Frailty trajectory and its associated factors in older patients undergoing abdominal surgery involving the digestive system: A longitudinal study

Jing Guo; Wenshuang Wang; Xiaoxue Zhang; Yulin Zheng; Xinran Wang

doi:10.1371/journal.pone.0330093

Peer Review History

Original SubmissionMarch 17, 2025
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Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF.--> Additional Editor Comments: The authors need to justify their methodology and presentation of results given table subheadings are often unclear. The decision to define older patients as > 60 years rather than the traditional WHO or UN definition needs to be discussed. Reviewers have also raised concerns regarding internal consistency and the multivariate models which need addressing. [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 Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: I Don't Know Reviewer #2: No ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: Reviewer Comments General Comments This study presents a highly original and clinically relevant analysis of dynamic changes in frailty status among older adults undergoing abdominal surgery. The use of latent class growth modeling (LCGM) to classify postoperative frailty trajectories is novel and valuable. Identifying four distinct frailty patterns provides meaningful insight that may support tailored perioperative care strategies. The authors are to be commended for addressing this important and underexplored topic. However, there are several methodological and presentation-related issues that need to be addressed to improve the clarity, clinical applicability, and transparency of the study. Major Concerns 1. Study Population Age Definition (Why ≥60 years?) The rationale for setting the inclusion criterion at age 60 rather than the more commonly used threshold of 65 years is unclear. A justification should be provided, especially given that frailty-related literature often focuses on populations ≥65 years. 2. Albumin and Other Nutritional Markers The study discusses nutritional status, yet serum albumin, total protein, and prealbumin—commonly used clinical markers—are not included as explanatory variables. Were these data unavailable, or were they excluded for another reason? Please clarify. 3. Surgical Approach Misrepresentation Table 1 lists “laparoscopy: 100%, laparotomy: 0%,” which is inconsistent with the types of procedures included (e.g., gastrectomy, pancreaticoduodenectomy), many of which are still commonly performed via open surgery. This discrepancy must be clarified. Actual surgical approach data (laparoscopic vs open) should be accurately reported. 4. Poor Table Design and Lack of Definitions Many of the tables are difficult to interpret. Variable names are inconsistently labeled or undefined (e.g., “income,” “gastric tube”). Some variables appear more than once (e.g., “preoperative gastric tube”), and the definitions of categorical cutoffs (e.g., “bed time,” “drainage”) are not provided. Without clear definitions, clinical interpretation is impaired. Please reformat the tables for clarity and include a variable definitions table or footnotes. Minor Concerns 1. Placement of Table 3 (Model Fitting Table) Table 3 presents technical statistics (AIC, BIC, entropy, BLRT) that may not be accessible or meaningful to general surgical readers. Since it does not contribute directly to the clinical narrative, I suggest moving Table 3 to the supplementary material and focusing the main text on clinically interpretable content such as Figure 2–5. 2. “One in Ten” Rule in Multivariable Models The multivariable analyses shown in Figures 3–5 include many predictors relative to the group sizes (e.g., 9 predictors in the improvement group with only 21 patients). This may violate the "one-in-ten rule" and lead to overfitting. The authors should clarify how variables were selected and consider model simplification or penalized regression techniques if appropriate. 3. Typographical and Formatting Issues There are minor inconsistencies in table formatting (e.g., alignment, repeated rows) that reduce readability and should be addressed during revision. Reviewer #2:** Dear Editor, This article explores the trajectory and influencing factors of frailty in patients undergoing gastrointestinal surgery, with a particular focus on the effects of BMI, Charlson comorbidity index score, type of surgery, intraoperative drainage tube retention time, first time to get out of bed after surgery, the time of the first oral feed after surgery, postoperative complications, mobility, nutritional risk, and anxiety on postoperative frailty. This study provides a contribution to the literature on this topic, offering detailed data and short-term follow-up of a population that has been digestive tract surgery. However, I still have some questions and suggestions: 1. Whether or not chemotherapy is administered after surgery can significantly impact the manifestation of frailty, as certain chemotherapy drugs can adversely affect physical condition and lead to frailty. Why did the author fail to include chemotherapy as an associated factor? 