Peer Review History
Original SubmissionMarch 7, 2022 |
---|
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-22-06832Appendiceal microbiome in uncomplicated and complicated acute appendicitis: a prospective cohort study (MAPPAC)PLOS ONE Dear Dr. Salminen, 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. I would like to sincerely apologise for the delay you have incurred with your submission. It has been exceptionally difficult to secure reviewers to evaluate your study. We have now received three completed reviews; the comments are available below. The reviewers have raised significant scientific concerns about the study, in particular about the study design and the lack of control group, that need to be addressed in a revision. Please revise the manuscript to address all the reviewer's comments in a point-by-point response in order to ensure it is meeting the journal's publication criteria. Please note that the revised manuscript will need to undergo further review, we thus cannot at this point anticipate the outcome of the evaluation process. Please submit your revised manuscript by Sep 09 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:
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, Miquel Vall-llosera Camps Senior 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 2. Please update your submission to use the PLOS LaTeX template. The template and more information on our requirements for LaTeX submissions can be found at http://journals.plos.org/plosone/s/latex. 3. You indicated that you had ethical approval for your study. In your Methods section, please ensure you have also stated whether you obtained consent from parents or guardians of the minors included in the study or whether the research ethics committee or IRB specifically waived the need for their consent. 4. Thank you for stating the following in the Funding Section of your manuscript: “The MAPPAC study was supported by research grants from the Mary and Georg C. Ehrnrooth Foundation, the Sigrid Jusélius Foundation, the Finnish Academy, Government research grant awarded to Turku University Hospital (EVO foundation), The Maud Kuistila Memorial Foundation, Paulo Foundation, Doctoral Programme in Clinical Research of University of Turku, and Turku University foundation.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The MAPPAC study was supported by research grants from the Mary and Georg C. Ehrnrooth Foundation, the Sigrid Jusélius Foundation, the Finnish Academy, Government research grant awarded to Turku University Hospital (EVO foundation), The Maud Kuistila Memorial Foundation, Paulo Foundation, Doctoral Program in Clinical Research at the University of Turku, and Turku University foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 5. Thank you for stating the following in the Competing Interests section: “EM is currently working as full-time Medical Advisor for Biocodex Nordics. PS reports receiving personal fees for lectures from Merck and Orion Pharma. AJH reports receiving personal fees for lectures from BioCodex, Merck and Pfizer. All other authors declare no competing interests.” Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. 6. 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 more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. [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: Yes Reviewer #2: Yes Reviewer #3: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ********** 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 ********** 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 ********** 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: In this manuscript, the authors describe the examination of the appendiceal microbiome comparing patients with complicated and uncomplicated appendicitis. They appear to show differences in the microbiome as their main finding. While the idea is great and important, there are significant issues that create confounders. One of the most important issues is that there is no control group. I know that the authors recognize this in their discussion as a limitation. However, this is a huge limitation for a number of reasons outlined below. In table 1, the authors outline the types of complications. Many of these are concerning in that they might create irregularities in data. For example, an appendicolith may simply be a stool fragment imbedded in the appendix. During sequencing would the microbiome of the appendicolith be what is determined rather than the appendicitis? Another concern is the perforation. In essences the perforation means the appendix is "draining"...albeit into the peritoneal cavity. Nonetheless it is decompressing the appendix. There are a number of events that might happen in this state. First the pathogenic microbes may diminish. Secondly, the perforated appendix patient may be more symptomatic with systemic symptoms such as fever. As a result is more likely to be on antibiotics. What antibiotics may or may not have been given to subjects? I cannot find a list of antibiotics or the use of antibiotics. This will most certainly influence the microbiome results. To correct these, at a minimum, the authors should disclose all antibiotic use and to which group these were used. Secondly, the number of days of antibiotics. Also, the number of days that the patients had symptoms and whether fever or other factors were present. Also, to analyzed perforation with out abscesss, appendicolith or tumor, would be helpful. Reviewer #2: Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. COMMENTS: In my opinion, since this study was a single-center arm of a multicenter MAPPAC (Microbiology Appendicitis Acuta) trial, the study should be treated as having different ‘Study design and methodology’. Therefore, quoting previously published protocol describing these [Study design and key methods have been reported previously (30)] is not correct. This quoted ‘study protocol is for the ‘MAPPAC trial’ and is definitely excellent, however, since this publication is not ‘one of the series’, giving sufficient details regarding ‘Study design and methodology’ are expected. That protocol is for two arms two clinical trials but the present one is single arm study. How can the ‘Study design and methodology’ be same? Therefore, is that really relevant quoting previously published protocol? In ‘Results’ section saying that “Altogether 308 patients were enrolled in the MAPPAC study between April 11, 2017, and March 29, 2019; Figure 1 shows the study flow” do you think has any meaning/relevance? May I request you to make a small change in title of study [“Appendiceal microbiome in uncomplicated and complicated acute appendicitis: a prospective cohort study (MAPPAC)”] because ‘MAPPAC’ is another trial. This is only a suggestion (as inclusion of the term ‘MAPPAC’) may cause confusion