Title: Association between hematocrit and mortality in critically ill patients with acute
pancreatitis: a retrospective cohort study
Version: 1 Date: 19 Jan 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I would like to congratulate the authors for their effort. Authors Zou et al., in this study,
analyzed the correlation between hematocrit levels and 28-day all-cause mortality in a critically
ill population with acute pancreatitis upon admission to the ICU and sought to determine if
it could be considered an independent prognosis marker for mortality. Furthermore, the study
explored nonlinear relationships of HCT with clinical outcomes, including whether a U-shaped
curve exists. These findings may also improve risk stratification and clinical decision-making
regarding AP management. It identified a U-shaped relationship between hematocrit levels and
28-day all-cause mortality in critically ill AP patients, whereby correspondence of both high
and low levels of HCT corresponds to an increased risk of mortality. Poorer outcomes were
significantly associated with lower levels of HCT, including higher in-hospital and 90-day
mortality. Nonlinear regression and survival analyses confirmed the prognostic value of HCT
as an independent risk factor.
Pancreatitis, inflammation of the pancreas, is a major cause of morbidity and mortality with a
high global health impact. The most frequent gastrointestinal reason for hospital admission in
the US is acute pancreatitis. Even though it is less common, chronic pancreatitis severely lowers
a patient's quality of life*.
(*: doi.org/10.1016/j.pmedr.2024.102722).
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. Use active voice where possible to enhance the readability of the manuscript.
2. Define abbreviations on first use and use them consistently throughout the manuscript.
In the title:
3. Should be more informative, I suggest for example “ Nonlinear Association Between
Hematocrit Levels and Mortality in ICU Patients with Acute Pancreatitis: Insights from a
Retrospective Cohort Study”.
In the Abstract:
4. Mention the significance of the U-shaped relationship in the conclusion to emphasize its
novelty.
In the Introduction:
5. Provide your rationale for choosing hematocrit over other markers, such as white blood cell
count or CRP in this study.
6. Highlight the gap in existing studies ( e.g., why ICU-focused data is needed).
In the Methodology section :
7. Improve the inclusion criteria, e.g. the ICD codes used for diagnosing AP.
8. Reference and explain the selection of cut-off points for hematocrit tertiles with references
to clinical norms or prior studies.
9. Why certain confounders, such as nutritional status, was excluded?
In the Results section:
10. The U-shaped relationship (Figure 3c could be highlighted more effectively).
11. Add interpretation for the lack of significance in the high-hematocrit group.
12. Add more descriptive captions to tables and figures, allowing them to stand alone.
13. Use color coding or annotations in Kaplan-Meier survival curves (Figure 4) to enhance
interpretability.
In the Discussion section:
14. improve the Discussion of potential physiological mechanisms underlying the U-shaped
relationship.
15. Improve limitation passage, e.g. add “Retrospective design and inherent selection bias, and
Lack of external validation for the findings” to the study limitations.
16. Discuss future prospective studies such as prospective studies or interventions based on
hematocrit-guided fluid management.
17. Discuss the novelty of findings and how they advance current knowledge.
Title: Association between hematocrit and mortality in critically ill patients with acute
pancreatitis: a retrospective cohort study
Version: 1 Date: 19 Jan 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I would like to congratulate the authors for their effort. Authors Zou et al., in this study,
analyzed the correlation between hematocrit levels and 28-day all-cause mortality in a critically
ill population with acute pancreatitis upon admission to the ICU and sought to determine if
it could be considered an independent prognosis marker for mortality. Furthermore, the study
explored nonlinear relationships of HCT with clinical outcomes, including whether a U-shaped
curve exists. These findings may also improve risk stratification and clinical decision-making
regarding AP management. It identified a U-shaped relationship between hematocrit levels and
28-day all-cause mortality in critically ill AP patients, whereby correspondence of both high
and low levels of HCT corresponds to an increased risk of mortality. Poorer outcomes were
significantly associated with lower levels of HCT, including higher in-hospital and 90-day
mortality. Nonlinear regression and survival analyses confirmed the prognostic value of HCT
as an independent risk factor.
Pancreatitis, inflammation of the pancreas, is a major cause of morbidity and mortality with a
high global health impact. The most frequent gastrointestinal reason for hospital admission in
the US is acute pancreatitis. Even though it is less common, chronic pancreatitis severely lowers
a patient's quality of life*.
(*: doi.org/10.1016/j.pmedr.2024.102722).
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. Use active voice where possible to enhance the readability of the manuscript.
2. Define abbreviations on first use and use them consistently throughout the manuscript.
In the title:
3. Should be more informative, I suggest for example “ Nonlinear Association Between
Hematocrit Levels and Mortality in ICU Patients with Acute Pancreatitis: Insights from a
Retrospective Cohort Study”.
In the Abstract:
4. Mention the significance of the U-shaped relationship in the conclusion to emphasize its
novelty.
In the Introduction:
5. Provide your rationale for choosing hematocrit over other markers, such as white blood cell
count or CRP in this study.
6. Highlight the gap in existing studies ( e.g., why ICU-focused data is needed).
In the Methodology section :
7. Improve the inclusion criteria, e.g. the ICD codes used for diagnosing AP.
8. Reference and explain the selection of cut-off points for hematocrit tertiles with references
to clinical norms or prior studies.
9. Why certain confounders, such as nutritional status, was excluded?
In the Results section:
10. The U-shaped relationship (Figure 3c could be highlighted more effectively).
11. Add interpretation for the lack of significance in the high-hematocrit group.
12. Add more descriptive captions to tables and figures, allowing them to stand alone.
13. Use color coding or annotations in Kaplan-Meier survival curves (Figure 4) to enhance
interpretability.
In the Discussion section:
14. improve the Discussion of potential physiological mechanisms underlying the U-shaped
relationship.
15. Improve limitation passage, e.g. add “Retrospective design and inherent selection bias, and
Lack of external validation for the findings” to the study limitations.
16. Discuss future prospective studies such as prospective studies or interventions based on
hematocrit-guided fluid management.
17. Discuss the novelty of findings and how they advance current knowledge.
Please review this paper.
user
Title: Association between hematocrit and mortality in critically ill patients with acute
pancreatitis: a retrospective cohort study
Version: 1 Date: 19 Jan 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I would like to congratulate the authors for their effort. Authors Zou et al., in this study,
analyzed the correlation between hematocrit levels and 28-day all-cause mortality in a critically
ill population with acute pancreatitis upon admission to the ICU and sought to determine if
it could be considered an independent prognosis marker for mortality. Furthermore, the study
explored nonlinear relationships of HCT with clinical outcomes, including whether a U-shaped
curve exists. These findings may also improve risk stratification and clinical decision-making
regarding AP management. It identified a U-shaped relationship between hematocrit levels and
28-day all-cause mortality in critically ill AP patients, whereby correspondence of both high
and low levels of HCT corresponds to an increased risk of mortality. Poorer outcomes were
significantly associated with lower levels of HCT, including higher in-hospital and 90-day
mortality. Nonlinear regression and survival analyses confirmed the prognostic value of HCT
as an independent risk factor.
Pancreatitis, inflammation of the pancreas, is a major cause of morbidity and mortality with a
high global health impact. The most frequent gastrointestinal reason for hospital admission in
the US is acute pancreatitis. Even though it is less common, chronic pancreatitis severely lowers
a patient's quality of life*.
(*: doi.org/10.1016/j.pmedr.2024.102722).
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. Use active voice where possible to enhance the readability of the manuscript.
2. Define abbreviations on first use and use them consistently throughout the manuscript.
In the title:
3. Should be more informative, I suggest for example “ Nonlinear Association Between
Hematocrit Levels and Mortality in ICU Patients with Acute Pancreatitis: Insights from a
Retrospective Cohort Study”.
In the Abstract:
4. Mention the significance of the U-shaped relationship in the conclusion to emphasize its
novelty.
In the Introduction:
5. Provide your rationale for choosing hematocrit over other markers, such as white blood cell
count or CRP in this study.
6. Highlight the gap in existing studies ( e.g., why ICU-focused data is needed).
In the Methodology section :
7. Improve the inclusion criteria, e.g. the ICD codes used for diagnosing AP.
8. Reference and explain the selection of cut-off points for hematocrit tertiles with references
to clinical norms or prior studies.
9. Why certain confounders, such as nutritional status, was excluded?
In the Results section:
10. The U-shaped relationship (Figure 3c could be highlighted more effectively).
11. Add interpretation for the lack of significance in the high-hematocrit group.
12. Add more descriptive captions to tables and figures, allowing them to stand alone.
13. Use color coding or annotations in Kaplan-Meier survival curves (Figure 4) to enhance
interpretability.
In the Discussion section:
14. improve the Discussion of potential physiological mechanisms underlying the U-shaped
relationship.
15. Improve limitation passage, e.g. add “Retrospective design and inherent selection bias, and
Lack of external validation for the findings” to the study limitations.
16. Discuss future prospective studies such as prospective studies or interventions based on
hematocrit-guided fluid management.
17. Discuss the novelty of findings and how they advance current knowledge.
assistant