Title: Construction and validation of a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage
Version: 3 Date: 05 Sep 2024
Reviewer's report:
This study aims to develop and validate a predictive model for the risk of rebleeding in
patients with esophageal and gastric varices hemorrhage (EGVH), a serious complication
of portal hypertension. The model is based on six clinical factors, including systolic blood
pressure, platelet count, and the severity of esophageal varices, and shows improved predictive
performance compared to the Glasgow-Blatchford and Rockall scores. While the model
demonstrates good specificity and AUC, its sensitivity remains relatively low. The study is
limited by its single-center retrospective design and the absence of external validation. Some
epidemiologic and clinical data regarding the patients was not mentioned in the study. Overall,
the model offers potential for better risk stratification but requires further validation in diverse
clinical settings to confirm its clinical utility.
I do have some concerns  that need to be answered regarding the study.
1. The language in some sections of the manuscript is verbose and could benefit from being more
concise. For instance, certain parts of the methodology and results are overly detailed, which
may distract readers from the core findings. I would suggest to simplify and clarify sentences,
especially in the methods and results section. Use clear and concise language to present the key
findings and statistical outcomes.
2. It would be beneficial to provide a deeper rationale for choosing certain statistical techniques,
such as why stepwise regression was used over other methods like LASSO or Ridge regression,
which are often preferred for handling multicollinearity and improving model interpretability.
Please include a justification for the choice of stepwise regression, and consider discussing
alternative methods that might have been appropriate. Providing a comparison of model
performance with these alternatives could further enhance the study’s robustness.
3. The study mentions several clinical factors included in the model, but it does not address
potential confounders in enough depth. For example - can you explain why CA 19.9 affects
the re-bleeding rates in patient with viral bleeding?  Factors such as liver function (e.g., MELD
score) and clinical information such as age, gender, fibrosis stage of the liver, etiology of varices,
and other background illnesses, which can influence rebleeding risk, were not mentioned or
accounted for. I would suggest at least mentioning potential confounders and explain how they
were addressed in the analysis (e.g., sensitivity analyses). If some confounders were not included
due to data limitations, discuss this as a limitation and suggest how future studies could account
for them.
4. In the discussion part you mentioned: “The positive correlation between CA199 and
rebleeding probability might be due to the close association of CA199 with disease progression
in gastrointestinal tumors such as gastric cancer, pancreatic cancer, and colorectal cancer, which
to some extent increases the risk of rebleeding.” Despite the discussion on this matter, I still do
not understand how CA 199 can explain rebleeding from viruses in patient with cirrhosis.
5.  While the manuscript includes detailed statistical results, it lacks sufficient interpretation
of the clinical implications of these findings. Specifically, how the predictive model will alter
clinical practice in managing patients at risk of rebleeding needs more elaboration.
6. In the abstract method part please change: “Compare the predictive power of the new
predictive model with GBS and pRS scoring systems”. This sentence should start with “We
compared”
Title: Construction and validation of a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage
Version: 3 Date: 05 Sep 2024
Reviewer's report:
This study aims to develop and validate a predictive model for the risk of rebleeding in
patients with esophageal and gastric varices hemorrhage (EGVH), a serious complication
of portal hypertension. The model is based on six clinical factors, including systolic blood
pressure, platelet count, and the severity of esophageal varices, and shows improved predictive
performance compared to the Glasgow-Blatchford and Rockall scores. While the model
demonstrates good specificity and AUC, its sensitivity remains relatively low. The study is
limited by its single-center retrospective design and the absence of external validation. Some
epidemiologic and clinical data regarding the patients was not mentioned in the study. Overall,
the model offers potential for better risk stratification but requires further validation in diverse
clinical settings to confirm its clinical utility.
I do have some concerns  that need to be answered regarding the study.
1. The language in some sections of the manuscript is verbose and could benefit from being more
concise. For instance, certain parts of the methodology and results are overly detailed, which
may distract readers from the core findings. I would suggest to simplify and clarify sentences,
especially in the methods and results section. Use clear and concise language to present the key
findings and statistical outcomes.
2. It would be beneficial to provide a deeper rationale for choosing certain statistical techniques,
such as why stepwise regression was used over other methods like LASSO or Ridge regression,
which are often preferred for handling multicollinearity and improving model interpretability.
Please include a justification for the choice of stepwise regression, and consider discussing
alternative methods that might have been appropriate. Providing a comparison of model
performance with these alternatives could further enhance the study’s robustness.
