Reviewer ’s report  
 
Title:  Children with cyclic vomiting syndrome: phenotypes, di sease burden and mitochondrial 
DNA analysis  
 
Version: 0 Date: 07 Dec 2017 
 
Reviewer:  Thangam  Venkatesan  
 
Reviewer’s report:  
 
To the Editor and the Authors  
 
I would like to commend the authors on this important work that describes the clinical 
characteristics of 42 children with cyclic vomiting syndrome from a tertiary referral center in 
China.  
 
 
Major issues  
 
The title states that th ere is an association with mitochondrial DNA single nucleotide 
polymorphisms (SNPs) and cyclic vomiting syndrome (CVS).  In fact, their data does not 
support this assertion.  In fact, the prevalence of 16519 T SNP was 30% and that of 3010 was 
15% in this s mall cohort of patients.  This is actually similar to that is seen in controls and does 
not indicate any association with CVS in this patient population.  
 
I would strongly suggest that the authors rewrite the manuscript as a descriptive study and with   
clinical features as well as the mitochondrial DNA SNPs that were noted in these patients.  They 
should also indicate that the prevalence of these mitochondrial DNA SNPs was similar to that 
seen in the general population.  I would also report prevalence of b oth 3010A and 16519T SNPs 
in the same individual.  In addition, this study was not powered to detect any significant 
differences in these SNPs.  
 
 
Minor issues  
 
1.  Page 32, line 34  
 
The authors state that episodes were stereotypic in onset and clinical fea tures.  It is unclear as to 
exactly what they exactly the authors are referring to by these comments about onset.  Were 
there for instance stating that episodes occur at the same time (early morning hours etc.).  This 
needs to be clarified.  
 
 
2.  Page 3, l ines 28 and 29.  
 
A diagnosis of pediatric CVS generally requires at least 5 episodes of vomiting in a year to make 
a diagnosis.  In general, 2 episodes was considered too small a number to make this diagnosis as 
other conditions like gastroenteritis may b e misdiagnosed as CVS which is a chronic condition.  
 
I would suggest that the authors refer to NASPHAGN guidelines, which is the norm to make this 
diagnosis.  
 
 
3.   Page 5, lines 37 -42  
 
The percentage of patients who had either a personal or family history of migraine is much lower 
than reported in studies from the West and this would be worth mentioning in the discussion.  
 
 
4.  The authors state that coffee -ground vomitus was present in 2 8.6% [almost a third of these 
patients].  While gastrointestinal bleeding can be complication from CVS, this number seems to 
be high and may reflect the differences in medical practice/medical care sort by patients in 
China.  For instance, it is possible t hat patients may seek medical care later in China versus the 
West. I would suggest that the authors discuss this issue and provide some details about how 
patients were treated in the hospital and possible delays in treatment.  
 
 
5.  Finally, there are multip le typographical errors throughout the manuscript and I would 
suggest that they seek professional help to ad  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, 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 fro m 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.  
 
None  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my rep ort 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 Creat ive 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:  Children with cyclic vomiting syndrome: phenotypes, di sease burden and mitochondrial 
DNA analysis  
 
Version: 0 Date: 07 Dec 2017 
 
Reviewer:  Thangam  Venkatesan  
 
Reviewer’s report:  
 
To the Editor and the Authors  
 
I would like to commend the authors on this important work that describes the clinical 
characteristics of 42 children with cyclic vomiting syndrome from a tertiary referral center in 
China.  
 
 
Major issues  
 
The title states that th ere is an association with mitochondrial DNA single nucleotide 
polymorphisms (SNPs) and cyclic vomiting syndrome (CVS).  In fact, their data does not 
support this assertion.  In fact, the prevalence of 16519 T SNP was 30% and that of 3010 was 
15% in this s mall cohort of patients.  This is actually similar to that is seen in controls and does 
not indicate any association with CVS in this patient population.  
 
I would strongly suggest that the authors rewrite the manuscript as a descriptive study and with   
clinical features as well as the mitochondrial DNA SNPs that were noted in these patients.  They 
should also indicate that the prevalence of these mitochondrial DNA SNPs was similar to that 
seen in the general population.  I would also report prevalence of b oth 3010A and 16519T SNPs 
in the same individual.  In addition, this study was not powered to detect any significant 
differences in these SNPs.  
 
