Diagnostic Value of Correlation Between Canine Chronic Enteropathy Clinical Activity Index (CCECAI) and Selected Hematological and Immunological Biomarkers in Dogs with Chronic Enteropathy: A Systematic Meta-Analysis
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDear Authors,
I really appreciate your tremendous effort you did for this meta-analysis in a very cutting-edge topic of canine chronic enteropathy, but for objective reasons, from my point of view, the manuscript, before to be accepted for publication, it must be re-write properly, because there already published a plethora of paper and studies.
Comments for author File: 
Comments.pdf
Author Response
Dear Professor,
Thank you very much for your effort to review our manuscript and for the reasonable comments. All of your comments were considered and addressed while revising the manuscript. We hope that all of our responses are satisfactory.
Comment
- The title is not really supported by the conclusion„ Diagnostic value of correlation between…”, „..CRP, PLR, and NLR were significantly associated with CCECAI..”; this review are just bringing together data from „11 studies”, and trying to match clinical indices(included in CCECAI) with CRP level, PLR, and NLR; this is in the best case a „correlation”(based on published data) not enough to predict a strong „ diagnostic value” please change the title accordingly
Response
Yes, the title was corrected to match the contents of the manuscript. Based on your recommendation and the recommendation of the second reviewer, the title was modified to mention the use of correlation for diagnosis.
Comment
- The aim of this review, lines 86-88 „ Therefore, the main objective of the present meta-analysis was to assess the credibility of CCECAI with hematological and immunological parameters for the diagnosis of CIE in dogs”, is this objective supported by your conclusions? Please provide additional proofs!
Response
Yes, according to your recommendations, the objectives were revised.
Comment
3.Key words: please keep just the most significant for this review, and exactly describing the content of review (Keywords: Biomarkers, CIE, Hematology, Inflammatory markers); what are the distinction between Biomarkers and inflammatory markers? What are the definition of biomarker?
Response
Yes, according to your recommendations, corrections were made.
Comment
- Please include the detailed description of CCECAI.
Response
Yes, done as recommended
Comment
- Please insert the paper published recently.
Response
Yes, two recent references were added to this manuscript
[1] Caulfield S, Priestnall SL, Lawson J, Kathrani A. Chronic inflammatory enteropathy without moderate to severe hypoalbuminemia: long-term outcome in 60 dogs. J Vet Intern Med. 2026;40.
[2] Heilmann RM, Jergens AE, Kathrani A, Allenspach K, Salavati Schmitz S, Priestnall SL, et al. ACVIM-endorsed statement: consensus statement and systematic review on guidelines for the diagnosis and treatment of chronic inflammatory enteropathy in dogs. J Vet Intern Med. 2026;40.
Comment
- In the Conclusions section, please emphasize what you concluded by this review, and the correlation mentioned in the title.
Response
Yes, the conclusion was revised to reflect the results of this review
Reviewer 2 Report
Comments and Suggestions for AuthorsDear authors,
Your manuscript entitled "Diagnostic value of correlation between Canine Chronic Enteropathy Clinical Activity Index (CCECAI) and selected hematological and immunological parameters in dogs with chronic enteropathy: A systematic meta-analysis is really interesting to develop the list of correlation parameters useful for obtaining evolution information related to the Canine Chronic Enteropathy Clinical Activity Index (CCECAI). But some aspects should be improved:
- The title is correct, but I suggest "Diagnostic Utility/Value of the Correlation Between the Canine Chronic Enteropathy Clinical Activity Index (CCECAI) and Selected Hematological and Immunological Markers: A Systematic Meta-Analysis in Dogs with Chronic Enteropathy. "Why diagnostic utility seems to be more clinically important, and markers instead of parameters because you used more in your manuscript (22 times versus times)
- The short summary should emphasize the most relevant findings and purposes, shouldn't it? It contains many values and advertisements of your work and findings. If you agree with this, make the necessary modification.
- The abstract doesn't contain the clear aim of the manuscript.
- The introduction mentioned that "Chronic inflammatory enteropathies (CIE) are a collection of diseases with an indefinite origin," and "Although confirmation of CIE depends mainly on histopathological examination [19, 20], histopathology results vary according to the stage of the disease. "So you can use this to support your work and obtain credibility for your meta-analysis. Also, that information gives me a lot of questions related to the absence of the absorption of the nutrients, and those can be used as corelation markers.
- The method used is transparent and clear from my point of view.
- Figure 1 should be placed next to the explications "3. Results / 3.1. Pooled Correlation."
- The conclusion section is according to your findings: prudent.
- The English is fine, and I believe that you used some words to avoid the increasing of the similarity percentage. "Indefinite origin//genetically liable individuals//to producing" - is the last one grammatically correct?
