Reviewer ’s report  
 
Title: Retrospective analysis of Clostridium difficile infection in patients with ulcerative colitis 
in a tertiary hospital in China  
 
Version: 3 Date: 12 Oct 2018  
 
Reviewer: Steven Lin  
 
Reviewer's report:  
 
In this single centered, retrospective case -controlled observational study by Xu et al, the authors 
seeked to assess the epidemiology and risk factors for CDI in patients with UC. This cohort 
looked specifically at patients that were hospitalized for a pre sumed flare and C. difficile toxin 
A/B (CDAB) were tested with 1:2 controls paired appropriately for gender, age. They found that 
recent use of antibiotics, prior hospitalization, and systemic use of steroids increased the risk of 
CDI, and that CMV infecti on was an independent risk factor for CDI. Overall, this study was 
simple and well -designed, with data carefully gathered to identify risk factors associated with 
active CDI. The major contributions of this study are adding to specific epidemiological data  
pertaining to CDI in UC patients in Beijing, though this is as the authors pointed out at a tertiary 
care center and with a sub -optimal c. difficile assay (lower sensitivity than the [overly] sensitive 
NAAT PCR, which has its own limitations as well). One  additional limitation to this study is the 
lack of CM detected on biopsies. Most of CMV infection were diagnosed on serologic testing. 
What was also omitted from the manuscript was details regarding endoscopic treatment. All that 
was reported was there we re more Mayo 3's in the CMV group. Details regarding how many of 
each group were actually endoscopically assessed and if biopsies were obtained.  
 
Another limitation inherent to the the study population is that most patients were on mesalamine 
therapy rath er than immunomodulatory or biologic therapy. A follow -up study could compare 
these patients to those on oral 5 -ASAs. A few other points:  
- Would use consistent epidemiology terms in the abstract, introduction, results, discussion, 
conclusions. the results  are not really providing us with an incidence rate of CDI in patients 
with UC flares and hospitalized  
 
- "The results demonstrate the difficulty in clinical differentiation of CDI from UC flare" - the 
results are not demonstrating this - this is a nuance a nd challenge of clinical care. rather, the 
results are characterizing risk factors associated with positive CDAB in this cohort and 
factors associated with recurrence.  
 
- Closer attention is needed to differentiate discussion section the following: CDI in UC 
patients in general, vs CDI in UC patients when they are flaring or symptomatic. Similarly, 
would be useful to more clearly compare and contrast briefly UC rates in China vs 
Europe/North America, and then discuss how CDI is different in UC patients in t hese groups  
 
- May want to address the fact 2 patients with recurrent CDI were treated with metronidazole, 
and whether vancomycin should be first line  
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:  
 
Needs some language corrections before  being published  
 
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 ma y 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 your reply is yes to any, please give details below.  
 
No to all of the above  
 
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 C reative 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: Retrospective analysis of Clostridium difficile infection in patients with ulcerative colitis 
in a tertiary hospital in China  
 
Version: 3 Date: 12 Oct 2018  
 
Reviewer: Steven Lin  
 
Reviewer's report:  
 
In this single centered, retrospective case -controlled observational study by Xu et al, the authors 
seeked to assess the epidemiology and risk factors for CDI in patients with UC. This cohort 
looked specifically at patients that were hospitalized for a pre sumed flare and C. difficile toxin 
A/B (CDAB) were tested with 1:2 controls paired appropriately for gender, age. They found that 
recent use of antibiotics, prior hospitalization, and systemic use of steroids increased the risk of 
CDI, and that CMV infecti on was an independent risk factor for CDI. Overall, this study was 
simple and well -designed, with data carefully gathered to identify risk factors associated with 
active CDI. The major contributions of this study are adding to specific epidemiological data  
pertaining to CDI in UC patients in Beijing, though this is as the authors pointed out at a tertiary 
care center and with a sub -optimal c. difficile assay (lower sensitivity than the [overly] sensitive 
NAAT PCR, which has its own limitations as well). One  additional limitation to this study is the 
lack of CM detected on biopsies. Most of CMV infection were diagnosed on serologic testing. 
What was also omitted from the manuscript was details regarding endoscopic treatment. All that 
was reported was there we re more Mayo 3's in the CMV group. Details regarding how many of 
each group were actually endoscopically assessed and if biopsies were obtained.  
 
