Title: Title: Prospective randomized, placebo-controlled study: Role of branched-chain amino
acids infusion as adjunct therapy post-liver surgery for patients in the intensive care unit
Version: 5 Date: 17 Dec 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?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics 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?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Although the authors have adequately addressed some of the
comments and clarified the manuscript, the main concerns regarding the validity and application
of the findings of this manuscript (loss of follow-up and basal differences that may impact
outcomes) still remain.
REQUESTED REVISIONS:
The authors have clarified several points of this manuscript, but there are still two main questions
that impact the validity and application of the findings:
It is understandable that patients are discharged early to other centers and, although possible,
that follow-up cannot be performed in other centers. However, this is a major bias of the study
since patients who are not discharged may be sicker than those discharged, and thus the authors
are only analyzing the worst patients (at the end of the follow-up, only 10 patients remained in
the placebo arm and six patients in the BCAA arm). Considering the nature of the outcomes, it
is unlikely that a reliable sensitivity or intention-to-treat analysis could be performed.
If the basal analysis was performed before the administration of BCAA, there is a relevant
baseline difference in several liver enzyme tests, such as ALT (albeit non significant). Apart
from providing an explanation for this finding, there is the risk of having included sicker patients
in the placebo group. Thus, the most appropriate marker would be a proportional value according
to baseline analysis or the reduction from baseline as the best marker.
In addition, the SOFA score was worse in the BCAA group, not “improved,” and thus patients
with BCAA did worse, despite the reliability of this comparison considering the low number
of patients in each group.
Title: Title: Prospective randomized, placebo-controlled study: Role of branched-chain amino
acids infusion as adjunct therapy post-liver surgery for patients in the intensive care unit
Version: 5 Date: 17 Dec 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?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics 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?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Although the authors have adequately addressed some of the
comments and clarified the manuscript, the main concerns regarding the validity and application
of the findings of this manuscript (loss of follow-up and basal differences that may impact
outcomes) still remain.
REQUESTED REVISIONS:
The authors have clarified several points of this manuscript, but there are still two main questions
that impact the validity and application of the findings:
It is understandable that patients are discharged early to other centers and, although possible,
that follow-up cannot be performed in other centers. However, this is a major bias of the study
since patients who are not discharged may be sicker than those discharged, and thus the authors
are only analyzing the worst patients (at the end of the follow-up, only 10 patients remained in
the placebo arm and six patients in the BCAA arm). Considering the nature of the outcomes, it
is unlikely that a reliable sensitivity or intention-to-treat analysis could be performed.
If the basal analysis was performed before the administration of BCAA, there is a relevant
baseline difference in several liver enzyme tests, such as ALT (albeit non significant). Apart
from providing an explanation for this finding, there is the risk of having included sicker patients
in the placebo group. Thus, the most appropriate marker would be a proportional value according
to baseline analysis or the reduction from baseline as the best marker.
In addition, the SOFA score was worse in the BCAA group, not “improved,” and thus patients
with BCAA did worse, despite the reliability of this comparison considering the low number
of patients in each group.
Please review this paper.
user
Title: Title: Prospective randomized, placebo-controlled study: Role of branched-chain amino
acids infusion as adjunct therapy post-liver surgery for patients in the intensive care unit
Version: 5 Date: 17 Dec 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?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics 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?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Although the authors have adequately addressed some of the
comments and clarified the manuscript, the main concerns regarding the validity and application
of the findings of this manuscript (loss of follow-up and basal differences that may impact
outcomes) still remain.
REQUESTED REVISIONS:
The authors have clarified several points of this manuscript, but there are still two main questions
that impact the validity and application of the findings:
It is understandable that patients are discharged early to other centers and, although possible,
that follow-up cannot be performed in other centers. However, this is a major bias of the study
since patients who are not discharged may be sicker than those discharged, and thus the authors
are only analyzing the worst patients (at the end of the follow-up, only 10 patients remained in
the placebo arm and six patients in the BCAA arm). Considering the nature of the outcomes, it
is unlikely that a reliable sensitivity or intention-to-treat analysis could be performed.
If the basal analysis was performed before the administration of BCAA, there is a relevant
baseline difference in several liver enzyme tests, such as ALT (albeit non significant). Apart
from providing an explanation for this finding, there is the risk of having included sicker patients
in the placebo group. Thus, the most appropriate marker would be a proportional value according
to baseline analysis or the reduction from baseline as the best marker.
In addition, the SOFA score was worse in the BCAA group, not “improved,” and thus patients
with BCAA did worse, despite the reliability of this comparison considering the low number
of patients in each group.
assistant