Reviewer’ s report
Title: The relationship between preoperative T helper cytokines in the ileal mucosa and the
pathogenesis of pouchitis
Version: 2Date: 29 Mar 2020
Reviewer: Zaid Ardalan
Reviewer's report:
Abstract: You write mRNA at the beginning of the sentence . I would recommend not starting
sentences with abbreviations. This should apply on other parts of the manuscript which start witham abbreviation.
Background:Page 2 line 18 Cytokine profiles in the colonic mucosa have been well-described in experimental
colitis models or IBD patients. Unnecessary. Adds nothing. This paragraph should be dedicated tothe role cytokines play in the pathogenesis of pouchitis.
In Methods:
Under patients and specimens-line 116: The 115 patients. Suggest deleting "the" and starting the sentence with 115 as a word.-Line 18 : what does poor quality of samples mean? Please clarify to ensure no selection bias.
Surgical procedures and diagnosis of pouchitis:
How was CD of the pouch confirmed? Distinguishing chronic antibiotic refractory pouchitis fromCrohn's disease can be difficult if the disease is not clearly stenosing, fistulising and with nogranulomas.
Statistical analysis
Results were expressed as the median values . Remove the "the"Comparisons were performed using the non parametric. Remove the "the"
Discussion :
The second paragraphThe aetiology of pouchitis is unknown...... It should rewritten to read better. For example, I wouldrecommend rewording "but so many different factors have been reported to
something like "Numerous risk factors have been identified". Furthermore, in all sentences where
you write "studies reported", I would recommend using the past perfect tense have reported.Lastly, If you want to keep influenced, I would suggest changing it to "other studies have reportedPSC, etc "to influence ". Also, I would assume the point of mentioning these risk factors is toclarify that in your cohort, the pouchitis and no pouchitis groups had no statistical difference in
these risk factors.This suggests that additional risk factors or aetiologic factors are needed to help
predict which patients are at risk of pouchitis. This also serves as a Segway to discussing the
significance of your finding.
Page 2 line 17: The paragraph that starts with "Traditionally" discusses the various immune
pathways in CD and UC and subsequently expands on the role Th17 and IL-23 have in IBDwithout linking this to IFN-γ, the positive association in the study. It therefore adds nothing and isnot pouch specific. Unless I have missed something, I see no reason for this paragraph here!
The paragraph which you use to support the role of IFN-y is broad lacks focus and most
importantly doesn't discuss the finding relevant to the topic of interest, which is predicting
pouchitis.
The whole discussion needs to change. When discussing risk factors or predicting factors for
pouchitis is important to accurately phenotype patients with pouchitis as acute antibiotic-responsive pouchitis is predominately microbially mediated in whereas chronic antibiotic-refractory pouchitis is predominately immune mediated, with antibiotic dependent pouchitis beingsomewhere in between. Moreover, patients with Crohn's disease of the pouch should also beincluded . Factors risking acute microbially mediated pouchitis may vary from those risking achronic immune mediated pouchitis. Going into your study, I was very interested to see whetherINF-γ predicted an immune mediated pouchitis early on. Furthermore, I was interested to see
whether any of the pouchitis patients who had low IFN-γ progressed from microbially mediated
pouchitis to immune mediated. Finally, should you indeed find a positive correlation betweenTNF-γ and immune mediated pouchitis and depending on the strength of such an association, it
would be good for you to suggest whether those who have a certain level should be counselledabout their risks of pouchitis to make an informed decision and whether they could be offeredprimary prophylaxis against pouchitis.
If you manage to answer these questions and discuss your findings in a way that reflects you
understand the current knowledge and unmet needs of pouchitis pathogenesis and pouchitis, Iwould be very interested in reading your work. You have good data, you just need to analyse it andpresent it in a better way and using better English.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
NoI agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding any attachments I upload will be posted on the website along with the authors'responses. I agree for my report to be made available under an Open Access Creative CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’ s report
Title: The relationship between preoperative T helper cytokines in the ileal mucosa and the
pathogenesis of pouchitis
Version: 2Date: 29 Mar 2020
Reviewer: Zaid Ardalan
Reviewer's report:
Abstract: You write mRNA at the beginning of the sentence . I would recommend not starting
sentences with abbreviations. This should apply on other parts of the manuscript which start witham abbreviation.
Background:Page 2 line 18 Cytokine profiles in the colonic mucosa have been well-described in experimental
colitis models or IBD patients. Unnecessary. Adds nothing. This paragraph should be dedicated tothe role cytokines play in the pathogenesis of pouchitis.
In Methods:
Under patients and specimens-line 116: The 115 patients. Suggest deleting "the" and starting the sentence with 115 as a word.-Line 18 : what does poor quality of samples mean? Please clarify to ensure no selection bias.
Surgical procedures and diagnosis of pouchitis:
How was CD of the pouch confirmed? Distinguishing chronic antibiotic refractory pouchitis fromCrohn's disease can be difficult if the disease is not clearly stenosing, fistulising and with nogranulomas.
Statistical analysis
Results were expressed as the median values . Remove the "the"Comparisons were performed using the non parametric. Remove the "the"
Discussion :
The second paragraphThe aetiology of pouchitis is unknown...... It should rewritten to read better. For example, I wouldrecommend rewording "but so many different factors have been reported to
something like "Numerous risk factors have been identified". Furthermore, in all sentences where
you write "studies reported", I would recommend using the past perfect tense have reported.Lastly, If you want to keep influenced, I would suggest changing it to "other studies have reportedPSC, etc "to influence ". Also, I would assume the point of mentioning these risk factors is toclarify that in your cohort, the pouchitis and no pouchitis groups had no statistical difference in
these risk factors.This suggests that additional risk factors or aetiologic factors are needed to help
predict which patients are at risk of pouchitis. This also serves as a Segway to discussing the
significance of your finding.
Page 2 line 17: The paragraph that starts with "Traditionally" discusses the various immune
pathways in CD and UC and subsequently expands on the role Th17 and IL-23 have in IBDwithout linking this to IFN-γ, the positive association in the study. It therefore adds nothing and isnot pouch specific. Unless I have missed something, I see no reason for this paragraph here!
The paragraph which you use to support the role of IFN-y is broad lacks focus and most
importantly doesn't discuss the finding relevant to the topic of interest, which is predicting
pouchitis.
The whole discussion needs to change. When discussing risk factors or predicting factors for
pouchitis is important to accurately phenotype patients with pouchitis as acute antibiotic-responsive pouchitis is predominately microbially mediated in whereas chronic antibiotic-refractory pouchitis is predominately immune mediated, with antibiotic dependent pouchitis beingsomewhere in between. Moreover, patients with Crohn's disease of the pouch should also beincluded . Factors risking acute microbially mediated pouchitis may vary from those risking achronic immune mediated pouchitis. Going into your study, I was very interested to see whetherINF-γ predicted an immune mediated pouchitis early on. Furthermore, I was interested to see
whether any of the pouchitis patients who had low IFN-γ progressed from microbially mediated
pouchitis to immune mediated. Finally, should you indeed find a positive correlation betweenTNF-γ and immune mediated pouchitis and depending on the strength of such an association, it
would be good for you to suggest whether those who have a certain level should be counselledabout their risks of pouchitis to make an informed decision and whether they could be offeredprimary prophylaxis against pouchitis.
If you manage to answer these questions and discuss your findings in a way that reflects you
understand the current knowledge and unmet needs of pouchitis pathogenesis and pouchitis, Iwould be very interested in reading your work. You have good data, you just need to analyse it andpresent it in a better way and using better English.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
NoI agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding any attachments I upload will be posted on the website along with the authors'responses. I agree for my report to be made available under an Open Access Creative CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Please review this paper.
user
Reviewer’ s report
Title: The relationship between preoperative T helper cytokines in the ileal mucosa and the
pathogenesis of pouchitis
Version: 2Date: 29 Mar 2020
Reviewer: Zaid Ardalan
Reviewer's report:
Abstract: You write mRNA at the beginning of the sentence . I would recommend not starting
sentences with abbreviations. This should apply on other parts of the manuscript which start witham abbreviation.