2. The surgical spot will influence the timing of the first postoperative meal and the placement of a peritoneal drainage tube. In other words, there is multicollinearity among these three factors. If the authors include all three factors in the multivariate analysis simultaneously, it will lead to greater errors and increase the instability of parameter estimation. How do the authors explain or avoid this influence? 3. In Figs. 3 and 4, the OR value of ADL is less than 0, while that of NRS2002 and STAI is are greater than 0. In Fig. 5, the above three values are reversed, while other factors such as bed time and complications are all greater than 0. The authors should provide an explanation for these discrepancies in the discussion section. 4. Many of the data presented in the manuscript are inconsistent and confusing: 1) In table 1, the number of smokers, education level, monthly income, and CCI are not equal to the total number (155). 2) In Table 3, the BIC of four-category model is higher than that of three-category model, however the description indicates the opposite. 3) The content described in the results shows “There were 41 patients in class 3, accounting for 26.7% of the total.” However, in Table 2, the frailty was only 33 before surgery (T1). 4) The numbers for the "no frailty" and "frailty improvement" in Table 4 are inconsistent with those presented in the preceding text. Additionally, there is a typographical error in the male column* frailty improvement" in Table 4. Furthermore, there are problems with the data of BMIfrailty exacerbation, Agepersistent frailty, Drinking statusfrailty exacerbation, Habitation statusfrailty exacerbation, persistent frailty, frailty improvement, Education levelno frailty, Monthly incomepersistent frailty, frailty improvement. 5) The data of Surgical spot* frailty exacerbation, frailty improvement�Preoperative pain* frailty exacerbation, frailty improvement�Preoperative urinary catheter* persistent frailty�Postoperative complications* no frailty, persistent frailty in Table 5 are problematic. 6) In the results section, should the second line of the "Frailty trajectories" section have "table2" instead of "table3"? ******** 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: Shokei Matsumoto 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. https://doi.org/10.1371/journal.pone.0330093.r001
Revision 1
15 Jul 2025 Author Response Dear reviewer, Thank you very much for your comments and professional advice. These opinions help to lmprove academic rigor of our article Based on your suggestion and request,we have made corrected modifications on the revised manuscript. Meanwhile. The manuscript had be reviewed and edited by language services of AJE.We hope that our work can be improved again.Furthermore,we would like to show the details as follows: Reviewer #1: Reviewer Comments Major Concerns 1. Study Population Age Definition (Why ≥60 years?) The rationale for setting the inclusion criterion at age 60 rather than the more commonly used threshold of 65 years is unclear. A justification should be provided, especially given that frailty-related literature often focuses on populations ≥65 years. Response 1 The-author's answer:The reasons for setting the inclusion criteria for the study population at ≥60 years old are as follows: On the one hand, the WHO defines the age of elderly individuals in developing countries as ≥60 years, and China's definition and regulations for the elderly also specify ≥60 years; additionally, this study considers that frailty is a non-specific state in older adults characterized by increased physical vulnerability and reduced stress resistance due to decreased physiological reserve. Such individuals are more significantly affected by grade III and IV major surgeries and more likely to develop frailty. Therefore, the population was defined as ≥60 years old based on the above reasons. 2. Albumin and Other Nutritional Markers The study discusses nutritional status, yet serum albumin, total protein, and prealbumin—commonly used clinical markers—are not included as explanatory variables. Were these data unavailable, or were they excluded for another reason? Please clarify. Response 2 The-author's answer:In the discussion of nutritional status, this study only used the NRS 2002 scale, and commonly used clinical indicators (e.g., serum albumin, total protein, and prealbumin) were not included as explanatory variables. This is primarily due to limitations related to the study location and time: the hospital where the study was conducted did not require all surgical patients to undergo the laboratory tests required by the study between 2023 and 2024, resulting in the study being unable to accurately obtain relevant data for each patient. Therefore, after discussion by the research team, a professional scale for nutritional risk assessment was selected, which also constitutes one of the limitations of the study. Moving forward, we will also carry out multidisciplinary collaboration to further improve the in-depth analysis of nutritional status. 