Title: Prognostic clinical indexes for prediction of acute gangrenous cholecystitis and acute
purulent cholecystitis
Version: 4 Date: 25 Jul 2022
Reviewer:  Ahmed Nassar
Reviewer's report:
Dear Author,
thank you for submitting your work to this journal. You aimed in your study to identify
criteria associated with severe forms of acute cholecystitis which I find it useful and can
improve outcomes of those patients. However, I have major concerns about the methodology
and subsequently, results of this study. I don't think this adds much to existing literature .
Below, are few points I would like to highlight:
Major concerns:
1- To establish prediction tool to predict severe forms of acute cholecystitis, a comparison needs
to be made with mild forms of cholecystitis , not chronic cholecystitis patients undergoing
elective operation.  Moreover, from the methodology point of view , I think including only
patients had surgery constitute a source of significant bias when trying for find predictive factors
of severe acute cholecystitis.
2- Inclusion criteria are not  clear . Did you include all patients had gallbladder removal whether
it was elective or emergency surgery? The reason I am asking this is because you mentioned in
your inclusion criteria that you included patients with cholecystitis according to Tokyo criteria
(1) . These guidelines only describes criteria of acute cholecystitis but not chronic cholecystitis.
One more point: definition of severe cholecystitis in Tokyo guidelines (1)  is totally different
from what has been defined in this study.  In your study you identified presence of gangrenous
cholecystitis , acute gangrenous cholecystitis or acute purulent cholecystitis is an indication of
severe cholecystitis whereas in Tokyo guidelines , presence of organ dysfunction is one of the
criteria of diagnosing acute cholecystitis.
Moreover, you did not mention specifically , what are diagnostic modalities used to diagnose
gallstone disease.
3- Definitions of gangrenous cholecystitis , acute gangrenous cholecystitis (is there any clinical
difference from the former one?) and acute purulent cholecystitis are insufficient. Are these
based on pathological examination?  and why specifically you included these sub-types.
4- Clinical picture of  patients with acute cholecystitis was not described which I think is a very
important aspect in deciding management plan.
5-  There was no satisfying explanation about the high conversion rate to open (>50%) and the
decision to perform primary open surgery in 97 out of 114 . were there any patients had sub-
total cholecystectomy?
Minor concerns:
1- grammatical inaccuracies across the manuscript.
2- Full explanations of abbreviations in table 1 and 2 .
3- t-test was used which assumes normal distribution of data and comparison of only two groups .
is this the case.
4- In the first Paragraph of the discussion, you mentioned ''In previous studies, neutrophil to
lymphocyte ratio (NLR) was widely used to differentiate SC from CC, as it was related to
inflammatory responses '' but you only mentioned one reference (2) which it does not look like
it is related to this topic at all as it is a reference to a study titled : Influence of dialysis modality
and membrane flux on quality of life in hemodialysis patients. Can you , please explain this?
References:
1- Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H, et al. New
diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines.
J Hepatobiliary Pancreat Sci. 2012;19:578–85
2-Knezevic MZ, Djordjevic VV, Radovanovic-Velickovic RM, Stankovic JJ, Cvetkovic TP,
Djordjevic VM. Influence of dialysis modality and membrane flux on quality of life in
hemodialysis patients. Ren Fail. 2012;34:849–55.
Title: Prognostic clinical indexes for prediction of acute gangrenous cholecystitis and acute
purulent cholecystitis
Version: 4 Date: 25 Jul 2022
Reviewer:  Ahmed Nassar
Reviewer's report:
Dear Author,
thank you for submitting your work to this journal. You aimed in your study to identify
criteria associated with severe forms of acute cholecystitis which I find it useful and can
improve outcomes of those patients. However, I have major concerns about the methodology
and subsequently, results of this study. I don't think this adds much to existing literature .
Below, are few points I would like to highlight:
Major concerns:
1- To establish prediction tool to predict severe forms of acute cholecystitis, a comparison needs
to be made with mild forms of cholecystitis , not chronic cholecystitis patients undergoing
elective operation.  Moreover, from the methodology point of view , I think including only
patients had surgery constitute a source of significant bias when trying for find predictive factors
of severe acute cholecystitis.
2- Inclusion criteria are not  clear . Did you include all patients had gallbladder removal whether
it was elective or emergency surgery? The reason I am asking this is because you mentioned in
your inclusion criteria that you included patients with cholecystitis according to Tokyo criteria
(1) . These guidelines only describes criteria of acute cholecystitis but not chronic cholecystitis.
One more point: definition of severe cholecystitis in Tokyo guidelines (1)  is totally different
from what has been defined in this study.  In your study you identified presence of gangrenous
cholecystitis , acute gangrenous cholecystitis or acute purulent cholecystitis is an indication of
severe cholecystitis whereas in Tokyo guidelines , presence of organ dysfunction is one of the
criteria of diagnosing acute cholecystitis.
