Title: Nucleated red blood cell distribution in critically ill patients with acute pancreatitis: a
retrospective cohort study
Version: 0 Date: 19 Aug 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study performed utilizing data from two large datasets (MIMIC III and
MIMIC IV).  It is a well conducted study with its key finding being an association between a
raised NRBC percentage and mortality in critically ill patients with pancreatitis.
Hereby follow my comments:
Abstract
a) Objectives need to be stated clearly. By reading the phrase : “The primary goal of this
investigation was to examine the potential association between nucleated red blood cell (NRBC)
levels and mortality in critically ill patients diagnosed with acute pancreatitis (AP), particularly
within the intensive care unit (ICU) environment where studies on this correlation are limited”
one may get confused: were critically ill patients outside ICU? What was the population of the
study ? ICU patients? Hospital patients?
b) Results section is a bit incomprehensible requires rewriting especially lines 34 to 38.
Eg escalation in NRBC?
“GradientBoostingClassifier … 0.982(0.970 – 0.994)” suggest writing something like “ we
analyzed different machine learning models utilizing 9 different variables (probably name them)
including NRBC and we identified that a GradientBoostingClassifier model demonstrated the
best predictive accuracy for 90-day mortality ( (AUC (95% CI) = 0.982(0.970 – 0.994).
Line 32 “an2—”  and line 33 “adju-2-213-sted” please correct.
c) Authors identified that NRBC levels have an impact on  outcome.  For these results to have
a practical impact a specific cut off will be required. It appears that having a NRBC percentage
above 1% is associated with worse outcome  maybe authors should emphasize on this in the
abstract results and discussion section.
Main manuscript
Methods s
a)Please provide more information on what sort of patients do the MIMIC IV and MIMIC
databases contain.
b)Overall 18538 patient records were identified, nevertheless 16622 records were duplicate ,
an extremely high number, could the authors elaborate more on this? I find this difficult to
understand.
c)Line 102-103 “NRBC were measured shortly after the patient was admitted to the ICU” could
the authors specify?
Results
a)Line 187  “presents compelling evidence of a pronounced elevation” I suggest softening the
remark after all both groups have a median of 1.
b)Line 179-181 in methods “The impact of NRBC levels on patient prognosis was assessed
using a generalized linear model (GLM) with a logit link, adjusting for potential confounders.
the association between NRBC levels and outcomes.”  And lines 202 in results “the outcome
parameters” should specify the outcome (90-day mortality)
c)Table 2 title needs to specify that investigates association for 90-day mortality
d)Figure 1 I suggest adding “%” next to NRBC so that can readers understand that the measured
value is percentage.
e)Table 3: footnote’s last line : “ NRBC, Sex, Age, SAPSII, APSIII, CHF, Vasopressin,
Norepinephrine, and MAP” does not make sense as model 3 is described just above. Is this
wrong? Please correct.
f)Figure 4c : why do the last 4 variables have different color from the first ones?
g)Figure 4e please make the explanatory little lines at the right side of the graph (were the risk
score is explained) thicker as one cannot easily tell the blue from the green line so one can
understand the graph better (lines in the main graph are ok)
Title: Nucleated red blood cell distribution in critically ill patients with acute pancreatitis: a
retrospective cohort study
Version: 0 Date: 19 Aug 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study performed utilizing data from two large datasets (MIMIC III and
MIMIC IV).  It is a well conducted study with its key finding being an association between a
raised NRBC percentage and mortality in critically ill patients with pancreatitis.
Hereby follow my comments:
Abstract
a) Objectives need to be stated clearly. By reading the phrase : “The primary goal of this
investigation was to examine the potential association between nucleated red blood cell (NRBC)
levels and mortality in critically ill patients diagnosed with acute pancreatitis (AP), particularly
within the intensive care unit (ICU) environment where studies on this correlation are limited”
one may get confused: were critically ill patients outside ICU? What was the population of the
study ? ICU patients? Hospital patients?
b) Results section is a bit incomprehensible requires rewriting especially lines 34 to 38.
Eg escalation in NRBC?
“GradientBoostingClassifier … 0.982(0.970 – 0.994)” suggest writing something like “ we
analyzed different machine learning models utilizing 9 different variables (probably name them)
including NRBC and we identified that a GradientBoostingClassifier model demonstrated the
best predictive accuracy for 90-day mortality ( (AUC (95% CI) = 0.982(0.970 – 0.994).
Line 32 “an2—”  and line 33 “adju-2-213-sted” please correct.
c) Authors identified that NRBC levels have an impact on  outcome.  For these results to have
a practical impact a specific cut off will be required. It appears that having a NRBC percentage
above 1% is associated with worse outcome  maybe authors should emphasize on this in the
abstract results and discussion section.
Main manuscript
Methods s
a)Please provide more information on what sort of patients do the MIMIC IV and MIMIC
databases contain.
b)Overall 18538 patient records were identified, nevertheless 16622 records were duplicate ,
an extremely high number, could the authors elaborate more on this? I find this difficult to
understand.
c)Line 102-103 “NRBC were measured shortly after the patient was admitted to the ICU” could
the authors specify?
Results
a)Line 187  “presents compelling evidence of a pronounced elevation” I suggest softening the
remark after all both groups have a median of 1.
b)Line 179-181 in methods “The impact of NRBC levels on patient prognosis was assessed
using a generalized linear model (GLM) with a logit link, adjusting for potential confounders.
the association between NRBC levels and outcomes.”  And lines 202 in results “the outcome
parameters” should specify the outcome (90-day mortality)
c)Table 2 title needs to specify that investigates association for 90-day mortality
d)Figure 1 I suggest adding “%” next to NRBC so that can readers understand that the measured
value is percentage.
e)Table 3: footnote’s last line : “ NRBC, Sex, Age, SAPSII, APSIII, CHF, Vasopressin,
Norepinephrine, and MAP” does not make sense as model 3 is described just above. Is this
wrong? Please correct.
f)Figure 4c : why do the last 4 variables have different color from the first ones?
g)Figure 4e please make the explanatory little lines at the right side of the graph (were the risk
score is explained) thicker as one cannot easily tell the blue from the green line so one can
understand the graph better (lines in the main graph are ok)
Please review this paper.
user
Title: Nucleated red blood cell distribution in critically ill patients with acute pancreatitis: a
retrospective cohort study
Version: 0 Date: 19 Aug 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study performed utilizing data from two large datasets (MIMIC III and
MIMIC IV).  It is a well conducted study with its key finding being an association between a
raised NRBC percentage and mortality in critically ill patients with pancreatitis.
Hereby follow my comments:
Abstract
a) Objectives need to be stated clearly. By reading the phrase : “The primary goal of this
investigation was to examine the potential association between nucleated red blood cell (NRBC)
levels and mortality in critically ill patients diagnosed with acute pancreatitis (AP), particularly
within the intensive care unit (ICU) environment where studies on this correlation are limited”
one may get confused: were critically ill patients outside ICU? What was the population of the
study ? ICU patients? Hospital patients?
b) Results section is a bit incomprehensible requires rewriting especially lines 34 to 38.
Eg escalation in NRBC?
“GradientBoostingClassifier … 0.982(0.970 – 0.994)” suggest writing something like “ we
analyzed different machine learning models utilizing 9 different variables (probably name them)
including NRBC and we identified that a GradientBoostingClassifier model demonstrated the
best predictive accuracy for 90-day mortality ( (AUC (95% CI) = 0.982(0.970 – 0.994).
Line 32 “an2—”  and line 33 “adju-2-213-sted” please correct.
c) Authors identified that NRBC levels have an impact on  outcome.  For these results to have
a practical impact a specific cut off will be required. It appears that having a NRBC percentage
above 1% is associated with worse outcome  maybe authors should emphasize on this in the
abstract results and discussion section.
Main manuscript
Methods s
a)Please provide more information on what sort of patients do the MIMIC IV and MIMIC
databases contain.
b)Overall 18538 patient records were identified, nevertheless 16622 records were duplicate ,
an extremely high number, could the authors elaborate more on this? I find this difficult to
understand.
c)Line 102-103 “NRBC were measured shortly after the patient was admitted to the ICU” could
the authors specify?
Results
a)Line 187  “presents compelling evidence of a pronounced elevation” I suggest softening the
remark after all both groups have a median of 1.
b)Line 179-181 in methods “The impact of NRBC levels on patient prognosis was assessed
using a generalized linear model (GLM) with a logit link, adjusting for potential confounders.
the association between NRBC levels and outcomes.”  And lines 202 in results “the outcome
parameters” should specify the outcome (90-day mortality)
c)Table 2 title needs to specify that investigates association for 90-day mortality
d)Figure 1 I suggest adding “%” next to NRBC so that can readers understand that the measured
value is percentage.
e)Table 3: footnote’s last line : “ NRBC, Sex, Age, SAPSII, APSIII, CHF, Vasopressin,
Norepinephrine, and MAP” does not make sense as model 3 is described just above. Is this
wrong? Please correct.
f)Figure 4c : why do the last 4 variables have different color from the first ones?
g)Figure 4e please make the explanatory little lines at the right side of the graph (were the risk
score is explained) thicker as one cannot easily tell the blue from the green line so one can
understand the graph better (lines in the main graph are ok)
assistant