Reviewer ’s report  
 
Title: Association between acute gastrointestinal injury and biomarkers of intestinal barrier  
function in critically ill patients  
 
Version: 0 Date: 16 Jan 2017  
 
Reviewer: Madhusudan Grover  
 
Reviewer's report:  
 
Li et al have exam ined associations between acute GI injury and biomarkers of intestinal barrier 
function in critically ill patients (BMGE -D-16-00507). The hypothesis is well grounded and the 
paper is designed and presented nicely. I have few concerns:  
 
 
 
1. Differentiating pr imary vs secondary AGI. The footnote in Table 1 details this. However, 
the manuscript doesn't highlight how many of the AGI cases included were primary. I 
think it would be important to see if the 3 markers associate with AGI differently in 
primary vs seco ndary cases.  
 
 
 
2. Authors are calling i -FABP, D -la, and LPS as markers of "barrier function". I would be 
cautious in that interpretation. The i -FABP levels can rise in response to enterocyte loss. 
Enterocyte loss will have a secondary effect on barrier but i t's not a primary barrier 
function marker. Similarly, conditions that raise D -lactate levels can cause elevated 
plasma D -lactate even in the presence of an intact barrier.  
 
 
 
3. It would be better to show values on the 3 markers from 50 healthy volunteers in the 
main test instead of the appendix and compare those with patients with AGI.    
 
 
 
Minor comments:  
 
1. Background: Second paragraph (4th last line) - Not sure if these markers are specific to 
small bowel. 3rd last line: should be "AGI" instead of "AG".  
 
 
2. Methods: In "patient selection", it says..a diagnosis of AGI within 72 h after admission 
were included. But then in the bottom, you say, hospitalization for <72 hr before 
diagnosis of AGI were excluded. Which one is correct?  
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 contro ls 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.  
 
Yes 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of compe ting 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 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 you r 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 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: Association between acute gastrointestinal injury and biomarkers of intestinal barrier  
function in critically ill patients  
 
Version: 0 Date: 16 Jan 2017  
 
Reviewer: Madhusudan Grover  
 
Reviewer's report:  
 
Li et al have exam ined associations between acute GI injury and biomarkers of intestinal barrier 
function in critically ill patients (BMGE -D-16-00507). The hypothesis is well grounded and the 
paper is designed and presented nicely. I have few concerns:  
 
 
 
1. Differentiating pr imary vs secondary AGI. The footnote in Table 1 details this. However, 
the manuscript doesn't highlight how many of the AGI cases included were primary. I 
think it would be important to see if the 3 markers associate with AGI differently in 
primary vs seco ndary cases.  
 
 
 
2. Authors are calling i -FABP, D -la, and LPS as markers of "barrier function". I would be 
cautious in that interpretation. The i -FABP levels can rise in response to enterocyte loss. 
Enterocyte loss will have a secondary effect on barrier but i t's not a primary barrier 
function marker. Similarly, conditions that raise D -lactate levels can cause elevated 
plasma D -lactate even in the presence of an intact barrier.  
 
 
 
3. It would be better to show values on the 3 markers from 50 healthy volunteers in the 
main test instead of the appendix and compare those with patients with AGI.    
 
 
 
Minor comments:  
 
1. Background: Second paragraph (4th last line) - Not sure if these markers are specific to 
small bowel. 3rd last line: should be "AGI" instead of "AG".  
 
 
2. Methods: In "patient selection", it says..a diagnosis of AGI within 72 h after admission 
were included. But then in the bottom, you say, hospitalization for <72 hr before 
diagnosis of AGI were excluded. Which one is correct?  
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 contro ls 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.  
 
Yes 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of compe ting 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 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 you r 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 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: Association between acute gastrointestinal injury and biomarkers of intestinal barrier  
function in critically ill patients  
 
Version: 0 Date: 16 Jan 2017  
 
Reviewer: Madhusudan Grover  
 
Reviewer's report:  
 
Li et al have exam ined associations between acute GI injury and biomarkers of intestinal barrier 
function in critically ill patients (BMGE -D-16-00507). The hypothesis is well grounded and the 
paper is designed and presented nicely. I have few concerns:  
 
 
 
1. Differentiating pr imary vs secondary AGI. The footnote in Table 1 details this. However, 
the manuscript doesn't highlight how many of the AGI cases included were primary. I 
think it would be important to see if the 3 markers associate with AGI differently in 
primary vs seco ndary cases.  
 
 
 
2. Authors are calling i -FABP, D -la, and LPS as markers of "barrier function". I would be 
cautious in that interpretation. The i -FABP levels can rise in response to enterocyte loss. 
Enterocyte loss will have a secondary effect on barrier but i t's not a primary barrier 
function marker. Similarly, conditions that raise D -lactate levels can cause elevated 
plasma D -lactate even in the presence of an intact barrier.  
 
 
 
3. It would be better to show values on the 3 markers from 50 healthy volunteers in the 
main test instead of the appendix and compare those with patients with AGI.    
 
 
 
Minor comments:  
 
1. Background: Second paragraph (4th last line) - Not sure if these markers are specific to 
small bowel. 3rd last line: should be "AGI" instead of "AG".  
 
 
2. Methods: In "patient selection", it says..a diagnosis of AGI within 72 h after admission 
were included. But then in the bottom, you say, hospitalization for <72 hr before 
diagnosis of AGI were excluded. Which one is correct?  
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 contro ls 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.  
 
Yes 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of compe ting 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 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 you r 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 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