Reviewer ’s report  
 
Title: A potential anatomic subtype of short bowel syndrome: a matched case -control study  
 
Version: 0 Date: 23 Nov 2015  
 
Reviewer: Arianeb  Mehrabi  
 
Reviewer's report:  
 
In this manuscript the authors investigate the differential role of intesti nal segments in the 
intestinal adaptation process in humans with short bowel syndrome. Intestinal adaptation and 
weaning from parenteral nutrition are challenging and associated to a high morbidity and 
mortality in case of failure. Therefore, the authors p resent a study with high clinical significance. 
Overall, the project is method -wise and straightforward. Moreover a cohort of 356 patients with 
short bowel syndrome possibly reflects the extent and experience of the center at which the study 
was conducted.  The average follow time of approx. 2.5 years is long enough to provide solid 
long-term data. However, there a few concerns about the study.  
  
Methods:  
Page 4, line 36: "…between January 1, 2001 and January 1, 2013…":  This represents a wide 
timespan of 1 2 years, during which significant therapeutical improvements emerged. The authors 
should provide if any changes in their therapeutical approach of SBS patients occurred during 
this period, as this could have significantly influenced the outcome in the long -term.  
Page 5, line 9: "IP patients were defined that the ratio of residual ileum/jejunum was larger than 
4:1." Do the authors refer to the length of remnant intestinal segment at time -point of interstinal 
resection? If they do so, this is the predominan t flaw of present study, as from a surgical point of 
view it seems very difficult to intraoperatively exactly define which part of intestine has been 
predominantly resected or kept. This can also be histologically difficult in case the intestine is 
comprom ised by i.e. ischemia. This is further problematic, due to the retrospective nature of the 
study.  
However, the quantity of the specific intestinal segment is of importance, as ileum and jejunum 
are differently subjected to intestinal adaptation possibly l eading to a differential intestinal 
resorptional situation in the long -term, depending on length of each. Therefore, the definition of 
"predominantly" ileum of jejunum and therefore the patient grouping in this study has to be 
reassessed.  
  
 
Results:  
Table  1: 1) Is "Age at the time of SBS (Mean±SD)" expressed in months or years? Instead of 
only mean±SD, providing the range (min -max) would ease the interpretation of the results, due 
to possibly differential adaptation capacities between different ages. Moreo ver, from the 
diagnoses leading to the short bowel syndrome, it appears that there might be a mix -up of 
pediatric and adult patients (e.g. small bowel volvulus occurs rather in children, while intestinal 
adhesion/obstruction might rather be a cause of a SB S rather in adults). As there is no clear 
specification on the patient's age and range, an interpretation of the data remains difficult, 
particularly in case children and adults are taken together in the same group. Furthermore, it 
appears necessary to pro vide information on the number of preterm children included as well as 
their gestational age (weeks of pregnancy). This is of importance as children have a higher 
growth potential during the last weeks of pregnancy (Struijs MC, Diamond IR, de Silva N, Wale s 
PW (2009) Establishing norms for intestinal length in children. J Pediatr Surg 44:933 -938). 
Therefore, the more premature the neonate is, the higher is the intestinal growth potential and the 
associated intestinal adaptation capacity, implicating a cruci al role of proving information about 
the percentage of preterm infants, if the intestinal resection occurred early after birth.  
  
Table 2:  
1) Is "Time of PN (Mean±SD, d)" really expressed in days, as it appears very short to me. 
Furthermore, are "Time of PN+EN" and "Time of EN" also expressed in days, as no feature 
size is provided there?  
2) As intestinal rehabilitation therapy might enhance the intestinal adaptation, possibly 
significantly impacting the general outcome, patients undergoing intestinal reha bilitation 
therapy should be differentiated from those who do not.  
3) Metabolic bone disease was only examined in a portion of patients: Please state the 
percentage of patients and present the percentage of pathologic results from all test 
performed.  
 Page 8, line 56: "…ending at January 1, 2015" this should be included in M&M.  
Page 9, line 17: The younger (OR=0.94; 95% CI: 0.88, 1.00, p=0.06) or larger BMI (OR=1.41; 
95% CI: 0.98, 2.03, p=0.06) increase the possibility of PN weaning, but the difference w as not 
statistically significant.  
It should probably say "younger age" and " higher BMI". However, an OR of 0.98 almost equals 
1.0, which means that there is no elevated ratio of PN weaning, instead of the stated "increased 
possibility".  
 
General:  
1) Overa ll linguistic improvements would ease the understanding and readability of the text. 
This would be the case, for example in following sentence: Page 6, line 50: "Once patients 
were EN intolerance mainly including high gastric residuals and vomiting, they w ould 
receive PN again home parenteral nutrition (HPN) and EN or intestinal rehabilitation therapy 
(IRT), which was chosen according to the intestine function and patients' wills."  
2) P=0.00 should be indicated as p<value  
Are the methods appropriate and well described?  
If not, please spe cify 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.  
 
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 s tatistical 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 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 ot her 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 t o any, please give details below.  
 
