A clinical prediction model to differentiate tuberculous spondylodiscitis from pyogenic spontaneous spondylodiscitis

Thamrong Lertudomphonwanit; Chirtwut Somboonprasert; Kittiphon Lilakhunakon; Suphaneewan Jaovisidha; Thumanoon Ruangchaijatuporn; Praman Fuangfa; Sasivimol Rattanasiri; Siriorn Watcharananan; Pongsthorn Chanplakorn

doi:10.1371/journal.pone.0290361

Peer Review History

Original SubmissionJune 12, 2023
3 Jul 2023 Decision Letter - Mohamed El-Sayed Abdel-Wanis, Editor PONE-D-23-17746A Clinical Prediction Model to Differentiate Tuberculous Spondylodiscitis from Pyogenic Spontaneous SpondylodiscitisPLOS ONE Dear Dr. Chanplakorn, 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 Aug 17 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. 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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. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 3. 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. 4. 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. Additional Editor Comments: This is a well-written manuscript. The authors make good use of figures and tables to highlight the literature search and data obtained from the analysis. The discussion is robust and well-cited. Introduction . Lines 59-60: “The incidence of SIS ranges from 8 to 24 cases/million inhabitants/year” Is this a global incidence or in in Thailand?   . Materials and Methods   . Line 109: “History of bacteremia or sepsis…” I think better to be corrected to “History suggestive of bacteremia or sepsis…” the authors must mention also some of the symptoms that they considered suggestive of bacteremia or sepsis.   . Results Line 153: “..history of bacteremia..” should be corrected to “..“history suggestive of bacteremia” Discussion . Line 293: “…then empirical antibiotic specified  to identified organism from blood culture, should be considered [20].”  As antibiotics is given according to culture, it could not be considered empirical. So, “empirical” should be deleted. . Line 298: “…are diagnostic clues..” better to be changed to “.. are highly suggestive diagnostic clues..”  . Lines 319-321: “This study identified ESR, neutrophil  fraction, WBC count and presence of paraspinal abscess on MRI as predictive factors for  differentiating TS from PS”. The data in this sentence was previously reported in the “discussion and this sentence should be deleted.   . Lines 341- 343: “However, we believe that the extended cohort, which included more patients compared with not using the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.”  The sentence should be better corrected to: “However, we believe that the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.” [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know 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: I have read this very interesting manuscript, and have only one comment: How did the authors account/differentiate patients who had concomitant TS and PS. There are several reports in the literature of combined tuberculous and pyogenic discitis and I would like the authors to elaborate on that. Reviewer #2: New idea. Of course its evidence base. Somehow its contrary to our clinical practice. We see high ESR level in Tuberculosis patient as compared to bacterial patient, probably due to delay in diagnosis of TB Spine patient in our community. Due to rapid rise in Blood markers in Bacterial spine infection it picked earlier. > and < these symbols are confusing as which one represent less than and which one more than. Therefore I suggest somewhere in article this must be mentioned in words that < means less than and > means more than. Reviewer #3: Thank you for your submission and the very good work. Abstract: well structured and clearly describing the contents of the manuscript Methodology: Please add more details to the description of the study setting including the bed capacity. Government VS Private facility, Type of reimbursement system whether it is cash vs insurance based Results: The tables are clear. Applying regression analysis was very important in such studies to accommodate for confounding factors. Discussion: Very smooth flow of the literature review highlighting some of the mot important publications in the same field and the same pathology ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No 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. https://doi.org/10.1371/journal.pone.0290361.r001
Revision 1
