Review for 10.1186/s12876-021-01904-4 (2021)

Reviewer’s report
Title: 
A rare case of nivolumab-related myasthenia gravis and myocarditis in a
patient with metastatic gastric cancer
Version: 
0 
Date: 
01 Jun 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: This is clinically relevant report of a rare immune-
related adverse effect of involumab, which has been described in 7 previous
studies in melanoma, lung, and renal cancer, but has not been described yet in
gastric cancer. Although rare, this adverse effect should be recognized,
especially in Asia, where gastric cancer is highly prevalent.
REQUESTED REVISIONS: 
The case report describes immune checkpoint inhibitor nivolumab related
myasthenia gravis (MG) and myocarditis in a patient with metastatic gastric
cancer. 
Treatment-related adverse effects of nivolumab are common and in some cases
they can be serious and can cause patient death. Although MG and myocarditis
have been previously described in treatment of other types of cancer, this is the
first report of MG and myocarditis in a patient with advanced gastric cancer.
The authors should address several points in order to improve the manuscript
1) Adverse effects of nivolumab in patients with metastatic gastric cancer were
summarized in a phase 3 
ATTRACTION-2 clinical trial (Kang Y-K et al, Lancet
2017; 390:2461-71). All-grade treatment-related adverse events reported in 5%
or more of patients in the nivolumab group were pruritus, diarrhea, rash, and
fatigue. In the nivolumab group, serious treatment-related adverse events
reported in two or more patients were interstitial lung disease (n=3) and colitis,
pyrexia, pneumonia, urinary tract infection, and diabetic ketoacidosis (n=2 each).
This information should be included in the Background section
2) In the Case presentation, English should be corrected in the first sentence: One
months after the initial diagnosis of gastric cancer in a ….
3) What were the first and second lines of therapy?
4) It appears in the Case presentation, that the symptoms developed after twenty-
four days. This is likely a typo, as symptoms probably appeared 24 hours after
the first nivolumab infusion. This should be clarified 
5) What is the difference between Figure 1a and b? The authors may consider to
replace one of these with image of myocardial injury at higher magnification
6) The Table 2 would benefit of adding clinical symptoms to the labs and
treatment
7) Did patient develop myositis?
8) What was the cause of death? Myastenic crisis, myocarditis or other? Was
autopsy performed?
9) In the Discussion and Conclusions section, the 2 last sentences from the first
paragraph are repeated from the Background. They are redundant and should be
removed.
10) The authors speculate that measuring the level of anti-striational antibodies
before initiating nivolumab therapy could predict MG and myocarditis. Do they
have any evidence to support this speculation? Without the evidence form this
case or other series this speculation does not make any sense.
11) Another statement is that anti-striational antibodies may have caused death
of the patient. Anti-striational antibodies are markers of disease; can authors
support their hypothesis that anti-striational antibodies can be involved in
pathogenesis of the disease? Otherwise, there is no evidence to support this
statement.
ADDITIONAL REQUESTS/SUGGESTIONS: 
English should be corrected through the manuscript
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
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Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes