Reviewer ’s report  
 
Title: Complications of Enterotomy and Related Risk Factor A nalysis of Very Early Onset  
Inflammatory Bowel Disease with Interleukin -10 Signalling Deficiency: A Single -Centre  
Retrospective Analysis  
 
Version: 2 Date: 01 Oct 2019  
 
Reviewer: Mikihiro Inoue  
 
Reviewer's report:  
 
This paper described a study about enterotomy characteristics, postoperative complications and 
related risk factors in patients with IL -10 signalling pathway deficiency. Although the patients 
with IL -10 signalling pathway deficiency often need surgical tre atment, where to position the 
operations in the treatment strategy of this monogenic disorder has not been established. This is 
the first study that focused on the surgical treatment for VEOIBD with IL -10 gene mutations and 
the authors found suggestive res ults. This study is worth for publishing after re -evaluation if the 
authors respond to the following comments and questions.  
 
 
 
Major comments  
 
1. Though I have no objection to the benefit of enterostomy in patients with IL -10 signalling 
pathway deficiency, h igh incidence of postoperative complication and extremely high mortality 
rate after emergency surgery due to severe infection and/or malnutrition are very importamt 
issue. This monogenic disorder itself might be responsible for these problems. But, there i s room 
for reconsidering timing of operation and surgical procedure for preventing complications. 
Importance of elective surgery should be further emphasized. Prophylactic enterostomy in an 
earlier stage may be indicated in some cases. Are there any predic tive factors about needs for 
surgery in comparison between the patients with and without enterostomy? To prevent incisional 
or peristomal complications, laparoscopic surgery might be one of the options of procedures. 
Stoma construction apart from the prima ry incision may also work for reduction of 
complications. I recommend the authors to discuss about more detailed surgical strategy 
including indication, timing and procedures.  
 
 
2. Are there any patients who underwent laparotomy or laparoscopic surgery witho ut 
enterostomy and were not enrolled in this study? If such patients exists, the study including all 
patients undergoing abdominal surgery, not only enterostomy, would be more informative.  
 
 
3. I wonder why the authors selected CRP and albumin as the baromet ers for efficacy of 
enterostomy. A decrease in CRP and an increase in albumin after operation are not surprise, 
because  many patients with intestinal perforation or obstruction were enrolled in this study.  
Minor comments  
 
1. Authors should change the term  "enterotomy" to "enterostomy".  
 
 
2. I recommend the authors to add the IRB approval number.  
 
 
3. Why the authors selected enterostomy in the patients with intestinal stenosis instead of 
anastomosis?  
 
 
4. As for HSCT, are 10 patients described in Table 1 and 7 p atients described in Follow -Up 
section overwrapped? Or, 10 patients in Table 1 have received HSCT preoperatively and 7 
patients n Follow -Up section have undergone HSCT after operation.  
 
 
5. In Fig. 2E, the data item "Pro" should be changed to "Post".  
 
 
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.  
 
No 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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:  
 
Accep table  
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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer revi ew policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Complications of Enterotomy and Related Risk Factor A nalysis of Very Early Onset  
Inflammatory Bowel Disease with Interleukin -10 Signalling Deficiency: A Single -Centre  
Retrospective Analysis  
 
Version: 2 Date: 01 Oct 2019  
 
Reviewer: Mikihiro Inoue  
 
Reviewer's report:  
 
This paper described a study about enterotomy characteristics, postoperative complications and 
related risk factors in patients with IL -10 signalling pathway deficiency. Although the patients 
with IL -10 signalling pathway deficiency often need surgical tre atment, where to position the 
operations in the treatment strategy of this monogenic disorder has not been established. This is 
the first study that focused on the surgical treatment for VEOIBD with IL -10 gene mutations and 
the authors found suggestive res ults. This study is worth for publishing after re -evaluation if the 
authors respond to the following comments and questions.  
 
 
 
Major comments  
 
1. Though I have no objection to the benefit of enterostomy in patients with IL -10 signalling 
pathway deficiency, h igh incidence of postoperative complication and extremely high mortality 
rate after emergency surgery due to severe infection and/or malnutrition are very importamt 
issue. This monogenic disorder itself might be responsible for these problems. But, there i s room 
for reconsidering timing of operation and surgical procedure for preventing complications. 
Importance of elective surgery should be further emphasized. Prophylactic enterostomy in an 
earlier stage may be indicated in some cases. Are there any predic tive factors about needs for 
surgery in comparison between the patients with and without enterostomy? To prevent incisional 
or peristomal complications, laparoscopic surgery might be one of the options of procedures. 
Stoma construction apart from the prima ry incision may also work for reduction of 
complications. I recommend the authors to discuss about more detailed surgical strategy 
including indication, timing and procedures.  
 
