Peer Review History

Original SubmissionJanuary 29, 2023
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-23-02554The Outcomes of Three Different Techniques of Coronary Artery Bypass Grafting: On-pump Arrested Heart, On-pump Beating Heart, and Off-pump.PLOS ONE

Dear Dr. Tepsuwan,

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.

==============================

ACADEMIC EDITOR: Although the manuscript addresses an interesting topic, it is affected by relevant shortcomings that require an in-depth revision. All issues are required.==============================

Please submit your revised manuscript by Apr 28 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

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 the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. 

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

4. 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. 

[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: No

Reviewer #2: Yes

**********

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: No

Reviewer #2: 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

**********

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: Congratulations for the arguments that authors have selected.

Materials and Method

Reasoning behind the exclusion from off-pump to on-pump surgery?

What kind of propensity matching algorithm did you use? After matching form smallest group (517 OPCAB) 443 remained.

Results

the quantity of grafts in groups was different?

present P-value for survival differences.

Coronary anastomosis is also taking into account sequential grafting or only graft numbers?

Very interesting results. Re-fine a little bit your propensity matching technique, usually it is well defined for two groups. In the tables the p-values are post hoc corrected? If not, do so to have a realistic number of p-values.

Reviewer #2: i read with great interest the MS by Phothikun et al.

the authors concluded OPCAB implementation resulted in a lower occurrence of postoperative ischemic injury than ONCAB and ONBHCAB. No differences in postoperative hemodynamic function in all three techniques were observed. OPCAB respectively were preferable techniques beneficial for long-term outcomes.

the MS is technically sound but i have several comments

1. the authors conducted PS-matching however the process of variables selection is not well defined; i agree n of cases per surgeon should remain adjustment variable but other essential variables (like in Table 1) other than ACEi inhibitors intake should be considered;

2. Authors adjust long-term survival with completeness of revascularization which is correct; why not to PS-match the patients with the n. of anastomoses and/or CR

3. authors mention converted patients were excluded from the study, but how many there were? it seems from the total numbers, OPCAB is not preferred technique (25% of total); are there any factors other than surgeons' preference to drive patients towards one or another approach?

4. OPCAB is further performed predominantly by one surgeon, with higher rates of complete revascularization in this group, contra-intuitively, it poses a limitation; the results of improved survival and reduced ischemia can, therefore, be translatable to broader population of patients only provided that surgeons performing OPCAB have experience in OPCAB and can offer complete revascularization.

5. language editing is required

**********

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: Rafik Margaryan

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. 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

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: No

Reviewer #2: Yes

Response: Thank you for pointing this out.

Our conclusion consists of

1. Postoperative ischemic injury (shown by the cardiac enzyme results); OPCAB implementation resulted in a lower occurrence of postoperative ischemic injury than ONCAB and ONBHCAB.

2. Postoperative hemodynamic function (shown by hemodynamic function results); No differences in postoperative hemodynamic function in all three techniques were observed.

3. Long-term outcomes (shown by the Survival curve and Free from MACE curve in the results); OPCAB respectively were preferable techniques beneficial for long-term outcomes.

That was all data drawn to support the conclusion.

Comment from reviewer 1

Reviewer #1: Congratulations for the arguments that authors have selected.

Comment 1: Materials and Method, Reasoning behind the exclusion from off-pump to on-pump surgery?

Response: Thank you for pointing this out.

1. Operative techniques were converted intraoperatively from OPCAB to on-pump CABG:

If the procedure was converted to ONBHCAB or ONCAB, it was an unplanned CABG procedure from the beginning. In other cases, the operation may have started as OPCAB but later, nearing the end of the procedure, the patient had to be converted, resulting in adverse outcomes from both OPCAB and on-CPB CABG.

2. Preoperative acute coronary syndrome, acute myocardial infarction:

Since this study requires the collection of cardiac enzymes to compare between groups, it may be difficult to interpret the rise in CK-MB and troponin levels if patients have an acute coronary syndrome or acute MI, as the increase in enzyme levels may not be solely attributed to postoperative values.

3. Preoperative shock:

The same reason as the acute MI, because this study needs to collect the hemodynamic data preoperative and postoperative to compare between groups, if patients have an unstable preoperative hemodynamic function, the postoperative value may be difficult to interpret.

4. Emergency CABG

In emergency cases, the PA catheter is usually not monitored, which means that hemodynamic values measured by the CCO monitor may not be collected. Additionally, emergency CABG surgeries may be complicated by severe acute MI or mechanical complications of MI, which often result in poor hemodynamic function."

Comment 2: What kind of propensity matching algorithm did you use? After matching form smallest group (517 OPCAB) 443 remained.

Response: Thank you for pointing this out.

A propensity score of multiple arms (3 groups), or the predicted probability of receiving ONCAB, OPCAB, and ONBHCAB, was calculated from the multinomial logistic regression model. (the picture for easier understanding was in the response to the reviewer.)

Step 1. we used multinomial logistic regression to create propensity scores for 3 groups. The variables included in the model for propensity score were described in the statistical analysis issue.

Then we got the propensity score of three groups.

Step 2. Make the pattern that creates from the propensity score in each patient.

After finishing we get patterns like 513, 432, 423, 323 …..

Step 3. Match all three groups with the same pattern (in the same way as conventional propensity score matching, but use a pattern instead of score)

Example

• Pattern 125 had only one patient in group1, so this one patient from group 1 was removed from the study. (total 1 patient before matching, 0 patient after matching)

• Pattern 224 had two patients in group0, and four patients in group1&2 (a total of 10 patients before matching), after matching group 1&2 reduce to two patients each. (total 6 patients after matching)

The reference for this method of propensity score matching was in the statistical analysis issue.

Comment 3: Results, the quantity of grafts in groups was different?

Response: Thank you for pointing this out.

We believe that the quantity of coronary anastomoses, as shown in Table 2, is a more important factor for long-term results than the number of graft conduits used. Therefore, we did not provide detailed information on the number of grafts used. However, in our CABG strategy, we typically use one graft conduit for each coronary main branch. When a connection to a sub-branch is needed, we usually connect the sequential graft conduit in the same main branch system. For example, we use LIMA to connect to the LAD and diagonal branch, radial artery to the OM branch and distal LCX, and SVG to the PD and/or PL."

Comment 4: present P-value for survival differences.

Response: Thank you for pointing this out.

We generated long-term survival curves and estimated freedom from MACE for patients who underwent three different types of CABG using flexible parametric survival regression (STPM2) with time-varying coefficients (TVC). As a result, the survival difference cannot be determined using the log-rank test. However, the hazard ratios (with p-value and 95%CI) for cardiac-related mortality and MACE were calculated using the same regression method. Additionally, in the supporting information (S2 Fig), we provided a crude analysis of Kaplan-Meier survival and freedom from MACE between the three groups, and we added the p-value for survival differences in the figures.

Comment 5: Coronary anastomosis is also taking into account sequential grafting or only graft numbers?

Response: Thank you for pointing this out.

Coronary anastomosis includes the counting from both sequential grafting (side-to-side anastomosis) and end-to-side anastomosis, and it was not account for the number of graft conduits.

Comment 6: Very interesting results. Re-fine a little bit your propensity matching technique, usually it is well defined for two groups. In the tables the p-values are post hoc corrected? If not, do so to have a realistic number of p-values.

Response: Thank you for pointing this out.

The p-values were post hoc analyses because the analysis of variance (ANOVA) with Bonferroni was applied for comparisons between groups.

Comment from reviewer 2

Reviewer #2: i read with great interest the MS by Phothikun et al.

the authors concluded OPCAB implementation resulted in a lower occurrence of postoperative ischemic injury than ONCAB and ONBHCAB. No differences in respectively were preferable techniques beneficial for long-term outcomes.

the MS is technically sound but i have several comments

Comment 1. the authors conducted PS-matching however the process of variables selection is not well defined; i agree n of cases per surgeon should remain adjustment variable but other essential variables (like in Table 1) other than ACEi inhibitors intake should be considered;

Response: Thank you for pointing this out.

We described in the statistical analysis issue that “The variables included in the model for propensity score were age, sex, New York Heart Association Functional Class, Canadian Cardiovascular Society Classification, the use of angiotensin-converting enzyme inhibitor drugs/angiotensin receptor blockers drugs, the use of pre-operative Aspirin, the pre-operative use of Clopidogrel, end-stage renal disease, coronary artery disease type, and left main coronary disease”. All of these variables were the statistically significant difference when compare between the three groups.

