Computational modeling of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis

Mary Hammes; Andres Moya-Rodriguez; Cameron Bernstein; Sandeep Nathan; Rakesh Navuluri; Anindita Basu

doi:10.1371/journal.pone.0254016

Peer Review History

Original SubmissionApril 7, 2021
7 Apr 2021 Author Response Attachments Attachment Submitted filename: PONE REVIEW Revision Comments Final, Final, Final.docx https://doi.org/10.1371/journal.pone.0254016.r001
18 May 2021 Decision Letter - Fang-Bao Tian, Editor PONE-D-21-10937 A novel computational model of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis PLOS ONE Dear Dr. Hammes, 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 Jul 02 2021 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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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.Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. 3.Thank you for stating the following in the Acknowledgments Section of your manuscript: "A. M-R was supported by the NSF GRFP fellowship. The work was partly funded by the Ginny and Simon Aronson Research Award, University of Chicago Institute of Translational Medicine Pilot Award, and A.B.’s research development funds." 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: "This publication was made possible by the National Institute of Diabetes and Digestive Diseases (NIDDK) and the National Institutes of Health (NIH) under award number RO1DK090769. " Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Additional Editor Comments: Thank you for resubmitting this work. I have invited a third person to give comments on the revision, who has a few major concerns. I would encourage you to carefully consider these comments, and revise the manuscript for further consideration. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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 overall aim of this work is to demonstrate the feasibility of computational modelling to unveil abnormal flow dynamics in the CA that are unique to individual patients. Five patient-specific models are reconstructed and considered by using commercial software. However, it is not convincing for me to accept it as the innovation as similar research has been conducted before. Even machine learning method has been considered to establish a model for the prediction of a similar hemodynamic problem. The major conclusion from this work is claimed to prove the importance of patient-specific model and the feasibility of using numerical simulation to resolve the flow dynamics, which is not brand new and sounds lacking deeper information. Actually, this point also agrees with the comments of Review 2. The patient-specific numerical simulation has been conducted, but detailed analysis is missing. I suggest the author to do more analysis in terms the change of the stenosis, and possible to provide some insights for the therapy. ****** 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 [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. https://doi.org/10.1371/journal.pone.0254016.r002
Revision 1
1 Jun 2021 Author Response PONE-D-21-10937 A novel computational model of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis PLOS ONE 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'. 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 Response: We reviewed the PLOS ONE’s style requirements and formatted our manuscript accordingly. 2.Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response: The ethics statement is written in the first paragraph of the Methods section. 3.Thank you for stating the following in the Acknowledgments Section of your manuscript: "A. M-R was supported by the NSF GRFP fellowship. The work was partly funded by the Ginny and Simon Aronson Research Award, University of Chicago Institute of Translational Medicine Pilot Award, and A.B.’s research development funds." 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: "This publication was made possible by the National Institute of Diabetes and Digestive Diseases (NIDDK) and the National Institutes of Health (NIH) under award number RO1DK090769. " Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We have deleted the statement, “A. M-R was supported by the NSF GRFP fellowship. The work was partly funded by the Ginny and Simon Aronson Research Award, University of Chicago Institute of Translational Medicine Pilot Award, and A.B.’s research development funds” from the Acknowledgements and would like this statement to be included in the Funding Statement. Additional Editor Comments: Thank you for resubmitting this work. I have invited a third person to give comments on the revision, who has a few major concerns. I would encourage you to carefully consider these comments, and revise the manuscript for further consideration. [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 Response: We have added in the discussion the limitations of the small sample size We provide in-depth descriptive, numerical and quantitative analysis. The future work will be to prospectively look at a large cohort of subjects to evaluate the statistical significance of computational modeling to predict clinical outcomes. ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ________________________________________ 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 ________________________________________ 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 overall aim of this work is to demonstrate the feasibility of computational modelling to unveil abnormal flow dynamics in the CA that are unique to individual patients. Five patient-specific models are reconstructed and considered by using commercial software. However, it is not convincing for me to accept it as the innovation as similar research has been conducted before. Even machine learning method has been considered to establish a model for the prediction of a similar hemodynamic problem. The major conclusion from this work is claimed to prove the importance of patient-specific model and the feasibility of using numerical simulation to resolve the flow dynamics, which is not brand new and sounds lacking deeper information. Actually, this point also agrees with the comments of Review 2. The patient-specific numerical simulation has been conducted, but detailed analysis is missing. I suggest the author to do more analysis in terms the change of the stenosis, and possible to provide some insights for the therapy. Response: We thank the reviewer for this comment. We agree with these comments and have removed the word ‘novel’ in the title as others have reconstructed hemodynamics using computational software. Previous computational work has been done as discussed in the Introduction with references 9-11, although our work moves the field forward as we use actual images obtained from IVUS and venogram in patient-specific models in 3D with along with computational modeling of flow using parameters from Doppler imaging, blood viscosity measurements, and patients’ vitals recorded at the time of different imaging used in the study. The 5 subjects studied had models created at 3 and 12 months with obvious hemodynamic changes depicted most significantly on the lower border of the bend in the cephalic arch. Follow-up clinical venograms at later time points (up to 5 years) showed significant stenosis with anatomic correlation. We have shown that changes as early as 3 months may be connected to later venous stenosis. The comments provided by the reviewer above have prompted us to discuss potential therapeutic solutions to the future complications, based on our modelling. The hemodynamic changes and resultant wall shear stresses are largely influenced by high flow velocity in the cephalic arch. Our hypothesis is that a reduction in flow velocity will change the turbulent flow toward laminar flow. We tested this by reducing the flow to 50%, 25% and 10% of the original velocities measured in two extreme cases (P96 at 3 months and P122 at 12 months) and have added these results to a new sub-section, ‘Simulations with decreased flow velocity’ along with a new supplementary figure (Figure S5). This can provide direct insights for therapy as reduced flow (more laminar) may prevent the complications caused by hemodynamic turbulence. Lower flow velocities could be achieved by limiting flow when the BCF is created by 1) limiting the size of the arteriotomy (reference 40 was added); 2) changing the angle of the anastomosis with devices such as a VasQ (reference 36); or 3) the design of the type of anastomosis to promote lower flow (references 38, 39 were added). These insights for the future were included in the discussion. 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 [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: Rebuttel letter Final June 1.docx https://doi.org/10.1371/journal.pone.0254016.r003
18 Jun 2021 Decision Letter - Fang-Bao Tian, Editor Computational modeling of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis PONE-D-21-10937R1 Dear Dr. Hammes, 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, Fang-Bao Tian 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: 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: No ****** 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: A conclusion of this work should be given at the end of this paper. The overall aim of this work is to demonstrate the feasibility of computational modelling to unveil abnormal flow dynamics in the CA that are unique to individual patients. The potential therapeutic solutions to the future complications based on the modelling is also discussed. ****** 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 https://doi.org/10.1371/journal.pone.0254016.r004
Formally Accepted
5 Jul 2021 Acceptance Letter - Fang-Bao Tian, Editor PONE-D-21-10937R1 Computational modeling of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis Dear Dr. Hammes: 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. Fang-Bao Tian Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0254016.r005

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