26 Jul 2023 Author Response Response to Reviewer’s Comments Response to Editor Comments The authors would like to thank the editor for your very valuable comment. We have addressed every single issue that you raised as below. 1. Introduction: - Lines 59-60: “The incidence of SIS ranges from 8 to 24 cases/million inhabitants/year” Is this a global incidence or in in Thailand? Response: This is a global incidence. We have added the below statements in Introduction section (page 2, line 33). The global incidence of SIS ranges from 8 to 24 cases/million inhabitants/year [1,2]. 2. Materials and Methods: Line 109: “History of bacteremia or sepsis…” I think better to be corrected to “History suggestive of bacteremia or sepsis…” the authors must mention also some of the symptoms that they considered suggestive of bacteremia or sepsis. Response: We have corrected “History of bacteremia or sepsis” to “History suggestive of bacteremia or sepsis” and added some of the symptoms of bacteremia as you suggested. (page 4, line 89) 3. Results - Line 153: “..history of bacteremia..” should be corrected to “..“history suggestive of bacteremia” Response: We have corrected “history of bacteremia” to “history suggestive of bacteremia” as you suggested. (page 6 , line 135) 4. Discussion - Line 293: “…then empirical antibiotic specified to identified organism from blood culture, should be considered [20].” As antibiotics is given according to culture, it could not be considered empirical. So, “empirical” should be deleted. Response: We have deleted “empirical” as you suggested. (page 15, line 276) - Line 298: “…are diagnostic clues..” better to be changed to “.. are highly suggestive diagnostic clues..” Response: We have corrected “..are diagnostic clues..” to “.. are highly suggestive diagnostic clues..” as you suggested. (page 15, line 281) - Lines 319-321: “This study identified ESR, neutrophil fraction, WBC count and presence of paraspinal abscess on MRI as predictive factors for differentiating TS from PS”. The data in this sentence was previously reported in the “discussion and this sentence should be deleted. Response: We have deleted “This study identified ESR, neutrophil fraction, WBC count and presence of paraspinal abscess on MRI as predictive factors for differentiating TS from PS” as you suggested. (page 16, line 302) - Lines 341- 343: “However, we believe that the extended cohort, which included more patients compared with not using the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.” The sentence should be better corrected to: “However, we believe that the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.” Response: We have corrected “However, we believe that the extended cohort, which included more patients compared with not using the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.” to: “However, we believe that the extended cohort, would enhance the validity of the study and made the results more precise for use in current practice.” as you suggested. (page 17, line 324) Reviewer #1: I have read this very interesting manuscript, and have only one comment: How did the authors account/differentiate patients who had concomitant TS and PS. There are several reports in the literature of combined tuberculous and pyogenic discitis and I would like the authors to elaborate on that. Response to Reviewer # 1: We appreciate your valuable comment. There were no patients who had concomitant tuberculous and pyogenic discitis in our cohort. We excluded two patients with simultaneous pyogenic spondylodiscitis and tuberculous spondylodiscitis (Figure 1). We have added the below statements in Materials and Methods section (exclusion criteria) (page 4, line 81). “…and (4) patients with simultaneous PS and TS (Fig 1).” We also added the below statements in Discussion section. Finally, we did not include the patients who had concomitant TS and PS in our study (Fig 1) so this may be limit the generalizability of our results for such patients who had concomitant TS and PS. (page 18, line 333). Reviewer #2: New idea. Of course its evidence base. Somehow its contrary to our clinical practice. We see high ESR level in Tuberculosis patient as compared to bacterial patient, probably due to delay in diagnosis of TB Spine patient in our community. Due to rapid rise in Blood markers in Bacterial spine infection it picked earlier. > and < these symbols are confusing as which one represent less than and which one more than. Therefore I suggest somewhere in article this must be mentioned in words that < means less than and > means more than. Response to Reviewer # 2: The authors would like to thank the reviewer for your valuable comment. We have corrected ”>” to “more than” and “<” to “less than” as you suggested as below. In Table 4: Absence of fever (T less than 38°C) (page 11) fever more than 38°C (Line 206, page 12) These scores were used to stratify the probability of TS into three categories, which were low (score less than 13) (Line 227, page 13) In table 6: score less than 13 (page 13) Fig. 5 Caption: The patient’s laboratory data were as follows: WBC more than 9,700/mm3, neutrophil fraction more than 78%, and ESR more than 92 mm/hr. (Line 252, page 14) Yoon et al. reported that fever was less common symptom in TS compared to PS patients, median time elapsed to diagnosis of spondylodiscitis