Comment 2. Authors adjust long-term survival with completeness of revascularization which is correct; why not to PS-match the patients with the n. of anastomoses and/or CR

Response: Thank you for pointing this out.

We used propensity scores based on the principle that the score refers to the chance of patients being selected into each of the three study groups. Therefore, the variable included in the model should be the variable from the preoperative data or baseline characteristics of the patients. We also think other variables based on perioperative or post-operative data should be used for adjustment in the statistical calculations instead of being included in the propensity score.

Comment 3. authors mention converted patients were excluded from the study, but how many there were? it seems from the total numbers, OPCAB is not preferred technique (25% of total); are there any factors other than surgeons' preference to drive patients towards one or another approach?

Response: Thank you for pointing this out.

"62 OPCAB patients (11.9%) were excluded from the study because they were converted to on-CPB CABG. There may have been several factors involved, such as the severity of aortic calcification, stage of kidney disease, LVEF, The severity of coronary stenosis, number of planned anastomosis sites, area of ischemia, and availability of graft conduits. Ultimately, the technique chosen depended on each surgeon's decision."

Comment 4. OPCAB is further performed predominantly by one surgeon, with higher rates of complete revascularization in this group, contra-intuitively, it poses a limitation; the results of improved survival and reduced ischemia can, therefore, be translatable to broader population of patients only provided that surgeons performing OPCAB have experience in OPCAB and can offer complete revascularization.

Response: Agree, Thank you for pointing this out.

As this was a retrospective study, the surgeon's experience and skills could have potentially introduced bias in comparative studies of CABG. To address this, we included the surgeon variable as an adjustment variable in our statistical calculations, taking into account differences in the number of CABG techniques used by each surgeon. We used the number of cases performed by each surgeon as a proxy for their experience, which was included in the analysis.

With regard to the completeness of revascularization, our center does not adhere to a strict definition. However, we have a policy of revascularizing all graftable targets in every territory for every case, if feasible, irrespective of techniques. In our study, the mean number of coronary anastomoses performed was 4, which is considered adequate compared to previous studies.

Comment 5. language editing is required

Response: Thank you for pointing this out.

In addition to the comments, all spelling and grammatical errors have been corrected again by the staff of the Chiang Mai university English language team (CELT) for language editing assistance.

We look forward to hearing from you in due time regarding our submission and to responding to any further questions and comments you may have.

Sincerely, yours

Attachments
Attachment
Submitted filename: Response to reviewer.docx
Decision Letter - Vincenzo Lionetti, Editor

PONE-D-23-02554R1The Outcomes of Three Different Techniques of Coronary Artery Bypass Grafting: On-pump Arrested Heart, On-pump Beating Heart, and Off-pump.PLOS ONE

Dear Dr. Tepsuwan,

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.

==============================

ACADEMIC EDITOR:The authors should add a new paragraph of discussion regarding perspectives on new early biomarkers of outcome in CABG patients. Recent study has demonstrated that plasma exosome levels increase at 3h and 72h after aortic clamping in older patients undergoing first-time on-pump coronary artery bypass graft and play an antiapoptotic role. In particular, troponin levels did not increase at 72h early after CABG (please see Geroscience 2021 Apr;43(2):773-789). These findings suggest the role of plasma exosomes as perioperative biomarker of tolerance against the perioperative ischemic insult of the heart in CABG patients, as demonstrated by other study (please see PLoS One. 2016 Apr 29;11(4):e0154274.; Acta Anaesthesiol Scand. 2019 Apr;63(4):483-492.) . Please add and discuss the abovementioned studies.

==============================

Please submit your revised manuscript by Jun 09 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

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: Comments are answered properly, please do make available de-identified data (see plos one data policy).

**********

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: Yes: Rafik Margaryan

**********

[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 2

Dear Vincenzo Lionetti, Acedemic Editor

Thank you for giving us the opportunity to re-submit a second revised draft of our manuscript titled “Outcomes of three different techniques of coronary artery bypass grafting: on-pump arrested heart, on-pump beating heart, and off-pump” to PLOS ONE. We appreciate the time and effort you and the reviewers have dedicated to providing valuable feedback on our manuscript. We are grateful to the reviewers for their insightful comments on our paper. We have been able to incorporate changes to reflect most of the suggestions provided by the reviewers.

Here is a point-by-point response to the academic editor’s and the reviewer’s comments and concerns.