 
2. Are there any patients who underwent laparotomy or laparoscopic surgery witho ut 
enterostomy and were not enrolled in this study? If such patients exists, the study including all 
patients undergoing abdominal surgery, not only enterostomy, would be more informative.  
 
 
3. I wonder why the authors selected CRP and albumin as the baromet ers for efficacy of 
enterostomy. A decrease in CRP and an increase in albumin after operation are not surprise, 
because  many patients with intestinal perforation or obstruction were enrolled in this study.  
Minor comments  
 
1. Authors should change the term  "enterotomy" to "enterostomy".  
 
 
2. I recommend the authors to add the IRB approval number.  
 
 
3. Why the authors selected enterostomy in the patients with intestinal stenosis instead of 
anastomosis?  
 
 
4. As for HSCT, are 10 patients described in Table 1 and 7 p atients described in Follow -Up 
section overwrapped? Or, 10 patients in Table 1 have received HSCT preoperatively and 7 
patients n Follow -Up section have undergone HSCT after operation.  
 
 
5. In Fig. 2E, the data item "Pro" should be changed to "Post".  
 
 
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.  
 
No 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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:  
 
Accep table  
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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer revi ew policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 editor s, 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: Complications of Enterotomy and Related Risk Factor A nalysis of Very Early Onset  
Inflammatory Bowel Disease with Interleukin -10 Signalling Deficiency: A Single -Centre  
Retrospective Analysis  
 
Version: 2 Date: 01 Oct 2019  
 
Reviewer: Mikihiro Inoue  
 
Reviewer's report:  
 
This paper described a study about enterotomy characteristics, postoperative complications and 
related risk factors in patients with IL -10 signalling pathway deficiency. Although the patients 
with IL -10 signalling pathway deficiency often need surgical tre atment, where to position the 
operations in the treatment strategy of this monogenic disorder has not been established. This is 
the first study that focused on the surgical treatment for VEOIBD with IL -10 gene mutations and 
the authors found suggestive res ults. This study is worth for publishing after re -evaluation if the 
authors respond to the following comments and questions.  
 
 
 
Major comments  
 
1. Though I have no objection to the benefit of enterostomy in patients with IL -10 signalling 
pathway deficiency, h igh incidence of postoperative complication and extremely high mortality 
rate after emergency surgery due to severe infection and/or malnutrition are very importamt 
issue. This monogenic disorder itself might be responsible for these problems. But, there i s room 
for reconsidering timing of operation and surgical procedure for preventing complications. 
Importance of elective surgery should be further emphasized. Prophylactic enterostomy in an 
earlier stage may be indicated in some cases. Are there any predic tive factors about needs for 
surgery in comparison between the patients with and without enterostomy? To prevent incisional 
or peristomal complications, laparoscopic surgery might be one of the options of procedures. 
Stoma construction apart from the prima ry incision may also work for reduction of 
complications. I recommend the authors to discuss about more detailed surgical strategy 
including indication, timing and procedures.  
 
 
2. Are there any patients who underwent laparotomy or laparoscopic surgery witho ut 
enterostomy and were not enrolled in this study? If such patients exists, the study including all 
patients undergoing abdominal surgery, not only enterostomy, would be more informative.  
 
 
3. I wonder why the authors selected CRP and albumin as the baromet ers for efficacy of 
enterostomy. A decrease in CRP and an increase in albumin after operation are not surprise, 
because  many patients with intestinal perforation or obstruction were enrolled in this study.  
Minor comments  
 
1. Authors should change the term  "enterotomy" to "enterostomy".  
 
 
2. I recommend the authors to add the IRB approval number.  
 
 
3. Why the authors selected enterostomy in the patients with intestinal stenosis instead of 
anastomosis?  
 
 
4. As for HSCT, are 10 patients described in Table 1 and 7 p atients described in Follow -Up 
section overwrapped? Or, 10 patients in Table 1 have received HSCT preoperatively and 7 
patients n Follow -Up section have undergone HSCT after operation.  
 
 
5. In Fig. 2E, the data item "Pro" should be changed to "Post".  
 
 
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.  
 
No 
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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:  
 
Accep table  
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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer revi ew policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant