Reviewer ’s report  
 
Title: NON -INFERIORITY COMPARATIVE CLINICAL TRIAL BETWEEN EARLY ORAL  
REFEEDING AND USUAL ORAL REFEEDING IN PREDICTED MILD ACUTE BILIARY  
PANCREATITIS  
 
Version: 2 Date: 13 Feb 2020  
 
Reviewer: Katalin Márta  
 
Reviewer's report:  
 
This original paper summarizes the result of a randomized controlled blinded (by statistician) 
clinical trial (RCT) of 120 patients. The RCT is re gistered and got the relevant ethical approval. 
The manuscript follows: Abstract, Background, Methods, Results, Discussion, Conclusion, 
Acknowledgements and References.  
 
The RCT examine the 'early oral feeding' versus 'usual oral feeding' in biliary mild ac ute 
pancreatitis. The topic has high importance, however I only recommend to publish the article 
after major revision.  
 
- English is quite poor, please have it improved by a native English speaker.  
 
- The title and whole manuscript suggest that the result r efers to all mild pancreatitis, however 
authors included one etiology (biliary).  
 
- Two outcome measurements are indicated as 'the length of hospitalization' (LOH) and 'hospital 
charges' calculated from the LOH. Authors also mention that in Group B (Protoc ol - Oral feeding  
 
- Group B) the attending physician decided about the oral refeeding according to own clinical 
judgement. If the decision making physician is familiar with the study, the personal preference to 
a group might have affected the result. This is a huge bias, which must be mentioned. If authors 
made effort to prevent this bias please provide the solutions.  
 
- Only mild pancreatitis was considered to include, however on admission, based on the Atlanta 
classification, it is better to say predicted mild during the whole study. If authors verified the 
severity during patient's discharge (UH), please provide the information.  
All patients were included in 24h after the onset of pancreatitis, which makes the study very 
relevant, however the short time course makes it difficult to decide the actual severity 
(peripancreatic or pleural fluid, cys need more time to develop). The ver ification on discharge 
might be important.  
 
- Authors included patients with biliary pancreatitis, however never mentioned the definition and 
certainty of this and only etiology (p6l35 "Once the diagnosis of acute biliary pancreatitis was 
confirmed" this se ction could be perfect to fulfil for this purpose). Ultrasonography was 
mentioned for the diagnosis of AP, but the presence of stones does not make it obviously biliary 
pancreatitis. Please mention how etiologies were investigated.  
 
- Background 2nd sentenc e; the mentioned statement refers to rare and severe cases, namely 
nectosectomy in severe AP with no relevance in this ms. Please consider to simplify the 
introduction and focus on more relevant points like guideline and lack of evidence.  
 
- I highly sugges t to cite the nutritional recommendation of IAP/APA guideline, the lack of 
evidences make a huge importance of this study. PMID: 24054878 (G20 -21) 
 
- English is poor (Tbl 1 please change 'Size (meters)' to High if really relevant to disseminate this 
data)  
 
- The CONSORT checklist was attached to the manuscript. I also suggest to use the CONSORT 
figure, and please refer to this guideline.  
 
- I also would like to suggest the following articles to widen the literature part:  
The Hungarian Pancreatic Study Group i n 2015 recognized and highlighted the lack of 
knowledge about nutritional recommendation, please refer. PMID: 25661970  
In 2016 a meta -analysis was published about the preventive effect of early enteral feeding (24h) 
in mild, moderate, and severe AP. PMID: 27775609  
In 2018 a RCT was designed to examine the relevance of early enteral feeding (24h) in all 
severity and etiology of AP. PMID: 2891219  
 
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 overwrite this text when adding your comments to the authors.  
 
Are the methods appropr iate 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.  
 
Unable to assess  
 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statist ical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written 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, 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 recei ved 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 competing interest.  
 
I agree to the open peer review 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 confidenti al comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: NON -INFERIORITY COMPARATIVE CLINICAL TRIAL BETWEEN EARLY ORAL  
REFEEDING AND USUAL ORAL REFEEDING IN PREDICTED MILD ACUTE BILIARY  
PANCREATITIS  
 
Version: 2 Date: 13 Feb 2020  
 
Reviewer: Katalin Márta  
 
Reviewer's report:  
 
This original paper summarizes the result of a randomized controlled blinded (by statistician) 
clinical trial (RCT) of 120 patients. The RCT is re gistered and got the relevant ethical approval. 
The manuscript follows: Abstract, Background, Methods, Results, Discussion, Conclusion, 
Acknowledgements and References.  
 
The RCT examine the 'early oral feeding' versus 'usual oral feeding' in biliary mild ac ute 
pancreatitis. The topic has high importance, however I only recommend to publish the article 
after major revision.  
 
- English is quite poor, please have it improved by a native English speaker.  
 
- The title and whole manuscript suggest that the result r efers to all mild pancreatitis, however 
authors included one etiology (biliary).  
 
- Two outcome measurements are indicated as 'the length of hospitalization' (LOH) and 'hospital 
charges' calculated from the LOH. Authors also mention that in Group B (Protoc ol - Oral feeding  
 
- Group B) the attending physician decided about the oral refeeding according to own clinical 
judgement. If the decision making physician is familiar with the study, the personal preference to 
a group might have affected the result. This is a huge bias, which must be mentioned. If authors 
made effort to prevent this bias please provide the solutions.  
 
- Only mild pancreatitis was considered to include, however on admission, based on the Atlanta 
classification, it is better to say predicted mild during the whole study. If authors verified the 
severity during patient's discharge (UH), please provide the information.  
All patients were included in 24h after the onset of pancreatitis, which makes the study very 
relevant, however the short time course makes it difficult to decide the actual severity 
(peripancreatic or pleural fluid, cys need more time to develop). The ver ification on discharge 
might be important.  
 
