Radiation exposure and clinical outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: Fluoroscopic versus conventional CT guidance

Francesco Somma; Vincenzo D’Agostino; Alberto Negro; Valeria Piscitelli; Stefania Tamburrini; Carmine Sicignano; Fabrizio Fasano; Silvio Peluso; Alessandro Villa; Gianvito Pace; Giuseppe Sarti; Giuseppe Maria Ernesto La Tessa; Giovanna Pezzullo; Gianluca Gatta; Ferdinando Caranci

doi:10.1371/journal.pone.0264767

Peer Review History

Original SubmissionSeptember 28, 2021
26 Jan 2022 Decision Letter - Suhairul Hashim, Editor PONE-D-21-30975Radiation exposure and Clinical Outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: Fluoroscopic versus Conventional CT guidance.PLOS ONE Dear Dr. Somma, 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 address the comments from all reviewers adequately especially reviewer #1 to improve the quality of your manuscript. All the best for your revised manuscript. Please submit your revised manuscript by Mar 10 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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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. Please ensure that you refer to Figure 1 and 2 in your text as, if accepted, production will need this reference to link the reader to the figure. 3. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear Editors, Dear Authors, Thank you for giving me the opportunity to review the article you submitted with the title "Radiation exposure and clinical outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: fluoroscopic versus conventional CT guidance". The topic of the manuscript refers to the socially significant problem of low back pain and the possibilities for its treatment with minimally invasive approaches. The authors compare radiation exposure and results of intradiscal ozone administration under fluoroscopic and CT control. The study presents data of primary scientific research and I found that the reported results have not been published elsewhere. The research meets all applicable standards for the ethics and research integrity. The article is presented in an intelligible fashion and adheres to appropriate reporting guidelines. Summary of results is given concisely in three tables and are clearly supported by accurate and good quality images. Conclusions are appropriate and the results as well as the discussion supports them. My comments regarding the manuscript are listed below: - Intradiscal procedures are not widely accepted for degenerative disc disease. Here no rationality or indications for ozone treatment are listed. In the context of the current article submitted for publication, the clinical results should overcome the risks of ration exposure, in particular of CT-guided procedures. - Levofloxacin is not considered as optimal perioperative antimicrobial prophylaxis. Furthermore, a 5-day treatment contradicts the principle for minimally invasive treatments with reduced risk for surgical site infections. It is not recommended in any related guideline alone and as a first line for preventions of surgical site infection. - The statistical methods need more detailed description regarding homogeneity of the groups of patients. However, the statistical and further analysis are performed to a high technical standard. - A major remark concerns the definition of “clinical success”. "Complete disappearance of symptoms" is inappropriate definition for clinical success. It contradicts the methodology to use the ODI measurement instrument, which is an accepted tool for that. Successful procedure, defined as reduction in the preoperative ODI values of at least 30% during follow-up, is acceptable. Note that the definition of “residual symptoms” correlate with the last. - The discussion of the authors’ results in the sense of other studies is adequate and fair except the comparison to those reported by Ezeldin (2018). The judgement that their ODI score is better is not appropriate because the follow-up is different (1- versus 6-month). - The statement that the results are not inferior to those obtained with other percutaneous disc decompression methods as well as surgical treatments is speculative. The comparison to other treatment modalities due to different selection criteria and indications implies bias. - Many technical errors and need for corrections are marked in the attached pdf file. In conclusion, despite my remarks and the inaccuracies found, the proposed study is substantiated and presented concisely. The stated aim to compare the radiation exposure and the clinical outcome of the discussed minimally invasive procedure under fluoroscopic and CT guidance is schieved. I would recommend the proposed article to be accepted for publication but after clearance of my comments. I would recommend the authors to pay more attention when preparing their manuscripts on methodology and punctuation. Yours Sincerely, Dr. Dilyan Ferdinandov Reviewer #2: This article clearly shows the object of study. In particular, notions of technique with exposure dose, clinical successes and complications are correctly highlighted. The statistical analysis is correct and the number of the population is satisfactory. Well done. Reviewer #3: The authors propose an original article comparing the technical, clinical, and dosimetric outcome of Ct and fluorscopy guided ozone nucleolysis. The topic is interesting, and there are few previous reports addressing this issue. There are some issues to address in the revision: -INTRODUCTION: too long and not focusing enough on the research topic, that is the difference in imaging guidance. the main differences of floroscopy-guided and CT guided procedures should be introduced here. - METHODS: the study design should be described more clearly, as it is not clear if it is a retrospective or prospective study. Inclusion and exclusiuon criteria for patient selkection should be stated. ****** 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:** Dr. Dilyan Ferdinandov, MD, MPH, PhD, FEBNS Associated Professor in Neurosurgery, Medical University – Sofia Senior Neurosurgeon, St. Ivan Rilski University Hospital 15 Acad. Ivan Geshov Blvd., 1431 Sofia, Bulgaria +359 888 678 549 d.ferdinandov@medfac.acad.bg Reviewer #2: No Reviewer #3: 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: PONE-D-21-30975 - PEER REVIEW.pdf https://doi.org/10.1371/journal.pone.0264767.r001
Revision 1