 
Minor issues  
 
1.  Page 32, line 34  
 
The authors state that episodes were stereotypic in onset and clinical fea tures.  It is unclear as to 
exactly what they exactly the authors are referring to by these comments about onset.  Were 
there for instance stating that episodes occur at the same time (early morning hours etc.).  This 
needs to be clarified.  
 
 
2.  Page 3, l ines 28 and 29.  
 
A diagnosis of pediatric CVS generally requires at least 5 episodes of vomiting in a year to make 
a diagnosis.  In general, 2 episodes was considered too small a number to make this diagnosis as 
other conditions like gastroenteritis may b e misdiagnosed as CVS which is a chronic condition.  
 
I would suggest that the authors refer to NASPHAGN guidelines, which is the norm to make this 
diagnosis.  
 
 
3.   Page 5, lines 37 -42  
 
The percentage of patients who had either a personal or family history of migraine is much lower 
than reported in studies from the West and this would be worth mentioning in the discussion.  
 
 
4.  The authors state that coffee -ground vomitus was present in 2 8.6% [almost a third of these 
patients].  While gastrointestinal bleeding can be complication from CVS, this number seems to 
be high and may reflect the differences in medical practice/medical care sort by patients in 
China.  For instance, it is possible t hat patients may seek medical care later in China versus the 
West. I would suggest that the authors discuss this issue and provide some details about how 
patients were treated in the hospital and possible delays in treatment.  
 
 
5.  Finally, there are multip le typographical errors throughout the manuscript and I would 
suggest that they seek professional help to ad  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, 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 fro m 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.  
 
None  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my rep ort 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 Creat ive 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:  Children with cyclic vomiting syndrome: phenotypes, di sease burden and mitochondrial 
DNA analysis  
 
Version: 0 Date: 07 Dec 2017 
 
Reviewer:  Thangam  Venkatesan  
 
Reviewer’s report:  
 
To the Editor and the Authors  
 
I would like to commend the authors on this important work that describes the clinical 
characteristics of 42 children with cyclic vomiting syndrome from a tertiary referral center in 
China.  
 
 
Major issues  
 
The title states that th ere is an association with mitochondrial DNA single nucleotide 
polymorphisms (SNPs) and cyclic vomiting syndrome (CVS).  In fact, their data does not 
support this assertion.  In fact, the prevalence of 16519 T SNP was 30% and that of 3010 was 
15% in this s mall cohort of patients.  This is actually similar to that is seen in controls and does 
not indicate any association with CVS in this patient population.  
 
I would strongly suggest that the authors rewrite the manuscript as a descriptive study and with   
clinical features as well as the mitochondrial DNA SNPs that were noted in these patients.  They 
should also indicate that the prevalence of these mitochondrial DNA SNPs was similar to that 
seen in the general population.  I would also report prevalence of b oth 3010A and 16519T SNPs 
in the same individual.  In addition, this study was not powered to detect any significant 
differences in these SNPs.  
 
 
Minor issues  
 
1.  Page 32, line 34  
 
The authors state that episodes were stereotypic in onset and clinical fea tures.  It is unclear as to 
exactly what they exactly the authors are referring to by these comments about onset.  Were 
there for instance stating that episodes occur at the same time (early morning hours etc.).  This 
needs to be clarified.  
 
 
2.  Page 3, l ines 28 and 29.  
 
A diagnosis of pediatric CVS generally requires at least 5 episodes of vomiting in a year to make 
a diagnosis.  In general, 2 episodes was considered too small a number to make this diagnosis as 
other conditions like gastroenteritis may b e misdiagnosed as CVS which is a chronic condition.  
 
I would suggest that the authors refer to NASPHAGN guidelines, which is the norm to make this 
diagnosis.  
 
 
3.   Page 5, lines 37 -42  
 
The percentage of patients who had either a personal or family history of migraine is much lower 
than reported in studies from the West and this would be worth mentioning in the discussion.  
 
 
4.  The authors state that coffee -ground vomitus was present in 2 8.6% [almost a third of these 
patients].  While gastrointestinal bleeding can be complication from CVS, this number seems to 
be high and may reflect the differences in medical practice/medical care sort by patients in 
China.  For instance, it is possible t hat patients may seek medical care later in China versus the 
West. I would suggest that the authors discuss this issue and provide some details about how 
patients were treated in the hospital and possible delays in treatment.  
 
 
5.  Finally, there are multip le typographical errors throughout the manuscript and I would 
suggest that they seek professional help to ad  
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, 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 fro m 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.  
 
None  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my rep ort 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 Creat ive 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