Review for 10.1186/s12876-025-03763-9 (2025)

Title: Optimizing Outcomes in Acute Pancreatitis: The Impact of of Heparin Therapy Duration
on Mortality in a Multi-Center Retrospective Study
Version: 1 Date: 26 Feb 2025
Reviewer's report:
This study explores the effects of heparin therapy on patients with acute pancreatitis, utilizing
data from the MIMIC and eICU databases. The study design is solid, with a multi-center,
retrospective approach and appropriate statistical methods to control for potential confounding
factors. By examining the duration of heparin therapy and its relationship to patient outcomes,
the research offers valuable insights for clinical practice. The findings are significant and provide
new perspectives on optimizing treatment for acute pancreatitis. In the following, I will present
several questions and suggestions that could help improve the study and guide future research
directions.
(1) The selection of the heparin dose is not sufficiently discussed in the manuscript. Given that
patients with acute pancreatitis may respond differently to heparin, particularly considering the
disease's various stages, comorbidities, and bleeding risks, it is recommended that the dosing
strategy be addressed in greater detail or that relevant recommendations for dose optimization
be provided in the study.
(2) As you mentioned, the heparin dose was adjusted based on clinical monitoring results. So,
are there data to support the adjustment of heparin doses between subgroups? Is it possible that
this could have led to differences in the intensity of treatment for patients within subgroups,
which could have affected the results of the study?
(3) What is the basis for the groupings? Why were the subgroups “<4 days” and “4-7 days”
chosen for the first two groups? Did you group patients in your study based only on the duration
of heparin therapy? Was the duration and severity of acute pancreatitis considered? Do these
factors influence treatment outcome and should they be used as one of the criteria for grouping?
(4) Are there patient subgroups whose treatment duration significantly deviates from the range
defined by the two groups in your study?  Does the current grouping potentially exclude or fail to
fully represent certain patient data, particularly those with exceptionally short or long treatment
durations?
(5) Has the study accounted for the potential impact of heparin's side effects (such as bleeding
risk) on the various patient groups? Should the monitoring of these side effects be incorporated
into the analysis, and how might these risks affect the final outcomes?
(6) Have differences in treatment protocols between hospitals or treatment centers in the
database been considered in the study’s outcomes? Specifically, did all patients follow the same
standardized heparin treatment protocol, or did physicians adjust treatment based on clinical
judgment?
(7) Several etiologies (drugs, infections, etc.) were mentioned in this study, but the response
to treatment in patients with different etiologies was not adequately analyzed, so why was it
analyzed for only three comorbidities?
(8) Current studies have focused on short-term mortality and clinical outcomes and lack
consideration of long-term efficacy and safety. Patients with acute pancreatitis may face a longer
recovery period, and whether heparin therapy affects their long-term organ function recovery or
risk of recurrence warrants further investigation.