https://orcid.org/0009-0008-4069-5042
Peer Review History
| Original SubmissionAugust 15, 2025 |
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-->PONE-D-25-38491-->-->Analysis of Risk Factors for ECMO-Associated Nosocomial Infections in Children After congenital heart disease Surgery-->-->PLOS ONE Dear Dr. Meng, 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 Nov 02 2025 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:-->
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, Giovanni Giordano 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. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. 3. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - https://doi.org/10.3389/fcvm.2022.1071575 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. 5. In the online submission form, you indicated that all data included in this study are available upon request by contact with the corresponding author. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 6. Please update your submission to use the PLOS LaTeX template. The template and more information on our requirements for LaTeX submissions can be found at http://journals.plos.org/plosone/s/latex. 7. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. [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 ********** -->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: Yes Reviewer #2: 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 ********** -->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: Thank you for allowing me the opportunity to review the manuscript "Analysis of Risk Factors for ECMO-Associated Nosocomial Infections in Children After congenital heart disease Surgery". My main concern is the definition of infection in the patient population - while positive respiratory cultures generally translates into infection, it could also be colonization. It would be interesting to look at the chest imaging and ECMO settings along with laboratory results to determine if they were real infections or not. On the other hand, the authors should also acknowledge the fact that positive cultures alone may underestimate clinical infections if antibiotics were used prior to cannulation. I also recommend to discuss potential confounding when it comes to ICU length of stay - a time-to-event analysis could be implemented. Reviewer #2: Major Comments The retrospective single-center design with a relatively small cohort (n=54) limits the generalizability of the findings. Please expand the discussion on how the limited sample size may affect the robustness of the logistic regression analysis. The authors rely exclusively on microbiological confirmation, without considering clinical and biochemical markers (e.g., CRP, PCT). This approach could underestimate clinically relevant infections. A comparison with alternative diagnostic criteria would strengthen the manuscript. In univariate analysis, both ICU stay and pre-ECMO ventilation duration showed associations with infection, but they lost significance in multivariate analysis. Please comment on possible interactions between these variables and preoperative intubation. The conclusion emphasizes avoiding preoperative intubation when possible. The authors should provide more practical recommendations (e.g., airway management strategies, antimicrobial prophylaxis protocols, VAP prevention bundles) to enhance clinical applicability. ********** -->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 ********** [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 |
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-->PONE-D-25-38491R1-->-->Analysis of Risk Factors for ECMO-Associated Nosocomial Infections in Children After congenital heart disease Surgery-->-->PLOS ONE Dear Dr. Meng, 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 Dec 22 2025 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:-->
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, Giovanni Giordano Academic Editor PLOS ONE Journal Requirements: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. [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 #2: (No Response) 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 #2: Yes Reviewer #3: Partly ********** -->3. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #2: Yes Reviewer #3: No ********** -->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 #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 #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 #2: The authors have substantially improved the manuscript and adequately addressed all major comments from the previous review. The discussion is now clearer and more clinically grounded, and the addition of practical recommendations increases the translational relevance. Only minor revisions remain. 1. Statistical limitations The authors added a paragraph on the limitations of small sample size for logistic regression. It would be useful to explicitly report the events-per-variable ratio (EPV) calculated for this model to quantify the degree of statistical limitation. 2. Diagnostic criteria paragraph The justification for microbiological-only diagnosis is sound, but please clarify whether negative cultures with high clinical suspicion (e.g., prior antibiotics) were recorded or excluded. This will help readers interpret potential underestimation bias. 3. Terminology consistency Use consistent terminology throughout: “ECMO-associated nosocomial infection” vs. “ECMO-related infection.” Consider harmonizing the terms in title, abstract, and text. 4. Discussion on causality The manuscript mentions the possible bidirectional relationship between ICU stay and infection. It would strengthen the discussion to acknowledge that reverse causality cannot be excluded in this retrospective design. Reviewer #3: Dear Authors, Thank you for the opportunity to review your manuscript investigating infections in pediatric patients undergoing ECMO after congenital heart surgery. The topic is clinically relevant and of great importance for improving patient safety and outcomes in intensive care settings. However, after a detailed review, I identified several methodological and structural aspects that limit the current quality and reproducibility of the study. Below, I provide point-by-point suggestions to help strengthen the manuscript and align it with international reporting standards. 