'I declare that I have no co mpeting interests'  
 
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 websi te along with the authors' 
responses. I agree for my report to be made available under a n 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 name d 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: A potential anatomic subtype of short bowel syndrome: a matched case -control study  
 
Version: 0 Date: 23 Nov 2015  
 
Reviewer: Arianeb  Mehrabi  
 
Reviewer's report:  
 
In this manuscript the authors investigate the differential role of intesti nal segments in the 
intestinal adaptation process in humans with short bowel syndrome. Intestinal adaptation and 
weaning from parenteral nutrition are challenging and associated to a high morbidity and 
mortality in case of failure. Therefore, the authors p resent a study with high clinical significance. 
Overall, the project is method -wise and straightforward. Moreover a cohort of 356 patients with 
short bowel syndrome possibly reflects the extent and experience of the center at which the study 
was conducted.  The average follow time of approx. 2.5 years is long enough to provide solid 
long-term data. However, there a few concerns about the study.  
  
Methods:  
Page 4, line 36: "…between January 1, 2001 and January 1, 2013…":  This represents a wide 
timespan of 1 2 years, during which significant therapeutical improvements emerged. The authors 
should provide if any changes in their therapeutical approach of SBS patients occurred during 
this period, as this could have significantly influenced the outcome in the long -term.  
Page 5, line 9: "IP patients were defined that the ratio of residual ileum/jejunum was larger than 
4:1." Do the authors refer to the length of remnant intestinal segment at time -point of interstinal 
resection? If they do so, this is the predominan t flaw of present study, as from a surgical point of 
view it seems very difficult to intraoperatively exactly define which part of intestine has been 
predominantly resected or kept. This can also be histologically difficult in case the intestine is 
comprom ised by i.e. ischemia. This is further problematic, due to the retrospective nature of the 
study.  
However, the quantity of the specific intestinal segment is of importance, as ileum and jejunum 
are differently subjected to intestinal adaptation possibly l eading to a differential intestinal 
resorptional situation in the long -term, depending on length of each. Therefore, the definition of 
"predominantly" ileum of jejunum and therefore the patient grouping in this study has to be 
reassessed.  
  
 
Results:  
Table  1: 1) Is "Age at the time of SBS (Mean±SD)" expressed in months or years? Instead of 
only mean±SD, providing the range (min -max) would ease the interpretation of the results, due 
to possibly differential adaptation capacities between different ages. Moreo ver, from the 
diagnoses leading to the short bowel syndrome, it appears that there might be a mix -up of 
pediatric and adult patients (e.g. small bowel volvulus occurs rather in children, while intestinal 
adhesion/obstruction might rather be a cause of a SB S rather in adults). As there is no clear 
specification on the patient's age and range, an interpretation of the data remains difficult, 
particularly in case children and adults are taken together in the same group. Furthermore, it 
appears necessary to pro vide information on the number of preterm children included as well as 
their gestational age (weeks of pregnancy). This is of importance as children have a higher 
growth potential during the last weeks of pregnancy (Struijs MC, Diamond IR, de Silva N, Wale s 
PW (2009) Establishing norms for intestinal length in children. J Pediatr Surg 44:933 -938). 
Therefore, the more premature the neonate is, the higher is the intestinal growth potential and the 
associated intestinal adaptation capacity, implicating a cruci al role of proving information about 
the percentage of preterm infants, if the intestinal resection occurred early after birth.  
  
Table 2:  
1) Is "Time of PN (Mean±SD, d)" really expressed in days, as it appears very short to me. 
Furthermore, are "Time of PN+EN" and "Time of EN" also expressed in days, as no feature 
size is provided there?  
2) As intestinal rehabilitation therapy might enhance the intestinal adaptation, possibly 
significantly impacting the general outcome, patients undergoing intestinal reha bilitation 
therapy should be differentiated from those who do not.  
3) Metabolic bone disease was only examined in a portion of patients: Please state the 
percentage of patients and present the percentage of pathologic results from all test 
performed.  
 Page 8, line 56: "…ending at January 1, 2015" this should be included in M&M.  
Page 9, line 17: The younger (OR=0.94; 95% CI: 0.88, 1.00, p=0.06) or larger BMI (OR=1.41; 
95% CI: 0.98, 2.03, p=0.06) increase the possibility of PN weaning, but the difference w as not 
statistically significant.  
It should probably say "younger age" and " higher BMI". However, an OR of 0.98 almost equals 
1.0, which means that there is no elevated ratio of PN weaning, instead of the stated "increased 
possibility".  
 
General:  
1) Overa ll linguistic improvements would ease the understanding and readability of the text. 
This would be the case, for example in following sentence: Page 6, line 50: "Once patients 
were EN intolerance mainly including high gastric residuals and vomiting, they w ould 
receive PN again home parenteral nutrition (HPN) and EN or intestinal rehabilitation therapy 
(IRT), which was chosen according to the intestine function and patients' wills."  
2) P=0.00 should be indicated as p<value  
Are the methods appropriate and well described?  
If not, please spe cify 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.  
 
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 s tatistical 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 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 ot her 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 t o any, please give details below.  
 