Moreover, you did not mention specifically , what are diagnostic modalities used to diagnose
gallstone disease.
3- Definitions of gangrenous cholecystitis , acute gangrenous cholecystitis (is there any clinical
difference from the former one?) and acute purulent cholecystitis are insufficient. Are these
based on pathological examination?  and why specifically you included these sub-types.
4- Clinical picture of  patients with acute cholecystitis was not described which I think is a very
important aspect in deciding management plan.
5-  There was no satisfying explanation about the high conversion rate to open (>50%) and the
decision to perform primary open surgery in 97 out of 114 . were there any patients had sub-
total cholecystectomy?
Minor concerns:
1- grammatical inaccuracies across the manuscript.
2- Full explanations of abbreviations in table 1 and 2 .
3- t-test was used which assumes normal distribution of data and comparison of only two groups .
is this the case.
4- In the first Paragraph of the discussion, you mentioned ''In previous studies, neutrophil to
lymphocyte ratio (NLR) was widely used to differentiate SC from CC, as it was related to
inflammatory responses '' but you only mentioned one reference (2) which it does not look like
it is related to this topic at all as it is a reference to a study titled : Influence of dialysis modality
and membrane flux on quality of life in hemodialysis patients. Can you , please explain this?
References:
1- Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H, et al. New
diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines.
J Hepatobiliary Pancreat Sci. 2012;19:578–85
2-Knezevic MZ, Djordjevic VV, Radovanovic-Velickovic RM, Stankovic JJ, Cvetkovic TP,
Djordjevic VM. Influence of dialysis modality and membrane flux on quality of life in
hemodialysis patients. Ren Fail. 2012;34:849–55.
Please review this paper.
user
Title: Prognostic clinical indexes for prediction of acute gangrenous cholecystitis and acute
purulent cholecystitis
Version: 4 Date: 25 Jul 2022
Reviewer:  Ahmed Nassar
Reviewer's report:
Dear Author,
thank you for submitting your work to this journal. You aimed in your study to identify
criteria associated with severe forms of acute cholecystitis which I find it useful and can
improve outcomes of those patients. However, I have major concerns about the methodology
and subsequently, results of this study. I don't think this adds much to existing literature .
Below, are few points I would like to highlight:
Major concerns:
1- To establish prediction tool to predict severe forms of acute cholecystitis, a comparison needs
to be made with mild forms of cholecystitis , not chronic cholecystitis patients undergoing
elective operation.  Moreover, from the methodology point of view , I think including only
patients had surgery constitute a source of significant bias when trying for find predictive factors
of severe acute cholecystitis.
2- Inclusion criteria are not  clear . Did you include all patients had gallbladder removal whether
it was elective or emergency surgery? The reason I am asking this is because you mentioned in
your inclusion criteria that you included patients with cholecystitis according to Tokyo criteria
(1) . These guidelines only describes criteria of acute cholecystitis but not chronic cholecystitis.
One more point: definition of severe cholecystitis in Tokyo guidelines (1)  is totally different
from what has been defined in this study.  In your study you identified presence of gangrenous
cholecystitis , acute gangrenous cholecystitis or acute purulent cholecystitis is an indication of
severe cholecystitis whereas in Tokyo guidelines , presence of organ dysfunction is one of the
criteria of diagnosing acute cholecystitis.
Moreover, you did not mention specifically , what are diagnostic modalities used to diagnose
gallstone disease.
3- Definitions of gangrenous cholecystitis , acute gangrenous cholecystitis (is there any clinical
difference from the former one?) and acute purulent cholecystitis are insufficient. Are these
based on pathological examination?  and why specifically you included these sub-types.
4- Clinical picture of  patients with acute cholecystitis was not described which I think is a very
important aspect in deciding management plan.
5-  There was no satisfying explanation about the high conversion rate to open (>50%) and the
decision to perform primary open surgery in 97 out of 114 . were there any patients had sub-
total cholecystectomy?
Minor concerns:
1- grammatical inaccuracies across the manuscript.
2- Full explanations of abbreviations in table 1 and 2 .
3- t-test was used which assumes normal distribution of data and comparison of only two groups .
is this the case.
4- In the first Paragraph of the discussion, you mentioned ''In previous studies, neutrophil to
lymphocyte ratio (NLR) was widely used to differentiate SC from CC, as it was related to
inflammatory responses '' but you only mentioned one reference (2) which it does not look like
it is related to this topic at all as it is a reference to a study titled : Influence of dialysis modality
and membrane flux on quality of life in hemodialysis patients. Can you , please explain this?
References:
1- Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H, et al. New
diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines.
J Hepatobiliary Pancreat Sci. 2012;19:578–85
2-Knezevic MZ, Djordjevic VV, Radovanovic-Velickovic RM, Stankovic JJ, Cvetkovic TP,
Djordjevic VM. Influence of dialysis modality and membrane flux on quality of life in
hemodialysis patients. Ren Fail. 2012;34:849–55.
assistant