1. Title The expression “nosocomial infection” is outdated. I recommend replacing it with the term “healthcare-associated infection (HAI)”, as endorsed by the World Health Organization (WHO) and CDC. Consider including the study design in the title, following STROBE recommendations for observational studies. 2. Abstract The objective stated in the abstract does not match the one described in the introduction; these must be harmonized to ensure consistency throughout the paper. Please clarify the study design explicitly (case-control or cohort). The current abstract does not mention it. Include a clear statement of main findings and conclusion that aligns with the results. 3. Introduction The introduction is overly brief. It should better contextualize the relevance of infections during ECMO, with updated epidemiological data and a clearer definition of the literature gap your study addresses. The objective should directly reflect the research question and align with both the abstract and methods. 4. Methods The methods section requires substantial expansion to meet STROBE and EQUATOR Network standards for transparency. Please specify: The setting of postoperative care (confirm if all patients were managed in an ICU). Whether the center is ELSO-certified, and how ECMO management is organized (nurse-led, perfusionist-led, or mixed). The nurse-to-patient ratio or staffing model, as these factors influence infection risk. The study design is described as “case-control”, but the approach appears more consistent with a retrospective cohort, since patients were divided according to infection occurrence. Please clarify. The definition of healthcare-associated infection appears to rely on outdated criteria (2009). Use current WHO or CDC definitions, and describe how each infection type (bloodstream, respiratory, urinary, etc.) was diagnosed. Indicate: Who was responsible for data collection and on which platform data were stored. How patient confidentiality and anonymization were ensured. Any bias-control procedures applied during data review. In the statistical analysis, describe: Criteria for variable selection in the regression model. Quality metrics (R², AUC, VIF, Hosmer-Lemeshow, etc.). How missing data were handled. 5. Results Please include a flow diagram or statement indicating the number of patients screened, included, and excluded, as recommended by STROBE. Tables should be reformatted for consistency — avoid box-style formatting, ensure uniform fonts, and standardize units of measurement across variables. Some numerical results lack dispersion measures (SD or IQR); please include them. 6. Discussion The discussion should more thoroughly address your main finding — the association between preoperative intubation and ventilator-associated infection. Expand the discussion by comparing your results to recent studies and highlighting how your findings add to or differ from existing evidence. The implications section currently appears as bullet points and lacks supporting references; please reframe it into a narrative form with appropriate citations. 7. Conclusion Present the conclusion as a separate section, summarizing the main findings, their implications for practice, and limitations. 8. References Only about 30% of the references are from the last five years. Updating the literature will strengthen the scientific relevance of the manuscript. I suggest including recent ECMO infection studies (2020–2024), particularly from ELSO centers. ********** -->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 #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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. |
| Revision 2 |
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-->PONE-D-25-38491R2-->-->Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study-->-->PLOS One Dear Dr. Meng, 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 Feb 12 2026 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:-->
-->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, Giovanni Giordano Academic Editor PLOS One Journal Requirements: 1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 2. 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 #2: All comments have been addressed Reviewer #4: (No Response) ********** -->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 #2: Yes Reviewer #4: Yes ********** -->3. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #2: Yes Reviewer #4: N/A ********** -->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 #2: Yes Reviewer #4: 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 #2: Yes Reviewer #4: 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 #2: The authors have satisfactorily addressed all previous concerns, providing the requested methodological clarifications, improving the structure of the Introduction and Methods, updating the terminology and references, and ensuring overall consistency throughout the manuscript. I have no additional revisions to recommend. Reviewer #4: Thank you for the opportunity to review the manuscript PONE-D-25-38491R2, entitled “Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study”. The authors have comprehensively addressed the concerns raised in the previous review round. The extensive revisions significantly enhance the manuscript's quality, particularly regarding methodological transparency (in line with STROBE guidelines), clarity of terminology, and the depth of the Discussion. All major comments from reviewer 2 and 3 have been satisfied, making the paper substantially ready for publication. The manuscript is now rigorous, clearly stating the finding that preoperative endotracheal intubation is an independent risk factor for ECMO-related healthcare-associated infections (HAI). However, the following minor revisions are required before final acceptance: -Response to reviewer 2: 1) Thank you for providing the specific EPV ratio of 7 in your response, which technically addresses the initial query regarding statistical limitations. As this value is above the critical threshold of 5, the use of standard logistic regression is methodologically defensible. However, for maximum scientific rigor and interpretative transparency, I must highlight that the 95% CI for the primary independent risk factor (preoperative endotracheal intubation: OR=4.852, 95% CI: 1.174–20.059) remains exceptionally wide. This broad CI is a clear statistical manifestation of