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: 3 Date: 06 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (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 minor issues
EXECUTION - Are the experiments and analyses performed with 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?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The primary strength of this study on the effects of Branched-
Chain Amino Acids (BCAAs) infusion post-liver surgery is the design as a randomized, double-
blind, placebo-controlled trial. However, the single-center nature of the study, short follow-up
period, and significant patient dropout limit its overall validity. These limitations along with
heterogeneous inclusion criteria and a somewhat unclear presentation of data, raise concerns
about the reliability and application of the findings.
REQUESTED REVISIONS:
The study design is appropriate, with randomization, double-blinding, and placebo control,
which strengthens its internal validity. However, the sample size is small, and the substantial
loss of patients during follow-up further compromises the robustness of the results. Another
major limitation is the lack of transparency regarding the handling of missing data from
patient dropouts. Regarding statistical analysis, the limited sample size for certain comparisons
significantly impacts the validity of the findings. Specifically, Table 2 should clearly indicate
the number of patients remaining in each group for different comparisons. Similarly, Table 3
would benefit from additional clarification regarding the number of patients analyzed.
Another relevant point that should be clarified is the timing of the baseline biochemical
measurements. Since BCAAs were administered postoperatively, the authors should indicate
when the baseline liver transaminases and other analytes were collected and when BCAAs were
administered. The observed differences in baseline values require explanation since it is unlikely
for the treatment to have had a measurable impact in such a short timeframe.
The study’s single-center design and short follow-up period, coupled with its heterogeneous
inclusion criteria, further restrict the generalizability of the findings. The study is directed
towards a clear objective, and the rationale is well-grounded although there are several
references clearly related with the topic that could be added:
Kikuchi N, Taketomi A, Harimoto N, et al. Oral administration of branched-chain amino
acids prevents post-hepatectomy ascites and pleural effusion in patients with hepatocellular
carcinoma. Ann Surg Oncol. 2016;23(8):2480-2488. doi:10.1245/s10434-016-5348-3
Beppu T, Okabe H, Shiraishi N, et al. The effect of branched-chain amino acid supplementation
on functional liver regeneration after portal vein embolization followed by hepatectomy:
A randomized control trial. J Gastroenterol Hepatol. 2015;30(4):667-673. doi:10.1007/
s00535-015-1067-y
San-In Group of Liver Surgery. Oral branched-chain amino acid supplementation after
curative resection of hepatocellular carcinoma: A prospective randomized trial. Br J Surg.
1997;84(11):1525-1529. doi:10.1002/bjs.6189471
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: 3 Date: 06 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (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 minor issues
EXECUTION - Are the experiments and analyses performed with 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?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The primary strength of this study on the effects of Branched-
Chain Amino Acids (BCAAs) infusion post-liver surgery is the design as a randomized, double-
blind, placebo-controlled trial. However, the single-center nature of the study, short follow-up
period, and significant patient dropout limit its overall validity. These limitations along with
heterogeneous inclusion criteria and a somewhat unclear presentation of data, raise concerns
about the reliability and application of the findings.
REQUESTED REVISIONS:
The study design is appropriate, with randomization, double-blinding, and placebo control,
which strengthens its internal validity. However, the sample size is small, and the substantial
loss of patients during follow-up further compromises the robustness of the results. Another
major limitation is the lack of transparency regarding the handling of missing data from
patient dropouts. Regarding statistical analysis, the limited sample size for certain comparisons
significantly impacts the validity of the findings. Specifically, Table 2 should clearly indicate
the number of patients remaining in each group for different comparisons. Similarly, Table 3
would benefit from additional clarification regarding the number of patients analyzed.
Another relevant point that should be clarified is the timing of the baseline biochemical
measurements. Since BCAAs were administered postoperatively, the authors should indicate
when the baseline liver transaminases and other analytes were collected and when BCAAs were
administered. The observed differences in baseline values require explanation since it is unlikely
for the treatment to have had a measurable impact in such a short timeframe.
The study’s single-center design and short follow-up period, coupled with its heterogeneous
inclusion criteria, further restrict the generalizability of the findings. The study is directed
towards a clear objective, and the rationale is well-grounded although there are several
references clearly related with the topic that could be added:
Kikuchi N, Taketomi A, Harimoto N, et al. Oral administration of branched-chain amino
acids prevents post-hepatectomy ascites and pleural effusion in patients with hepatocellular
carcinoma. Ann Surg Oncol. 2016;23(8):2480-2488. doi:10.1245/s10434-016-5348-3
Beppu T, Okabe H, Shiraishi N, et al. The effect of branched-chain amino acid supplementation
on functional liver regeneration after portal vein embolization followed by hepatectomy:
A randomized control trial. J Gastroenterol Hepatol. 2015;30(4):667-673. doi:10.1007/
s00535-015-1067-y
San-In Group of Liver Surgery. Oral branched-chain amino acid supplementation after
curative resection of hepatocellular carcinoma: A prospective randomized trial. Br J Surg.
1997;84(11):1525-1529. doi:10.1002/bjs.6189471
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: 3 Date: 06 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (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 minor issues
EXECUTION - Are the experiments and analyses performed with 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?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The primary strength of this study on the effects of Branched-
Chain Amino Acids (BCAAs) infusion post-liver surgery is the design as a randomized, double-
blind, placebo-controlled trial. However, the single-center nature of the study, short follow-up
period, and significant patient dropout limit its overall validity. These limitations along with
heterogeneous inclusion criteria and a somewhat unclear presentation of data, raise concerns
about the reliability and application of the findings.
REQUESTED REVISIONS:
The study design is appropriate, with randomization, double-blinding, and placebo control,
which strengthens its internal validity. However, the sample size is small, and the substantial
loss of patients during follow-up further compromises the robustness of the results. Another
major limitation is the lack of transparency regarding the handling of missing data from
patient dropouts. Regarding statistical analysis, the limited sample size for certain comparisons
significantly impacts the validity of the findings. Specifically, Table 2 should clearly indicate
the number of patients remaining in each group for different comparisons. Similarly, Table 3
would benefit from additional clarification regarding the number of patients analyzed.
Another relevant point that should be clarified is the timing of the baseline biochemical
measurements. Since BCAAs were administered postoperatively, the authors should indicate
when the baseline liver transaminases and other analytes were collected and when BCAAs were
administered. The observed differences in baseline values require explanation since it is unlikely
for the treatment to have had a measurable impact in such a short timeframe.
The study’s single-center design and short follow-up period, coupled with its heterogeneous
inclusion criteria, further restrict the generalizability of the findings. The study is directed
towards a clear objective, and the rationale is well-grounded although there are several
references clearly related with the topic that could be added:
Kikuchi N, Taketomi A, Harimoto N, et al. Oral administration of branched-chain amino
acids prevents post-hepatectomy ascites and pleural effusion in patients with hepatocellular
carcinoma. Ann Surg Oncol. 2016;23(8):2480-2488. doi:10.1245/s10434-016-5348-3
Beppu T, Okabe H, Shiraishi N, et al. The effect of branched-chain amino acid supplementation
on functional liver regeneration after portal vein embolization followed by hepatectomy:
A randomized control trial. J Gastroenterol Hepatol. 2015;30(4):667-673. doi:10.1007/
s00535-015-1067-y
San-In Group of Liver Surgery. Oral branched-chain amino acid supplementation after
curative resection of hepatocellular carcinoma: A prospective randomized trial. Br J Surg.
1997;84(11):1525-1529. doi:10.1002/bjs.6189471
assistant