Review for 10.1186/s12876-021-01847-w (2021)

Reviewer’s report
Title: 
Gastrointestinal Manifestations of Synthetic Cannabinoids: A
retrospective cohort study
Version: 
1 
Date: 
12 Feb 2021
Reviewer's report:
"PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses one
or several testable research questions? (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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient
technical rigor to allow confidence in the results?
No - there are minor 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 - Has the author addressed your
concerns sufficiently for you to now recommend the work as a technically sound
contribution? If not, can further revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Please understand that this paper was reviewed
before, so I will use the outline of a re-review even though I was not one of the
original reviewers. 
I have read the response to the original review and have read
the paper and have also reviewed it as if I were an original reviewer
HAVE THE AUTHORS RESPONDED ADEQUATELY TO EACH OF THE
QUESTIONS YOU RAISED IN YOUR COMMENTS 
Yes the authors addressed the prior comments
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE
MANUSCRIPT 
Yes I think they replied appropriately to the comments raised BUT please see the
number of comments I have raised
WHAT IS YOUR OVERALL IMPRESSION OF THE REVISED
MANUSCRIPT 
I like this paper and with appropriate revision, it will definitely add to the
literature. There is one major change that needs to be done; any direct
association of SC toxicity and intestinal ischemia cannot be supported by 
one
patient 
of the 21 patients reviewed and especially with no other patients with
abdominal pain having vasospasm on CT angiography. 
The paper may
""hypothesize"" that SC can cause intestinal 
ischemia, but this study certainly
does not prove it but 
only that SC was associated with intestinal ischemia that
may have also been due to other concomitant drugs.
DOES THIS MEET BEST PRACTICE
Yes I think so but it really is a retrospective review and addresses a potentially
important topic
REQUESTED REVISIONS: 
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS SHOULD
MAKE 
1. Page 2 line 40-41. With only one patient in 21 of developing what was
interpreted as intestinal ischemia, you really cannot say the SC can lead to
intestinal ischemia; one patient is not supportive of 
such a definitive statement,
but you can say " and even to symptoms suggesting intestinal ischemia"
2. Page 3 line 0 move the abbreviation of (SC) to after the word ""compounds""
3. Page 3 line 7 replace "they" with "SC"
4. Page 3 line 11 add the phrase " in the United States" after the word
""students"" to differentiate this study from reference 3 
5. Page 3 line 36 I would delete the word ""rat"" and say "animal-oriented
poisons"
6. Page 3 lines51-52. If there are no data on the 
presence of CBr2 in the GI tract ,
then you cannot say the action is caused by exciting CBr 2 receptors moreover,
ref 12 addresses the kidney, not the GI tract and by affecting the kidney you
cannot say that SC affects the GI tract- you need to be specific !
7. Page 5 lines 2-3. While I understand why you would "want " to present the
data as means +/- SD, some of your data are not normally distributed such as
length ( actually which should be "duration"") of longest hospitalization and
hospitalization, 
also in table 2 ALT, lactate, when the SD is too large it means
the data are not normally distributed. Also please round off the potassium levels
to only the tenth of a Meq/l; these will need to be presented in non parametric
ways as median and interquartile range and preferably also with range please
consult your statistician
8 page 6 line 17. Delete the word scan ( tomography means scan)
9. Page 8 lines 18-22,page 7 lines3-4 and 
page 8 lines 22-22 
And 36-39 again the
one patient 
with arterial thrombosis and intestinal perforation you might
""suspect"" to be related to SC, but as you say, with the unknown effects of other
concomitant drugs, you cannot be certain that the SC caused the ischemia but
what you can say is that the SC toxicity can suppress symptoms of intestinal
ischemia and may even exacerbate the ischemia. 
But you cannot say SC toxicity
causes intestinal ischemia. See your sentence stating on page 7 line 8
10. Page 7 line 0-1 again these studies do NOT address the GI track- sorry and
especially if the CBr2 receptor is not found in the GI track 
11. Page 7 lines 28-31 I am sorry but this is purely conjecture and should be
deleted; duodenal ulcers have many causes, and most are NOT due to intestinal
ischemia-indeed chronic 
intestinal ischemia is not associated with 
duodenal
ulcers; delete this reference it is not evidence-based. 
To make your point clearly,
you need to stick to the data; 
you have good data please do not speculate on
topics that you cannot support with data
12.Page 7 lines 35-39. This sentence makes no sense if the pain was caused by
intestinal vasospasm, you should have seen it in patients with pain. This
sentence should be deleted
13. Page 9 line 4. Here at the end you may want to postulate that SC may cause
mesenteric vasospasm that might progress to intestinal ischemia, but the data
supporting this theory are ""definitive". 
Your hypothesis 
is reasonable, but it is
your ""hypothesis"" and it would 
it need to be proven. One patient does not
prove this!"
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Is the study design appropriate to answer the research question (including the use
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presented?
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Yes
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Yes
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from apparent manipulation?
Yes