Reviewer ’s report  
 
Title: Imbalanced Mucosal Microcirculation in the Remission Stage of Ulcerative Colitis using 
Probe -based Confocal Laser Endomicroscopy  
 
Version: 0 Date: 20 Jan 2019  
 
Reviewer: John Gásdal Karstensen  
 
Reviewer's report:  
 
To the authors,  
 
It was a pleasure reading your paper. I find the topic very interesting; however, I have some 
comments and concerns that I would like to share with you.  
 
 
Major comments  
 
Abstract  
 
Please clarify the design of the study and state the primary endpoint. Was it retrospective or 
prospective?  
 
Please explain the word microcosomic. I have never met it before.  
 
The results section is very confusing. I had read it several times, and don´t understand the 
meaning. I suggest that you begin with a comparison between h ealthy controls and UC and then 
explain differences for UC patients.  
 
The English language is very poor. Please consider letting a native review the paper 
linguistically.  
Introduction  
 
The first sentence is quite difficult to understand. Again you might consider having a look at the 
language. Furthermore, the introduction is very long and you might want to sharpen it a bit.  
 
I suggest that you include some of the nice CLE papers that have already been looking at 
vascular structures in IBD:  
 
Assessment of Crohn's disease activity by confocal laser endomicroscopy.  
Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, Neurath MF, Mudter J.  
Inflamm Bowel Dis. 2012 Dec;18(12):2261 -9. doi: 10.1002/ibd.22907. Epub 2012 Feb 16.  
 
Confocal laser endomicrosc opy in ulcerative colitis: a longitudinal study of endomicroscopic 
changes and response to medical therapy (with videos).  
Karstensen JG, Săftoiu A, Brynskov J, Hendel J, Ciocalteu A, Klausen P, Klausen TW, Riis LB, 
Vilmann P.  
Gastrointest Endosc. 2016 Aug; 84(2):279 -286.e1. doi: 10.1016/j.gie.2016.01.069. Epub 2016 
Mar 2.  
 
Quantitative assessment of mucosal architecture using computer -based analysis of confocal laser 
endomicroscopy in inflammatory bowel diseases.  
Quénéhervé L, David G, Bourreille A, Hardouin JB, Rahmi G, Neunlist M, Brégeon J, Coron E.  
Gastrointest Endosc. 2018 Aug 16. pii: S0016 -5107(18)32925 -0. 
 
There are several more.  
 
 
Methods  
 
Please clearly state the design of the study. If it was prospective , please insert clinicaltrial.gov 
number and power calculation.  
 
When a t -test is applied, the different observations need to be independent. However, the 
measurements are from the same person. Please explain.  
 
How was recurrence registered? Any endoscopi c follow -up? 
 
Please clearly state how MDV, DSD etc. were defined.  
 
Any approval from the ethics committee?  
 
 
Results  
 
Please define the difference between Mayo 0 and the unaffected segments. Were the unaffected 
segments in UC patients or healthy controls ? 
 
 
Discussion  
 
The discussion is extremely long, when considering the limited amount of data presented in the 
results section. Please insert limitations of the study.  
 
 
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.  
 
Yes 
 
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 t he 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 wr itten 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 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 o f 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 no conflict of interest  
 
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 made 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 can 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: Imbalanced Mucosal Microcirculation in the Remission Stage of Ulcerative Colitis using 
Probe -based Confocal Laser Endomicroscopy  
 
Version: 0 Date: 20 Jan 2019  
 
Reviewer: John Gásdal Karstensen  
 
Reviewer's report:  
 
To the authors,  
 
It was a pleasure reading your paper. I find the topic very interesting; however, I have some 
comments and concerns that I would like to share with you.  
 
 
Major comments  
 
Abstract  
 
Please clarify the design of the study and state the primary endpoint. Was it retrospective or 
prospective?  
 
Please explain the word microcosomic. I have never met it before.  
 
The results section is very confusing. I had read it several times, and don´t understand the 
meaning. I suggest that you begin with a comparison between h ealthy controls and UC and then 
explain differences for UC patients.  
 
The English language is very poor. Please consider letting a native review the paper 
linguistically.  
Introduction  
 
The first sentence is quite difficult to understand. Again you might consider having a look at the 
language. Furthermore, the introduction is very long and you might want to sharpen it a bit.  
 
I suggest that you include some of the nice CLE papers that have already been looking at 
vascular structures in IBD:  
 
Assessment of Crohn's disease activity by confocal laser endomicroscopy.  
Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, Neurath MF, Mudter J.  
Inflamm Bowel Dis. 2012 Dec;18(12):2261 -9. doi: 10.1002/ibd.22907. Epub 2012 Feb 16.  
 
