does Y mean? RESPONSE: Y means yes What do the percentages mean? RESPONSE: Percentages mean the Percentage of Total In Figure 1: What is p(subjects). What time point is meant for p(race)? RESPONSE: We have clarified this. Figure 1 appears between the tables RESPONSE: This is how we organize the data. Attachments Attachment Submitted filename: Comments SL.docx https://doi.org/10.1371/journal.pone.0288868.r002
6 Jul 2023 Decision Letter - Rasheed Ahmad, Editor Immune marker reductions in black and white Americans following sleeve gastrectomy in the short term phase of surgical weight loss PONE-D-22-23672R1 Dear Dr. Grayson, 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, Rasheed Ahmad, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0288868.r003
Formally Accepted
13 Jul 2023 Acceptance Letter - Rasheed Ahmad, Editor PONE-D-22-23672R1 Immune marker reductions in black and white Americans following sleeve gastrectomy in the short-term phase of surgical weight loss Dear Dr. Grayson: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Rasheed Ahmad Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0288868.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .