Reviewer's report
Title:Outcome of liver transplantation with Histidine-Tryptophan-Ketoglutarate vs.
University of Wisconsin preservation solution: A retrospective observational
double-center trial
Version:2Date:7 May 2014
Reviewer: Homan Wai
Reviewer's report:
The authors have submitted a manuscript that tries to address an interesting
question: does the choice of preservation solution affect the outcome after liver
transplantation in terms of patient and graft survival. A retrospective analysis was
done on 2 separate cohorts from 2 centers. The results were analyzed separated
in each cohort. The primary endpoints included short term patient survival, long
term patient survival, short term graft survival, and long term graft survival.
Secondary endpoints included occurrence of post transplant complications (list
included), necessity of operative revisions, length of stay, and length of stay in
the ICU. The authors found that after adjusting for different variables in the
multivariate analyses, none of the outcomes had any statistically significant
differences between the two types of solutions studied: THK and UW. Overall the
question is valid and the method is valid. I think the language can improved and I
have provided some suggestion below. Though this feels like 2 separate paper
as the 2 cohorts are analyzed separately, I think it is permitted. Though I would
like to see more uniformity or explanation as to why, for example, that subset
analysis was only done in the Hannover cohort and economic evaluation only
done in the Kiel cohort. There were also some differences in Era that were
shown in the tables that were not explained in detail in the discussion.
Furthermore, I feel that more graphs and tables are in order to represent the
result in that manner. Not just for selected outcomes. This is a workable paper
but does need much revision.
I have the following specific comments for consideration:
A) Major Compulsory Revisions (The author must respond to these before a
decision on publication can be reached. For example, additional necessary
experiments or controls, statistical mistakes, errors in interpretation.)
- some of these issues may be best answered by a statistician.
1. - Under Results in the abstract, the 2nd secondary outcome (necessity of
operative revisions) was not mentioned.
2. - I don’t think the fact that HTK is easier to handle/less expensive should be
under the Result section. Perhaps under discussion would be more suitable.
3. - Why was subset analysis only done in the Hannover cohort but not the Kiel?
4. - Under Figure 1, why was the usage of solutions over the follow up time not
shown for the Kiel cohort?
5. - Why is the Kaplan Meier analysis of the Hannover cohort shown in Figure 2
but not the Kiel cohort?
6. - A graphical demonstration of the dose effect regarding the amount of PS
would be nice.
7. - In Table 2A, the THK and UW under Era IV does not add up to 100%.
8. - Under Results -> The Kiel cohort -> re: Patient and graft survival, were those
long term or short term?
9. - Under Results -> The Kiel cohort -> how come there was discussion
regarding occurrence of biliary complications but not of other types of
complications post transplant? Were there no data re: HAT, PVT, CVT, post op
hemorrhage, and LOS?
10. - How come the economic evaluation was done only under the Kiel cohort
and not the Hannover?
11. - Under Discussion: “Further[more], UW and HTK were both applied in nearly
fifty-fifty distribution” - one cannot claim a 50:50 distribution with with 57% vs
43% in the Hannover Cohort, and 62% vs 38% in the Kiel cohort.
12. - There was a wealth of data presented in Table 2A and 2B delineating trends
as one goes from Era I to IV. Not much of this data was discussed in the text at
all. I may suggest elaborating more on it or not show this much details at all.
B) Minor Essential Revisions (The author can be trusted to make these. For
example, missing labels on figures, the wrong use of a term, spelling mistakes.)
1. - Under Background in abstract: The question [of] whether…
2. - I would advise describing the primary and secondary outcomes under the
methods section in the abstract.
3. - Under Results in the abstract, This was confirmed [in subgroup analysis of ]
living donor and pediatric transplantation and...
4. - Table 2A, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
5. - Table 2B, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
6. - Under Background: Both have been applied for decades… preferences [with]
several [known] differences.
7. - Under Background: Additionally, a focused investigation of biliary
complications [was] part of this analysis.
