Reviewer ’s report  
 
Title: Initially Elevated Arterial Lactate as an Independent Predi ctor of Poor Outcomes in Sev ere 
Acute Pancreatitis  
 
Version: 0 Date: 16 Jul 2019  
 
Reviewer: Jayanta Saman ta 
 
Reviewer's report:  
 
The manuscript has a very relevant topic on the issue of acute pancreatitis and the authors try to 
answer a very pertinent question of the need for suitable markers for prediction of SAP.  The 
following are my recommendations which needs to be addressed:  
 
 
Major Issues:  
 
1) in the methodology section, no mention has been done of the management protocol followed 
including the schedule of fluid resuscitation, whereon later the authors mention th at lactate levels 
rose in the non -survivor group even after "adequate" fluid resuscitation  
 
2) Abdominal compartment syndrome has been mentioned as an outcome measure, technique 
and definition used needs to be mentioned, and whether all patients underwent m onitoring of 
IAP 
 
3) In table 1., mean serum calcium was lower (1.9 vs 2; p=0.01) in the normal lactate group, 
whereas proportion of patients with serum calcium &lt;2 was higher in the elevated lactate group 
(61% vs 45%, p=0.06)!!! How can this be explained ? 
 
4) In table 1., patients with serum creatinine &gt;2 mg/dL was 74 (total). Modified Marshall 
score suggests creatinine &gt;1.9 mg/dL to have score of 2, and hence defines renal failure. 
Thus, by table 1.,  74 patients had renal failure, while in Table 2.  the combined patients having 
renal failure was 88 (17+52+19). Why this difference, needs clarification.  
 
5) For renal failure, by table 1., elevated lactate group had higher rates (29% vs 9%, p= &lt;0.01). 
Renal failure is known to cause rise in serum lacta te levels, hence would be a confounding 
factor, how have the authors accounted for that in the analysis. Similarly, cardiovascular failure 
was higher in the elevated lactate level group, which again is a confounding factor. The timing of 
development of the  organ failure versus measurement of lactate levels is important in this 
scenario, needs clarification  
 
6) The imaging severity scoring used wo rld wide is the CTSI, whereas the authors have used 
only the Balthazar grading, any particular reason for it  
 
7) The authors have mentioned in the abstract as well as the text regarding the measurement of 
serial lactate levels for 7 days. Fig 3 shows the graph for that, but no details has been mentioned 
in the results regarding the analysis used for that or the ob jective value other than just "trend in 
arterial lactate levels also different ......", needs further clarification.  
 
8) Arterial lactate levels measured at baseline during admission(first 3 days illness) may help 
predict severity of AP, but how can it help  predict development of septic shock or peri -pancreatic 
infection (mentioned as primary outcome measure in the study) which are infective 
complications and develop well beyond 1st week of illness, needs justification.  
 
 
Minor Issues:  
 
1) In the background, i t is stated "the morbidity and mortality of SAP may reach 15 -20% and 30 -
50%, respectively..", the figures have interchanged as morbidity will be higher than mortality  
 
2) In the background, it is written "Acute Physiology and Chronic Health Examination 
(APA CHE Ⅱ), systemic inflammatory response Syndrome (SIRS), blood urea nitrogen (BUN), 
creatinine, hematocrit, serum calcium, procalcitonin, Creactive protein (CRP), and "... the 
sentence abruptly ends with "and", needs correction.  
 
3) In the outcomes paragraph , the secondary outcomes sentence ends abruptly in "hospital stay in 
the." needs correction.  
 
This is just to mention a few. The  language of the manuscript needs major revamp and adequate 
proof reading before it can be taken up for publication.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the aut hors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical re view?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language i n the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursement s, fees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to al l of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my nam e will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made availabl e under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will no t be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Initially Elevated Arterial Lactate as an Independent Predi ctor of Poor Outcomes in Sev ere 
Acute Pancreatitis  
 
Version: 0 Date: 16 Jul 2019  
 
Reviewer: Jayanta Saman ta 
 
Reviewer's report:  
 
The manuscript has a very relevant topic on the issue of acute pancreatitis and the authors try to 
answer a very pertinent question of the need for suitable markers for prediction of SAP.  The 
following are my recommendations which needs to be addressed:  
 
 
Major Issues:  
 
1) in the methodology section, no mention has been done of the management protocol followed 
including the schedule of fluid resuscitation, whereon later the authors mention th at lactate levels 
rose in the non -survivor group even after "adequate" fluid resuscitation  
 
2) Abdominal compartment syndrome has been mentioned as an outcome measure, technique 
and definition used needs to be mentioned, and whether all patients underwent m onitoring of 
IAP 
 
3) In table 1., mean serum calcium was lower (1.9 vs 2; p=0.01) in the normal lactate group, 
whereas proportion of patients with serum calcium &lt;2 was higher in the elevated lactate group 
(61% vs 45%, p=0.06)!!! How can this be explained ? 
 
4) In table 1., patients with serum creatinine &gt;2 mg/dL was 74 (total). Modified Marshall 
score suggests creatinine &gt;1.9 mg/dL to have score of 2, and hence defines renal failure. 
Thus, by table 1.,  74 patients had renal failure, while in Table 2.  the combined patients having 
renal failure was 88 (17+52+19). Why this difference, needs clarification.  
 
