Title:  Sex-related Differences in Profiles and Clinical Outcomes of Inflammatory Bowel
Disease: A Systematic Review and Meta-Analysis
Version: 1 Date: 06 Oct 2024
Reviewer's report:
This is a systematic review and meta-analysis of the impact of sex on the inflammatory bowel
disease (IBD) course and clinical outcomes, showing that, while males have higher risks of early
death and indications for IBD-surgery, females experience more anxiety and depression.
Major Comments
1. The manuscript presents new, updated data on sex-based differences in IBD outcomes,
particularly with a focus on mortality, biologic treatment, and mental health outcomes. However,
much of the broader focus on sex differences in IBD has been explored in previous literature,
limiting the conceptual novelty. Like the study by Goodman et al. (Nat Rev Gastroenterol
Hepatol 2020;17:740-754.), the manuscript emphasizes the impact of sex differences on clinical
outcomes, particularly regarding surgery and quality of life.
2. Unlike other studies such as the one published in Xu L, et al. (Inflamm Bowel Dis
2022;28:1766-1775), the manuscript does not explore in depth the potential mechanisms of
sex differences, such as the role of sex hormones (e.g., estrogen and progesterone) in IBD
progression. Integrating this dimension would have strengthened the manuscript's discussion of
the biological basis for the observed sex differences.
3. The manuscript acknowledges significant heterogeneity in certain aspects like disease
characteristics, hospitalization rates, and biologics usage. While heterogeneity is expected in
systematic reviews, the methods used to address these variations could be expanded upon. More
subgroup analyses or adjustments for study-level factors (e.g., geographic location, disease
severity) would improve the generalizability of the findings, as seen in other studies that explore
sex-based differences across populations (e.g., Rasmussen NF, et al. Syst Rev 2024;13:164).
4. The authors conducted Egger’s regression tests and funnel plots to detect publication bias,
and they concluded that there was no significant bias for most outcomes. However, the funnel
plots showed some asymmetry in certain areas (e.g., depression), and while the regression test
results were non-significant, publication bias may still exist. The authors could strengthen this
section by using more robust methods like the “trim-and-fill” method to adjust for potential
publication bias.
5. The authors could provide more details on how they handled non-normal data. Reporting
sensitivity analyses based on the original non-parametric measures (median and IQR) could
serve as a robustness check.
6. Although the manuscript focuses on sex differences in IBD, it does not fully explore other
potential confounders, such as age, comorbidities, or socioeconomic status, which could also
influence outcomes like surgery, quality of life, or medication use. Including additional analyses
that control for potential confounders, either through stratified analyses or meta-regression,
would provide a deeper understanding of the sex differences observed.
Title:  Sex-related Differences in Profiles and Clinical Outcomes of Inflammatory Bowel
Disease: A Systematic Review and Meta-Analysis
Version: 1 Date: 06 Oct 2024
Reviewer's report:
This is a systematic review and meta-analysis of the impact of sex on the inflammatory bowel
disease (IBD) course and clinical outcomes, showing that, while males have higher risks of early
death and indications for IBD-surgery, females experience more anxiety and depression.
Major Comments
1. The manuscript presents new, updated data on sex-based differences in IBD outcomes,
particularly with a focus on mortality, biologic treatment, and mental health outcomes. However,
much of the broader focus on sex differences in IBD has been explored in previous literature,
limiting the conceptual novelty. Like the study by Goodman et al. (Nat Rev Gastroenterol
Hepatol 2020;17:740-754.), the manuscript emphasizes the impact of sex differences on clinical
outcomes, particularly regarding surgery and quality of life.
2. Unlike other studies such as the one published in Xu L, et al. (Inflamm Bowel Dis
2022;28:1766-1775), the manuscript does not explore in depth the potential mechanisms of
sex differences, such as the role of sex hormones (e.g., estrogen and progesterone) in IBD
progression. Integrating this dimension would have strengthened the manuscript's discussion of
the biological basis for the observed sex differences.