8. - Under Statistical methods: To avoid over-fitting[,] all variables with an
alpha…
9. - Under Clinical handling of UW and HTK: Before application[,] several
additives, such [as] prostaglandin E1…
10. - Under Results -> The Hannover cohort -> Complications after LTX: The
choice of PS did [not] influence….. [nor] the necessity of operative revisions…
11. - “Furthermore” instead of “Further” in multiple places of the paper
12. - Under Results -> The Hannover cohort -> Length of hospital and ICU stay:
Neither… after LTX were [affected by the choice of] applied PS.
13. - Under Discussion: PS on outcome… complications [(]especially in the
biliary tract [)], and rejection…
C) Discretionary Revisions (These are recommendations for improvement which
the author can choose to ignore. For example clarifications, data that would be
useful but not essential.)
1. - Under Results -> The Hannover cohort -> Patient survival…. consider
replacing “Three-month mortality” with “Short-term patient survival” to be clear
that this is one of the primary endpoints that is being discussed.
2. - There was some comparison in Table 1 of the top 5 indicators of liver
transplantation between the 2 group, and under Patients and Methods there was
mention of sex, age, and range of follow up of the 2 groups. It would be nice to
have a large table comparing the characteristics of the 2 groups side by side,
with explanation of why they are analyzed separately instead of together.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
nothing to declare
Reviewer's report
Title:Outcome of liver transplantation with Histidine-Tryptophan-Ketoglutarate vs.
University of Wisconsin preservation solution: A retrospective observational
double-center trial
Version:2Date:7 May 2014
Reviewer: Homan Wai
Reviewer's report:
The authors have submitted a manuscript that tries to address an interesting
question: does the choice of preservation solution affect the outcome after liver
transplantation in terms of patient and graft survival. A retrospective analysis was
done on 2 separate cohorts from 2 centers. The results were analyzed separated
in each cohort. The primary endpoints included short term patient survival, long
term patient survival, short term graft survival, and long term graft survival.
Secondary endpoints included occurrence of post transplant complications (list
included), necessity of operative revisions, length of stay, and length of stay in
the ICU. The authors found that after adjusting for different variables in the
multivariate analyses, none of the outcomes had any statistically significant
differences between the two types of solutions studied: THK and UW. Overall the
question is valid and the method is valid. I think the language can improved and I
have provided some suggestion below. Though this feels like 2 separate paper
as the 2 cohorts are analyzed separately, I think it is permitted. Though I would
like to see more uniformity or explanation as to why, for example, that subset
analysis was only done in the Hannover cohort and economic evaluation only
done in the Kiel cohort. There were also some differences in Era that were
shown in the tables that were not explained in detail in the discussion.
Furthermore, I feel that more graphs and tables are in order to represent the
result in that manner. Not just for selected outcomes. This is a workable paper
but does need much revision.
I have the following specific comments for consideration:
A) Major Compulsory Revisions (The author must respond to these before a
decision on publication can be reached. For example, additional necessary
experiments or controls, statistical mistakes, errors in interpretation.)
- some of these issues may be best answered by a statistician.
1. - Under Results in the abstract, the 2nd secondary outcome (necessity of
operative revisions) was not mentioned.
2. - I don’t think the fact that HTK is easier to handle/less expensive should be
under the Result section. Perhaps under discussion would be more suitable.
3. - Why was subset analysis only done in the Hannover cohort but not the Kiel?
4. - Under Figure 1, why was the usage of solutions over the follow up time not
shown for the Kiel cohort?
5. - Why is the Kaplan Meier analysis of the Hannover cohort shown in Figure 2
but not the Kiel cohort?
6. - A graphical demonstration of the dose effect regarding the amount of PS
would be nice.
7. - In Table 2A, the THK and UW under Era IV does not add up to 100%.
8. - Under Results -> The Kiel cohort -> re: Patient and graft survival, were those
long term or short term?
9. - Under Results -> The Kiel cohort -> how come there was discussion
regarding occurrence of biliary complications but not of other types of
complications post transplant? Were there no data re: HAT, PVT, CVT, post op
hemorrhage, and LOS?