more than 7 days was a risk factor associated with TS, and bacteremia was significantly associated with PS [11] (Line 272, page 15) Kim et al. reported the following biomarker cutoff values indicating TS: WBC count: 10,000/mm3, neutrophil fraction ≤ 75%, ESR: 40 mm/hr, CRP more than 5 mg/dL, and alkaline phosphatase less than 120 IU/L [3]. (Line 284, page 16) Reviewer #3: Thank you for your submission and the very good work. Abstract: well structured and clearly describing the contents of the manuscript Methodology: Please add more details to the description of the study setting including the bed capacity. Government VS Private facility, Type of reimbursement system whether it is cash vs insurance based Results: The tables are clear. Applying regression analysis was very important in such studies to accommodate for confounding factors. Discussion: Very smooth flow of the literature review highlighting some of the mot important publications in the same field and the same pathology Response to Reviewer # 3: The authors would like to thank the reviewer for your valuable comment. We have addressed the issue that you raised as below. - Methodology: Please add more details to the description of the study setting including the bed capacity. Government VS Private facility, Type of reimbursement system whether it is cash vs insurance based Response: Our hospital is 1300-bed, University hospital with government support. Reimbursement systems at our hospital are covered by multiple sources such as cash, universal coverage by government, workers’ insurance, government pay for government personnel, and private insurance. We have added the above statements in Materials and Methods section (page 3-4, line 67-71). The edited parts were highlighted with track changes. Thank you very much for your help in improving this manuscript. Attachments Attachment Submitted filename: Response to Reviewer 24.7.23 PLOS ONE.docx https://doi.org/10.1371/journal.pone.0290361.r002
31 Jul 2023 Decision Letter - Mohamed El-Sayed Abdel-Wanis, Editor PONE-D-23-17746R1A Clinical Prediction Model to Differentiate Tuberculous Spondylodiscitis from Pyogenic Spontaneous SpondylodiscitisPLOS ONE Dear Dr. Chanplakorn, Thank you for submitting your manuscript to PLOS ONE. Thank you again for addressing the editorial and reviewer comments. I would like to recommend minimal correction as follow: Data collection Lines 89-91 . History suggestive of bacteremia (the presence of viable bacteria in the circulating  blood with or without following symptoms: fever, chill, tachypnea, altered sensorium or hypotension, etc.) should be corrected to:   “History suggestive of bacteremia e.g. fever and chill.” Please submit your revised manuscript by Sep 14 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, Mohamed El-Sayed Abdel-Wanis, Ph.D. 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.] [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.0290361.r003
Revision 2
2 Aug 2023 Author Response Response to Reviewer’s Comments Response to Editor Comments The authors would like to thank the editor for your very valuable comment. We have addressed the issue that you raised below. Editor’s comment Data collection Lines 89-91 1. History suggestive of bacteremia (the presence of viable bacteria in the circulating blood with or without following symptoms: fever, chill, tachypnea, altered sensorium or hypotension, etc.) should be corrected to: “History suggestive of bacteremia e.g. fever and chill.” History suggestive of bacteremia e.g. fever and chill. Response: We have corrected “History suggestive of bacteremia (the presence of viable bacteria in the circulating blood with or without following symptoms: fever, chill, tachypnea, altered sensorium or hypotension, etc.)” to “History suggestive of bacteremia e.g. fever and chill.” as you suggested. (Page 4 line 89) It was highlight in gray. Thank you very much for your help in improving this manuscript. Attachments Attachment Submitted filename: Response to Reviewer 2.8.23 PLOS ONE.docx https://doi.org/10.1371/journal.pone.0290361.r004
7 Aug 2023 Decision Letter - Mohamed El-Sayed Abdel-Wanis, Editor A Clinical Prediction Model to Differentiate Tuberculous Spondylodiscitis from Pyogenic Spontaneous Spondylodiscitis PONE-D-23-17746R2 Dear Dr. Pongsthorn Chanplakorn 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, Mohamed El-Sayed Abdel-Wanis, Ph.D. Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0290361.r005
Formally Accepted
10 Aug 2023 Acceptance Letter - Mohamed El-Sayed Abdel-Wanis, Editor PONE-D-23-17746R2 A Clinical Prediction Model to Differentiate Tuberculous Spondylodiscitis from Pyogenic Spontaneous Spondylodiscitis Dear Dr. Chanplakorn: 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. Dr Mohamed El-Sayed Abdel-Wanis Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0290361.r006

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