Review for 10.1186/s12876-021-02078-9 (2022)

Reviewer’s report
Title: 
Combined therapy with early initiation of infliximab following drainage of
perianal fistulising Crohn’s disease  a retrospective cohort study
Version: 
0 
Date: 
05 Sep 2021
Reviewer's report:
Thank you to the authors for their submission of a manuscript describing the
experience of perianal Crohn's disease management a single tertiary centre, an
important topic. Comments regarding the manuscript are below.
Terminology
- Use of the term combination may be confusing for readers - could be inferred
as meaning combination infliximab with an immunomodulator; suggest
consideration of alternative terminology eg early or delayed infliximab induction
(given delay is more so relating to the infliximab commencement vs the
multidisciplinary management)
- presentation of numbers in words if ten or less eg 2-3 months = two to three
months
- consistent use of acronyms throughout text eg PFCD 
- inconsistency of use of tense (past and present tense interchangeably used)
- additional typographical errors: please perform further editing and proof
reading
Abstract
- Maintenance infliximab therapy > 3 times: what does this mean ?at least three
maintenance infliximab doses
- Presence of abscess also negatively influenced (vs influence) 
- an example of
the need to maintain consistent tense
- Conclusion: how is the superiority of early initiation of infliximab therapy
demonstrated when no statistical difference apparent between the two treatment
groups
Background
Outcome
- Suggest rewording: We also aim to identify predictive factors associated with
fistula closure and the need for surgical reintervention within the early
combination (or ?infliximab group if terminology to change)
Methods
- There are multiple classification systems in the AGA review that has been
cited; please be more specific and cite the original article for the classification
system that was used eg Parkes
- Who assessed for fistula closure ?was it a patient reported outcome or assessed
via examination; is the outcome being referred to closure or is it healing? 
- Define SD
- It is unclear what determined the timing of infliximab commencement - I
presume at the discretion of the physician however what factors influenced this
decision, and have they been accounted for in the analysis; I am concerned that
the comparative results will be confounded by the underlying reasons for the
decision early vs delayed timing of infliximab 
- Analysis: ?why not consider a MV analysis of factors that influence fistula
closure and have as one of the factors the timing of infliximab commencement to
determine the impact of the timing; the obvious limitation of this is that surgical
procedures were specifically performed in the delayed group to facilitate closure;
is it possible to have a sub-analysis and exclude patients who underwent surgical
procedures beyond seton insertion to help further assess this question?
- No data about the use of antibiotics - given the impact on short/medium term
outcomes, this is critical
- Suggest comment regarding the prescribing restrictions in China regarding the
use of maintenance infliximab here (vs leaving to discussion)
Results
- Presumably there are differences between the two groups (which haven't been
identified) that have resulted in the choice of seton insertion vs fistulotomy/other
surgical intervention; ie merely classifying as complex (Y or N) is not
accounting for differences in fistula morphology and resultant surgical
interventions; such unaccounted differences could be the explanation as to why
there was early vs delayed induction with IFX
- All BMIs <20 ?is this of concern or reflection of issues with the application of
BMI to Chinese population
- Difference in follow up about ~ 6months ?why ?impact
- Multivariate analysis includes presence of abscess at baseline (vs the indication
for reintervention) = this needs to be clearer in the table please
- I cannot find data regarding proportion of patients with seton removal; how can
fistula closure be achieved in the presence of a seton and accordingly has this
influenced outcomes? 
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
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Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes