A systematic review on the prognostic role of radiologically-proven sarcopenia on the clinical outcomes of patients with acute pancreatitis

Khang Duy Ricky Le; Harsh Patel; Emma Downie

doi:10.1371/journal.pone.0322409

Peer Review History

Original SubmissionAugust 2, 2024
2 Aug 2024 Author Response https://doi.org/10.1371/journal.pone.0322409.r001
29 Jan 2025 Decision Letter - James Wright, Editor PONE-D-24-32431A systematic review on clinical outcomes associated with radiologically-proven sarcopenia on patients with acute pancreatitis.PLOS ONE Dear Dr. Le, 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. I have explained why we have only one review of this manuscript below. Please primarily focus on the points I have made below that need to be corrected when you resubmit. You should also reflect on the comments by Reviewer 1 and expand the Discussion appropriately. Please submit your revised manuscript by Mar 15 2025 11:59PM. 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Please note that providing these underlying data is a requirement for publication in this journal, and if these data are not provided your manuscript might be rejected. Additional Editor Comments: We have had a very difficult time finding reviewers for this prognosis review of the effect of sarcopenia on adverse outcomes in patients with acute pancreatitis. Only 1 person out of over 40 people invited has provided a review. I think the difficulty is due to the fact that the question being asked is of little importance and interest. Despite that the review has some merit but will require significant improvements listed below. 1. This is a prognosis review and that must be reflected in the title and throughout. The authors appear not to appreciate this and refer to randomization etc. which are relevant to intervention reviews but are impossible for a prognosis review. 2. The authors imply in the background and throughout that the question of the effect of sarcopenia on mortality and other outcomes in chronic pancreatitis is answered with robust evidence. I do not accept that conclusion. The effect on mortality is based on one small short term trial. The actual evidence in chronic pancreatitis must be presented in detail so that readers can come to their own conclusions. As it is presented it is misleading and inaccurate. 3. The calculations of risk in Figures 2-6 are not done properly. You are attempting to estimate the degree to which sarcopenia increases the adverse outcomes compared to the absence of sarcopenia. The labels should reflect that such as increased with sarcopenia on the right and decreased with sarcopenia on the left. The number of events is high so using Risk ratio is more appropriate than odds ratio. Therefore numbers greater than 1 reflect poor prognosis and numbers less than one reflect the opposite. 4. The Figures 2-6 must include the outcome being measured. 5. Table 3. Including the Effect size without 95% CI is meaningless for a reader. It should be RR with 95% CI demonstrating that none are close to statistically significant. [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 ******** 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? 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Reviewer #1: 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: Dear Authors, this systematic review is very well performed, methodologically sound and clearly written. The issue of sarcopenia in AP is very interesting, since sarcopenia has been associated with poorer patients outcomes in various diseases and conditions. In the introduction part, I'd emphasize that Atlanta classification is not used to predict the severity of AP, but it's a classification system with clearly defined criteria for mild, moderate, and severe AP. There is very little data on the impact of sarcopenia on AP outcomes, and it is not clear whether sarcopenia is a cause or a consequence in patients with severe pancreatitis. The fact is that more than 25% of patients with AP have sarcopenia on admission. However, it would be very important to determine to what extent sarcopenia changes during hospitalisation and how the possible worsening of sarcopenia affects the outcome in AP. CT is a fairly reliable method for detecting sarcopenia, but it is very important to point out that CT in AP is very often not performed on admission of the patient, but only after a few days. The aforementioned period in severe AP can only worsen the sarcopenia compared to the period of the patient's admission to hospital or the onset of symptoms. There is also the question of the appropriateness of nutritional intervention in these patients. Most patients with AP, especially in retrospective analyses, actually have a mild to moderate form of the disease, and even when the authors state that the predicted severe forms of the disease are included in the study, a large proportion of these patients do not ultimately have severe AP. In these patients, sarcopenia is unlikely to have a significant impact on the outcome of the disease. It would also be good to include the presence of comorbidities in the data analysis, because other diseases, especially chronic diseases, can significantly influence the presence of sarcopenia and the outcome of AP. In addition to the limitations of your research already mentioned, I think the discussion should be expanded to include the above comments. ****** 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. 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Revision 1
13 Mar 2025 Author Response We thank the editor and reviewer for their time an expertise in improving our manuscript. We have judiciously attended to the comments provided and are pleased to submit a revised manuscript in line with the goals and expectations of PLOS One. Please find attached to this submission a revised manuscript with tracked changes in addition to revised figures 2-6 and additional supplementary tables (1 and 2). Below are our responses to the editor and reviewer comments which are provided verbatim for ease of orientation. Editor comments. "This is a prognosis review and that must be reflected in the title and throughout. The authors appear not to appreciate this and refer to randomization etc. which are relevant to intervention reviews but are impossible for a prognosis review.: We thank the editor for their comment. Indeed this is a systematic review on the prognostic impact of radiologically-proven sarcopenia in acute pancreatitis outcomes. We have amended our manuscript to account for this as suggested. "The authors imply in the background and throughout that the question of the effect of sarcopenia on mortality and other outcomes in chronic pancreatitis is answered with robust evidence. I do not accept that conclusion. The effect on mortality is based on one small short term trial. The actual evidence in chronic pancreatitis must be presented in detail so that readers can come to their own conclusions. As it is presented it is misleading and inaccurate." We thank the editor for their comments. We agree with this comment and have attended to the section of the discussion in question by improving the wording and supporting the statements made with the underlying evidence to provide the readership a clearer understanding of the underlying evidence in chronic pancreatitis patients. "The calculations of risk in Figures 2-6 are not done properly. You are attempting to estimate the degree to which sarcopenia increases the adverse outcomes compared to the absence of sarcopenia. The labels should reflect that such as increased with sarcopenia on the right and decreased with sarcopenia on the left. The number of events is high so using Risk ratio is more appropriate than odds ratio. Therefore, numbers greater than 1 reflect poor prognosis and numbers less than one reflect the opposite." We thank the editor for their feedback. We have attended to this statistical analysis and reporting as suggested. "The Figures 2-6 must include the outcome being measured." We thank the editor for their comment, we have amended the figure titles to reflect this and note that these figures 2-6 will be presented alongside the figure titles/legends to avoid any confusion about the outcome. "Table 3. Including the Effect size without 95% CI is meaningless for a reader. It should be RR with 95% CI demonstrating that none are close to statistically significant." We thank the editor for their comments. We have updated table 3 as suggested to incorporate these parameters. Reviewer comments "In the introduction part, I'd emphasize that Atlanta classification is not used to predict the severity of AP, but it's a classification system with clearly defined criteria for mild, moderate, and severe AP." We thank the reviewer for their comment. We agree with this and have therefore amended the introduction to reflect this. "There is very little data on the impact of sarcopenia on AP outcomes, and it is not clear whether sarcopenia is a cause or a consequence in patients with severe pancreatitis. The fact is that more than 25% of patients with AP have sarcopenia on admission. However, it would be very important to determine to what extent sarcopenia changes during hospitalisation and how the possible worsening of sarcopenia affects the outcome in AP." We thank the reviewer for their feedback and for raising this important and clinically relevant research question. The fact of the matter is that of the included studies, only 1 explored the temporal impact of body composition changes on acute pancreatitis, and this was in the necrotising pancreatitis cohort. Essentially, the purpose of this systematic review and the remaining studies were to identify sarcopenia at start of admission as a prognostic indicator of outcomes. Therefore, the question about temporal changes in sarcopenia/degree of sarcopenia, particularly with severe cases of acute pancreatitis remains underexplored. We have incorporated comments related to this in the discussion and highlight this as a gap in the literature. "CT is a fairly reliable method for detecting sarcopenia, but it is very important to point out that CT in AP is very often not performed on admission of the patient, but only after a few days. The aforementioned period in severe AP can only worsen the sarcopenia compared to the period of the patient's admission to hospital or the onset of symptoms." We thank the reviewer for this comment which aligns very closely with the aforementioned comment on sarcopenia and body composition change during admission. We have attended to this by considering the impact of this variable into the discussion. "There is also the question of the appropriateness of nutritional intervention in these patients." We thank the reviewer for their comment. Nutritional interventions remains an area of ongoing research however it is an important consideration. As suggested, comments related to this have been incorporated into the discussion. "Most patients with AP, especially in retrospective analyses, actually have a mild to moderate form of the disease, and even when the authors state that the predicted severe forms of the disease are included in the study, a large proportion of these patients do not ultimately have severe AP. In these patients, sarcopenia is unlikely to have a significant impact on the outcome of the disease." We thank the reviewer for their comment. We agree that this is the case and therefore have included comments about the study population and the severity of disease, particularly in relation to subgroup analyses and our inability to do this due to the limitations in data. "It would also be good to include the presence of comorbidities in the data analysis, because other diseases, especially chronic diseases, can significantly influence the presence of sarcopenia and the outcome of AP. In addition to the limitations of your research already mentioned, I think the discussion should be expanded to include the above comments." We thank the reviewer for their comment. We agree the presence of comorbidities can also influence the development of sarcopenia. We note however that these comorbidities were underreported in the literature and therefore have raised this as a limitation of this underlying evidence. https://doi.org/10.1371/journal.pone.0322409.r003
21 Mar 2025 Decision Letter - James Wright, Editor A systematic review on the prognostic role of radiologically-proven sarcopenia on clinical outcomes of patients with acute pancreatitis. PONE-D-24-32431R1 Dear Dr. Le, 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, James M Wright Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0322409.r004
Formally Accepted
Acceptance Letter - James Wright, Editor PONE-D-24-32431R1 PLOS ONE Dear Dr. Le, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. 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 Professor James M Wright Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0322409.r005

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