the imprecision and limited statistical power inherent to the small sample size (n=54) and the low number of events (n=14). While the analysis is technically valid, the wide range indicates significant uncertainty, confirming that the estimate is not precise. I strongly recommend the authors integrate an explicit caution into the Discussion/Limitations section, acknowledging that despite the EPV being technically acceptable, the resultant broad confidence interval necessitates a careful and cautious interpretation of the multivariate findings. This is not a critique of the methodology, but a crucial measure to enhance the scientific rigor of the interpretation. Additionally, the statement in the Methods section regarding the contingency plan to use Firth logistic regression " If the EPV (Events Per Variable) is less than 5, Firth logistic regression analysis should be adopted to reduce the risk of overfitting in small samples” describes a procedure that was ultimately not executed, as the reported EPV was 7. Since the Methods section should strictly detail the procedures that were actually performed, this sentence should be removed from the Statistical Analysis subsection. The calculation of an EPV of 7 and the subsequent use of standard logistic regression should instead be referenced in the Results, noting that the sample size constraints are already appropriately discussed in the Limitations section. 2) Thank you for clarifying the strict case definition used for the infection group. The decision to exclude children with clinically highly suspected infection but negative culture results (despite receiving empirical antibiotics) from the primary infection group provides methodological consistency by relying solely on microbiological confirmation. This approach is transparent and helps mitigate the risk of misdiagnosis in the complex context of ECMO-related systemic inflammation. However, for maximum transparency and to aid readers in interpreting potential biases, two actions are required for the final manuscript: 1) This critical exclusion criterion must be explicitly stated within the Methods section (specifically, under the data collection or diagnostic criteria subheading). It cannot remain solely in the response to reviewers. 2) Given that children with high clinical suspicion who received antibiotics were excluded, there is a potential for underestimation bias regarding the true incidence of infection (especially due to the suppression of bacterial growth from prior antimicrobial therapy). I strongly recommend the authors explicitly acknowledge this potential underestimation bias in the Discussion/Limitations section of the manuscript. 3) While the authors responded that the inconsistent terminology was "Modified", a meticulous review reveals that the implementation of the agreed-upon term "healthcare-associated infection (HAI)" has been incomplete. This incomplete harmonization constitutes an essential editorial failure that must be corrected before acceptance. The term "nosocomial infection" or variations thereof must be entirely replaced by "healthcare-associated infection (HAI)" throughout the manuscript. Specifically, the following instances of the outdated term persist: 1. Inconsistencies within the main text: - Methods/Exclusion Criteria: The exclusion criterion still refers to the "Presence of nosocomial infection before ECMO initiation". This must be changed to "healthcare-associated infection". - Results/Multivariate Analysis: The sentence describing the key finding uses the phrase: "Variables with p < 0.05 in the univariate analysis were included in the multivariate logistic regression analysis, which revealed that preoperative endotracheal intubation in children with congenital heart disease (OR = 4.852, 95% CI: 1.174-20.059; p = 0.029) was an independent risk factor for nosocomial ECMO-related infections in pediatric postcardiotomy patients." This must be harmonized to "ECMO-related healthcare-associated infections”. 2. Inconsistencies within Tables and Figures - Table 1 Title: The title of Table 1 remains "Pathogenic Microorganisms of ECMO-Associated Nosocomial Infections in children...". - Table 2 Title: The title of Table 2 remains "Univariate Analysis of ECMO-Associated Nosocomial Infections in children...". The authors must perform a final, comprehensive search-and-replace to ensure that every instance of "nosocomial infection" (including text, definitions, tables, and figure captions) is harmonized with "healthcare-associated infection (HAI)" to ensure full editorial and scientific consistency as agreed. 4) The authors have adequately acknowledged the potential for a bidirectional relationship and the impossibility of excluding reverse causality due to the retrospective design, as requested. - Response to reviewer 3 1) As previously noted (in the detailed response to Reviewer 2, Point 3), the outdated term "nosocomial infection" persists in crucial parts of the manuscript, despite the authors' claim that the terminology was "Modified." This persistent error is evident in the titles of Table 1 and Table 2, the exclusion criteria, and the Results section. For the sake of scientific consistency, the authors must perform a final correction to replace this term with the modern "healthcare-associated infection (HAI)" everywhere. Furthermore, the authors successfully implemented the structural requirement of including the study design in the title, following STROBE recommendations for observational studies, which is now acceptable. 2) The authors have successfully revised the Abstract to ensure its objective is harmonized with the Introduction. Furthermore, the study design is now explicitly stated as a "retrospective cohort study", and the Abstract includes a clear summary of the main statistical findings and conclusions. 3) The authors successfully expanded the Introduction to provide better context and relevance. They incorporated updated epidemiological data and clearly defined the literature gap regarding risk factors for HAI in pediatric post-cardiac surgery ECMO patients. Furthermore, the objective of the study is now clearly stated and aligned with the Abstract and Methods sections, making the Introduction logically sound and comprehensive. 