Author Response
Dear Professor,
Thank you very much for your effort to review our manuscript and for the reasonable comments. All of your comments were considered and addressed while revising the manuscript. We hope that all of our responses are satisfactory.
Comment
- The title is correct, but I suggest "Diagnostic Utility/Value of the Correlation Between the Canine Chronic Enteropathy Clinical Activity Index (CCECAI) and Selected Hematological and Immunological Markers: A Systematic Meta-Analysis in Dogs with Chronic Enteropathy. "Why diagnostic utility seems to be more clinically important, and markers instead of parameters because you used more in your manuscript (22 times versus times)
Response
Yes, your opinion is great, I have corrected the title as recommended
Comment
The short summary should emphasize the most relevant findings and purposes, shouldn't it? It contains many values and advertisements of your work and findings. If you agree with this, make the necessary modification.
Response
Yes, done as recommended
Comment
The abstract doesn't contain the clear aim of the manuscript.
Response
Clear aim was added to abstract
Comment
The introduction mentioned that "Chronic inflammatory enteropathies (CIE) are a collection of diseases with an indefinite origin," and "Although confirmation of CIE depends mainly on histopathological examination [19, 20], histopathology results vary according to the stage of the disease. "So you can use this to support your work and obtain credibility for your meta-analysis. Also, that information gives me a lot of questions related to the absence of the absorption of the nutrients, and those can be used as corelation markers.
Response
Yes, done as recommended
- The method used is transparent and clear from my point of view.
Comment
Figure 1 should be placed next to explications "3. Results / 3.1. Pooled Correlation."
Response
The figure place was kept avoiding interruption of results
Comment
The conclusion section is according to your findings: prudent.
Response
Yes, the conclusion was revised as recommended
Comment
The English is fine, and I believe that you used some words to avoid the increasing of the similarity percentage. "Indefinite origin//genetically liable individuals//to producing" - is the last one grammatically correct?
Response
The manuscript as a whole was revised according to your instructions
Reviewer 3 Report
Comments and Suggestions for AuthorsThe experimental design system, data is relatively detailed, the conclusion has certain innovativeness, the overall structure is complete, and it has potential for publication. However, in terms of language expression, logical coherence, citation of charts, and format standardization, further meticulous revision and improvement are still needed. The following are specific review comments and modification suggestions.
1. Follow the template of this journal's paper format and modify and standardize the paper format.
2. In the 49th line, the first letter of the keywords should be capitalized.
3. The reference number should be marked in the upper right corner of the citation and numbered according to the sequence of appearance.
4. In line 62, the bracket after "(clinical pathology" is redundant. In line 64, "CCECAI is an insufficient diagnostic marker because it is subjective and variable" should be corrected to "CCECAI is not an adequate diagnostic marker because it is subjective and variable." In line 74, "fecal protection" has a spelling error. In line 75, the abbreviation "neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, PLR" should be placed in parentheses. In line 79, "as rapid, reliable, safe, and fast" are synonymous and using them together appears repetitive. In line 81, "to producing a single" has a grammatical error. In line 87, "assess the credibility of CCECAI with" should check if the research purpose is to evaluate the credibility of CCECAI.
5. In line 92, the title is "Ethical approval" but the content does not mention ethical approval at all. In line 96, "Reference dogs" is not a standard academic term. In line 105, "Pub-Med" has no hyphen.
6. It is recommended to supplement information such as dog breed, age, weight, severity grading of the disease, and the score range of CCECAI.
7. In line 115, "Estimation of CRP level" is an incomplete sentence. In line 136, "evaluate the quality of the listed studies' quality" has repeated "quality... quality". In line 143, "I2" should use superscript. In line 147, "P-value equal to or less than 0.05 was considered an indicative of statistical significance." has a grammatical error.
8. In line 156, "Table 1 shows the complete data of the 11 studies included in the meta-analysis." Table 1 only shows 5 studies of CRP and does not display the data of all 11 studies. In line 169, "Where Pooled correlation:" is incomplete.
9. In line 176, "Heterogenicity" has a spelling error. In line 177, "estimate was 0.47" In Table 4, the random effect combined correlation coefficient of NLR is 0.41, and the PLR data is also inconsistent. Please check Table 4. 10. "191 lines from 0.22 0.19" has a formatting error. On line 294, "neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)" has already been defined, so there is no need to elaborate further here.
11. On line 339, "This implies that the effect of PLR may be somewhat inflated by small-study effects but is still clinically relevant." There is a grammar error. On line 345, "very influential" is an informal expression.
12. On line 362, "CRP demonstrated consistent findings across the studies, PLR showed moderate stability" has a grammar error.
13. It is suggested to add a sentence about the future research direction at the end.
14. [26] and [72] are the same literature. Please carefully check. [1] The name abbreviation format is incorrect. [6] The abbreviation of the journal name should be the full name of the journal, and the first letter of the real words should be capitalized and not italicized. There are cases of inconsistent capitalization in the titles, and they should all be capitalized at the beginning of the sentence.
Author Response
Dear Professor,
Thank you very much for your effort to review our manuscript and for the reasonable comments. All of your comments were considered and addressed while revising the manuscript. We hope that all of our responses are satisfactory.
Comment
- Follow the template of this journal's paper format and modify and standardize the paper format.
Response
Yes, done as recommended
Comment
- In the 49th line, the first letter of the keywords should be capitalized.
Response
Yes, done
The reference number should be marked in the upper right corner of the citation and numbered according to the sequence of appearance.
Response
We followed the instructions of the author
Comment
- In line 62, the bracket after "(clinical pathology" is redundant. In line 64, "CCECAI is an insufficient diagnostic marker because it is subjective and variable" should be corrected to "CCECAI is not an adequate diagnostic marker because it is subjective and variable." In line 74, "fecal protection" has a spelling error. In line 75, the abbreviation "neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, PLR" should be placed in parentheses. In line 79, "as rapid, reliable, safe, and fast" are synonymous and using them together appears repetitive. In line 81, "to producing a single" has a grammatical error. In line 87, "assess the credibility of CCECAI with" should check if the research purpose is to evaluate the credibility of CCECAI.
Response
Yes, all corrections were made as recommended
Comment
- In line 92, the title is "Ethical approval" but the content does not mention ethical approval at all. In line 96, "Reference dogs" is not a standard academic term. In line 105, "Pub-Med" has no hyphen.
Response
Corrections were made as directed
Comment
6. It is recommended to supplement information such as dog breed, age, weight, severity grading of the disease, and the score range of CCECAI.
Response
Yes, as there were variations in breed, age and wight with each study, our findings were supported by the reference which include all data
Comment
- In line 115, "Estimation of CRP level" is an incomplete sentence. In line 136, "evaluate the quality of the listed studies' quality" has repeated "quality... quality". In line 143, "I2" should use superscript. In line 147, "P-value equal to or less than 0.05 was considered an indicative of statistical significance." has a grammatical error.
Response
Yes, corrections were done
Comment
- In line 156, "Table 1 shows the complete data of the 11 studies included in the meta-analysis." Table 1 only shows 5 studies of CRP and does not display the data of all 11 studies. In line 169, "Where Pooled correlation:" is incomplete.
Response
Yes, this sentence was deleted because it makes confusion .
Comment
- In line 176, "Heterogenicity" has a spelling error. In line 177, "estimate was 0.47" In Table
4, the random effect combined correlation coefficient of NLR is 0.41, and the PLR data is also inconsistent. Please check Table 4.
Response
Yes, corrections were made
Comment
- "191 lines from 0.22 0.19" has a formatting error. On line 294, "neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)" has already been defined, so there is no need to elaborate further here.
Response
Done
Comment
- On line 339, "This implies that the effect of PLR may be somewhat inflated by small-study effects but is still clinically relevant." There is a grammar error. On line 345, "very influential" is an informal expression.
Response
Yes, revision was done
Comment
- On line 362, "CRP demonstrated consistent findings across the studies, PLR showed moderate stability" has a grammar error
Response
Corrections were made
Comment
- It is suggested to add a sentence about the future research direction at the end.
Response
Done
Comment
- [26] and [72] are the same literature. Please carefully check. [1] The name abbreviation format is incorrect. [6] The abbreviation of the journal name should be the full name of the journal, and the first letter of the real words should be capitalized and not italicized. There are cases of inconsistent capitalization in the titles, and they should all be capitalized at the beginning of the sentence.
Response
Yes, the correction was done as directed. Based on the author's guide, the journal abbreviations were added
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsDear Author,
I am happy with the deep revision you did for this Review, and really appreciate your tremendous effort to accurately revise this manuscript. The manuscript is ready to be accepted for publication.
Comments for author File: Comments.pdf
Author Response
Dear Professor,
Thank you very much for your effort to review our manuscript, and great appreciation for your valuable comments. All of the comments were addressed while revising the manuscript.
Comment
-A very „fine tuning” suggestion for title:
„Diagnostic value of correlation between canine chronic enteropathy clinical
activity index (CCECAI) and selected hematological and immunological
biomarkers in dogs with chronic enteropathy: A systematic meta-analysis”
Response
Done as recommended
Reviewer 2 Report
Comments and Suggestions for AuthorsDear authors,
I agree to your improvements.
Author Response
Dear professor,
Thank you very much for your effort in reviewing our manuscript, and for your valuable comments. We are happy as our responses were satisfactory to you
