Reviewer ’s report  
 
Title:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 16 Feb 2017 
 
Reviewer:  Robert  Batat  
 
Reviewer’s report:  
 
This is an interesting, novel study assessing LL37 serum leve ls and IBD disease 
characteristics/outcomes.  
 
 
Abstract:  
 
Syntax/editing needed generally  
 
Also, claim to be attempting to determine if this marker reflects IBD disease development, which 
was not done in this study.  
 
 
Introduction  
 
Generally needs English editi ng. First sentence for example.  
 
Focus on strictures, but no mention of fistulas which carry significant morbidity in CD.  
 
This biomarker not elevated in CD but we are analyzing it?  
 
 
Methods:  
 
Objectives: should not be in point form  
 
Unclear why only aiming for intestinal stricture formation, especially if these can be either non 
inflammatory (fibrostenotic) or inflammatory. Also unclear why general disease phenotype is not 
analyzed. No mention of penetrating disease.  
 
LL37 as prognost ic factor, was therapy used/other variables controlled for?  
 
General editing: example: blood was collected for "healthy control" should read controls.  
 
Names of doctors collecting samples not needed  
Cohort 1: which center were they collected from.  
 
Unclear w hy 2 cohorts were used  
 
Inclusion criteria: IBD patients? Not stated.  
 
Clinical and Endoscopic scores: collected prospectively or retrospective, if the latter, then how 
were they scored.  
 
LL37 and CRP collection: At a one time visit with cross sectional c linical/endoscopic data 
collection? Unclear and not well described.  
 
Power analysis: calculated to determine differences between CD and UC but these were not the 
aims of the study.  
 
 
Results:  
 
What is mean LL37 levels in figure 1B and mean CRP in fig 1c (re mission/different disease 
activities)  
 
Figure 2: sensitivities/specificities should be mentioned in the text  
 
Page 9: Is the outcome clinical remission or steroid free clinical remission? Both should be 
analyzed. Furthermore, you should control for medicat ion use to avoid confounders. This should 
be done for both UC and CD  
 
Cutoffs for endoscopic scores (LL37 and CRP) along with AUC should be mentioned in text. 
This is an important point and specificities should be mentioned in text  
 
I believe the logic of clinical remission leading to strictures is flawed. Active disease predisposes 
to strictures. Therefore the clinical utility of combining clinical remission with low LL37 is 
questionable. Furthermore, it should be differentiated if t hese were considered fibrostenotic 
strictures or inflammatory strictures if possible.  
 
 
Conclusion: should not be point form  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments  to the authors.  
 
Unable to assess  
 
Are 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 further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality 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 this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain o r 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.  
 
I declare  that I have no competing interests  
 
I 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 report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be ma de available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report c an be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 16 Feb 2017 
 
Reviewer:  Robert  Batat  
 
Reviewer’s report:  
 
This is an interesting, novel study assessing LL37 serum leve ls and IBD disease 
characteristics/outcomes.  
 
 
Abstract:  
 
Syntax/editing needed generally  
 
Also, claim to be attempting to determine if this marker reflects IBD disease development, which 
was not done in this study.  
 
 
Introduction  
 
Generally needs English editi ng. First sentence for example.  
 
Focus on strictures, but no mention of fistulas which carry significant morbidity in CD.  
 
This biomarker not elevated in CD but we are analyzing it?  
 
 
Methods:  
 
Objectives: should not be in point form  
 
Unclear why only aiming for intestinal stricture formation, especially if these can be either non 
inflammatory (fibrostenotic) or inflammatory. Also unclear why general disease phenotype is not 
analyzed. No mention of penetrating disease.  
 
LL37 as prognost ic factor, was therapy used/other variables controlled for?  
 
General editing: example: blood was collected for "healthy control" should read controls.  
 
Names of doctors collecting samples not needed  
Cohort 1: which center were they collected from.  
 
Unclear w hy 2 cohorts were used  
 
Inclusion criteria: IBD patients? Not stated.  
 
Clinical and Endoscopic scores: collected prospectively or retrospective, if the latter, then how 
were they scored.  
 