4) as previously requested by the reviewer 3, the authors should explicitly state whether the Fuwai Central China Cardiovascular Hospital ECMO Center holds official ELSO certification. The authors must provide the typical nurse-to-patient ratio in the Pediatric ICU where these patients were managed, as this directly affects the generalizability of infection control findings. Additionally, please provide a brief statement detailing who collected the data, the original storage method, and the confidentiality/anonymization procedures used. The authors should report at least one quality metric for the final multivariate logistic regression model in the Results section to demonstrate model fit and robustness. Additionally, please specify the approach used for missing data, or declare if no variables had missing data. 5) The authors have substantially resolved the methodological requirements for the Results section: a flow diagram (Figure 1) has been established, and the authors clarified the correct use of mean ± SD versus Median (IQR) for data presentation in the Material and Methods section. However, the editorial implementation remains incomplete, as previously noted: the obsolete term "Nosocomial Infections" persists in the titles of Table 1 and Table 2, constituting a critical inconsistency that must be corrected. Furthermore, for maximal clarity, the authors must ensure that units of measurement, utilized fonts, and the use of capitalization and lowercase letters are uniform throughout the tables, and that a clear description of the format used for variable descriptions is formally stated in the table caption to fully satisfy the requirements for data presentation rigor. In addition, I recommend consistently using the lowercase p of p-value (i.e., “p-value" instead of "P-value") throughout the manuscript, as this is the preferred convention in formal statistical reporting. 6) The authors have successfully expanded the Discussion section, achieving the required standard. They provided deeper mechanistic insight into the association between preoperative intubation and HAI risk, included comparisons with recent relevant meta-analyses, and fully converted the implications section into a narrative format. 7) The authors have successfully presented the Conclusion as a dedicated, separate section that fully complies with the request. It provides a concise summary of the main findings, clinical implications, necessary future studies, and explicitly details the study's limitations. 8) The authors have adequately updated the bibliography with six highly relevant, recent references (2023–2025), including ELSO registry data, substantially strengthening the manuscript's scientific relevance. A comprehensive review of the tables and figures reveals several unresolved issues regarding formatting, statistical reporting consistency, and terminology that must be addressed before final acceptance. 1. Global formatting and consistency issues (Tables 1, 2, and 3) - The obsolete term "Nosocomial Infections" persists in the titles of Table 1 and Table 2. This must be corrected to "Healthcare-associated Infections (HAI)" for full manuscript consistency. - The use of capitalization and lowercase letters must be uniform across all tables. - The separators used in text (e.g., "/" in "Gender (male/female)" versus "vs." in other parts of the text) should be standardized across the entire manuscript for uniform style. - The authors must ensure that a clear description of the data format (e.g., Mean ± SD or Median (IQR)) is formally stated in the table caption for clarity. 2. Table 2: Univariate analysis specific issues - For the univariate analysis of the Admission diagnosis variable (row “admission diagnosis/n”), only a pooled p-value (0.318) is reported, and the corresponding X2 statistic is not shown. Given the very small cell counts for several diagnostic categories in the infected group, the authors must clarify in the Methods section whether these categories were grouped or collapsed before applying the Chi-square test. They also should systematically review all categorical variables in Table 2. Wherever expected cell frequencies are <5 in more than 20% of cells, the p-values must be recalculated using Fisher’s Exact Test, and any updated values should be clearly reported. - While the text mentions variables were measured "before extracorporeal membrane oxygenation (ECMO)", the column headers for biochemical values (lactate, BUN, creatinine, bilirubin, albumin) should be explicitly labeled (e.g., "Pre-ECMO Blood lactate") to eliminate any ambiguity. 3. Figure 1: Flow Diagram - The current figure caption "Fig1: Healthcare-associated Infections of ECMO in Children After congenital heart disease Surgery" is overly descriptive. Please revise it to a standard formal title such as "Flow diagram of patient selection" ********** -->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 #2: No Reviewer #4: 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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. --> |
| Revision 3 |
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<div>PONE-D-25-38491R3-->-->Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study-->-->PLOS One Dear Dr. Meng, 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 Apr 03 2026 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:-->
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, Giovanni Giordano Academic Editor PLOS One Journal Requirements: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. [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 #4: (No Response) Reviewer #5: (No Response) ********** -->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 #4: Yes Reviewer #5: No ********** -->3. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #4: Yes Reviewer #5: No ********** -->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 #4: Yes Reviewer #5: 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 #4: Yes Reviewer #5: No ********** -->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 #4: Dear Authors, Thank you for providing the revised version of your manuscript and for your detailed responses to the previous round of comments. I appreciate the efforts made to improve the statistical transparency of the study. However, after a careful review of the updated text, I find that the implementation of the requested changes is still incomplete and requires further refinement before the manuscript can be accepted. Please address the following issues: 1- The statement regarding the contingency plan to use Firth logistic regression ("If the EPV... is less than 5, Firth logistic regression analysis should be adopted...") still remains in the Statistical Analysis subsection of the Methods. As previously noted, the Methods section must strictly reflect the procedures actually performed. Since your reported EPV was 7, this sentence must be removed. 