Review for 10.1186/s12876-025-04033-4 (2025)

Title: Association between the immune-inflammation index and the severity and clinical
outcomes of patients with inflammatory bowel disease: a systematic review and meta-analysis
Version: 0 Date: 27 Mar 2025
Reviewer's report:
The manuscript is well-organized and presents valuable findings on the association between the
immune-inflammation index and clinical outcomes in inflammatory bowel disease (IBD). The
study has been well discussed and offering meaningful insights into the clinical implications
of immune-inflammatory responses in IBD patients. The authors have appropriately conducted
a sensitivity analysis to address significant heterogeneity. However, several aspects require
revision to improve the manuscript's consistency and methodological robustness.
Major Revisions:
1. Abstract (Results Section): The results section of the abstract should be revised to include key
meta-analysis findings, such as odds ratios (OR), standardized mean differences (SMD), and p-
values, to provide a more comprehensive summary of the study’s outcomes.
2. Discrepancy in Study Count (Section 3.3.1, Line 194): The manuscript states that 45
retrospective studies were included in the correlation analysis between NLR and IBD. However,
Figure 1 (PRISMA diagram) indicates that only 35 full-text articles were included. This
discrepancy should be corrected to ensure consistency between the text and the figure.
3. Forest Plot Interpretation (Meta-Analysis Results Section): The results state that "the severe
IBD group exhibited a marked elevation in NLR levels compared with the mild IBD group (SMD
= 0.90, 95% CI: 0.60 to 1.21, P = 0.02, Figure 2A)." However, the diamond in the forest plot
appears to favor the mild IBD group, suggesting contradictory findings. Similar inconsistencies
are observed in multiple forest plots. It is recommended that the authors carefully review the
labeling of the left and right sides of the plots, as the direction of effect may have been inverted.
4. Choice of Statistical Model: The authors should consider using a fixed-effects model when I2
= 0%, as this suggests no observed heterogeneity. Additionally, the manuscript should clarify
whether any significant differences arise when comparing fixed-effects and random-effects
models. Consultation with a statistician is recommended to ensure the most appropriate model
selection.
5. Interpretation of NLR as a Predictor of Disease Severity: The manuscript states that "In the
categorical variable analysis of NLR for predicting disease severity in IBD patients, NLR could
not predict severity (OR = 1.81, 95% CI: 0.79 to 4.13; p = 0.16, Fig. 2A)." However, the authors
conclude that NLR is effective in predicting disease severity. While the continuous analysis
suggests an association (higher NLR in severe cases), the categorical analysis does not support
NLR as a strong predictor. For a biomarker to be considered an effective predictor, it should
yield consistent and statistically significant results across different analytical methods. The
inconsistency between the categorical and continuous analyses weakens the predictive validity
of NLR, and I think this issue should be addressed.