31 Jan 2022 Author Response RESPONSE TO REVIEWERS Authors (A): First and foremost, the authors would like to express their gratitude to all reviewers for the appreciable work performed on the proposed manuscript. All suggestions have been expressly considered in the attached revision. Please find below our response to your highly valued recommendations. Reviewer (R) #1: R: Dear Authors, thank you for giving me the opportunity to review the article you submitted with the title "Radiation exposure and clinical outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: fluoroscopic versus conventional CT guidance". The topic of the manuscript refers to the socially significant problem of low back pain and the possibilities for its treatment with minimally invasive approaches. The authors compare radiation exposure and results of intradiscal ozone administration under fluoroscopic and CT control. The study presents data of primary scientific research and I found that the reported results have not been published elsewhere. The research meets all applicable standards for the ethics and research integrity. The article is presented in an intelligible fashion and adheres to appropriate reporting guidelines. Summary of results is given concisely in three tables and are clearly supported by accurate and good quality images. Conclusions are appropriate and the results as well as the discussion supports them. My comments regarding the manuscript are listed below. A: Dear dr. Ferdinandov, we are extremely glad for the recognition of the strengths of our work. With particular regard to the fact that the topic of our manuscript has never been published, previously. Thank you very much for spending your time in improving our paper. R: Intradiscal procedures are not widely accepted for degenerative disc disease. Here no rationality or indications for ozone treatment are listed. In the context of the current article submitted for publication, the clinical results should overcome the risks of ration exposure, in particular of CT-guided procedures. A: As stated in the Ethics section, the studied procedure is ordinarily performed in our institution, and is not considered experimental, thus meaning that the risk due to radiation exposure are not superior to the clinical relief in the vast majority of patients with no previous response to drugs, even in patients undergoing conventional CT guidance. R: The statistical methods need more detailed description regarding homogeneity of the groups of patients. However, the statistical and further analysis are performed to a high technical standard. A: In the beginning of the Result section, more detailed information regarding groups’ homogeneity were provided, as requested. In particular, the two groups were found homogeneous in terms of patient age, patient weight, level treated and side of disc herniation. R: A major remark concerns the definition of “clinical success”. "Complete disappearance of symptoms" is inappropriate definition for clinical success. It contradicts the methodology to use the ODI measurement instrument, which is an accepted tool for that. Successful procedure, defined as reduction in the preoperative ODI values of at least 30% during follow-up, is acceptable. Note that the definition of “residual symptoms” correlate with the last. A: As the reviewer properly denoted, in the field of topic clinical success is not the Complete disappearance of symptoms but the reduction in the preoperative ODI values of at least 30% during follow-up. Therefore, the erroneous definition was removed and the right one was properly highlighted in the Mat&Met section Outcome measure subsection. R: The discussion of the authors’ results in the sense of other studies is adequate and fair except the comparison to those reported by Ezeldin (2018). The judgement that their ODI score is better is not appropriate because the follow-up is different (1- versus 6-month). A: According to the reviewer suggestion, the the following sentence was added to make the reader aware of different follow up time: “even if the results are slightly comparable due to the different follow up period considered” R: The statement that the results are not inferior to those obtained with other percutaneous disc decompression methods as well as surgical treatments is speculative. The comparison to other treatment modalities due to different selection criteria and indications implies bias. A: As suggested by the reviewer, we changed the sentence in a more cautious way, as reported below: “Also, our results showed a clinical outcome not inferior to what described in previously published papers describing other percutaneous disc decompression methods as well as surgical treatments, but further research comparing intradiscal ozone therapy and different discal treatments are needed to confirm this point”. R: Many technical errors and need for corrections are marked in the attached pdf file. A: A deep editing and language revision has been performed. Reviewer (R) #2: R: This article clearly shows the object of study. In particular, notions of technique with exposure dose, clinical successes and complications are correctly highlighted. The statistical analysis is correct and the number of the population is satisfactory. Well done. A: Thank you very much for your appreciable comments. Reviewer (R) #3: R: The authors propose an original article comparing the technical, clinical, and dosimetric outcome of CT and fluorscopy guided ozone nucleolysis. The topic is interesting, and there are few previous reports addressing this issue. There are some issues to address in the revision. A: We would like to thank you for the valuable comments helping us to improve our manuscript. R: INTRODUCTION: too long and not focusing enough on the research topic, that is the difference in imaging guidance. the main differences of floroscopy-guided and CT guided procedures should be introduced here. A: According to the reviewer suggestion, the Discussion section was shortened and re-written in order to focus radiation exposure and protection. R: METHODS: the study design should be described more clearly, as it is not clear if it is a retrospective or prospective study. Inclusion and exclusion criteria for patient selection should be stated. A: In order to clear the study design we added the following text in the section Mat&Med subsection Patients Population: “All cases were retrospectively reviewed”. Inclusion and exclusion criteria were added. In conclusion, all authors would like to thank Editors and Reviewers for their time and the expertise provided in the revision of our manuscript. Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS R1.doc https://doi.org/10.1371/journal.pone.0264767.r002
17 Feb 2022 Decision Letter - Suhairul Hashim, Editor Radiation exposure and Clinical Outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: Fluoroscopic versus Conventional CT guidance. PONE-D-21-30975R1 Dear Dr. Somma, 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. 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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 Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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: (No Response) Reviewer #2: For revisioned version of this paper, acceptable revisions have been made. I confirm my positive opinion Reviewer #3: The authors fully adressed all the questions raised in the previous revision. In particular, according to my suggestion, the Discussion section was shortened and re-written in order to focus radiation exposure and protection. In addition, they added the following text in the section Mat&Med subsection Patients Population: “All cases were retrospectively reviewed”. Inclusion and exclusion criteria were added. ****** 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:** Dilyan Ferdinandov, MD, MPH, PhD Reviewer #2: No Reviewer #3: No https://doi.org/10.1371/journal.pone.0264767.r003
Formally Accepted
1 Mar 2022 Acceptance Letter - Suhairul Hashim, Editor PONE-D-21-30975R1 Radiation exposure and Clinical Outcome in patients undergoing percutaneous intradiscal ozone therapy for disc herniation: Fluoroscopic versus Conventional CT guidance. Dear Dr. Somma: 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. Suhairul Hashim Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0264767.r004

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