Review for 10.1186/s12876-025-04019-2 (2025)

Title: Prognostic Significance of Red Cell Distribution Width to Albumin Ratio in ICU Patients
with NAFLD: A Retrospective Analysis
Version: 1 Date: 28 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the manuscript provides a clear rationale for studying RAR in ICU patients with
NAFLD, it could benefit from a deeper discussion of existing literature on RAR’s role in other
populations, particularly in non-ICU patients. A more detailed comparison of RAR in ICU
versus non-ICU NAFLD patients might have provided more context for the results.
-Although the manuscript identifies RDW and albumin as potential biomarkers for prognostic
assessment, there is little exploration of the underlying biological mechanisms linking these
factors with NAFLD progression, particularly in critically ill patients. A more detailed
discussion of how systemic inflammation, oxidative stress, and other pathophysiological factors
influence RDW and albumin levels would help clarify the findings.
-The exclusion criteria could be expanded upon. For example, the exclusion of patients with
viral hepatitis, autoimmune liver disease, or heavy drinking may limit the generalizability of the
findings to broader NAFLD populations. It would be useful to address how these exclusions
might affect the study's external validity.
-While the study adjusts for a broad range of comorbidities, some other potential confounders
(e.g., socioeconomic factors, medications, or ICU-specific interventions) are not considered. A
more thorough discussion of potential confounding factors, especially in critically ill patients,
could strengthen the study's internal validity.
-The handling of missing data, though addressed through interpolation and mean substitution,
could introduce bias, especially if the missing data is not missing at random. The authors could
provide more details about the sensitivity of their results to different approaches for handling
missing data.
-While the study is based on a large database, external validation of the results in other cohorts
(e.g., other hospitals or countries) is not addressed. This is important to assess the external
validity and generalizability of the findings, particularly since MIMIC-IV is a single-center
database.
-The manuscript focuses on RAR as a prognostic marker but does not explore any potential
interventions or treatments based on RAR levels. Including a discussion on how RAR could
influence clinical decision-making or treatment choices would provide a more comprehensive
understanding of its clinical utility.
-The manuscript uses quartiles of RAR to group patients, but a more nuanced approach could
be considered, such as evaluating RAR as a continuous variable to explore the dose-response
relationship further. This could provide more detailed insights into how small changes in RAR
impact patient outcomes.
-While the authors acknowledge that the study is retrospective and may be subject to unmeasured
confounding factors, they do not explore this limitation in sufficient depth. It would be helpful
to discuss specific potential confounders (e.g., medications, socioeconomic status) that could
affect the relationship between RAR and mortality outcomes in ICU patients with NAFLD.
-While the biological mechanisms linking RDW and albumin to NAFLD are discussed, there
is little emphasis on the unique features of critically ill patients that may influence RAR levels
(e.g., organ dysfunction, ICU-specific treatments, or infection). A deeper discussion on how
critical illness might interact with RDW and albumin levels to affect mortality in this specific
population would enrich the interpretation.
-While the discussion highlights the prognostic value of RAR, there is no mention of potential
clinical interventions based on RAR levels. It would be beneficial to address whether RAR
could help guide specific treatment strategies or identify patients who might benefit from more
intensive monitoring or therapeutic interventions.
-The nonlinear relationship between RAR and 365-day all-cause mortality is noted in the
discussion, but there is no detailed explanation of what this nonlinear pattern implies. For
instance, the authors could explore whether certain thresholds of RAR might be particularly
predictive of mortality or whether RAR behaves differently at various levels, offering more
granular insights into its prognostic value.