2- The discussion regarding the wide 95% Confidence Interval (95% CI: 1.174–20.059) for preoperative endotracheal intubation has been inserted into the Discussion/Limitations section almost verbatim as a response to a reviewer, using phrases like "I must highlight that...". This should be rewritten as an integrated methodological limitation in the authors' own voice, explicitly acknowledging that the broad CI is a manifestation of limited statistical power and small sample size. 3- In the Discussion, the claim that the results are "usually reliable" tends to downplay the significant uncertainty indicated by the wide confidence interval previously highlighted. Please ensure the tone reflects the necessary scientific caution requested. 4- You have added the explanation regarding empirical antibiotic therapy and the exclusion of culture-negative patients in two different sections (Data Collection and ECMO Management). Please consolidate this information into a single, clear paragraph. It is vital to explicitly state—without ambiguity—that microbiological confirmation was a mandatory requirement for the "infection group" to maintain the study's specificity. 5- The mention of underestimation bias in the Limitations section remains somewhat superficial. I recommend expanding this to explicitly state that prior antimicrobial therapy might have suppressed bacterial growth, leading to false-negative cultures, which is a common challenge in ECMO-related HAI diagnosis. I look forward to receiving your final, harmonized revision. Reviewer #5: The manuscript in its current form is not acceptable for publication. Despite claims of modification, significant errors flagged in previous rounds persist. There is a pattern of "false compliance," where the authors state a point is "Modified" in the rebuttal letter, but the manuscript remains unchanged or contains incomplete data. The following issues must be resolved: #1 Ethical Transparency & Methodology. a. Data Integrity Statement (Ignored): The request to detail who collected the data, storage methods, and anonymization procedures was ignored. You must add this to the Methods section to comply with ethical standards. b. Evaluation of Model Performance and Fit: The authors present the results of the multivariate logistic regression solely in terms of Odds Ratios and p-values. However, providing coefficient estimates without assessing the overall performance of the model is methodologically insufficient, particularly given the small sample size (n=54) and the low number of events (n=14).In small datasets, logistic regression models are prone to overfitting, where the model describes random error rather than underlying relationships. To demonstrate the robustness of the findings, the authors must report: Discrimination: The C-statistic (or Area Under the ROC Curve - AUC), which indicates the model's ability to distinguish between patients who developed an infection and those who did not. An OR of 4.85 is of limited value if the model's discriminative ability is poor (e.g., AUC < 0.7). Calibration (Goodness-of-Fit): A measure such as the Hosmer-Lemeshow test to assess how well the predicted probabilities match the observed outcomes should be performed. Action: Please calculate and report the AUC (with 95% CI) and a goodness-of-fit metric for the final multivariate model in the Results section. If the model demonstrates poor fit or discrimination, this must be transparently discussed as a limitation. c. ELSO Certification: Explicitly state if the center holds official ELSO certification or only domestic accreditation. d. Nurse-to-Patient Ratio: Clarify the "1.9" value. Use standard ratio format (e.g., 1:2 or 2:1). #2 Data Presentation & Tables a. Missing Data in Tables: In the table regarding baseline characteristics, the row labeled "admission diagnosis/n" reports a p-value of 0.448, yet the cells for the specific groups are empty. Reporting a p-value without the corresponding descriptive statistics is scientifically invalid. b. Missing Captions and Definitions (Table 3): Table 3 appears to be raw output pasted directly into the document. It lacks a descriptive Title/Caption and Footnotes. Per PLOS ONE guidelines, tables must be self-explanatory. You must define all abbreviations (B, S.E., Wald, etc.) in the footnotes. c. Uninterpretable Table Formatting: The tables depicting microorganisms lack descriptive headers for the data columns (e.g., describing what the figures "14" and "3" represent). Remove all vertical gridlines and ensure every column has a clear header. #3 Editorial Integrity a. Inappropriate Narrative Voice: The paragraph discussing the EPV and Confidence Intervals contains text copied directly from reviewer correspondence ("I must highlight that...") and defensive phrasing ("results... are usually reliable"). Action: Delete that paragraph and replace with: "Although the EPV ratio (>5) justifies the use of standard logistic regression, it is important to acknowledge that the 95% Confidence Interval for preoperative endotracheal intubation (OR=4.852, 95% CI: 1.174–20.059) remains wide. This width suggests a degree of estimation uncertainty, likely attributable to the limited number of events within this specific subgroup, and warrants a cautious interpretation of the magnitude of the risk." b. Removal of Meta-Text: In the Methods, remove "In accordance with the request...". State facts directly (e.g., "Data access commenced on..."). c. Abstract/Methods Redundancy: Remove the disjointed sentence "This was a retrospective cohort study" from the middle of the Methods. Integrate it into the opening sentence. #4 Scientific Consistency a. Hypothetical Methods: Remove the sentence "If the EPV... is less than 5, Firth logistic regression... should be adopted". Since EPV was >5, this procedure was not performed and should not be listed. b. Missing Statistical Test: The sentence "compared using either chi-square test , as appropriate" is incomplete. Correct to: "...compared using either the Chi-square test or Fisher's exact test, as appropriate." #5 Formatting & Proofreading a. Typographical Errors: "VS" formatting: Change "27.7%VS7.9%" to "27.7% vs. 7.9%". Spacing: Fix missing spaces after periods (e.g., "support.Our", "ICU.All"). Punctuation: Remove the colon in "According to relevant literature:". Double Punctuation: Remove double periods (e.g., "[4].."). b. Non-Standard Symbols: Remove circled numbers (①, ②) and use standard lists. c. Syntax: Fix the dangling phrase starting with "Retrospective cohort study,the ECMO-related...". ********** -->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 #4: Yes:Gaetano Gazzé Reviewer #5: 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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. |