and average reader like me, will take the present study as MAPPAC. You may not follow this as this one is my subjective opinion [please free to take appropriate decision]. Since this study is based on ‘single-arm design’, may I further request to read the following [which is pasted from one standard textbook on ‘Research Methodology’]: For a pilot study it is alright to have ‘single-arm design’, or it is alright when that is the only possibility’, however, It is very essential to keep the limitations in mind while interpreting results. Further, note that a classical/ideal clinical trial/study needs/requires a concurrently {but similarly} handled/treated appropriately selected/chosen control/comparison parallel group/arm. Note further that “Inferential statistics (i.e., hypothesis testing + estimation of CI) is built on the population model [which means the underlying assumption is that there is/are population(s) and we are dealing with random sample(s) drawn from that/those population(s)]. Although in clinical trial (involving at least two groups) we do not really deal with random samples (generally a non-probabilistic convenience sampling), ‘allocation’ to treatment groups is ‘randomly’ done which enable us to evoke the population model and we can use inferential statistics safely. But when there is only one group (so that there is no question of random allocation), with ‘non-random’ selection, it may be questionable to use inferential statistics even if you have two measurement sets as ‘pre-post’ or use ‘internal grouping for comparison” [like here uncomplicated acute appendicitis compared to complicated appendicitis but this is an ‘internal grouping’]. I am sure that these learned authors already know these things, however, it is very essential to keep the limitations in mind while interpreting results {note that I am not asking you to change the study design}. What exactly do you mean by ‘excluded due to failed library preparation (n=26)’? Please note that any ‘regression models / regression techniques’ are not originally developed for head-to-head between group comparison(s), [Alpha diversity analyses were performed using standard linear regression models with alpha diversity measure (Chao1, Shannon entropy or number of observed species) as the response variable]. Nevertheless, limitations of the study highlighted on page 14 are highly appreciated. However, as pointed out in ‘important note’ above “This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ should be assessed separately/independently [one should carefully consider/look at the clinical implications of the study]. One last minor doubt, refer to page 15 where you said “To our knowledge, this is the first prospective study with a large patient cohort and standardized clinical definitions of appendicitis severity comparing the microbial composition of the appendix (may be true) in adult patients between uncomplicated and complicated acute appendicitis” and quoted reference number 14 for this. My doubt is ‘What evidence this reference provided?’ to say you so or ‘what in this reference is indicative of this fact?’. Except these minor points, in my opinion, this article/manuscript is good and needs a small amount of re-vision (which is quite possible). After minor revision, this manuscript may be accepted [provided clinical implications of these findings/results are valuable]. Reviewer #3: I have read a very interesting manuscript and I provide the following minor queries for the authors to address. 1. Provide a succinct definition of how was a complicated versus a non complicated acute appendicitis defined. 2. Microbiome dysbiosis of the appendix has been recently advanced as causal re the pathogenesis of appendicits, was there scope from the data reported to further highlight appendix microbiome dysbiosis as a feature in this study? 3. The presence of oral bacterial pathogens in the large bowel and consequently the appendix elicits the query as to how do these pathogens travel to these sites. As such then were any patients on proton pump inhibitors that in reducing stomach acid reduces this barrier to orally ingested microbes? This perhaps explaining in part how a pathogen such as Porphyromonas endodontalis is in the appendix. ********** 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: No Reviewer #3: Yes: Luis Vitetta ********** [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.
|
Revision 1 |
Appendiceal microbiome in uncomplicated and complicated acute appendicitis: a prospective cohort study PONE-D-22-06832R1 Dear Dr. Paulina Salminen, 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, Vipa Thanachartwet, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): All issues raised by the reviewers are addressed. 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 #2: (No Response) Reviewer #3: 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 #2: (No Response) Reviewer #3: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: (No Response) 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 #2: (No Response) 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 #2: (No Response) Reviewer #3: (No Response) ********** 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 #2: COMMENTS: Since most of the comments made on earlier draft [though not all were/are attended/followed and I am not very much convinced for reasons given or arguments made (for example, in response to one query/comment you said “Since uncomplicated and complicated appendicitis are recognized as two different forms of acute appendicitis, the comparisons are essentially made between two populations with representative samples rather than internal grouping comparison”) with which I do not agree at all. I never said (and I can very-well understand it) that uncomplicated and complicated appendicitis are recognized as two different forms of acute appendicitis but how can the comparison was between two populations with representative samples when samples were not selected from these two populations?) and so definitely not happy], I recommend the acceptance, because the manuscript now has achieved acceptable level [I had earlier said that after minor revision (suggested), this manuscript may be accepted]. Reviewer #3: I have read the revised manuscript with all queries that have been addressed and as such I have no further remakrs to add. ********** 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: Dr. Sanjeev Sarmukaddam Reviewer #3: Yes: Luis Vitetta ********** |
Formally Accepted |
PONE-D-22-06832R1 Appendiceal microbiome in uncomplicated and complicated acute appendicitis: a prospective cohort study Dear Dr. Salminen: 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 Associate Professor Vipa Thanachartwet Academic Editor PLOS ONE |
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 .