3. The manuscript acknowledges significant heterogeneity in certain aspects like disease
characteristics, hospitalization rates, and biologics usage. While heterogeneity is expected in
systematic reviews, the methods used to address these variations could be expanded upon. More
subgroup analyses or adjustments for study-level factors (e.g., geographic location, disease
severity) would improve the generalizability of the findings, as seen in other studies that explore
sex-based differences across populations (e.g., Rasmussen NF, et al. Syst Rev 2024;13:164).
4. The authors conducted Egger’s regression tests and funnel plots to detect publication bias,
and they concluded that there was no significant bias for most outcomes. However, the funnel
plots showed some asymmetry in certain areas (e.g., depression), and while the regression test
results were non-significant, publication bias may still exist. The authors could strengthen this
section by using more robust methods like the “trim-and-fill” method to adjust for potential
publication bias.
5. The authors could provide more details on how they handled non-normal data. Reporting
sensitivity analyses based on the original non-parametric measures (median and IQR) could
serve as a robustness check.
6. Although the manuscript focuses on sex differences in IBD, it does not fully explore other
potential confounders, such as age, comorbidities, or socioeconomic status, which could also
influence outcomes like surgery, quality of life, or medication use. Including additional analyses
that control for potential confounders, either through stratified analyses or meta-regression,
would provide a deeper understanding of the sex differences observed.
Please review this paper.
user
Title:  Sex-related Differences in Profiles and Clinical Outcomes of Inflammatory Bowel
Disease: A Systematic Review and Meta-Analysis
Version: 1 Date: 06 Oct 2024
Reviewer's report:
This is a systematic review and meta-analysis of the impact of sex on the inflammatory bowel
disease (IBD) course and clinical outcomes, showing that, while males have higher risks of early
death and indications for IBD-surgery, females experience more anxiety and depression.
Major Comments
1. The manuscript presents new, updated data on sex-based differences in IBD outcomes,
particularly with a focus on mortality, biologic treatment, and mental health outcomes. However,
much of the broader focus on sex differences in IBD has been explored in previous literature,
limiting the conceptual novelty. Like the study by Goodman et al. (Nat Rev Gastroenterol
Hepatol 2020;17:740-754.), the manuscript emphasizes the impact of sex differences on clinical
outcomes, particularly regarding surgery and quality of life.
2. Unlike other studies such as the one published in Xu L, et al. (Inflamm Bowel Dis
2022;28:1766-1775), the manuscript does not explore in depth the potential mechanisms of
sex differences, such as the role of sex hormones (e.g., estrogen and progesterone) in IBD
progression. Integrating this dimension would have strengthened the manuscript's discussion of
the biological basis for the observed sex differences.
3. The manuscript acknowledges significant heterogeneity in certain aspects like disease
characteristics, hospitalization rates, and biologics usage. While heterogeneity is expected in
systematic reviews, the methods used to address these variations could be expanded upon. More
subgroup analyses or adjustments for study-level factors (e.g., geographic location, disease
severity) would improve the generalizability of the findings, as seen in other studies that explore
sex-based differences across populations (e.g., Rasmussen NF, et al. Syst Rev 2024;13:164).
4. The authors conducted Egger’s regression tests and funnel plots to detect publication bias,
and they concluded that there was no significant bias for most outcomes. However, the funnel
plots showed some asymmetry in certain areas (e.g., depression), and while the regression test
results were non-significant, publication bias may still exist. The authors could strengthen this
section by using more robust methods like the “trim-and-fill” method to adjust for potential
publication bias.
5. The authors could provide more details on how they handled non-normal data. Reporting
sensitivity analyses based on the original non-parametric measures (median and IQR) could
serve as a robustness check.
6. Although the manuscript focuses on sex differences in IBD, it does not fully explore other
potential confounders, such as age, comorbidities, or socioeconomic status, which could also
influence outcomes like surgery, quality of life, or medication use. Including additional analyses
that control for potential confounders, either through stratified analyses or meta-regression,
would provide a deeper understanding of the sex differences observed.
assistant