Confocal laser endomicrosc opy in ulcerative colitis: a longitudinal study of endomicroscopic 
changes and response to medical therapy (with videos).  
Karstensen JG, Săftoiu A, Brynskov J, Hendel J, Ciocalteu A, Klausen P, Klausen TW, Riis LB, 
Vilmann P.  
Gastrointest Endosc. 2016 Aug; 84(2):279 -286.e1. doi: 10.1016/j.gie.2016.01.069. Epub 2016 
Mar 2.  
 
Quantitative assessment of mucosal architecture using computer -based analysis of confocal laser 
endomicroscopy in inflammatory bowel diseases.  
Quénéhervé L, David G, Bourreille A, Hardouin JB, Rahmi G, Neunlist M, Brégeon J, Coron E.  
Gastrointest Endosc. 2018 Aug 16. pii: S0016 -5107(18)32925 -0. 
 
There are several more.  
 
 
Methods  
 
Please clearly state the design of the study. If it was prospective , please insert clinicaltrial.gov 
number and power calculation.  
 
When a t -test is applied, the different observations need to be independent. However, the 
measurements are from the same person. Please explain.  
 
How was recurrence registered? Any endoscopi c follow -up? 
 
Please clearly state how MDV, DSD etc. were defined.  
 
Any approval from the ethics committee?  
 
 
Results  
 
Please define the difference between Mayo 0 and the unaffected segments. Were the unaffected 
segments in UC patients or healthy controls ? 
 
 
Discussion  
 
The discussion is extremely long, when considering the limited amount of data presented in the 
results section. Please insert limitations of the study.  
 
 
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.  
 
Yes 
 
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 t he 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 wr itten 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 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 o f 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 no conflict of interest  
 
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 made 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 can 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: Imbalanced Mucosal Microcirculation in the Remission Stage of Ulcerative Colitis using 
Probe -based Confocal Laser Endomicroscopy  
 
Version: 0 Date: 20 Jan 2019  
 
Reviewer: John Gásdal Karstensen  
 
Reviewer's report:  
 
To the authors,  
 
It was a pleasure reading your paper. I find the topic very interesting; however, I have some 
comments and concerns that I would like to share with you.  
 
 
Major comments  
 
Abstract  
 
Please clarify the design of the study and state the primary endpoint. Was it retrospective or 
prospective?  
 
Please explain the word microcosomic. I have never met it before.  
 
The results section is very confusing. I had read it several times, and don´t understand the 
meaning. I suggest that you begin with a comparison between h ealthy controls and UC and then 
explain differences for UC patients.  
 
The English language is very poor. Please consider letting a native review the paper 
linguistically.  
Introduction  
 
The first sentence is quite difficult to understand. Again you might consider having a look at the 
language. Furthermore, the introduction is very long and you might want to sharpen it a bit.  
 
I suggest that you include some of the nice CLE papers that have already been looking at 
vascular structures in IBD:  
 
Assessment of Crohn's disease activity by confocal laser endomicroscopy.  
Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, Neurath MF, Mudter J.  
Inflamm Bowel Dis. 2012 Dec;18(12):2261 -9. doi: 10.1002/ibd.22907. Epub 2012 Feb 16.  
 
Confocal laser endomicrosc opy in ulcerative colitis: a longitudinal study of endomicroscopic 
changes and response to medical therapy (with videos).  
Karstensen JG, Săftoiu A, Brynskov J, Hendel J, Ciocalteu A, Klausen P, Klausen TW, Riis LB, 
Vilmann P.  
Gastrointest Endosc. 2016 Aug; 84(2):279 -286.e1. doi: 10.1016/j.gie.2016.01.069. Epub 2016 
Mar 2.  
 
Quantitative assessment of mucosal architecture using computer -based analysis of confocal laser 
endomicroscopy in inflammatory bowel diseases.  
Quénéhervé L, David G, Bourreille A, Hardouin JB, Rahmi G, Neunlist M, Brégeon J, Coron E.  
Gastrointest Endosc. 2018 Aug 16. pii: S0016 -5107(18)32925 -0. 
 
There are several more.  
 
 
Methods  
 
Please clearly state the design of the study. If it was prospective , please insert clinicaltrial.gov 
number and power calculation.  
 
When a t -test is applied, the different observations need to be independent. However, the 
measurements are from the same person. Please explain.  
 
How was recurrence registered? Any endoscopi c follow -up? 
 
Please clearly state how MDV, DSD etc. were defined.  
 
Any approval from the ethics committee?  
 
 
Results  
 
Please define the difference between Mayo 0 and the unaffected segments. Were the unaffected 
segments in UC patients or healthy controls ? 
 
 
Discussion  
 
The discussion is extremely long, when considering the limited amount of data presented in the 
results section. Please insert limitations of the study.  
 
 
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.  
 
Yes 
 
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 t he 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 wr itten 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 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 o f 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 no conflict of interest  
 
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 made 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 can 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