5) For renal failure, by table 1., elevated lactate group had higher rates (29% vs 9%, p= &lt;0.01). 
Renal failure is known to cause rise in serum lacta te levels, hence would be a confounding 
factor, how have the authors accounted for that in the analysis. Similarly, cardiovascular failure 
was higher in the elevated lactate level group, which again is a confounding factor. The timing of 
development of the  organ failure versus measurement of lactate levels is important in this 
scenario, needs clarification  
 
6) The imaging severity scoring used wo rld wide is the CTSI, whereas the authors have used 
only the Balthazar grading, any particular reason for it  
 
7) The authors have mentioned in the abstract as well as the text regarding the measurement of 
serial lactate levels for 7 days. Fig 3 shows the graph for that, but no details has been mentioned 
in the results regarding the analysis used for that or the ob jective value other than just "trend in 
arterial lactate levels also different ......", needs further clarification.  
 
8) Arterial lactate levels measured at baseline during admission(first 3 days illness) may help 
predict severity of AP, but how can it help  predict development of septic shock or peri -pancreatic 
infection (mentioned as primary outcome measure in the study) which are infective 
complications and develop well beyond 1st week of illness, needs justification.  
 
 
Minor Issues:  
 
1) In the background, i t is stated "the morbidity and mortality of SAP may reach 15 -20% and 30 -
50%, respectively..", the figures have interchanged as morbidity will be higher than mortality  
 
2) In the background, it is written "Acute Physiology and Chronic Health Examination 
(APA CHE Ⅱ), systemic inflammatory response Syndrome (SIRS), blood urea nitrogen (BUN), 
creatinine, hematocrit, serum calcium, procalcitonin, Creactive protein (CRP), and "... the 
sentence abruptly ends with "and", needs correction.  
 
3) In the outcomes paragraph , the secondary outcomes sentence ends abruptly in "hospital stay in 
the." needs correction.  
 
This is just to mention a few. The  language of the manuscript needs major revamp and adequate 
proof reading before it can be taken up for publication.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the aut hors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical re view?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language i n the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursement s, fees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to al l of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my nam e will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made availabl e under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will no t be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Initially Elevated Arterial Lactate as an Independent Predi ctor of Poor Outcomes in Sev ere 
Acute Pancreatitis  
 
Version: 0 Date: 16 Jul 2019  
 
Reviewer: Jayanta Saman ta 
 
Reviewer's report:  
 
The manuscript has a very relevant topic on the issue of acute pancreatitis and the authors try to 
answer a very pertinent question of the need for suitable markers for prediction of SAP.  The 
following are my recommendations which needs to be addressed:  
 
 
Major Issues:  
 
1) in the methodology section, no mention has been done of the management protocol followed 
including the schedule of fluid resuscitation, whereon later the authors mention th at lactate levels 
rose in the non -survivor group even after "adequate" fluid resuscitation  
 
2) Abdominal compartment syndrome has been mentioned as an outcome measure, technique 
and definition used needs to be mentioned, and whether all patients underwent m onitoring of 
IAP 
 
3) In table 1., mean serum calcium was lower (1.9 vs 2; p=0.01) in the normal lactate group, 
whereas proportion of patients with serum calcium &lt;2 was higher in the elevated lactate group 
(61% vs 45%, p=0.06)!!! How can this be explained ? 
 
4) In table 1., patients with serum creatinine &gt;2 mg/dL was 74 (total). Modified Marshall 
score suggests creatinine &gt;1.9 mg/dL to have score of 2, and hence defines renal failure. 
Thus, by table 1.,  74 patients had renal failure, while in Table 2.  the combined patients having 
renal failure was 88 (17+52+19). Why this difference, needs clarification.  
 
5) For renal failure, by table 1., elevated lactate group had higher rates (29% vs 9%, p= &lt;0.01). 
Renal failure is known to cause rise in serum lacta te levels, hence would be a confounding 
factor, how have the authors accounted for that in the analysis. Similarly, cardiovascular failure 
was higher in the elevated lactate level group, which again is a confounding factor. The timing of 
development of the  organ failure versus measurement of lactate levels is important in this 
scenario, needs clarification  
 
6) The imaging severity scoring used wo rld wide is the CTSI, whereas the authors have used 
only the Balthazar grading, any particular reason for it  
 
7) The authors have mentioned in the abstract as well as the text regarding the measurement of 
serial lactate levels for 7 days. Fig 3 shows the graph for that, but no details has been mentioned 
in the results regarding the analysis used for that or the ob jective value other than just "trend in 
arterial lactate levels also different ......", needs further clarification.  
 
8) Arterial lactate levels measured at baseline during admission(first 3 days illness) may help 
predict severity of AP, but how can it help  predict development of septic shock or peri -pancreatic 
infection (mentioned as primary outcome measure in the study) which are infective 
complications and develop well beyond 1st week of illness, needs justification.  
 
 
Minor Issues:  
 
1) In the background, i t is stated "the morbidity and mortality of SAP may reach 15 -20% and 30 -
50%, respectively..", the figures have interchanged as morbidity will be higher than mortality  
 
2) In the background, it is written "Acute Physiology and Chronic Health Examination 
(APA CHE Ⅱ), systemic inflammatory response Syndrome (SIRS), blood urea nitrogen (BUN), 
creatinine, hematocrit, serum calcium, procalcitonin, Creactive protein (CRP), and "... the 
sentence abruptly ends with "and", needs correction.  
 
3) In the outcomes paragraph , the secondary outcomes sentence ends abruptly in "hospital stay in 
the." needs correction.  
 
This is just to mention a few. The  language of the manuscript needs major revamp and adequate 
proof reading before it can be taken up for publication.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the aut hors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical re view?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language i n the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursement s, fees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to al l of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my nam e will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made availabl e under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will no t be published.  
 
I agree to the open peer review policy of the journal  
assistant