LL37 and CRP collection: At a one time visit with cross sectional c linical/endoscopic data 
collection? Unclear and not well described.  
 
Power analysis: calculated to determine differences between CD and UC but these were not the 
aims of the study.  
 
 
Results:  
 
What is mean LL37 levels in figure 1B and mean CRP in fig 1c (re mission/different disease 
activities)  
 
Figure 2: sensitivities/specificities should be mentioned in the text  
 
Page 9: Is the outcome clinical remission or steroid free clinical remission? Both should be 
analyzed. Furthermore, you should control for medicat ion use to avoid confounders. This should 
be done for both UC and CD  
 
Cutoffs for endoscopic scores (LL37 and CRP) along with AUC should be mentioned in text. 
This is an important point and specificities should be mentioned in text  
 
I believe the logic of clinical remission leading to strictures is flawed. Active disease predisposes 
to strictures. Therefore the clinical utility of combining clinical remission with low LL37 is 
questionable. Furthermore, it should be differentiated if t hese were considered fibrostenotic 
strictures or inflammatory strictures if possible.  
 
 
Conclusion: should not be point form  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments  to the authors.  
 
Unable to assess  
 
Are 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 further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality 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 this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain o r 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.  
 
I declare  that I have no competing interests  
 
I 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 report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be ma de available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report c an be included as confidential comments 
to 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:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 16 Feb 2017 
 
Reviewer:  Robert  Batat  
 
Reviewer’s report:  
 
This is an interesting, novel study assessing LL37 serum leve ls and IBD disease 
characteristics/outcomes.  
 
 
Abstract:  
 
Syntax/editing needed generally  
 
Also, claim to be attempting to determine if this marker reflects IBD disease development, which 
was not done in this study.  
 
 
Introduction  
 
Generally needs English editi ng. First sentence for example.  
 
Focus on strictures, but no mention of fistulas which carry significant morbidity in CD.  
 
This biomarker not elevated in CD but we are analyzing it?  
 
 
Methods:  
 
Objectives: should not be in point form  
 
Unclear why only aiming for intestinal stricture formation, especially if these can be either non 
inflammatory (fibrostenotic) or inflammatory. Also unclear why general disease phenotype is not 
analyzed. No mention of penetrating disease.  
 
LL37 as prognost ic factor, was therapy used/other variables controlled for?  
 
General editing: example: blood was collected for "healthy control" should read controls.  
 
Names of doctors collecting samples not needed  
Cohort 1: which center were they collected from.  
 
Unclear w hy 2 cohorts were used  
 
Inclusion criteria: IBD patients? Not stated.  
 
Clinical and Endoscopic scores: collected prospectively or retrospective, if the latter, then how 
were they scored.  
 
LL37 and CRP collection: At a one time visit with cross sectional c linical/endoscopic data 
collection? Unclear and not well described.  
 
Power analysis: calculated to determine differences between CD and UC but these were not the 
aims of the study.  
 
 
Results:  
 
What is mean LL37 levels in figure 1B and mean CRP in fig 1c (re mission/different disease 
activities)  
 
Figure 2: sensitivities/specificities should be mentioned in the text  
 
Page 9: Is the outcome clinical remission or steroid free clinical remission? Both should be 
analyzed. Furthermore, you should control for medicat ion use to avoid confounders. This should 
be done for both UC and CD  
 
Cutoffs for endoscopic scores (LL37 and CRP) along with AUC should be mentioned in text. 
This is an important point and specificities should be mentioned in text  
 
I believe the logic of clinical remission leading to strictures is flawed. Active disease predisposes 
to strictures. Therefore the clinical utility of combining clinical remission with low LL37 is 
questionable. Furthermore, it should be differentiated if t hese were considered fibrostenotic 
strictures or inflammatory strictures if possible.  
 
 
Conclusion: should not be point form  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments  to the authors.  
 
Unable to assess  
 
Are 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 further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality 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 this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain o r 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.  
 
I declare  that I have no competing interests  
 
I 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 report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be ma de available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report c an be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant