Cerebral hemodynamics in stroke thrombolysis (CHiST) study

Man Y. Lam; Victoria J. Haunton; Ronney B. Panerai; Thompson G. Robinson

doi:10.1371/journal.pone.0238620

Peer Review History

Original SubmissionJune 2, 2020
1 Jul 2020 Decision Letter - Ehab Farag, Editor PONE-D-20-16644 Cerebral Hemodynamics in Stroke Thrombolysis (CHiST) Study PLOS ONE Dear Dr. Man Yee Lam 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 appreciate if pay careful attention to the reviewer's comments in your revised manuscript. Please submit your revised manuscript by Aug 15 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Ehab Farag, MD FRCA FASA 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. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. 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 identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). 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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 Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests 4. Please include a copy of Tables 1 to 6 which you refer to in your text. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Additional Editor Comments (if provided): [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 ******** 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: 1. What are the main claims of the paper and how significant are they for the discipline? � Main purpose of the paper was to conduct a pilot study in intravenous thrombolysis patients to detect changes in cerebral autoregulation during and following successful recanalization at 4 time points in the acute, subacute and chronic stages after an acute ischemic stroke. Transcranial doppler data sets, blood pressure, and endtidal Co2 were monitored. This pilot study is significant for the discipline given a knowledge gap in understanding the patterns of cerebral autoregulation in various stroke patterns at different time points including the chronic phase and the role the data plays in reperfusion injury after recanalization. 2. Are the claims properly placed in the context of the previous literature? Have the authors treated the literature fairly? � Literature was treated fairly. 3. Do the data and analyses fully support the claims? If not, what other evidence is required? � Data analyses revealed a reduction in BP during intravenous thrombolysis. Reduction in heart rate, reduction in critical closing pressure in the affected and non-affected hemisphere were observed post iv thrombolysis across visits to the 3-month mark. Endtidal CO2 increased during subacute and chronic stages. No changes in cerebral blood velocity, coherence, gain, and Autoregulation Index during the follow-up period. � It would be important to mention whether any or no medication management was applied in the acute phase and in the post-stroke chronic phase while the patients were evaluated. E.g. change in antihypertensive medication, new use of antiarrhythmic drugs (beta blockade for arrhythmia or tachycardia), application or need for supplemental oxygen or anxiolytic, analgesic medication with or without supplemental oxygen, especially when the patient’s airway maintenance was at risk or the patient was agitated. Patients’ altered spontaneous breathing efforts can interfere with systemic blood pressure and cerebral perfusion pressure, as well as fluctuation of etCO2 . 4. PLOS ONE encourages authors to publish detailed protocols and algorithms as supporting information online. Do any particular methods used in the manuscript warrant such treatment? If a protocol is already provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred? � Authors did follow a detailed protocol, all methods were addressed, no deviations apparent for reviewer. 2 patients were excluded with difficulties to obtain the appropriate TCD windows. This reduced the patient group to 11 study patients and limited the ability to address subgroups. 5. If the paper is considered unsuitable for publication in its present form, does the study itself show sufficient potential that the authors should be encouraged to resubmit a revised version? � I recommend considering this pilot study for publication. The discussion includes reasons why more data is required after this pilot study to better understand the effects of changes in cerebral blood pressure/systemic blood pressure affecting reperfusion injury. 6. Are original data deposited in appropriate repositories and accession/version numbers provided for genes, proteins, mutants, diseases, etc.? � Yes 7. Are details of the methodology sufficient to allow the experiments to be reproduced? � Yes 8. Is the manuscript well organized and written clearly enough to be accessible to non-specialists? � Yes. I do compliment the research team for their candid data review and laying out the limitations of this small pilot study and their interest to address these limitations in a larger cohort to optimize individualized patient care. The manuscript is written clearly, though methods and techniques applied use specific terminology that the non-specialist may not be familiar with, however use of proper terminology cannot be avoided in this context. ****** 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: Yes:** Dorothea Rosenberger MD PhD [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.0238620.r001
Revision 1