- Authors included patients with biliary pancreatitis, however never mentioned the definition and 
certainty of this and only etiology (p6l35 "Once the diagnosis of acute biliary pancreatitis was 
confirmed" this se ction could be perfect to fulfil for this purpose). Ultrasonography was 
mentioned for the diagnosis of AP, but the presence of stones does not make it obviously biliary 
pancreatitis. Please mention how etiologies were investigated.  
 
- Background 2nd sentenc e; the mentioned statement refers to rare and severe cases, namely 
nectosectomy in severe AP with no relevance in this ms. Please consider to simplify the 
introduction and focus on more relevant points like guideline and lack of evidence.  
 
- I highly sugges t to cite the nutritional recommendation of IAP/APA guideline, the lack of 
evidences make a huge importance of this study. PMID: 24054878 (G20 -21) 
 
- English is poor (Tbl 1 please change 'Size (meters)' to High if really relevant to disseminate this 
data)  
 
- The CONSORT checklist was attached to the manuscript. I also suggest to use the CONSORT 
figure, and please refer to this guideline.  
 
- I also would like to suggest the following articles to widen the literature part:  
The Hungarian Pancreatic Study Group i n 2015 recognized and highlighted the lack of 
knowledge about nutritional recommendation, please refer. PMID: 25661970  
In 2016 a meta -analysis was published about the preventive effect of early enteral feeding (24h) 
in mild, moderate, and severe AP. PMID: 27775609  
In 2018 a RCT was designed to examine the relevance of early enteral feeding (24h) in all 
severity and etiology of AP. PMID: 2891219  
 
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 overwrite this text when adding your comments to the authors.  
 
Are the methods appropr iate 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.  
 
Unable to assess  
 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statist ical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written 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, 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 recei ved 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 competing interest.  
 
I agree to the open peer review 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 confidenti al 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: NON -INFERIORITY COMPARATIVE CLINICAL TRIAL BETWEEN EARLY ORAL  
REFEEDING AND USUAL ORAL REFEEDING IN PREDICTED MILD ACUTE BILIARY  
PANCREATITIS  
 
Version: 2 Date: 13 Feb 2020  
 
Reviewer: Katalin Márta  
 
Reviewer's report:  
 
This original paper summarizes the result of a randomized controlled blinded (by statistician) 
clinical trial (RCT) of 120 patients. The RCT is re gistered and got the relevant ethical approval. 
The manuscript follows: Abstract, Background, Methods, Results, Discussion, Conclusion, 
Acknowledgements and References.  
 
The RCT examine the 'early oral feeding' versus 'usual oral feeding' in biliary mild ac ute 
pancreatitis. The topic has high importance, however I only recommend to publish the article 
after major revision.  
 
- English is quite poor, please have it improved by a native English speaker.  
 
- The title and whole manuscript suggest that the result r efers to all mild pancreatitis, however 
authors included one etiology (biliary).  
 
- Two outcome measurements are indicated as 'the length of hospitalization' (LOH) and 'hospital 
charges' calculated from the LOH. Authors also mention that in Group B (Protoc ol - Oral feeding  
 
- Group B) the attending physician decided about the oral refeeding according to own clinical 
judgement. If the decision making physician is familiar with the study, the personal preference to 
a group might have affected the result. This is a huge bias, which must be mentioned. If authors 
made effort to prevent this bias please provide the solutions.  
 
- Only mild pancreatitis was considered to include, however on admission, based on the Atlanta 
classification, it is better to say predicted mild during the whole study. If authors verified the 
severity during patient's discharge (UH), please provide the information.  
All patients were included in 24h after the onset of pancreatitis, which makes the study very 
relevant, however the short time course makes it difficult to decide the actual severity 
(peripancreatic or pleural fluid, cys need more time to develop). The ver ification on discharge 
might be important.  
 
- Authors included patients with biliary pancreatitis, however never mentioned the definition and 
certainty of this and only etiology (p6l35 "Once the diagnosis of acute biliary pancreatitis was 
confirmed" this se ction could be perfect to fulfil for this purpose). Ultrasonography was 
mentioned for the diagnosis of AP, but the presence of stones does not make it obviously biliary 
pancreatitis. Please mention how etiologies were investigated.  
 
- Background 2nd sentenc e; the mentioned statement refers to rare and severe cases, namely 
nectosectomy in severe AP with no relevance in this ms. Please consider to simplify the 
introduction and focus on more relevant points like guideline and lack of evidence.  
 
- I highly sugges t to cite the nutritional recommendation of IAP/APA guideline, the lack of 
evidences make a huge importance of this study. PMID: 24054878 (G20 -21) 
 
- English is poor (Tbl 1 please change 'Size (meters)' to High if really relevant to disseminate this 
data)  
 
- The CONSORT checklist was attached to the manuscript. I also suggest to use the CONSORT 
figure, and please refer to this guideline.  
 
- I also would like to suggest the following articles to widen the literature part:  
The Hungarian Pancreatic Study Group i n 2015 recognized and highlighted the lack of 
knowledge about nutritional recommendation, please refer. PMID: 25661970  
In 2016 a meta -analysis was published about the preventive effect of early enteral feeding (24h) 
in mild, moderate, and severe AP. PMID: 27775609  
In 2018 a RCT was designed to examine the relevance of early enteral feeding (24h) in all 
severity and etiology of AP. PMID: 2891219  
 
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 overwrite this text when adding your comments to the authors.  
 
Are the methods appropr iate 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.  
 
Unable to assess  
 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statist ical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written 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, 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 recei ved 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 competing interest.  
 
I agree to the open peer review 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 confidenti al comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant