Study on the relationship between microbial composition within obstructive biliary stents and the severity of obstruction and duration of stent placement

Ichiro Sugawara; Yosuke Kawahara; Lena Takayasu; Kimio Isshi; Masayuki Kato; Shingo Ono; Yuko Hara; Toshiki Futakuchi; Hiroto Furuhashi; Rina Kurokawa; Kazuki Sumiyama; Wataru Suda

doi:10.1371/journal.pone.0317230

Peer Review History

Original SubmissionJuly 17, 2024
6 Nov 2024 Decision Letter - Wenguo Cui, Editor PONE-D-24-29177Microbial composition in obstructed biliary stent is altered depending on the occlusion severity and the duration of stent placementPLOS ONE Dear Dr. Furuhashi, 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 Dec 21 2024 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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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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 ****** 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 ****** 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: This article discusses the correlation between the composition of microorganisms in biliary stent obstruction and the degree of obstruction and the time of stent placement. It is valuable to find the correlation between the species of microorganisms in biliary stent obstruction and the time and degree of obstruction. 16 s rRNA amplification son sequencing can effectively make up for the defect of traditional culture, especially for training and testing of anaerobic bacteria. At the same time, the appropriate and accurate statistical analysis of this study, prospective clinical trial standard, strict, can come to the conclusion. In addition, the authors provide sufficient research data to support the conclusions of the manuscript. Therefore, we suggest that receive the manuscripts. However, several concerns need to be considered by the authors. First, a total of 27 patients were enrolled in this study, which was a small number of patient cases. Suggestion to increase the number of cases, antibiotics, patients with underlying disease in analysis. For example: to investigate the antibiotic use, time whether can affect the kinds of microbial composition in obstructed biliary stent? When bacteria become sensitive to antibiotics, they are eliminated, while bacteria that are resistant or tolerant to antibiotics proliferate and become the dominant strain of infection. Second, this study included patient information about 6 years ago (August 1, 2017 to November 20, 2018). Please make it clear that this is a prospective study rather than a retrospective study. Third, the interval of case information is too long. Are there cases missed, errors, and research selection bias? Reviewer #2: The authors selected 27 patients and studied the relationship between the microbial composition inside obstructive biliary stents, the severity of obstruction, and the duration of stent placement. The manuscript still has the following shortcomings, and it is recommended to further improve the quality of the manuscript: 1，I believe the title needs to be revised to better suit the requirements of a research paper title, such as: "Study on the Relationship between Microbial Composition within Obstructive Biliary Stents and the Severity of Obstruction and Duration of Stent Placement." 2，It is recommended to further supplement the introduction with information on the causes of biliary obstruction, current treatment methods, and the challenges associated with them. 3, It is advisable to conclude the introduction by highlighting the significance of this study, such as providing guidance from a microbial perspective for early prevention of biliary stent obstruction. 4, It is suggested to further increase the sample size. 5, The manuscript lacks a conclusion section. ****** 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 ******** [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. 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Revision 1
23 Nov 2024 Author Response Thank you for taking the time to respectfully review our manuscript. Many of the points the reviewers raised were all important and we believe that by addressing them we have further improved the quality of our manuscript. We also thank you for pointing out the descriptions that do not meet the submission guidelines as journal requirements. We have corrected all of them and hopefully you will take another look at the manuscript. Reviewer #1: Comment no.1: First, a total of 27 patients were enrolled in this study, which was a small number of patient cases. Suggestion to increase the number of cases, antibiotics, patients with underlying disease in analysis. For example: to investigate the antibiotic use, time whether can affect the kinds of microbial composition in obstructed biliary stent? When bacteria become sensitive to antibiotics, they are eliminated, while bacteria that are resistant or tolerant to antibiotics proliferate and become the dominant strain of infection. Our response: We deeply understand and agree with your concerns about the impact of antimicrobials and other clinical variables on the results. We have in fact been considering the possibility of addressing these effects from the time of the experimental design. However, there are dozens of factors such as antimicrobials, background disease, gender, age, length of indwelling, effect of anti-acids and bowel regulators, presence of other medications, type of stent, presence of clinical infection symptoms, presence of jaundice, and so on. Correcting for all of these would require more than 10 cases per factor, i.e., more than several hundred cases. With few microbiome studies on bile duct stent occluded contents, we decided that it would be difficult to obtain patient consent and funding for more than several hundred cases as an exploratory study, given the uncertain feasibility of such a study. We hope that the results of this study will be understood as the results of an exploratory and preliminary design study that has proven its feasibility. Based on the results of this study, we have obtained results on the amount of DNA that can be collected and the number of reads, and we would like to continue the experiment with more cases in future studies to address these biases. We have revised the manuscript by adding statements in the second limitation, in the Discussion section. Comment no.2: Second, this study included patient information about 6 years ago (August 1, 2017 to November 20, 2018). Please make it clear that this is a prospective study rather than a retrospective study. Our response: We apologize for the ambiguity of the description. Samples were prospectively collected with written consent through a biobank study in which endoscopically available specimens were comprehensively allowed to be used for bacterial experiments. However, statistical and bacterial analysis of the microbiome in relation to occlusions in bile duct stents, focusing on the level of occlusion was performed after the sample collection. In other words, strictly speaking, it is appropriate to consider this study a retrospective study. We have revised the manuscript accordingly. Comment no.3: Third, the interval of case information is too long. Are there cases missed, errors, and research selection bias? Our response: We appreciate your suggestion. Patient recruitment for this study was conducted at only one facility (Jikei University Katsushika Medical Center). The annual number of biliary endoscopies at this facility is about 270. Of these, one-third of the total involved removal of a stent. Of these, we excluded cases in which information about the stent was unknown because a bile duct stent had been inserted at another hospital, cases in which consent could not be obtained, and cases in which aseptic specimen collection was difficult due to the absence of laboratory technicians. In particular, since endoscopic stent removal was often performed at night as an emergency procedure, the absence of lab technicians caused a decrease in the number of cases. We have maintained case continuity for cases meeting the eligibility criterion. We have revised the manuscript in this regard. Reviewer #2: The authors selected 27 patients and studied the relationship between the microbial composition inside obstructive biliary stents, the severity of obstruction, and the duration of stent placement. The manuscript still has the following shortcomings, and it is recommended to further improve the quality of the manuscript:  1，I believe the title needs to be revised to better suit the requirements of a research paper title, such as: "Study on the Relationship between Microbial Composition within Obstructive Biliary Stents and the Severity of Obstruction and Duration of Stent Placement." Our response: Thank you for your meaningful remarks. We have revised the title as you suggested.  2，It is recommended to further supplement the introduction with information on the causes of biliary obstruction, current treatment methods, and the challenges associated with them. Our response: We appreciate your very important suggestions. We have added to the Introduction section a description of the current challenges and coping strategies related to obstructive jaundice and cholangitis practice. We hope that these additions will help readers unfamiliar with cholangitis treatment to understand this article. 3, It is advisable to conclude the introduction by highlighting the significance of this study, such as providing guidance from a microbial perspective for early prevention of biliary stent obstruction. Our response: We appreciate very much for the reviewer’s very useful remarks. We have added descriptins at the end of the introduction about the effects of the study results.  4, It is suggested to further increase the sample size. Our response: We agree with your comments on the desirability of increasing the sample size. We would appreciate it if you could refer to our comments on reviewer number 1's first point.  5, The manuscript lacks a conclusion section. Our response: We apologize for the missing discussion section in the manuscript. We have revised the title as you suggested. https://doi.org/10.1371/journal.pone.0317230.r002
26 Dec 2024 Decision Letter - Wenguo Cui, Editor Study on the relationship between microbial composition within obstructive biliary stents and the severity of obstruction and duration of stent placement. PONE-D-24-29177R1 Dear Dr. Furuhashi, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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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 ******** 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 ****** 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: After revision, the quality of the manuscript met the requirements and was recommended for acceptance. Reviewer #2: Good modification for publication. The authors have well addressed my concerns. I recommend the acceptance of the manuscript. ****** 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 ******** https://doi.org/10.1371/journal.pone.0317230.r003
Formally Accepted
30 Dec 2024 Acceptance Letter - Wenguo Cui, Editor PONE-D-24-29177R1 PLOS ONE Dear Dr. Furuhashi, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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 Professor Wenguo Cui Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0317230.r004

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