Risk prediction of all-cause mortality in hospitalized patients with severe acute pancreatitis by serum urea nitrogen/albumin ratio

Huisi Qiu; Yongshuai Fu; Ziwen Lv; Xingyu Zhu; Junhui Gu; Zhuo Gao; Dong Liu

doi:10.1371/journal.pone.0326543

Peer Review History

Original SubmissionNovember 12, 2024
27 Jan 2025 Decision Letter - Ramya Iyadurai, Editor Dear Dr. Lv, 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 Mar 12 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. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. 6. Please amend the manuscript submission data (via Edit Submission) to include authors Dr. Junhui Gu and Dr. Zhuo Gao. 7. Please amend your authorship list in your manuscript file to include author Dr. Qi Feng. 8. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information . 9. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: BAR ratio in acute pancreatitis outcomes I would like to appreciate the authors for an interesting study, the importance of the study I believe lies in the fact that a simple and easily available blood test can be used to predict mortality in a very severe illness. I have a few recommendations for the manuscript, Recommendation 1 : The results can include the numerical values, the percentages and other interesting statistics baseline characteristics of the study group, the mean age of the study group, the gender distribution, significant comorbidities, substance use, the etiology for the pancreatitis, outcomes, complications, and other values of interest in acute pancreatitis like blood sugar levels, calcium levels, SOFA scores, this will easier for the reader to read and assimilate if included in the manuscript, instead of having to refer to the tables at each point. In the results the authors can discuss what factors were significantly different and provide numerical values for clarity for the readers. Recommendation 2 : The authors can also discuss in the results on whether they identified any other factors they found of interest in the study that could be interesting for the readers and lead to future studies. Recommendation 3: The authors can discuss the results under models 2 and 3, especially model 3 clarify what they indicate by mentioning clinical expertise, how this was derived for scientific interest. The authors can mention and explain the factors that were selected by the Baruta and the SHAP algorithm in the results. It will be of interest of the authors explain the figures on the importance of Z score, the SHAP and the BAR, the BAR figure has a legend of 2 groups 0,1 but it is not clear what is 0 and what is 1, can the authors label the legends of the figure for more clarity. The plot of HR is pictorially represented as a forest plot, but usually forest plots are usually drawn with 0 and values on either side, for significance, here the plot is represented with 1, so it may appear to the readers that values are nor significant when they actually are, can authors look into this and if they do not want to change the present representation explain the same in the results so that it will be clearer for the readers. Recommendation 4 It will be useful for the readers if the authors can mention the subgroups chosen for analysis and the reasoning behind their choice of the subgroups for analysis in the methodology. The authors can mention in the results the values for the subgroups that are not significant as well, since in the results only the factors that were significant are mentioned. Recommendation 5: The authors have excluded patients with HIV, kidney disease and malignant neoplasms, I assume this is probably since the patients would be sicker and have low albumin, Can the authors clarify this in the manuscript, as it will be of value to the readers. Recommendation 6: Under the discussion the authors can discuss the results of their study and the similarities of baseline characteristics of their study group with other studies in pancreatitis, for the readers to identify the applicability of the study in their clinical practice. The authors can discuss the varied values of BAR in various diseases rather than its importance in other diseases in a general way and limit it to diseases similar to pancreatitis such as illnesses with multi organ dysfunction such as sepsis. The authors can discuss BAR and the cut off values to be used in pancreatitis and the why behind the cutoff values, for clarity for the readers. Looking forward to resubmission after addressing the recommendations. [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? Reviewer #1: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes ****** Reviewer #1: The study establishes a correlation between BAR and mortality, it is essential to address how this biomarker compares with existing prognostic tools used in acute pancreatitis. The statistical methods employed are good. However providing confidence intervals for all key statistics would improve the comprehensiveness of the results. Discussing the feasibility of implementing routine BAR testing in clinical settings, including cost-effectiveness and accessibility issues, would provide practical insights for clinicians.The reported odds ratio for BAR is significant, however, including how BAR can be integrated into current clinical practice would enhance the discussion.Overall, this study presents significant findings regarding the serum urea nitrogen-to-albumin ratio as a predictor of mortality in acute pancreatitis patients. Addressing these comments will enhance clarity, depth, and applicability of the research outcomes. ****** what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy Reviewer #1: Yes: Nawahirsha ******** [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 https://doi.org/10.1371/journal.pone.0326543.r001
Revision 1
11 Mar 2025 Author Response Reviewer 1 Added or modified in the revised manuscript as requested Reviewer 2 Comment 1� Results can include numerical values, percentages, and other interesting statistical baseline characteristics for the study group, mean age of the study group, gender distribution, significant comorbidities, drug use, etiology, outcomes, complications of pancreatitis, and other values of interest in acute pancreatitis, such as blood glucose levels, calcium levels, SOFA scores, if included in the manuscript, It will be easier for the reader to read and absorb than to refer to the table at every point. In the results, the authors can discuss which factors differ significantly and provide numerical values so that the reader can see them. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. Details have been added in P12-13, Line 239~264. Comment 2� Authors can also discuss in the results whether they found other interesting factors in the study that might be interesting to the reader and lead to future research. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. Details have been added in P16, Line 325~330. Comment 3� The authors could discuss the results under Models 2 and 3, specifically Model 3, by mentioning clinical expertise to clarify what they indicate and how this knowledge was derived from scientific interest. The authors can mention and explain in the results the factors selected by the Baruta and SHAP algorithms. Interested authors will explain the importance of the Z-score, SHP and BAR in the BAR plot, there are two groups of icons, 0, 1 but it is not clear what is 0 and what is 1, the author can annotate the plot to be clearer. The plots of HR are represented as forest plots on the chart, but usually forest plots are usually represented by 0 and values on both sides, for the sake of meaning, the plots here are represented by 1, so the reader may feel that these values are not important, but in fact they are not important, can the author look into this issue? If they don't want to change the current presentation, they can explain the same thing in the results so that the reader will be clearer. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. The selection of covariates for adjustment in our model was informed by a systematic review of existing literature on mortality risk factors in acute pancreatitis, supplemented by feature importance analyses using SHAP (SHapley Additive exPlanations) and Boruta machine learning algorithms. This dual approach ensured that variables were prioritized based on both evidence from prior studies and data-driven predictive relevance.and we use R to calculate, and the HR we calculate is greater than 1, so we use starting from 1 in the forest graph.and In the early stage, we read a large number of relevant literature and summarized the relevant important variables.Following the determination of the relevance of the study variables, feature selection was a crucial step in reducing the number of features in the large dataset. A crucial method of feature selection was the Boruta algorithm, which was based on the random forest classifier method.Details have been added in P27 Line 564-566 and P11, Line 213~226. Comment 4� It would be helpful if the authors could mention the analysis subgroup they chose and the rationale behind their methodological choice of the analysis subgroup. The authors can mention the values of unimportant subgroups in the results because only the important factors are mentioned in the results. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. Details have been added in P15-16, Line 306~317 and P10-11, Line 200~211. Comment 5� The authors excluded patients with HIV, kidney disease, and malignancies, which I think may be due to the fact that the patients are more severely ill and have lower albumin. Could the author please clarify this in the manuscript as it is valuable to the reader. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. Details have been added in P5, Line 86~94. Comment 6� During the discussion, authors may discuss the results of their study, as well as the similarity of the baseline characteristics of their study arm to other pancreatitis studies, so that the reader can identify the applicability of the study in clinical practice. The authors could discuss the different values of BAR in various diseases, rather than discussing its importance in other diseases in general, and limit it to pancreatitis-like diseases, such as those with multiple organ dysfunction, such as sepsis. The authors can discuss the BAR and cut-offs used in pancreatitis, as well as the reasons behind the cut-offs, so that it is clear to the reader. It is expected that it will be resubmitted once the recommendations have been implemented. Response Thank you very much for your suggestion,We think this is an excellent suggestion. We carefully reviewed the literature and made changes to the discussion section of the revised manuscript. Details have been added in P13-14, Line 269~283 and P7, Line 134~139. Reference�Since the 40th reference in the original manuscript was required for the revision of the reviewer's comments, this reference has been placed in the 28th paragraph of the revised manuscript. We tried our best to improve the manuscript and made some changes We appreciate for Editor and Reviewers’ warm work earnestly, and hope the correction will meet with approval. Once again, thank you very much for your comments and suggestions. Attachments Attachment Submitted filename: Response to reviewer.docx https://doi.org/10.1371/journal.pone.0326543.r002
1 Jun 2025 Decision Letter - Ramya Iyadurai, Editor Risk prediction of all-cause mortality in hospitalized patients with severe acute pancreatitis by serum urea nitrogen/albumin ratio PONE-D-24-51800R1 Dear Dr. Lv, 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. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Ramya Iyadurai Academic Editor PLOS ONE Additional Editor Comments (optional): The font of the tables keep shifting can you please make the font uniform. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: (No Response) Reviewer #3: All comments have been addressed Reviewer #4: All comments have been addressed Reviewer #5: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: I Don't Know Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: No ****** Reviewer #2: The author mentioned vasopressin, octreotide, and mechanical ventilation were associated with in-hospital mortality. whereas vasopressin, octreotide, and mechanical ventilation are started as a treatment when the patient's condition is worsened. So these treatment modalities would not be considered as associated factors for mortality. so please rephrase the sentences from line 173 to 176 Reviewer #3: Comment 1, The authors have responded to the previous review comments one by one, which has improved the overall interpretation of the research data. From the existing data, after the correction in Model 3, the BAR still shows some predictive ability for the prognosis of acute severe pancreatitis. However, it is noteworthy that during the assessment of acute severe pancreatitis, BUN and ALB as individual indicators can already indicate the severity of acute pancreatitis. The authors also mentioned the predictive efficacy of BUN and ALB in the discussion section. Based on the evidence presented in the paper, it seems that the predictive efficacy of BAR is primarily due to these individual indicators, which is reasonable as a disease stratification tool. Comment 2, Despite the adjustments made in the statistical model, it is undeniable that, at baseline, patients with a BAR > 10.45 have more severe conditions and higher mortality rates, which is expected. Rather than considering BAR as a single predictive factor, it more accurately reflects a state of high catabolic metabolism upon admission. However, due to the significant statistical correlation, I believe the authors' conclusions are justifiable. Reviewer #4: The study, through rigorous methodological design and comprehensive data analysis, has confirmed the predictive value of the "Blood Urea Nitrogen to Albumin Ratio (BAR)" for in-hospital mortality risk in patients with severe acute pancreatitis (SAP). The research addresses key reviewer comments, is methodologically sound, and its conclusions are robust. It is suitable for publication. Reviewer #5: Tables are less in number,There is no graphical representations of any of ur variables of data.IIn Data extraction heading -Why u didn't remove whole missing data,why to remove more than 30%missing variables,as it may affect the organisation of data n ur study outcomes ****** 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: Yes: Jennie Santhanam Reviewer #3: No Reviewer #4: Yes: Lei Chen Reviewer #5: No ******** https://doi.org/10.1371/journal.pone.0326543.r003
Formally Accepted
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