Reviewer ’s report  
 
Title: CYSTINOSIS BEYOND KIDNEYS: GASTROINTESTINAL SYSTEM AND MUSCLE  
INVOLVEMENT  
 
Version: 1 Date: 21 Apr 2020  
 
Reviewer: Research Square  Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
No - there are major issues  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
No - there are majo r issues  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are major issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
Maybe - with major revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
This is a case series on 21 patients with nephropathic cystinosis and variable compliance with 
therapy, who were screened for medium -term GI and muscle complications. The results are 
presented clearly and provide some insight into the overall prevalence of thes e complications.  
1. The manuscript is entitled, GASTROINTESTINAL SYSTEM INVOLVEMENT & 
EXTRARENAL COMPLICATIONS IN CYSTINOSIS, but it chiefly reviews some aspects of 
GI involvement, limited skeletal muscle, and perhaps smooth muscle involvement.  
2. The evaluation is not in enough depth; what is described has been known for a while. In its 
current form, the manuscript fails to add to the existing literature on the subject.  
 
REQUESTED REVISIONS:  
The data presented by the authors is quite clear. The  concern I have is its lack of novelty. Data 
presented in this ms. are reasonably well recognized on long -term follow -up of patients with 
cystinosis.  
1. In that sense, these findings are not likely to add to the existing literature on the subject.  
2. It wo uld be useful to incorporate a detailed evaluation of GI and liver functions, including: 
enzyme secretion; elastography; and endoscopy, in all patients with suspected portal 
hypertension.  
3. Description of findings on EMG (electromyography, not electromye lography) of distal 
muscles is necessary, as is detailed presentation of findings  related to cine 
pharyngoeosaphagography.  
4. Formal evaluation for gastroesophageal reflux using pH monitoring would have been 
preferred.  
5. The Discussion should be slightly  more focused and related to GI and muscle involvement.  
 
 
Are the methods appropriate and  well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
 
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 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 futu re? 
 
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.  
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with  
declared or apparent competing interests are not  utilized for these reviews. This reviewer has  
agreed to publication of their comments online under a Creative Commons Attribution License  
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe.  Honoraria for reviews such as this are paid regardless of the reviewer  
recommendation.  
 
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 nam ed 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 un derstand 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: CYSTINOSIS BEYOND KIDNEYS: GASTROINTESTINAL SYSTEM AND MUSCLE  
INVOLVEMENT  
 
Version: 1 Date: 21 Apr 2020  
 
Reviewer: Research Square  Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
No - there are major issues  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
No - there are majo r issues  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are major issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
Maybe - with major revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
This is a case series on 21 patients with nephropathic cystinosis and variable compliance with 
therapy, who were screened for medium -term GI and muscle complications. The results are 
presented clearly and provide some insight into the overall prevalence of thes e complications.  
1. The manuscript is entitled, GASTROINTESTINAL SYSTEM INVOLVEMENT & 
EXTRARENAL COMPLICATIONS IN CYSTINOSIS, but it chiefly reviews some aspects of 
GI involvement, limited skeletal muscle, and perhaps smooth muscle involvement.  
2. The evaluation is not in enough depth; what is described has been known for a while. In its 
current form, the manuscript fails to add to the existing literature on the subject.  
 
REQUESTED REVISIONS:  
The data presented by the authors is quite clear. The  concern I have is its lack of novelty. Data 
presented in this ms. are reasonably well recognized on long -term follow -up of patients with 
cystinosis.  
1. In that sense, these findings are not likely to add to the existing literature on the subject.  
2. It wo uld be useful to incorporate a detailed evaluation of GI and liver functions, including: 
enzyme secretion; elastography; and endoscopy, in all patients with suspected portal 
hypertension.  
3. Description of findings on EMG (electromyography, not electromye lography) of distal 
muscles is necessary, as is detailed presentation of findings  related to cine 
pharyngoeosaphagography.  
4. Formal evaluation for gastroesophageal reflux using pH monitoring would have been 
preferred.  
5. The Discussion should be slightly  more focused and related to GI and muscle involvement.  
 
 
Are the methods appropriate and  well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
 
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 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 futu re? 
 
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.  
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with  
declared or apparent competing interests are not  utilized for these reviews. This reviewer has  
agreed to publication of their comments online under a Creative Commons Attribution License  
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe.  Honoraria for reviews such as this are paid regardless of the reviewer  
recommendation.  
 
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 nam ed 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 un derstand 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: CYSTINOSIS BEYOND KIDNEYS: GASTROINTESTINAL SYSTEM AND MUSCLE  
INVOLVEMENT  
 
Version: 1 Date: 21 Apr 2020  
 
Reviewer: Research Square  Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
No - there are major issues  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
No - there are majo r issues  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
No - there are major issues  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
Maybe - with major revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
This is a case series on 21 patients with nephropathic cystinosis and variable compliance with 
therapy, who were screened for medium -term GI and muscle complications. The results are 
presented clearly and provide some insight into the overall prevalence of thes e complications.  
1. The manuscript is entitled, GASTROINTESTINAL SYSTEM INVOLVEMENT & 
EXTRARENAL COMPLICATIONS IN CYSTINOSIS, but it chiefly reviews some aspects of 
GI involvement, limited skeletal muscle, and perhaps smooth muscle involvement.  
2. The evaluation is not in enough depth; what is described has been known for a while. In its 
current form, the manuscript fails to add to the existing literature on the subject.  
 
REQUESTED REVISIONS:  
The data presented by the authors is quite clear. The  concern I have is its lack of novelty. Data 
presented in this ms. are reasonably well recognized on long -term follow -up of patients with 
cystinosis.  
1. In that sense, these findings are not likely to add to the existing literature on the subject.  
2. It wo uld be useful to incorporate a detailed evaluation of GI and liver functions, including: 
enzyme secretion; elastography; and endoscopy, in all patients with suspected portal 
hypertension.  
3. Description of findings on EMG (electromyography, not electromye lography) of distal 
muscles is necessary, as is detailed presentation of findings  related to cine 
pharyngoeosaphagography.  
4. Formal evaluation for gastroesophageal reflux using pH monitoring would have been 
preferred.  
5. The Discussion should be slightly  more focused and related to GI and muscle involvement.  
 
 
Are the methods appropriate and  well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
 
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 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 futu re? 
 
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.  
 
This reviewer has been recruited by a partner organization, Research Square. Reviewers with  
declared or apparent competing interests are not  utilized for these reviews. This reviewer has  
agreed to publication of their comments online under a Creative Commons Attribution License  
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe.  Honoraria for reviews such as this are paid regardless of the reviewer  
recommendation.  
 
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 nam ed 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 un derstand 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