Background:Page 2 line 18 Cytokine profiles in the colonic mucosa have been well-described in experimental
colitis models or IBD patients. Unnecessary. Adds nothing. This paragraph should be dedicated tothe role cytokines play in the pathogenesis of pouchitis.
In Methods:
Under patients and specimens-line 116: The 115 patients. Suggest deleting "the" and starting the sentence with 115 as a word.-Line 18 : what does poor quality of samples mean? Please clarify to ensure no selection bias.
Surgical procedures and diagnosis of pouchitis:
How was CD of the pouch confirmed? Distinguishing chronic antibiotic refractory pouchitis fromCrohn's disease can be difficult if the disease is not clearly stenosing, fistulising and with nogranulomas.
Statistical analysis
Results were expressed as the median values . Remove the "the"Comparisons were performed using the non parametric. Remove the "the"
Discussion :
The second paragraphThe aetiology of pouchitis is unknown...... It should rewritten to read better. For example, I wouldrecommend rewording "but so many different factors have been reported to
something like "Numerous risk factors have been identified". Furthermore, in all sentences where
you write "studies reported", I would recommend using the past perfect tense have reported.Lastly, If you want to keep influenced, I would suggest changing it to "other studies have reportedPSC, etc "to influence ". Also, I would assume the point of mentioning these risk factors is toclarify that in your cohort, the pouchitis and no pouchitis groups had no statistical difference in
these risk factors.This suggests that additional risk factors or aetiologic factors are needed to help
predict which patients are at risk of pouchitis. This also serves as a Segway to discussing the
significance of your finding.
Page 2 line 17: The paragraph that starts with "Traditionally" discusses the various immune
pathways in CD and UC and subsequently expands on the role Th17 and IL-23 have in IBDwithout linking this to IFN-γ, the positive association in the study. It therefore adds nothing and isnot pouch specific. Unless I have missed something, I see no reason for this paragraph here!
The paragraph which you use to support the role of IFN-y is broad lacks focus and most
importantly doesn't discuss the finding relevant to the topic of interest, which is predicting
pouchitis.
The whole discussion needs to change. When discussing risk factors or predicting factors for
pouchitis is important to accurately phenotype patients with pouchitis as acute antibiotic-responsive pouchitis is predominately microbially mediated in whereas chronic antibiotic-refractory pouchitis is predominately immune mediated, with antibiotic dependent pouchitis beingsomewhere in between. Moreover, patients with Crohn's disease of the pouch should also beincluded . Factors risking acute microbially mediated pouchitis may vary from those risking achronic immune mediated pouchitis. Going into your study, I was very interested to see whetherINF-γ predicted an immune mediated pouchitis early on. Furthermore, I was interested to see
whether any of the pouchitis patients who had low IFN-γ progressed from microbially mediated
pouchitis to immune mediated. Finally, should you indeed find a positive correlation betweenTNF-γ and immune mediated pouchitis and depending on the strength of such an association, it
would be good for you to suggest whether those who have a certain level should be counselledabout their risks of pouchitis to make an informed decision and whether they could be offeredprimary prophylaxis against pouchitis.
If you manage to answer these questions and discuss your findings in a way that reflects you
understand the current knowledge and unmet needs of pouchitis pathogenesis and pouchitis, Iwould be very interested in reading your work. You have good data, you just need to analyse it andpresent it in a better way and using better English.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
NoI agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding any attachments I upload will be posted on the website along with the authors'responses. I agree for my report to be made available under an Open Access Creative CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant