Review for 10.1186/s12876-025-04035-2 (2025)

Title: PREDICTIVE ACCURACY OF FECAL CALPROTECTIN IN ASSESSING
CLINICAL ACTIVITY AND DISEASE SEVERITY IN PATIENTS WITH ULCERATIVE
COLITIS AND CROHN’S DISEASE
Version: 2 Date: 15 Mar 2025
Reviewer's report:
Reviewer Comments
The manuscript addresses an important topic regarding the role of fecal calprotectin (FCP) in
assessing disease activity in IBD. While the study presents relevant findings, several issues need
to be addressed before the manuscript can be considered for publication.
1. Misstatement Regarding Colonoscopy (Line 139)
The authors describe colonoscopy as an invasive treatment, which is a minor misstatement.
Colonoscopy needs to be described as an invasive diagnostic procedure, not a treatment.
2. Prognostic Value (Line 155)
The study claims to assess the prognostic value of FCP, but the design does not support
such an analysis. A prognostic study requires a long-term follow-up and well-defined clinical
endpoints such as hospitalization, therapeutic failure, or the need for surgery. Here, FCP was
only correlated with clinical and endoscopic indices at two time points, which does not establish
prognostic significance. To make such a claim, the study would need predictive models such as
logistic regression or survival analysis. I recommend rewording this section to reflect the actual
scope of the study.
3. Diagnostic Accuracy (Line 182)
The manuscript refers to the diagnostic reliability of FCP using sensitivity and specificity.
However, this study does not assess the diagnostic accuracy of FCP for IBD, as all participants
were already diagnosed, and there was no control group for comparison. The study evaluates
disease activity, not IBD diagnosis. Any reference to sensitivity and specificity should clearly
indicate that these metrics apply to detecting disease activity rather than diagnosing IBD.
4. Statistical Analysis
The study uses Pearson’s correlation to assess the relationship between FCP and disease activity
indices. However, since these data may not follow a normal distribution, non-parametric tests
(such as Spearman’s correlation) should have been considered for validation. Additionally, the
analysis does not control for confounding factors. Incorporating adjusted regression models
would strengthen the findings. I recommend discussing these limitations and, if possible,
refining the statistical approach.
5. Graphs and Figure Legends
The ROC curves should include explicit annotation of AUC values along with 95% confidence
intervals to provide a clearer interpretation of FCP’s accuracy in detecting disease activity.
Additionally, the legends should specify the comparison groups (e.g., active vs. remission) for
clarity.
6. Discussion – Population Characteristics (Line 283)
The study is not designed to compare the clinical and demographic characteristics of the
population with other studies. Its primary objective is to evaluate the association between FCP
and disease activity. While presenting baseline characteristics in a table is standard and expected,
extensive comparisons with other studies that specifically focus on describing age distribution
and gender prevalence (such as those in line 283) do not directly contribute to answering the
study's main research question. I recommend refocusing the discussion on the clinical relevance
of FCP rather than on demographic comparisons.
7. Conclusion
The conclusion states that "FCP levels may serve as a stand-in marker for tracking mucosal
health and forecasting endoscopic remission in individuals with IBD." This overstates the
findings, as the study does not establish a predictive role for FCP in endoscopic remission.
While FCP correlates with disease activity, predicting remission would require a longer follow-
up and predictive modeling. I suggest rewording the conclusion to reflect that FCP correlates
with disease activity but requires further investigation as a prognostic tool.
Final Recommendation
The study explores an important area, but several methodological and interpretative issues must
be addressed. The limited sample size affects the generalizability of the findings, and clarifying
the study's scope, refining the statistical analysis, improving the ROC curve presentation, and
correcting overstatements regarding FCP’s diagnostic and prognostic role will enhance the
manuscript’s quality and suitability for publication.