Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia

Min-I. Su; Cheng-Wei Liu

doi:10.1371/journal.pone.0252030

Peer Review History

Original SubmissionApril 5, 2021
29 Apr 2021 Decision Letter - Timir Paul, Editor PONE-D-21-11099 Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia PLOS ONE Dear Dr. Liu, 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. Editor's comments: Overall well written manuscript, 5 years data, overall low sample size due to CLI. Please address following comments: - low extremity artery disease (LEAD)- would be lower extremity not low extremity. -Please expand the clinical utility of this results, How we prevent mortality in CLI patients after checking NLR? - although the strengths and limitations have been mentioned I suggest to write all limitations in one paragraph Please submit your revised manuscript by May 30th. 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: 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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Also, would like to know if there was any other medical problems that cofound or affect the ratio ? ****** 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 [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". 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Revision 1
5 May 2021 Author Response Editor's comments: Overall well written manuscript, 5 years data, overall low sample size due to CLI. Please address following comments: - low extremity artery disease (LEAD)- would be lower extremity not low extremity. Response to the editor: We replaced "low extremity" with "lower extremity" (page 4, line 60.) Thanks for the editor's comment. -Please expand the clinical utility of this results, How we prevent mortality in CLI patients after checking NLR? Response to the editor: The CLI patients had high mortality, and an NLR ratio can be used as a simple predictor of all-cause mortality independent of the Rutherford stages and the presence of acute limb ischemia. Therefore, we think that the patients with NLR < 8 should receive aggressive endovascular treatment, even catheter-directed thrombolysis, to improve survival probability and limb salvage. On the contrary, the patient with NLR ≥ 8 undergoing percutaneous transluminal angioplasty still had high mortality due to inflammation and sepsis, although they received advanced antibiotic treatment and wound debridement. In this condition, surgical intervention such as bypass surgery or amputation might be the other therapeutic choice for patients with NLR ≥ 8. We added this paragraph in the first paragraph of the discussions. (page 20, line 198-206) - although the strengths and limitations have been mentioned I suggest to write all limitations in one paragraph Response to the editor: We combined the limitations into one paragraph as the editor's comment, including "A weakness of our study……" (page 22 line 240) and "another limitation……" (page 24 line 272). Reviewer #1: (1)Very nice article and focus on important aspect of cardiology. I would like to know more about the NLR measurement, is it the first CBC or is it the hospitalization count average, pre and post intervention, follow up NLR ? Response to reviewer #1: Thanks for the review's appreciation. We measured complete blood count and white blood cell differential at our emergency department before the patients received percutaneous transluminal angioplasty. We added a sentence in the second paragraph of the method section. "We measured complete blood count and white blood cell differential at our emergency department before the patients received percutaneous transluminal angioplasty." (page 5 line80-81) Reviewer #1: (2) ... did the authors depend on just the initial NLR for their study. Also, would like to know if there was any other medical problems that cofound or affect the ratio ? Response to reviewer #1: As we described from page 19, line 183 to page 20, line 190, "The percentage of white blood cells accounted for by neutrophils increases as the immune response activates against bacterial infection in CLI patients with sepsis; a higher neutrophil ratio indicates a stronger inflammatory response and is associated with a poor prognosis in patients with LEAD [15]. Lymphocytes play a role in adaptive immunity, and a lower lymphocyte ratio was found to indicate a lower survival probability in previous studies of patients with sepsis [16]. In our study, patients with a lower lymphocytes ratio were relatively immunocompromised and predisposed to all-cause mortality resulting from CLI-induced sepsis." Therefore, inflammatory response induced by both sepsis and atherosclerotic plaques can increase neutrophil counts. Besides, the patients with severe stresses such as cardiogenic shock or heart failure would have elevated NLR. We added a sentence in the first paragraph of the discussions. "The patients with severe physiologic stresses such as cardiogenic shock or heart failure would have elevated NLR." (page 20 line 191-193) Attachments Attachment Submitted filename: Response to the editor and reviewer.docx https://doi.org/10.1371/journal.pone.0252030.r002
10 May 2021 Decision Letter - Timir Paul, Editor Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia PONE-D-21-11099R1 Dear Dr. Liu, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Timir Paul Academic Editor PLOS ONE Additional Editor Comments (optional): All comments were appropriately addressed. Reviewers' comments: https://doi.org/10.1371/journal.pone.0252030.r003
Formally Accepted
17 May 2021 Acceptance Letter - Timir Paul, Editor PONE-D-21-11099R1 Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia Dear Dr. Liu: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Timir Paul Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0252030.r004

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