3. The study mentions several clinical factors included in the model, but it does not address
potential confounders in enough depth. For example - can you explain why CA 19.9 affects
the re-bleeding rates in patient with viral bleeding?  Factors such as liver function (e.g., MELD
score) and clinical information such as age, gender, fibrosis stage of the liver, etiology of varices,
and other background illnesses, which can influence rebleeding risk, were not mentioned or
accounted for. I would suggest at least mentioning potential confounders and explain how they
were addressed in the analysis (e.g., sensitivity analyses). If some confounders were not included
due to data limitations, discuss this as a limitation and suggest how future studies could account
for them.
4. In the discussion part you mentioned: “The positive correlation between CA199 and
rebleeding probability might be due to the close association of CA199 with disease progression
in gastrointestinal tumors such as gastric cancer, pancreatic cancer, and colorectal cancer, which
to some extent increases the risk of rebleeding.” Despite the discussion on this matter, I still do
not understand how CA 199 can explain rebleeding from viruses in patient with cirrhosis.
5.  While the manuscript includes detailed statistical results, it lacks sufficient interpretation
of the clinical implications of these findings. Specifically, how the predictive model will alter
clinical practice in managing patients at risk of rebleeding needs more elaboration.
6. In the abstract method part please change: “Compare the predictive power of the new
predictive model with GBS and pRS scoring systems”. This sentence should start with “We
compared”
Please review this paper.
user
Title: Construction and validation of a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage
Version: 3 Date: 05 Sep 2024
Reviewer's report:
This study aims to develop and validate a predictive model for the risk of rebleeding in
patients with esophageal and gastric varices hemorrhage (EGVH), a serious complication
of portal hypertension. The model is based on six clinical factors, including systolic blood
pressure, platelet count, and the severity of esophageal varices, and shows improved predictive
performance compared to the Glasgow-Blatchford and Rockall scores. While the model
demonstrates good specificity and AUC, its sensitivity remains relatively low. The study is
limited by its single-center retrospective design and the absence of external validation. Some
epidemiologic and clinical data regarding the patients was not mentioned in the study. Overall,
the model offers potential for better risk stratification but requires further validation in diverse
clinical settings to confirm its clinical utility.
I do have some concerns  that need to be answered regarding the study.
1. The language in some sections of the manuscript is verbose and could benefit from being more
concise. For instance, certain parts of the methodology and results are overly detailed, which
may distract readers from the core findings. I would suggest to simplify and clarify sentences,
especially in the methods and results section. Use clear and concise language to present the key
findings and statistical outcomes.
2. It would be beneficial to provide a deeper rationale for choosing certain statistical techniques,
such as why stepwise regression was used over other methods like LASSO or Ridge regression,
which are often preferred for handling multicollinearity and improving model interpretability.
Please include a justification for the choice of stepwise regression, and consider discussing
alternative methods that might have been appropriate. Providing a comparison of model
performance with these alternatives could further enhance the study’s robustness.
3. The study mentions several clinical factors included in the model, but it does not address
potential confounders in enough depth. For example - can you explain why CA 19.9 affects
the re-bleeding rates in patient with viral bleeding?  Factors such as liver function (e.g., MELD
score) and clinical information such as age, gender, fibrosis stage of the liver, etiology of varices,
and other background illnesses, which can influence rebleeding risk, were not mentioned or
accounted for. I would suggest at least mentioning potential confounders and explain how they
were addressed in the analysis (e.g., sensitivity analyses). If some confounders were not included
due to data limitations, discuss this as a limitation and suggest how future studies could account
for them.
4. In the discussion part you mentioned: “The positive correlation between CA199 and
rebleeding probability might be due to the close association of CA199 with disease progression
in gastrointestinal tumors such as gastric cancer, pancreatic cancer, and colorectal cancer, which
to some extent increases the risk of rebleeding.” Despite the discussion on this matter, I still do
not understand how CA 199 can explain rebleeding from viruses in patient with cirrhosis.
5.  While the manuscript includes detailed statistical results, it lacks sufficient interpretation
of the clinical implications of these findings. Specifically, how the predictive model will alter
clinical practice in managing patients at risk of rebleeding needs more elaboration.
6. In the abstract method part please change: “Compare the predictive power of the new
predictive model with GBS and pRS scoring systems”. This sentence should start with “We
compared”
assistant