| Revision 4 |
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-->PONE-D-25-38491R4-->-->Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study-->-->PLOS One Dear Dr. Meng, 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 Apr 16 2026 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:-->
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, Giovanni Giordano Academic Editor PLOS One Journal Requirements: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Additional Editor Comments: Dear Dr. Meng, Thank you for submitting the revised version of your manuscript entitled: “Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study”. We have now completed the evaluation of your revised manuscript. One reviewer considers the manuscript potentially suitable for publication, while another reviewer continues to raise important concerns regarding methodological presentation, interpretation of results, and overall manuscript clarity. After careful consideration of the reviewers’ comments and the current version of the manuscript, we believe that the study addresses a clinically relevant question and has potential merit. However, significant issues remain that must be resolved before the manuscript can be considered for acceptance. We are therefore offering you one final opportunity to revise the manuscript (Major Revision). Please note that this revision must be comprehensive and meticulous. 1. Interpretation of Model Performance The multivariable model reports: AUC = 0.686 (95% CI: 0.514–0.858) Hosmer-Lemeshow p = 0.221 While calibration appears acceptable, the discriminatory ability is marginal, and the lower bound of the confidence interval approaches 0.50. You must: Remove statements describing the model discrimination as “acceptable”. Clearly state that the discriminatory ability is marginal. Explicitly acknowledge in the Limitations section that the wide confidence interval and small number of events limit the robustness and clinical applicability of the model. 2. Statistical Methods - Descriptive, Not Prescriptive The Statistical Analysis section must describe the analyses actually performed, written in past tense and objective tone. Please: Remove any prescriptive phrasing (e.g., “must be recalculated”). Rewrite the section to clearly state what was done (e.g., “Fisher’s exact test was used when expected cell frequencies were <5…”). 3. Removal of Rebuttal Language and First-Person Statements The manuscript still contains language copied from prior correspondence (e.g., “I explicitly state…”). All such phrasing must be removed. The manuscript must: Use objective scientific tone. Avoid first-person singular pronouns. Eliminate any defensive or reviewer-directed language. 4. Abstract and Administrative Text The Abstract must function as a standalone scientific summary. Please remove: Administrative timeline descriptions related to data access. Any text referring to “requests for transparency”. The study design and timeframe may be stated concisely in standard format. 5. Formatting and Readability Substantial formatting and language issues remain, including: Typographical errors (e.g., “Data acess”). Non-standard punctuation (e.g., “1-->-->、”-->-->). Inconsistent spacing. Table alignment problems. Residual track-change artifacts. You must conduct a complete professional language and formatting revision of the manuscript prior to resubmission. We strongly recommend the use of a professional English language editing service. If such service is used, please provide confirmation upon resubmission. We recognize the clinical relevance of your study and the effort invested in prior revisions. However, after four rounds of review, the manuscript must now meet full scientific and editorial standards. Failure to comprehensively address the issues outlined above may result in rejection. We look forward to receiving your thoroughly revised manuscript. Sincerely, Giovanni Giordano [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 #4: All comments have been addressed Reviewer #5: (No Response) ********** -->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 #4: Yes Reviewer #5: No ********** -->3. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #4: Yes Reviewer #5: No ********** -->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 #4: Yes Reviewer #5: 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 #4: Yes Reviewer #5: No ********** -->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 #4: The manuscript has matured significantly in this fourth revision, and it is clear that the authors have put a great deal of effort into precisely addressing the technical and editorial concerns raised during the previous round. The statistical analysis section is now much more transparent and logically sound; by removing hypothetical descriptions of procedures like the Firth regression that weren't actually utilized, the methodology feels much more honest and focused. I particularly appreciate the inclusion of the model performance metrics, such as the AUC of 0.686 and the Hosmer-Lemeshow test results. While the sample size is inherently limited, providing these figures gives the reader a solid, transparent basis to evaluate the robustness of the multivariate model. Furthermore, the discussion regarding the wide 95% Confidence Interval for preoperative intubation has been integrated thoughtfully into the narrative. It no longer reads like a defensive response to a reviewer but rather as a mature methodological reflection that correctly invites scientific caution. The paper has also gained a high level of credibility through the new details on data management, anonymization, and storage, which ensure ethical transparency. Similarly, explicitly stating the center's ELSO certification and the 2:1 nurse-to-patient ratio helps ground the study in a clear clinical context of high-level operative standards. The presentation of data in the tables is now excellent; Table 2 is finally complete with the necessary descriptive statistics for admission diagnoses, and Table 3 is fully accessible with clear definitions for all statistical abbreviations. Finally, the removal of meta-text and the correction of previous typographical errors have resulted in a professional, fluid, and highly readable manuscript. I believe the authors have fully satisfied all requests, and the findings regarding preoperative endotracheal intubation as a risk factor offer valuable and practical insights for the pediatric cardiac surgery community. I am happy to recommend this paper for acceptance. Reviewer #5: I appreciate the authors' efforts in revising the manuscript and providing the additional statistical analyses requested. The inclusion of the Hosmer-Lemeshow test and ROC curve analysis significantly enhances the methodological transparency of the study. However, further refinements are necessary regarding the interpretation of the statistical output, the proper contextualization of the methodology, and, crucially, a severe revision of the manuscript's readability and formatting, which remains inadequate for a final submission at this stage (R4). 1. Interpretation of Model Discrimination (AUC): I commend the addition of the model performance metrics. The calibration of the model appears adequate (Hosmer-Lemeshow p=0.221). However, an interpretative adjustment regarding the discrimination metric (AUC) is required. The reported AUC is 0.686 (95% CI: 0.514–0.858). In standard biostatistical practice, an AUC between 0.6 and 0.7 is generally classified as "poor" rather than "acceptable". Furthermore, the lower bound of the 95% CI (0.514) approaches 0.50 (random chance). Concluding that the model demonstrates an "acceptable level of both discriminatory ability and goodness-of-fit" overstates its predictive robustness. Action Required (Results): Please retain the phrase "marginal but statistically significant discriminatory ability," but remove the concluding claim that the discrimination is "acceptable." Action Required (Limitations): Please explicitly integrate this marginal discrimination into the Limitations section. Add a statement acknowledging that because the AUC is marginal and its lower confidence bound approaches 0.5, the predictive power of the multivariable model is limited, requiring a cautious clinical application of the reported Odds Ratios. 2. Inadequate Narrative and Missing Methodological Context for Statistical Tests: The reporting of the multivariate analysis in the Results section reads like raw statistical software output rather than a cohesive scientific narrative. Appending isolated data fragments (e.g., "Hosmer-Lemeshow test: chi^2=10.67, df=8, p=0.221") without proper sentence structure is poor scientific writing. Furthermore, the methodology behind these specific tests must be formally introduced in the Methods section before the results are presented. Action Required (Methods): Please update the Statistical Analysis section to explicitly state your methodology for evaluating the model (e.g., "Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test, and discrimination was evaluated using the Area Under the Receiver Operating Characteristic curve (AUC).") Action Required (Results): Please rewrite the isolated data fragments into proper, grammatically correct sentences that provide narrative context. 3. Inappropriate Prescriptive Language in Statistical Analysis: In the Methods section, the sentence "Wherever expected cell frequencies are <5 in more than 20% of cells, the p-values must be recalculated using Fisher’s Exact Test" is stylistically inappropriate. The Methods section must serve as a descriptive record of the analysis actually performed (written in the past tense), rather than prescribing rules or pasting direct instructions from reviewers ("must be recalculated"). Action Required: Please revise this sentence to reflect standard, objective scientific writing (e.g., "Fisher’s exact test was used to compare categorical variables when expected cell frequencies were less than 5 in more than 20% of the cells."). 4. Inappropriate Narrative Voice and Residual Rebuttal Text: Similar to the issue above, the manuscript contains sentences written in the first-person singular that appear to be copied directly from rebuttal correspondence. Specifically, the phrase "I explicitly state that prior antimicrobial therapy might have suppressed bacterial growth" is highly inappropriate for a multi-authored scientific manuscript and breaks the objective tone of the paper. Action Required: Please review the entire manuscript to remove any first-person singular pronouns ("I") and defensive/rebuttal phrasing. Revise this specific sentence to an objective scientific statement, such as: "Furthermore, prior antimicrobial therapy might have suppressed bacterial growth." 5. Residual Meta-Text in the Abstract: The Abstract currently contains administrative details regarding the review process. The Abstract must serve as a standalone summary of the scientific work. Action Required: Please completely delete the following sentences from the Abstract: "In accordance with the request for methodological transparency, we report that access to the dataset for the specific purposes of this study commenced on 1st June 2024. Formal data analysis specific to the research questions outlined herein began on 1st December 2024 and concluded on 1st March 2025. Statistical analysis was performed on the relevant factors." 6. Phrasing and Typographical Errors in the Methods Timeline: In the main text (Methods section), the newly added sentences detailing the timeline of data access contain a typographical error and overly bureaucratic phrasing. Action Required: Please correct the typo ("Data acess") and simplify the syntax. I suggest replacing the current sentences with standard phrasing: "Data access began on June 1, 2024. Data analysis was conducted from December 1, 2024, to March 1, 2025." 