14 Aug 2020 Author Response 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: Many thanks for these instructions. We confirmed we have read the PLOS ONE’s style requirements carefully and uploaded the revised manuscript, cover letter and figures to the website accordingly. 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. 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 identifying or sensitive patient information) 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. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. 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. Response: Thank you for the guidance. We confirm there are no restrictions to data access and we have uploaded the minimal anonymized data set as Supporting Information files. 3. Thank you for stating the following in the Competing Interests section: 'Professor Thompson G Robinson is the NIHR senior investigator, otherwise, no other authors have 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. Response: We have confirmed that ‘Professor Thompson G Robinson is the NIHR senior investigator, otherwise, no other authors have competing interests, this does not alter our adherence to PLOS ONE policies on sharing data and materials’ on revised manuscript (Tracked version: page 1; Clean version: page 1). Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. Response: We confirm we have updated the competing interest statement in our revised cover letter. 4. Please include a copy of Tables 1 to 6 which you refer to in your text. Response: Many thanks for the comment, we have included a copy of Tables 1 to 6 in the revised manuscript. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response: This can be confirmed as well. We have included our raw data on the Supporting Information Files. Additional Editor Comments (if provided): [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 ________________________________________ 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: 1. What are the main claims of the paper and how significant are they for the discipline? � Main purpose of the paper was to conduct a pilot study in intravenous thrombolysis patients to detect changes in cerebral autoregulation during and following successful recanalization at 4 time points in the acute, subacute and chronic stages after an acute ischemic stroke. Transcranial doppler data sets, blood pressure, and endtidal Co2 were monitored. This pilot study is significant for the discipline given a knowledge gap in understanding the patterns of cerebral autoregulation in various stroke patterns at different time points including the chronic phase and the role the data plays in reperfusion injury after recanalization. 2. Are the claims properly placed in the context of the previous literature? Have the authors treated the literature fairly? � Literature was treated fairly. 3. Do the data and analyses fully support the claims? If not, what other evidence is required? � Data analyses revealed a reduction in BP during intravenous thrombolysis. Reduction in heart rate, reduction in critical closing pressure in the affected and non-affected hemisphere were observed post iv thrombolysis across visits to the 3-month mark. Endtidal CO2 increased during subacute and chronic stages. No changes in cerebral blood velocity, coherence, gain, and Autoregulation Index during the follow-up period. � It would be important to mention whether any or no medication management was applied in the acute phase and in the post-stroke chronic phase while the patients were evaluated. E.g. change in antihypertensive medication, new use of antiarrhythmic drugs (beta blockade for arrhythmia or tachycardia), application or need for supplemental oxygen or anxiolytic, analgesic medication with or without supplemental oxygen, especially when the patient’s airway maintenance was at risk or the patient was agitated. Patients’ altered spontaneous breathing efforts can interfere with systemic blood pressure and cerebral perfusion pressure, as well as fluctuation of etCO2 . Response: Many thanks for this important comment. We have confirmed that none of the patients required antihypertensive medication or analgesia during IVT infusion. One patient required supplemental oxygen (1 litre via nasal cannula) during IVT infusion. 4 patients were discharged with additional antihypertensive medication, with two additional patients receiving antihypertensive medication at visit 4 (3 months post stroke symptom onset) (Tracked version: page 10; Clean version: page 9). 4. PLOS ONE encourages authors to publish detailed protocols and algorithms as supporting information online. Do any particular methods used in the manuscript warrant such treatment? If a protocol is already provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred? � Authors did follow a detailed protocol, all methods were addressed, no deviations apparent for reviewer. 2 patients were excluded with difficulties to obtain the appropriate TCD windows. This reduced the patient group to 11 study patients and limited the ability to address subgroups. 5. If the paper is considered unsuitable for publication in its present form, does the study itself show sufficient potential that the authors should be encouraged to resubmit a revised version? � I recommend considering this pilot study for publication. The discussion includes reasons why more data is required after this pilot study to better understand the effects of changes in cerebral blood pressure/systemic blood pressure affecting reperfusion injury. 6. Are original data deposited in appropriate repositories and accession/version numbers provided for genes, proteins, mutants, diseases, etc.? � Yes 7. Are details of the methodology sufficient to allow the experiments to be reproduced? � Yes 8. Is the manuscript well organized and written clearly enough to be accessible to non-specialists? � Yes. I do compliment the research team for their candid data review and laying out the limitations of this small pilot study and their interest to address these limitations in a larger cohort to optimize individualized patient care. The manuscript is written clearly, though methods and techniques applied use specific terminology that the non-specialist may not be familiar with, however use of proper terminology cannot be avoided in this context. ________________________________________ 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: Yes: Dorothea Rosenberger MD PhD Attachments Attachment Submitted filename: PLOS One ML Rebuttal FINAL 11082020.docx https://doi.org/10.1371/journal.pone.0238620.r002
21 Aug 2020 Decision Letter - Ehab Farag, Editor Cerebral Hemodynamics in Stroke Thrombolysis (CHiST) Study PONE-D-20-16644R1 Dear Dr. Man Yee Lam 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, Ehab Farag, MD FRCA FASA Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0238620.r003
Formally Accepted
27 Aug 2020 Acceptance Letter - Ehab Farag, Editor PONE-D-20-16644R1 Cerebral hemodynamics in stroke thrombolysis (CHiST) study Dear Dr. Lam: 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. Ehab Farag Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0238620.r004

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