Review for 10.1186/s12876-024-03379-5 (2024)

Title: Nomogram for assistant diagnosing acute suppurative cholangitis: a case-control study
Version: 3 Date: 15 Jul 2024
Reviewer's report:
I appreciate the authors' responses. Based on their feedback, several issues require more detailed
clarification:
1. For an epidemiological association study, the definition and measurement of the outcome
are critical. The authors should specify how the outcome, suppurative cholangitis, was defined
and measured in the Methods section. In the Results section (line 153), the authors state,
"suppurative bile observed during drainage." These statements belong in the Methods section,
and it is important to describe how the suppurativeness of bile was observed. For example, in
Br. J. Surg. 1992, 655-658, only 80% of pre-operatively diagnosed cholangitis cases actually
had cholangitis.
1.1) If all cases of suppurative cholangitis were diagnosed by clinical observation only, the
authors should provide data on the diagnostic yield of the proposed algorithm for identifying
true culture-positive ASC from all cases who had bile culture. By conducting the sensitivity
analysis of those cases who actually had bile culture, is the cut-off value similar to or different
from clinically diagnosed ASC?
1.2) In addition to describing the "gold standard" of bile suppurativeness in this study in the
Methods section, whether managed by observation or direct culture, the methods of drainage
should also be detailed. Perhaps the rate of bile suppurativeness from different managements
(surgery, PTCD, PTGD, ERCP, etc.) should be provided to help readers interpret the accuracy
of the gold standard.
2. Please discuss the limitations suggested by the flow diagram. From 650 cases diagnosed
with acute cholangitis, 146 without bile drainage were excluded. These excluded cases might
represent either mild disease or severe clinical conditions, potentially causing selection bias.
Alternatively, the authors may want to explore these excluded cases by comparing their age,
sex, severity, prognosis, etc., to persuade readers that the selection did not introduce bias.
3. "Table 3: The Sensitivity and Specificity of TG18" raises concerns. The authors suggest
that the sensitivity and specificity of TG18 in diagnosing suppurative cholangitis are 60.8%
and 52.5%, respectively. However, using the same data, the sensitivity and specificity of
suppurativeness in diagnosing moderate-to-severe cholangitis were 30.4% and 79.7%. This
indicates that the absence of bile suppurativeness is a relatively specific marker for the absence
of moderate/severe cholangitis, which might have better clinical utility than the current study
suggests.
4. The concurrent cholecystitis rate was up to 60% in this study, with 73.5% in the surgical
drainage group in the derivative cohort. However, "bile suppurative" for acute cholangitis should
refer to the suppurativeness of bile in the bile duct, not necessarily the same as bile in the
gallbladder. Similar to point 1.1, the authors should provide a sensitivity analysis stratifying the
performance of the nomogram by the presence or absence of concurrent cholecystitis to persuade
readers of the algorithm's usefulness.
I appreciate the authors' detailed responses to the previous review. The manuscript addresses
an important topic in epidemiological research on suppurative cholangitis. However, there are
several key areas that require further clarification and improvement. Addressing these concerns,
particularly those related to the definition and measurement of outcomes, potential selection
bias, and the interpretation of diagnostic performance, will significantly strengthen the study. I
look forward to the revised manuscript that incorporates these critical revisions.
Based on the current state of the manuscript, I recommend a revision to address the
aforementioned issues before it can be considered for acceptance.