'I declare that I have no co mpeting interests'  
 
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 websi te along with the authors' 
responses. I agree for my report to be made available under a n 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 name d 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: A potential anatomic subtype of short bowel syndrome: a matched case -control study  
 
Version: 0 Date: 23 Nov 2015  
 
Reviewer: Arianeb  Mehrabi  
 
Reviewer's report:  
 
In this manuscript the authors investigate the differential role of intesti nal segments in the 
intestinal adaptation process in humans with short bowel syndrome. Intestinal adaptation and 
weaning from parenteral nutrition are challenging and associated to a high morbidity and 
mortality in case of failure. Therefore, the authors p resent a study with high clinical significance. 
Overall, the project is method -wise and straightforward. Moreover a cohort of 356 patients with 
short bowel syndrome possibly reflects the extent and experience of the center at which the study 
was conducted.  The average follow time of approx. 2.5 years is long enough to provide solid 
long-term data. However, there a few concerns about the study.  
  
Methods:  
Page 4, line 36: "…between January 1, 2001 and January 1, 2013…":  This represents a wide 
timespan of 1 2 years, during which significant therapeutical improvements emerged. The authors 
should provide if any changes in their therapeutical approach of SBS patients occurred during 
this period, as this could have significantly influenced the outcome in the long -term.  
Page 5, line 9: "IP patients were defined that the ratio of residual ileum/jejunum was larger than 
4:1." Do the authors refer to the length of remnant intestinal segment at time -point of interstinal 
resection? If they do so, this is the predominan t flaw of present study, as from a surgical point of 
view it seems very difficult to intraoperatively exactly define which part of intestine has been 
predominantly resected or kept. This can also be histologically difficult in case the intestine is 
comprom ised by i.e. ischemia. This is further problematic, due to the retrospective nature of the 
study.  
However, the quantity of the specific intestinal segment is of importance, as ileum and jejunum 
are differently subjected to intestinal adaptation possibly l eading to a differential intestinal 
resorptional situation in the long -term, depending on length of each. Therefore, the definition of 
"predominantly" ileum of jejunum and therefore the patient grouping in this study has to be 
reassessed.  
  
 
Results:  
Table  1: 1) Is "Age at the time of SBS (Mean±SD)" expressed in months or years? Instead of 
only mean±SD, providing the range (min -max) would ease the interpretation of the results, due 
to possibly differential adaptation capacities between different ages. Moreo ver, from the 
diagnoses leading to the short bowel syndrome, it appears that there might be a mix -up of 
pediatric and adult patients (e.g. small bowel volvulus occurs rather in children, while intestinal 
adhesion/obstruction might rather be a cause of a SB S rather in adults). As there is no clear 
specification on the patient's age and range, an interpretation of the data remains difficult, 
particularly in case children and adults are taken together in the same group. Furthermore, it 
appears necessary to pro vide information on the number of preterm children included as well as 
their gestational age (weeks of pregnancy). This is of importance as children have a higher 
growth potential during the last weeks of pregnancy (Struijs MC, Diamond IR, de Silva N, Wale s 
PW (2009) Establishing norms for intestinal length in children. J Pediatr Surg 44:933 -938). 
Therefore, the more premature the neonate is, the higher is the intestinal growth potential and the 
associated intestinal adaptation capacity, implicating a cruci al role of proving information about 
the percentage of preterm infants, if the intestinal resection occurred early after birth.  
  
Table 2:  
1) Is "Time of PN (Mean±SD, d)" really expressed in days, as it appears very short to me. 
Furthermore, are "Time of PN+EN" and "Time of EN" also expressed in days, as no feature 
size is provided there?  
2) As intestinal rehabilitation therapy might enhance the intestinal adaptation, possibly 
significantly impacting the general outcome, patients undergoing intestinal reha bilitation 
therapy should be differentiated from those who do not.  
3) Metabolic bone disease was only examined in a portion of patients: Please state the 
percentage of patients and present the percentage of pathologic results from all test 
performed.  
 Page 8, line 56: "…ending at January 1, 2015" this should be included in M&M.  
Page 9, line 17: The younger (OR=0.94; 95% CI: 0.88, 1.00, p=0.06) or larger BMI (OR=1.41; 
95% CI: 0.98, 2.03, p=0.06) increase the possibility of PN weaning, but the difference w as not 
statistically significant.  
It should probably say "younger age" and " higher BMI". However, an OR of 0.98 almost equals 
1.0, which means that there is no elevated ratio of PN weaning, instead of the stated "increased 
possibility".  
 
General:  
1) Overa ll linguistic improvements would ease the understanding and readability of the text. 
This would be the case, for example in following sentence: Page 6, line 50: "Once patients 
were EN intolerance mainly including high gastric residuals and vomiting, they w ould 
receive PN again home parenteral nutrition (HPN) and EN or intestinal rehabilitation therapy 
(IRT), which was chosen according to the intestine function and patients' wills."  
2) P=0.00 should be indicated as p<value  
Are the methods appropriate and well described?  
If not, please spe cify 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.  
 
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 s tatistical 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 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 ot her 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 t o any, please give details below.  
 
'I declare that I have no co mpeting interests'  
 
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 websi te along with the authors' 
responses. I agree for my report to be made available under a n 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 name d 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