Reviewer ’s report  
 
Title: Faecal Calprotectin Level f or Assessing Endoscopic Activity and Predicting Future Clinical  
Course in Patients with Moderately Active Ulcerative Colitis Undergoing 
Granulomonocytapheresis:  A Prospective Cohort Study  
 
Version: 1 Date: 25 Jun 2018  
 
Reviewer: Renata D'Inca  
 
Reviewer's repo rt: 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be  included in a text format.  
Please oLiterature about the reliability of fecal calprotectin is rapidly expanding in several settings 
of IBD field.  
GMA is a therapeutic option for the treatment of UC  patients, largely employed in Japan, less in 
Western coun tries where it is generally considered best suitable for mild to moderate disease 
activity.  
Literature about fecal calprotectin and GMA is lacking.  
The present study is well designed and conducted, especially because endoscopy was undertaken 
in all patient s. 
All patients had active disease at entry with a Mayo endoscopic subscore ≥2 (Mayo 0 -1 was 
considered as Mucosal Healing) and the median FC level at entry was 140 (52 -317) ug/g. This is 
a quite low value for at least endoscopically moderate disease and o ften reported in the FC 
literature as a level that could identify remission of the disease.  
Patients who achieved clinical remission and mucosal healing had even lower levels (99 and 59.5 
ug/g) at study entry. These values are incredibly low and generally used to discriminate healthy 
people from patients with GI symptoms, not often found in patients with known IBD in their active 
phase.  
Although there was a significant decrease in FC levels after GMA treatment, patients responding 
(remission and mucosal hea ling) were those with even lower levels of FC, therefore with milder 
disease. This behavior is different from the treatment with biologics, in which a fast and sharp 
decrease in FC levels has been demonstrated after induction regimens.  
Furthermore, PPV and  NPV are not that satisfying.  
In conclusion, the present work is clinically relevant and well conducted.  
However, results are not generalizable and somewhat in contrast with the knowledge acquired 
about FC and for sure need to be further validated.  
 
verwri te this text when adding your comments to the authors.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
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 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 am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
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, fund ing, 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 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, w rite 'I declare that I have no competing interests' below. 
If your reply is yes to any, please give details below.  
no 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
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 A ccess 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 confiden tial comments to the 
editors, which will not be published.  
I agree to the open pe er review policy of the journal  
Reviewer ’s report  
 
Title: Faecal Calprotectin Level f or Assessing Endoscopic Activity and Predicting Future Clinical  
Course in Patients with Moderately Active Ulcerative Colitis Undergoing 
Granulomonocytapheresis:  A Prospective Cohort Study  
 
Version: 1 Date: 25 Jun 2018  
 
Reviewer: Renata D'Inca  
 
Reviewer's repo rt: 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be  included in a text format.  
Please oLiterature about the reliability of fecal calprotectin is rapidly expanding in several settings 
of IBD field.  
GMA is a therapeutic option for the treatment of UC  patients, largely employed in Japan, less in 
Western coun tries where it is generally considered best suitable for mild to moderate disease 
activity.  
Literature about fecal calprotectin and GMA is lacking.  
The present study is well designed and conducted, especially because endoscopy was undertaken 
in all patient s. 
All patients had active disease at entry with a Mayo endoscopic subscore ≥2 (Mayo 0 -1 was 
considered as Mucosal Healing) and the median FC level at entry was 140 (52 -317) ug/g. This is 
a quite low value for at least endoscopically moderate disease and o ften reported in the FC 
literature as a level that could identify remission of the disease.  
Patients who achieved clinical remission and mucosal healing had even lower levels (99 and 59.5 
ug/g) at study entry. These values are incredibly low and generally used to discriminate healthy 
people from patients with GI symptoms, not often found in patients with known IBD in their active 
phase.  
Although there was a significant decrease in FC levels after GMA treatment, patients responding 
(remission and mucosal hea ling) were those with even lower levels of FC, therefore with milder 
disease. This behavior is different from the treatment with biologics, in which a fast and sharp 
decrease in FC levels has been demonstrated after induction regimens.  
Furthermore, PPV and  NPV are not that satisfying.  
In conclusion, the present work is clinically relevant and well conducted.  
However, results are not generalizable and somewhat in contrast with the knowledge acquired 
about FC and for sure need to be further validated.  
 
verwri te this text when adding your comments to the authors.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
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 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 am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
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, fund ing, 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 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, w rite 'I declare that I have no competing interests' below. 
If your reply is yes to any, please give details below.  
no 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
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 A ccess 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 confiden tial comments to the 
editors, which will not be published.  
I agree to the open pe er review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Faecal Calprotectin Level f or Assessing Endoscopic Activity and Predicting Future Clinical  
Course in Patients with Moderately Active Ulcerative Colitis Undergoing 
Granulomonocytapheresis:  A Prospective Cohort Study  
 
Version: 1 Date: 25 Jun 2018  
 
Reviewer: Renata D'Inca  
 
Reviewer's repo rt: 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be  included in a text format.  
Please oLiterature about the reliability of fecal calprotectin is rapidly expanding in several settings 
of IBD field.  
GMA is a therapeutic option for the treatment of UC  patients, largely employed in Japan, less in 
Western coun tries where it is generally considered best suitable for mild to moderate disease 
activity.  
Literature about fecal calprotectin and GMA is lacking.  
The present study is well designed and conducted, especially because endoscopy was undertaken 
in all patient s. 
All patients had active disease at entry with a Mayo endoscopic subscore ≥2 (Mayo 0 -1 was 
considered as Mucosal Healing) and the median FC level at entry was 140 (52 -317) ug/g. This is 
a quite low value for at least endoscopically moderate disease and o ften reported in the FC 
literature as a level that could identify remission of the disease.  
Patients who achieved clinical remission and mucosal healing had even lower levels (99 and 59.5 
ug/g) at study entry. These values are incredibly low and generally used to discriminate healthy 
people from patients with GI symptoms, not often found in patients with known IBD in their active 
phase.  
Although there was a significant decrease in FC levels after GMA treatment, patients responding 
(remission and mucosal hea ling) were those with even lower levels of FC, therefore with milder 
disease. This behavior is different from the treatment with biologics, in which a fast and sharp 
decrease in FC levels has been demonstrated after induction regimens.  
Furthermore, PPV and  NPV are not that satisfying.  
In conclusion, the present work is clinically relevant and well conducted.  
However, results are not generalizable and somewhat in contrast with the knowledge acquired 
about FC and for sure need to be further validated.  
 
verwri te this text when adding your comments to the authors.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
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 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 am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
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, fund ing, 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 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, w rite 'I declare that I have no competing interests' below. 
If your reply is yes to any, please give details below.  
no 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
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 A ccess 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 confiden tial comments to the 
editors, which will not be published.  
I agree to the open pe er review policy of the journal  
assistant