7. Severe Readability and Formatting Issues (Text): Despite previous requests to fix formatting and spacing, the manuscript suffers from a severe lack of readability. The text is poorly structured and riddled with non-standard punctuation. Inclusion/Exclusion Criteria and Definitions of Infections: These sections are compressed, retain missing spaces ("telephone.Inclusion"), use non-standard punctuation ("1、"), and inexplicably include text left in red font (unaccepted track-changes). Action Required: A meticulous, line-by-line proofreading of the entire manuscript is mandatory. Remove all non-standard symbols, ensure proper spacing after punctuation marks, use standard line breaks or bullet points for lists, and remove all residual track-change formatting (red text). 8. Inadequate Table Formatting: Despite previous attention drawn to table presentation, the current tables remain highly difficult to read. The variable name cells are vertically expanded, while the corresponding data values remain vertically center-aligned in their respective cells. This misalignment forces the reader to guess which value belongs to which variable across the row. Action Required: Please reformat all tables to ensure clear, horizontal alignment (e.g., top-aligning the contents of the cells or strictly ensuring line-by-line correspondence) so that readers can easily and accurately track the data rows. ********** -->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 #4: No Reviewer #5: 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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. |
| Revision 5 |
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-->PONE-D-25-38491R5-->-->Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study-->-->PLOS One Dear Dr. Meng, 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 May 03 2026 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:-->
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, Giovanni Giordano Academic Editor PLOS One Journal Requirements: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Additional Editor Comments: Dear Authors, Thank you for submitting the revised version of your manuscript entitled “Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study.” We appreciate the substantial effort you have made in addressing the reviewers’ previous comments. The manuscript has improved in several important aspects, particularly in the clarification of the statistical methodology, the revision of the model performance interpretation, and the overall structure of the Results and Methods sections. However, after careful evaluation, several critical issues remain that must be addressed before the manuscript can be considered for publication. Given the multiple rounds of revision already completed, please consider this decision as a final opportunity to revise the manuscript. We therefore encourage you to address the following points thoroughly and carefully. <h3 class="western">Major Points</h3> 1. Interpretation of the multivariable model and causal language The current manuscript continues to describe preoperative endotracheal intubation as an “independent risk factor.” Given the small sample size, wide confidence intervals (OR 4.852, 95% CI 1.174–20.059), and marginal discrimination (AUC 0.686, 95% CI 0.514–0.858), this wording is too strong. Please revise throughout the manuscript to use more appropriate language, such as:
Causal implications should be avoided. 2. Confounding by severity (major methodological concern) Preoperative intubation is very likely a marker of underlying clinical severity rather than a direct causal factor. This introduces a substantial risk of confounding by indication. This issue is currently underdeveloped in the Discussion. Please:
3. Model robustness and statistical limitations Although you have improved the reporting of model performance, the limitations are still not sufficiently emphasized. Please strengthen the Limitations section by clearly stating:
The model should be presented as exploratory and hypothesis-generating, not predictive. 4. Definition and potential misclassification of infections The study includes only microbiologically confirmed infections, while clinically suspected but culture-negative cases were excluded despite receiving treatment. This approach introduces potential selection and misclassification bias, and may underestimate the true incidence of infection. Additionally, the finding that 100% of infections were respiratory in origin warrants further discussion. Please:
5. Interpretation of ICU length of stay The manuscript discusses ICU length of stay as a variable associated with infection; however, this variable is likely influenced by the occurrence of infection itself (reverse causation). Please:
6. Overinterpretation and clinical recommendations The Discussion includes extended recommendations (e.g., airway management protocols, VAP prevention strategies) that are not directly supported by the study data. Please revise this section to:
<h3 class="western">Minor Points</h3>
The study addresses a clinically relevant topic and has improved during the revision process. However, the issues outlined above—particularly regarding causal interpretation, confounding, and model limitations—must be fully addressed. We therefore invite you to submit a revised version that carefully and comprehensively responds to all points raised above. Please note that this will be considered the final round of revision, and further decisions will be based on the completeness and quality of your response. We look forward to receiving your revised manuscript. Sincerely, Giovanni Giordano [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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. |
| Revision 6 |
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<p>Risk Factors for Healthcare-associated Infections in Children Undergoing ECMO After Cardiac Surgery for Congenital Heart Disease: A Retrospective Study PONE-D-25-38491R6 Dear Dr. Meng, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support. 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, Giovanni Giordano Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: |
| Formally Accepted |
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PONE-D-25-38491R6 PLOS One Dear Dr. Meng, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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. Giovanni Giordano Academic Editor PLOS One |
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