Review for 10.1186/s12876-024-03221-y (2024)

Title: Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem
cell transplantation
Version: 1 Date: 06 Mar 2024
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?
Yes - experiments and analyses were performed appropriately
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?
Yes - the author's interpretation is reasonable
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?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: HAVE THE AUTHORS RESPONDED ADEQUATELY TO
EACH OF THE QUESTIONS YOU RAISED IN YOUR COMMENTS
Yes thank you authors
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE MANUSCRIPT
Very much so and they markedly improved t the readability and justification of the
diagnosis of iTAM which was the major criticism of the past submission
WHAT IS YOUR OVERALL IMPRESSION OF THE REVISED MANUSCRIPT
This revised submission is a potentially very important advance in the diagnosis and
management of patients with stem cell transplants. Also it points out the potential trial difficulty
of diagnosing GVHD. And/or CMV infection either alone or in conjunction with iTAM.
ADDITIONAL REQUESTS/SUGGESTIONS:
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS SHOULD MAKE I have
read the revised manuscript in its entirety
1. Lines 78- 82 . If this is the pathogenesis, then this represents an ischemia of the mucosa. Is
that correct ? And if so how can you measure and/or  differentiate ischemia from CMV and
GVHD? This really gets at the question of how you made the diagnosis of  iTAM in your patients
and exclude  all these findings you describe from GVHD and CMV. Did you see blot clots or
thrombosis on all these patients ( line 80)? Were there other areas that are exclusively ischemic
injuries? Did all the patients in whom you made the diagnosis of iTAM have endothelial swelling
and is that a required finding to make the diagnosis?
2. Line 84 if the pathogenesis (not the etiology but the pathogenesis) is ischemia, can you treat
this with agents designed to increase blood flow to the gut or agents that might mitigate ischemic
injury.
3. Lines 105-115. Fantastic! thus answers all of our questions cc how you made a diagnosis of
iTAM!
4. Line 156 to reinforce your diagnosis of iTAM why not add this phrase at the end of the
sentence in addition to the findings of endothelia swelling, endothelial cell separation and the
other pathognomonic findings of iTAM.”  I really thought l this will solidify your recognition
of BOTH iTAM and either GVHD and/or CMV.
5. Line 166. Do GVHD and CMV also cause the final ga in blood vessels that you use to diagnose
iTAM if not you should say that here again because many of the mucosal findings you describe
for iTAM also occur with GVHD and CMV.
6. Line 209 I would suggest that you add the phrase “based on the pathognomonic changes we
outlined above in the small blood vessels” after the word “specimens” this will again solidify
how to differentiate the causes of mucosal changes according to the etiology of iTAM.
7 lines 212-222 well done authors.  This is very important because  the treatment of iTAM and
G HD AND CMV are different and that may be the most important as you state in line 230 and
232! This really is the important part of your now excellent paper!