3. Surgical Approach Misrepresentation Table 1 lists “laparoscopy: 100%, laparotomy: 0%,” which is inconsistent with the types of procedures included (e.g., gastrectomy, pancreaticoduodenectomy), many of which are still commonly performed via open surgery. This discrepancy must be clarified. Actual surgical approach data (laparoscopic vs open) should be accurately reported. Response 3 The-author's answer: The We re-investigated the original medical records of the study participants to verify the surgical approach (laparotomy vs. laparoscopy), clarified the inaccurate data in the report, and made corrections (laparoscopy: 66.45% vs. laparotomy: 33.55%). 4. Poor Table Design and Lack of Definitions Many of the tables are difficult to interpret. Variable names are inconsistently labeled or undefined (e.g., “income,” “gastric tube”). Some variables appear more than once (e.g., “preoperative gastric tube”), and the definitions of categorical cutoffs (e.g., “bed time,” “drainage”) are not provided. Without clear definitions, clinical interpretation is impaired. Please reformat the tables for clarity and include a variable definitions table or footnotes. Response 4 The-author's answer:Thanks for your suggestion.However, We have rechecked data related to study participants and revised the table content, including standardizing variable names, clarifying their specific definitions, verifying the data, adding footnotes, and other adjustments. Details are presented in the table. And we hope the revised manuscript could be acceptable for you. Minor Concerns 1. Placement of Table 3 (Model Fitting Table) Table 3 presents technical statistics (AIC, BIC, entropy, BLRT) that may not be accessible or meaningful to general surgical readers. Since it does not contribute directly to the clinical narrative, I suggest moving Table 3 to the supplementary material and focusing the main text on clinically interpretable content such as Figure 2–5. The-author's answer:We think this is an excellent suggestion. We have adjusted the position of the table based on your suggestions, so that it is now presented as supplementary material. 2. “One in Ten” Rule in Multivariable Models The multivariable analyses shown in Figures 3–5 include many predictors relative to the group sizes (e.g., 9 predictors in the improvement group with only 21 patients). This may violate the "one-in-ten rule" and lead to overfitting. The authors should clarify how variables were selected and consider model simplification or penalized regression techniques if appropriate. The-author's answer:Thank you for your valuable suggestions. In the multivariate analysis, we incorporated the multivariate model analysis based on the results of the univariate analysis. This may violate the "one-in-ten rule" and lead to overfitting. After group discussion, simplifying the model might affect the conclusions of this study. Therefore, we plan to further include more study subjects, expand the sample size, and conduct in-depth analysis of the influencing factors in subsequent research. 3. Typographical and Formatting Issues There are minor inconsistencies in table formatting (e.g., alignment, repeated rows) that reduce readability and should be addressed during revision. The-author's answer:Thanks for your careful checks. We are sorry for our carelessness. Based on your comments, we have revised the typesetting and formatting issues, especially the tables. Reviewer #2: Dear Editor, 1.Whether or not chemotherapy is administered after surgery can significantly impact the manifestation of frailty, as certain chemotherapy drugs can adversely affect physical condition and lead to frailty. Why did the author fail to include chemotherapy as an associated factor? Response 1 The-author's answer:This study primarily focused on the impact of abdominal surgery-related factors on frailty in elderly patients, with a follow-up period extending to 1 month postoperatively. Although chemotherapy, as one of the adjuvant therapies for cancer patients, may lead to decline in physical function and frailty, it was not included in the primary analytical dimension after comprehensively considering its limited relevance to the research objective. 