Another limitation inherent to the the study population is that most patients were on mesalamine 
therapy rath er than immunomodulatory or biologic therapy. A follow -up study could compare 
these patients to those on oral 5 -ASAs. A few other points:  
- Would use consistent epidemiology terms in the abstract, introduction, results, discussion, 
conclusions. the results  are not really providing us with an incidence rate of CDI in patients 
with UC flares and hospitalized  
 
- "The results demonstrate the difficulty in clinical differentiation of CDI from UC flare" - the 
results are not demonstrating this - this is a nuance a nd challenge of clinical care. rather, the 
results are characterizing risk factors associated with positive CDAB in this cohort and 
factors associated with recurrence.  
 
- Closer attention is needed to differentiate discussion section the following: CDI in UC 
patients in general, vs CDI in UC patients when they are flaring or symptomatic. Similarly, 
would be useful to more clearly compare and contrast briefly UC rates in China vs 
Europe/North America, and then discuss how CDI is different in UC patients in t hese groups  
 
- May want to address the fact 2 patients with recurrent CDI were treated with metronidazole, 
and whether vancomycin should be first line  
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:  
 
Needs some language corrections before  being published  
 
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 ma y 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 your reply is yes to any, please give details below.  
 
No to all of the above  
 
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 C reative 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: Retrospective analysis of Clostridium difficile infection in patients with ulcerative colitis 
in a tertiary hospital in China  
 
Version: 3 Date: 12 Oct 2018  
 
Reviewer: Steven Lin  
 
Reviewer's report:  
 
In this single centered, retrospective case -controlled observational study by Xu et al, the authors 
seeked to assess the epidemiology and risk factors for CDI in patients with UC. This cohort 
looked specifically at patients that were hospitalized for a pre sumed flare and C. difficile toxin 
A/B (CDAB) were tested with 1:2 controls paired appropriately for gender, age. They found that 
recent use of antibiotics, prior hospitalization, and systemic use of steroids increased the risk of 
CDI, and that CMV infecti on was an independent risk factor for CDI. Overall, this study was 
simple and well -designed, with data carefully gathered to identify risk factors associated with 
active CDI. The major contributions of this study are adding to specific epidemiological data  
pertaining to CDI in UC patients in Beijing, though this is as the authors pointed out at a tertiary 
care center and with a sub -optimal c. difficile assay (lower sensitivity than the [overly] sensitive 
NAAT PCR, which has its own limitations as well). One  additional limitation to this study is the 
lack of CM detected on biopsies. Most of CMV infection were diagnosed on serologic testing. 
What was also omitted from the manuscript was details regarding endoscopic treatment. All that 
was reported was there we re more Mayo 3's in the CMV group. Details regarding how many of 
each group were actually endoscopically assessed and if biopsies were obtained.  
 
Another limitation inherent to the the study population is that most patients were on mesalamine 
therapy rath er than immunomodulatory or biologic therapy. A follow -up study could compare 
these patients to those on oral 5 -ASAs. A few other points:  
- Would use consistent epidemiology terms in the abstract, introduction, results, discussion, 
conclusions. the results  are not really providing us with an incidence rate of CDI in patients 
with UC flares and hospitalized  
 
- "The results demonstrate the difficulty in clinical differentiation of CDI from UC flare" - the 
results are not demonstrating this - this is a nuance a nd challenge of clinical care. rather, the 
results are characterizing risk factors associated with positive CDAB in this cohort and 
factors associated with recurrence.  
 
- Closer attention is needed to differentiate discussion section the following: CDI in UC 
patients in general, vs CDI in UC patients when they are flaring or symptomatic. Similarly, 
would be useful to more clearly compare and contrast briefly UC rates in China vs 
Europe/North America, and then discuss how CDI is different in UC patients in t hese groups  
 
- May want to address the fact 2 patients with recurrent CDI were treated with metronidazole, 
and whether vancomycin should be first line  
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:  
 
Needs some language corrections before  being published  
 
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 ma y 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 your reply is yes to any, please give details below.  
 
No to all of the above  
 
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 C reative 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