Review for 10.1186/s12876-022-02537-x (2022)

Title: Serum Soluble T-Cell Immunoglobulin Mucin Domain-3 as an Early Predictive Marker
for Severity of Acute Pancreatitis This study was a retrospective analysis
Version: 4 Date: 22 Apr 2022
Reviewer's report:
Thank you for your responses. However, serious unresolved concerns still remain in the
manuscript. Please see additional comments.
Major
• The reviewer could not understand what was being compared in Table 1 and Table 2. What
do the P-values mean? Is SAP compared with MAP + MSAP? If so, a sentence “the length of
hospital stay was longer in patients with MSAP and SAP” on the 3rd-4th lines on page 6 dose
not make sense. Please specify.
Answer: Differences in numeric variables among multiple groups and between two groups were
analyze using analysis of variance (ANOVA) and Student-Newman-Keuls (SNK), respectively.
Differences in ratio among multiple groups were analyzed using the Cochran-Mantel-Haenszel
(CMH) method.
Additional comments: As you mentioned in the Abstract and the Introduction sections, the
purpose of this study was to clarify the usefulness of sTIM-3 on the early prediction for SAP.
Therefore, it was confusing to compare the trend of three variables MAP, MSAP, and SAP in
Table 1 and Table 2 instead of comparing SAP with other than SAP.
• The reviewer could not understand a sentence “the concentration of IL-10 cytokine was not
different significantly among various group” on the 7th-8th lines on page 6 because the P-value
was 0.012 described in Table 2.
Answer: SAP patients had significantly lower IL-10 cytokine level (P<0.05) compared with
MAP patients, there was no significant difference in IL-10 level between other two groups (Table
2, Figure 1C).
Additional comment: None.
• According to Table 2, significant differences (p<0.001) were also shown in white blood cell
count, CRP, Creatinine, and IL-6 not only in sTIM3 and severity scores. Why were they omitted
from subsequent analysis?
Answer: We have adjustments for age, gender, BMI, temperature, heart rate, pulse oxygen
saturation, mean arterial pressure, white blood cell count, red blood cell count, platelet count,
CRP, direct bilirubin, creatinine, procalcitonin and length of hospital stay.
Additional comments: The reviewer could not understand the answer. To study the early
prediction of SAP, multivariate logistic regression analysis is recommended, instead of
multivariate linear regression analysis.
It is confusing that APACHE II score, BISAP score and MCTSI score are described in Table 2
because these scores were evaluated at 48 hours post-admission, while the results of laboratory
data were tested on admission as described in the title of Table 2. The scores should be shown
separated from the laboratory data. It is well known the APACHE II score and BISAP score can
be evaluated on admission. The reviewer could not understand why these scores were evaluated
at 48 hours after admission although the laboratory tests were evaluated on admission.
• The reviewer could not understand model2 and model3 of multivariable linear regression
analysis. Why were heart rate, respiratory rate, and white blood cell count were adjusted? They
are the factors included in the APACHE II score.
Answer: This is indeed a complex issue. Temperature, heart rate, pulse oxygen saturation, mean
arterial pressure, and white blood cell count are important factors for AP patients. APACHE II
score consists of three parts: acute physiology (12 physiological parameters), age, and chronic
health evaluation. I think heart rate, respiratory rate, and white blood cell count don’t interfere
with APACHE II score statistical significance.
Additional comments: The multivariate logistic regression analysis is recommended to clarify
the early prediction for SAP. Multivariate linear regression analysis is not suitable in this
situation.
• The reviewer thinks it is necessary to calculate the optimal cutoff value for sTim3 to diagnose
SAP. And the sensitivity and specificity of sTim3 to diagnose SAP should be compared with
those of other markers and severity scores.
Answer: Modified.
Additional comments: After the multivariate logistic regression analysis, all explanatory
variables which were estimated as significant should be calculated optimal cutoff value and be
used for sensitivity / specificity analysis.
Minor
• A sentence “AP or pregnancy induced by trauma” does not make sense on the 6th line on page 4.
Answer: This sentence was deleted.
Additional comment: The sentence still remains in the revised manuscript.
• Please specify how many hours taken on admission on average after the onset of AP.
Answer: We measured and compared the levels of serum sTIM-3 in AP patients with an onset
time of less than 48 h. Exclusion criteria were set as follows: time from pain onset to admission
>48 h. 11th line on Page 4.
Additional comments: None.
• Please specify when the vital signs listed in Table 1 were measured.
Answer: After admission, vital sign (temperature, heart rate, pulse oxygen saturation, blood
pressure) were recorded.
Additional comment: The answer is not appropriate. Please specify and describe in the text.
• It is not stated what * means in Figure 1.
Answer: Modified.
Additional comment: None.
• In Figure 1A, the vertical axis is not “SCORE”.
Answer: Modified.
Additional comment: None.