2.The surgical spot will influence the timing of the first postoperative meal and the placement of a peritoneal drainage tube. In other words, there is multicollinearity among these three factors. If the authors include all three factors in the multivariate analysis simultaneously, it will lead to greater errors and increase the instability of parameter estimation. How do the authors explain or avoid this influence? Response 2 The-author's answer:Before conducting multivariate logistic regression analysis, the study first performed univariate analysis on all variables (including surgical site, timing of the first postoperative meal, and placement of peritoneal drainage tube). Independent influencing factors were screened, and only variables with statistical significance (P<0.05) in the univariate analysis were included in the final multivariate model. This screening process effectively eliminates highly correlated variables, avoids simultaneously including factors with multicollinearity, and thereby reduces model errors and the instability of parameter estimation. Additionally, the surgical sites involved in this study included the gastrointestinal tract, hepatobiliary system, and pancreas. In the preliminary literature review, no significant evidence was found to confirm obvious multicollinearity among surgical site, timing of the first postoperative meal, and peritoneal drainage tube placement. Of course, we have deeply reflected on and discussed the issue raised by the expert. This aspect was not considered in the preliminary research, and we will conduct in-depth studies to further explore how to minimize such errors and enhance the stability of parameters. 3.In Figs. 3 and 4, the OR value of ADL is less than 0, while that of NRS2002 and STAI is are greater than 0. In Fig. 5, the above three values are reversed, while other factors such as bed time and complications are all greater than 0. The authors should provide an explanation for these discrepancies in the discussion section. Response 3 The-author's answer:Thank you for carefully reading the article and putting forward some valuable suggestions. In response to the issues you raised, we conducted a discussion among the research team and revised the errors. The details are as follows: The We re-reviewed the original data, conducted statistical analysis and statistical testing, and have revised the OR values in Figures 3 and 4: An OR value <1 indicates a protective factor for frailty status (worsening, persistence, improvement); an OR value >1 indicates an exposure factor, and supplementary explanations have been added in the discussion section. 4. Many of the data presented in the manuscript are inconsistent and confusing: 1) In table 1, the number of smokers, education level, monthly income, and CCI are not equal to the total number (155). 2) In Table 3, the BIC of four-category model is higher than that of three-category model, however the description indicates the opposite. 3) The content described in the results shows “There were 41 patients in class 3, accounting for 26.7% of the total.” However, in Table 2, the frailty was only 33 before surgery (T1). 4) The numbers for the "no frailty" and "frailty improvement" in Table 4 are inconsistent with those presented in the preceding text. Additionally, there is a typographical error in the male column* frailty improvement" in Table 4. Furthermore, there are problems with the data of BMIfrailty exacerbation, Agepersistent frailty, Drinking statusfrailty exacerbation, Habitation statusfrailty exacerbation, persistent frailty, frailty improvement, Education levelno frailty, Monthly incomepersistent frailty, frailty improvement. 5) The data of Surgical spot* frailty exacerbation, frailty improvement�Preoperative pain* frailty exacerbation, frailty improvement�Preoperative urinary catheter* persistent frailty�Postoperative complications* no frailty, persistent frailty in Table 5 are problematic. 6) In the results section, should the second line of the "Frailty trajectories" section have "table2" instead of "table3"? Response 4 The-author's answer:We were really sorry for our careless mistakes.Thank you for yourreminder. 1)We have re-reviewed the original data, revised the values of the number of smokers, education level, monthly income, and Charlson Comorbidity Index (CCI), 2)We have reconducted statistical calculations to adjust the Bayesian Information Criterion (BIC) value of the four-category model. 3)We re-analyzed and recalculated the original data of the study subjects and revised Data in Table 2. 4)Data in Table 4 have been revised. 5)Data in Table 5 have been revised. 6)Table 2 has been revised to Table 3 in "Frailty trajectories" section. Thank you very much for your attention and time.Look for ward to-hearing from you. Yours sincerely, Xinran Wang 2025.7.12 Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0330093.r002
27 Jul 2025 Decision Letter - Barry Kweh, Editor Frailty trajectory and its associated factors in older patients undergoing abdominal surgery involving the digestive system:A longitudinal study PONE-D-25-12651R1 Dear Dr. Wang, 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, Barry Kweh Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have clarified the difference between their univariate and multivariate analysis, updated their tables and provided a more nuanced discussion of the relevant literature. Reviewers' comments: https://doi.org/10.1371/journal.pone.0330093.r003
Formally Accepted
Acceptance Letter - Barry Kweh, Editor PONE-D-25-12651R1 PLOS ONE Dear Dr. Wang, 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. Barry Kweh Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0330093.r004

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