ACADEMIC EDITOR: The authors should add a new paragraph of discussion regarding perspectives on new early biomarkers of outcome in CABG patients. Recent study has demonstrated that plasma exosome levels increase at 3h and 72h after aortic clamping in older patients undergoing first-time on-pump coronary artery bypass graft and play an antiapoptotic role. In particular, troponin levels did not increase at 72h early after CABG (please see Geroscience 2021 Apr;43(2):773-789). These findings suggest the role of plasma exosomes as perioperative biomarker of tolerance against the perioperative ischemic insult of the heart in CABG patients, as demonstrated by other study (please see PLoS One. 2016 Apr 29;11(4):e0154274.; Acta Anaesthesiol Scand. 2019 Apr;63(4):483-492.) . Please add and discuss the abovementioned studies.

Response: Thank you for pointing this out.

We add a new paragraph of discussion regarding perspectives on “exosome” outcomes in CABG as you recommend. The reference was also added as the same recommendation.

The passage below was the added new passage to the discussion issue.

“In recent times, new biomarkers have emerged that can be compared to cardiac troponin, the current 'gold standard' surrogate biomarker of myocardial damage. Plasma exosomes are small extracellular vesicles that are released into the bloodstream and contain various molecular cargoes that play a role in intercellular communication. During cardiac surgery, ischemia-reperfusion injury can lead to tissue damage and inflammation, resulting in exosome release from injured or stressed cells [16]. Emanueli et al. studied exosomes containing cardiac microRNAs and found that plasma concentrations of exosomes and their cargo of cardiac microRNAs increased in patients undergoing CABG and correlated with cardiac troponin levels [17]. Carrozzo et al. studied between plasma exosomes and serum cardiac troponin I levels in older (on-CPB) CABG patients. After aortic de-clamping, exosome levels significantly increased at both 3 hours and 72 hours, while troponin I level peaked at 3 hours and then gradually decreased [18]. Moreover, Frey et al. discovered that exosome release was related to ischemic/reperfusion injury and associated with myocardial tissue protection [19]. Therefore, due to their persistence and specific biomarkers for cardiac injury, exosomes have the potential to be a valuable new standard tool in the detection and monitoring of myocardial injury in the near future.”

Comments to the Author

Comment from Reviewer 1

Reviewer #1:

Comment 4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: No

Response: Thank you for pointing this out.

The new shared data set (data set ver.2) was the data before we had done the propensity matching. We shared the supplyment1 Data “The minimal data set used for analyzed” with the data availability statement: All relevant data are within the paper and its Supporting Information files. Moreover, the new minimal data set can access via; https://doi.org/10.6084/m9.figshare.22723688.v1

Comment 6. Review Comments to the Author

Reviewer #1: Comments are answered properly, please do make available de-identified data (see plos one data policy).

Response: Thank you for pointing this out.

We made available de-identified data in the new shared data set (data set ver.2).

We look forward to hearing from you in due time regarding our re-submission and to respond to any further questions and comments you may have.

Sincerely, yours

Amarit Phothikun, MD

Cardiovascular and Thoracic Surgery Unit,

Department of Surgery Faculty of Medicine,

Chiang Mai University, Chiang Mai, Thailand

110 Intravaroros Road, Sriphum, Mueng,

Chiang Mai 50200, Thailand

Email: armadillos176@gmail.com Tel: +66 89 6333 66 1

Thitipong Tepsuwan, MD

Cardiovascular and Thoracic Surgery Unit,

Department of Surgery Faculty of Medicine,

Chiang Mai University, Chiang Mai, Thailand

110 Intravaroros Road, Sriphum, Mueng,

Chiang Mai 50200, Thailand

Email: tepsuwanthitipong@gmail.com Tel: +66815956287

Attachments
Attachment
Submitted filename: Response to reviewer ver2.docx
Decision Letter - Vincenzo Lionetti, Editor

The Outcomes of Three Different Techniques of Coronary Artery Bypass Grafting: On-pump Arrested Heart, On-pump Beating Heart, and Off-pump.

PONE-D-23-02554R2

Dear Dr. Tepsuwan,

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,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Vincenzo Lionetti, Editor

PONE-D-23-02554R2

The outcomes of three different techniques of coronary artery bypass grafting: on-pump arrested heart,  on-pump beating heart, and off-pump

Dear Dr. Tepsuwan:

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

Prof. Vincenzo Lionetti

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 .