Development and internal validation of a prediction model incorporating SOFA, Prognostic Nutritional Index, and Neutrophil-to-Albumin Ratio for early prediction of in-hospital mortality in patients with Sepsis: A single-center retrospective study

Lutian Yi; Tao Yu; Xiaolu Zheng

doi:10.1371/journal.pone.0353124

Peer Review History

Original SubmissionMay 27, 2026
14 Jun 2026 Decision Letter - Benjamin Liu, Editor -->PONE-D-26-25132-->-->Development and Internal Validation of a Prediction Model Incorporating SOFA, Prognostic Nutritional Index, and Neutrophil-to-Albumin Ratio for Early Prediction of In-Hospital Mortality in Patients with Sepsis: A Single-Center Retrospective Study-->-->PLOS One Dear Dr. Yi, 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. 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Revision 1
16 Jun 2026 Author Response Manuscript ID: PONE-D-26-25132 Title: Development and Internal Validation of a Prediction Model Incorporating SOFA, Prognostic Nutritional Index, and Neutrophil-to-Albumin Ratio for Early Prediction of In-Hospital Mortality in Patients with Sepsis: A Single-Center Retrospective Study Corresponding Author: Lutian Yi Dear Dr. Benjamin M. Liu and the Reviewers, Thank you for your thoughtful and constructive comments on our manuscript. We have carefully addressed all the points raised by the Academic Editor and the reviewers. Below we provide a point-by-point response. All changes in the revised manuscript have been highlighted using track changes. Response to Academic Editor Comment: The authors should add introduction that blood cultures play a central diagnostic role in detecting sepsis, particularly when bloodstream infection (bacteremia or fungemia) is suspected but blood cultures suffer from long turnaround time, low sensitivity, requirement of specific culture conditions and difficulties of growing fastidious organisms. More references should be cited, with this two (PMID: 41246370; PMID: 34142857) as examples (citing is optional). Response: We thank the Editor for this valuable suggestion. We agree that the limitations of blood cultures provide important context for the use of rapid, culture-independent biomarkers and clinical scoring systems. Accordingly, we have revised the Introduction by replacing the original opening sentence of the biomarker paragraph (“Biomarkers play a key role in assessing infection severity and prognosticating sepsis outcomes.”) with the following sentences (inserted immediately after the Sepsis-3 definition and before the discussion of conventional markers such as CRP and PCT): “Although blood cultures remain the reference standard for identifying causative pathogens in sepsis, they suffer from long turnaround time, limited sensitivity, and difficulty in cultivating fastidious organisms [5,6]. Consequently, culture-independent biomarkers and clinical scoring systems have gained increasing attention for early risk stratification. Conventional markers including C-reactive protein (CRP) and procalcitonin (PCT) facilitate diagnosis but demonstrate limited prognostic utility [7]. Emerging evidence suggests that sepsis prognosis is determined not solely by the inciting pathogen but by the interplay between systemic inflammation and the patient’s physiological reserve. Hypoalbuminemia, prevalent in septic patients, correlates with adverse outcomes and reflects both malnutrition and the systemic inflammatory response [8].” We have incorporated the two suggested references into the revised Introduction. All subsequent reference numbers have been updated throughout the manuscript accordingly. The revised text is highlighted in red in the tracked-changes version. Response to Reviewer #1 Comment: The technique suggested by author can be accepted as a method for sepsis validation the data set is adequate. Such studies are a benefit to critical ill hospital patients. Very few articles available on above subject. The only problem I found with the manuscript is that the authors have not adequately explained or declared as to how they came up with the formula for the logistic regression (lines 131-132). I feel like this should be explained in the final manuscript. Response: We thank the reviewer for this important comment. In the original manuscript, the logistic regression equation was presented without explicitly stating how it was derived. As shown in Table 2, the β coefficients for all model terms, including the intercept, were already reported. To make the derivation transparent, we have revised the Methods section (Model development subsection) in the marked-up manuscript, where the changes are highlighted in red. The revised text reads as follows: “Given the limited number of outcome events, a parsimonious multivariable logistic regression model was developed. Multicollinearity was assessed using the variance inflation factor (VIF); all values were <5, indicating no significant collinearity. Using the β coefficients from the multivariable logistic regression model (Table 2), the final prediction equation was constructed as follows: logit(p) = −1.842 + 0.581 × SOFA − 0.097 × PNI + 3.348 × NAR, where p denotes the predicted probability of in-hospital mortality. Predicted probability was calculated as p = 1 / (1 + e^−logit(p)). Univariate logistic regression results for all candidate variables are presented in Supplementary Table 1.” The coefficients in the equation are identical to those reported in Table 2. We believe this revision fully addresses the reviewer’s concern. Response to Reviewer #2 Comment: The technique suggested by author can be accepted as a method for sepsis validation the data set is adequate. Such studies are a benefit to critical ill hospital patients. Very few articles available on above subject. Response: We sincerely thank the reviewer for the positive and encouraging comments. We are pleased that the reviewer found our study and dataset appropriate for this purpose and recognized the potential clinical value of the model in critically ill patients with sepsis. We agree that further external validation will be important before routine clinical application, and we hope our work may serve as a useful foundation for future studies in this area. Response to Journal Requirements 1.PLOS ONE style requirements and file naming We have checked the PLOS ONE style requirements and file naming conventions and confirm that the revised files have been prepared accordingly. 2. Code sharing guidelines We have reviewed PLOS ONE’s code sharing policy. No author-generated custom code was developed for this study. All statistical analyses were performed using standard functions in SPSS version 25.0 (IBM Corp.) and R version 4.5.0 with publicly available packages (pROC, rms, rmda, boot). Therefore, code sharing does not apply to this submission. 3. Funding statement removal from Acknowledgments We have removed all funding-related text from the manuscript. The Acknowledgments section now contains only non-financial acknowledgments and does not include any funding information. Funding information appears only in the Funding Statement in the online submission system, as required. 4. Matching grant information We confirm that the correct grant number is 2024KY369 from the Zhejiang Provincial Medical and Health Research Program. The same grant information has been provided consistently in the submission materials. 5. Role of funder The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This statement has been included in the cover letter as requested. 6. Data availability statement The anonymized dataset used for this analysis has been provided as Supporting Information (S1 Dataset). No third-party contact is required. 7. ORCID iD for corresponding author The corresponding author has created and validated an ORCID iD in Editorial Manager via the “Update my Information → Fetch/Validate” link. 8. Ethics statement location We confirm that the ethics statement appears only in the Methods section under the subheading “Ethical Approval.” The duplicate ethics statement previously located in the Declarations section has been removed. 9. Citation of recommended works We have cited the two references recommended by the Academic Editor (PMID: 41246370 and PMID: 34142857) in the revised Introduction (now numbered as [5] and [6]). These references are relevant to the added discussion on blood culture limitations. No other reviewer-recommended citations were requested. 10. Reference list completeness and retractions We have carefully reviewed the reference list and made the necessary corrections to ensure completeness and accuracy. We also verified that none of the cited references have been retracted. We believe the revised manuscript is now suitable for publication in PLOS ONE. We thank the Academic Editor and reviewers again for their time and valuable input. Sincerely, Lutian Yi, MD Corresponding author Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0353124.r002
18 Jun 2026 Decision Letter - Benjamin Liu, Editor Development and Internal Validation of a Prediction Model Incorporating SOFA, Prognostic Nutritional Index, and Neutrophil-to-Albumin Ratio for Early Prediction of In-Hospital Mortality in Patients with Sepsis: A Single-Center Retrospective Study PONE-D-26-25132R1 Dear Dr. Yi, 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, Benjamin M. Liu, PhD, D(ABMM), MB(ASCP) Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0353124.r003
Formally Accepted
Acceptance Letter - Benjamin Liu, Editor PONE-D-26-25132R1 PLOS One Dear Dr. Yi, 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. Benjamin M. Liu Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0353124.r004

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