10. - How come the economic evaluation was done only under the Kiel cohort
and not the Hannover?
11. - Under Discussion: “Further[more], UW and HTK were both applied in nearly
fifty-fifty distribution” - one cannot claim a 50:50 distribution with with 57% vs
43% in the Hannover Cohort, and 62% vs 38% in the Kiel cohort.
12. - There was a wealth of data presented in Table 2A and 2B delineating trends
as one goes from Era I to IV. Not much of this data was discussed in the text at
all. I may suggest elaborating more on it or not show this much details at all.
B) Minor Essential Revisions (The author can be trusted to make these. For
example, missing labels on figures, the wrong use of a term, spelling mistakes.)
1. - Under Background in abstract: The question [of] whether…
2. - I would advise describing the primary and secondary outcomes under the
methods section in the abstract.
3. - Under Results in the abstract, This was confirmed [in subgroup analysis of ]
living donor and pediatric transplantation and...
4. - Table 2A, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
5. - Table 2B, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
6. - Under Background: Both have been applied for decades… preferences [with]
several [known] differences.
7. - Under Background: Additionally, a focused investigation of biliary
complications [was] part of this analysis.
8. - Under Statistical methods: To avoid over-fitting[,] all variables with an
alpha…
9. - Under Clinical handling of UW and HTK: Before application[,] several
additives, such [as] prostaglandin E1…
10. - Under Results -> The Hannover cohort -> Complications after LTX: The
choice of PS did [not] influence….. [nor] the necessity of operative revisions…
11. - “Furthermore” instead of “Further” in multiple places of the paper
12. - Under Results -> The Hannover cohort -> Length of hospital and ICU stay:
Neither… after LTX were [affected by the choice of] applied PS.
13. - Under Discussion: PS on outcome… complications [(]especially in the
biliary tract [)], and rejection…
C) Discretionary Revisions (These are recommendations for improvement which
the author can choose to ignore. For example clarifications, data that would be
useful but not essential.)
1. - Under Results -> The Hannover cohort -> Patient survival…. consider
replacing “Three-month mortality” with “Short-term patient survival” to be clear
that this is one of the primary endpoints that is being discussed.
2. - There was some comparison in Table 1 of the top 5 indicators of liver
transplantation between the 2 group, and under Patients and Methods there was
mention of sex, age, and range of follow up of the 2 groups. It would be nice to
have a large table comparing the characteristics of the 2 groups side by side,
with explanation of why they are analyzed separately instead of together.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
nothing to declare
Please review this paper.
user
Reviewer's report
Title:Outcome of liver transplantation with Histidine-Tryptophan-Ketoglutarate vs.
University of Wisconsin preservation solution: A retrospective observational
double-center trial
Version:2Date:7 May 2014
Reviewer: Homan Wai
Reviewer's report:
The authors have submitted a manuscript that tries to address an interesting
question: does the choice of preservation solution affect the outcome after liver
transplantation in terms of patient and graft survival. A retrospective analysis was
done on 2 separate cohorts from 2 centers. The results were analyzed separated
in each cohort. The primary endpoints included short term patient survival, long
term patient survival, short term graft survival, and long term graft survival.
Secondary endpoints included occurrence of post transplant complications (list
included), necessity of operative revisions, length of stay, and length of stay in
the ICU. The authors found that after adjusting for different variables in the
multivariate analyses, none of the outcomes had any statistically significant
differences between the two types of solutions studied: THK and UW. Overall the
question is valid and the method is valid. I think the language can improved and I
have provided some suggestion below. Though this feels like 2 separate paper
as the 2 cohorts are analyzed separately, I think it is permitted. Though I would
like to see more uniformity or explanation as to why, for example, that subset
analysis was only done in the Hannover cohort and economic evaluation only
done in the Kiel cohort. There were also some differences in Era that were
shown in the tables that were not explained in detail in the discussion.
Furthermore, I feel that more graphs and tables are in order to represent the
result in that manner. Not just for selected outcomes. This is a workable paper
but does need much revision.
I have the following specific comments for consideration:
A) Major Compulsory Revisions (The author must respond to these before a
decision on publication can be reached. For example, additional necessary
experiments or controls, statistical mistakes, errors in interpretation.)
- some of these issues may be best answered by a statistician.
1. - Under Results in the abstract, the 2nd secondary outcome (necessity of
operative revisions) was not mentioned.
2. - I don’t think the fact that HTK is easier to handle/less expensive should be
under the Result section. Perhaps under discussion would be more suitable.
3. - Why was subset analysis only done in the Hannover cohort but not the Kiel?
4. - Under Figure 1, why was the usage of solutions over the follow up time not
shown for the Kiel cohort?
5. - Why is the Kaplan Meier analysis of the Hannover cohort shown in Figure 2
but not the Kiel cohort?
6. - A graphical demonstration of the dose effect regarding the amount of PS
would be nice.
7. - In Table 2A, the THK and UW under Era IV does not add up to 100%.
8. - Under Results -> The Kiel cohort -> re: Patient and graft survival, were those
long term or short term?
9. - Under Results -> The Kiel cohort -> how come there was discussion
regarding occurrence of biliary complications but not of other types of
complications post transplant? Were there no data re: HAT, PVT, CVT, post op
hemorrhage, and LOS?
10. - How come the economic evaluation was done only under the Kiel cohort
and not the Hannover?
11. - Under Discussion: “Further[more], UW and HTK were both applied in nearly
fifty-fifty distribution” - one cannot claim a 50:50 distribution with with 57% vs
43% in the Hannover Cohort, and 62% vs 38% in the Kiel cohort.
12. - There was a wealth of data presented in Table 2A and 2B delineating trends
as one goes from Era I to IV. Not much of this data was discussed in the text at
all. I may suggest elaborating more on it or not show this much details at all.
B) Minor Essential Revisions (The author can be trusted to make these. For
example, missing labels on figures, the wrong use of a term, spelling mistakes.)
1. - Under Background in abstract: The question [of] whether…
2. - I would advise describing the primary and secondary outcomes under the
methods section in the abstract.
3. - Under Results in the abstract, This was confirmed [in subgroup analysis of ]
living donor and pediatric transplantation and...
4. - Table 2A, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
5. - Table 2B, Column for Era IV, Row for 3 months mortality, the number was
not centered on the cell.
6. - Under Background: Both have been applied for decades… preferences [with]
several [known] differences.
7. - Under Background: Additionally, a focused investigation of biliary
complications [was] part of this analysis.
8. - Under Statistical methods: To avoid over-fitting[,] all variables with an
alpha…
9. - Under Clinical handling of UW and HTK: Before application[,] several
additives, such [as] prostaglandin E1…
10. - Under Results -> The Hannover cohort -> Complications after LTX: The
choice of PS did [not] influence….. [nor] the necessity of operative revisions…
11. - “Furthermore” instead of “Further” in multiple places of the paper
12. - Under Results -> The Hannover cohort -> Length of hospital and ICU stay:
Neither… after LTX were [affected by the choice of] applied PS.
13. - Under Discussion: PS on outcome… complications [(]especially in the
biliary tract [)], and rejection…
C) Discretionary Revisions (These are recommendations for improvement which
the author can choose to ignore. For example clarifications, data that would be
useful but not essential.)
1. - Under Results -> The Hannover cohort -> Patient survival…. consider
replacing “Three-month mortality” with “Short-term patient survival” to be clear
that this is one of the primary endpoints that is being discussed.
2. - There was some comparison in Table 1 of the top 5 indicators of liver
transplantation between the 2 group, and under Patients and Methods there was
mention of sex, age, and range of follow up of the 2 groups. It would be nice to
have a large table comparing the characteristics of the 2 groups side by side,
with explanation of why they are analyzed separately instead of together.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
nothing to declare
assistant