Title: The association between inflammatory biomarkers and gallstones in Americans under 50
years old
Version: 0 Date: 16 Mar 2025
Reviewer:  Sidra Naz
Reviewer's report:
This study makes a valuable contribution by demonstrating a strong association between
inflammatory biomarkers and gallstones, particularly in younger adults. However, addressing
these comments will further strengthen the manuscript and understanding the clinical
implications of these findings.
1. Since the study is cross-sectional, it would be helpful to acknowledge more explicitly
that causality cannot be established and suggest future longitudinal studies to confirm these
associations.
2. The identification of an inflection point for SIRI is an interesting finding. However, further
discussion on the potential biological mechanisms behind this nonlinear relationship would
enhance the interpretation.
3. The reliance on self-reported gallstone diagnoses introduces recall bias. Providing a sensitivity
analysis or discussing how this limitation might impact the findings would strengthen the study’s
rigor.
4. Given the interaction between inflammatory biomarkers, gallstones, and diabetes, a more
detailed discussion on how diabetes type may influence these relationships would add depth to
the findings. If NHANES data do not distinguish between type 1 and type 2 diabetes, consider
acknowledging this as a limitation and proposing alternative datasets for future research.
5. While the discussion touches on potential mechanisms linking inflammation to gallstone
formation, further elaboration on the role of adaptive and innate immunity, NETs, and bile acid
metabolism could enhance the translational relevance of the study.
6. Some statistical interpretations, such as the meaning of the inflection point and the effect size
of inflammatory markers, could be elaborated to ensure clarity for readers unfamiliar with these
methodologies.
Title: The association between inflammatory biomarkers and gallstones in Americans under 50
years old
Version: 0 Date: 16 Mar 2025
Reviewer:  Sidra Naz
Reviewer's report:
This study makes a valuable contribution by demonstrating a strong association between
inflammatory biomarkers and gallstones, particularly in younger adults. However, addressing
these comments will further strengthen the manuscript and understanding the clinical
implications of these findings.
1. Since the study is cross-sectional, it would be helpful to acknowledge more explicitly
that causality cannot be established and suggest future longitudinal studies to confirm these
associations.
2. The identification of an inflection point for SIRI is an interesting finding. However, further
discussion on the potential biological mechanisms behind this nonlinear relationship would
enhance the interpretation.
3. The reliance on self-reported gallstone diagnoses introduces recall bias. Providing a sensitivity
analysis or discussing how this limitation might impact the findings would strengthen the study’s
rigor.
4. Given the interaction between inflammatory biomarkers, gallstones, and diabetes, a more
detailed discussion on how diabetes type may influence these relationships would add depth to
the findings. If NHANES data do not distinguish between type 1 and type 2 diabetes, consider
acknowledging this as a limitation and proposing alternative datasets for future research.
5. While the discussion touches on potential mechanisms linking inflammation to gallstone
formation, further elaboration on the role of adaptive and innate immunity, NETs, and bile acid
metabolism could enhance the translational relevance of the study.
6. Some statistical interpretations, such as the meaning of the inflection point and the effect size
of inflammatory markers, could be elaborated to ensure clarity for readers unfamiliar with these
methodologies.
Please review this paper.
user
Title: The association between inflammatory biomarkers and gallstones in Americans under 50
years old
Version: 0 Date: 16 Mar 2025
Reviewer:  Sidra Naz
Reviewer's report:
This study makes a valuable contribution by demonstrating a strong association between
inflammatory biomarkers and gallstones, particularly in younger adults. However, addressing
these comments will further strengthen the manuscript and understanding the clinical
implications of these findings.
1. Since the study is cross-sectional, it would be helpful to acknowledge more explicitly
that causality cannot be established and suggest future longitudinal studies to confirm these
associations.
2. The identification of an inflection point for SIRI is an interesting finding. However, further
discussion on the potential biological mechanisms behind this nonlinear relationship would
enhance the interpretation.
3. The reliance on self-reported gallstone diagnoses introduces recall bias. Providing a sensitivity
analysis or discussing how this limitation might impact the findings would strengthen the study’s
rigor.
4. Given the interaction between inflammatory biomarkers, gallstones, and diabetes, a more
detailed discussion on how diabetes type may influence these relationships would add depth to
the findings. If NHANES data do not distinguish between type 1 and type 2 diabetes, consider
acknowledging this as a limitation and proposing alternative datasets for future research.
5. While the discussion touches on potential mechanisms linking inflammation to gallstone
formation, further elaboration on the role of adaptive and innate immunity, NETs, and bile acid
metabolism could enhance the translational relevance of the study.
6. Some statistical interpretations, such as the meaning of the inflection point and the effect size
of inflammatory markers, could be elaborated to ensure clarity for readers unfamiliar with these
methodologies.
assistant