Review for 10.1186/s12876-023-02892-3 (2023)

Title: Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel
crohn’s disease?
Version: 1 Date: 23 May 2023
Reviewer's report:
This single-center retrospective study aimed to investigate the use of balloon-assisted
enteroscopy (BAE) for assessing disease activity in patients with small bowel Crohn's disease
(CD). The study findings indicated that a higher small-bowel simple endoscopic score for
CD (SES-CD # 7, compared to 0-6) and the presence of stenosis with “cannot be passed”
increased the risk of surgery and negatively impacted surgery-free survival. However, the
presence of ulcers did not show a significant association with the risk of surgery. Therefore,
BAE demonstrates potential in assessing disease activity and predicting surgical risk in small
bowel CD patients. Nevertheless, several issues require further clarification.
1. Were patients who had undergone any types of small bowel resection or had surgically altered
anatomy, not limited to ileostomy or ileocecectomy, excluded by the authors? The inclusion and
exclusion criteria, particularly regarding the variable "prior surgery" in TABLE 1, should be
elaborated upon, including a specific description of the surgical procedures considered.
2. Did BAE encompass the examination of all segments of the small bowel? The definition of
an adequate BAE procedure should be provided in the Materials and Methods section.
3. It appears impractical to collect data on "step-up after BAE" at the exact date of BAE. This
issue should be appropriately addressed and adjusted in the study.
4. Why was a cut-off value of 7 chosen for the small bowel SES-CD? The methodology
employed for selecting this particular cut-off should be explained in detail within the Materials
and Methods section.
5. Why did the authors focus on the most severe small bowel SES-CD score over the total score,
such as the jejunum plus ileum? The rationale for this choice should be provided.
6. Was there any investigation conducted on the combined use of the small bowel SES-CD score
and cross-sectional imaging score, such as the simplified magnetic resonance index of activity
(MARIAs), to predict the same outcomes?
7. Is there an association between the small bowel SES-CD score treated as a continuous variable
and the occurrence of surgery?
8. Further description of TABLE 1 is required. This could be present only male gender.
9. In the Results section, there is a discrepancy concerning perianal disease, which is described
as comparable initially but later identified as significantly different. This inconsistency should
be clarified.
10.  The recommendation for the number of events per predictor variable in a multivariable Cox
regression model is typically 10-20 events. Having an adequate number of events per predictor
variable is crucial for stabilizing regression estimates and ensuring sufficient statistical power
to detect meaningful associations. In this study, there were 23 events, yet the authors utilized
10 factors (including small-bowel SES-CD of 0-6 vs. # 7, CD duration, perianal disease, HBI,
albumin, CRP levels, concomitant biologic use, step-up after BAE, biologic therapy initiation
or dose intensification after BAE, and balloon dilatation at BAE) in the multivariable Cox
regression, while only 4 factors were presented in TABLE 3. This issue requires reconsideration.
11. The variables "Step-up after BAE" and "Biologic start or dose intensification after BAE" are
time-dependent predictors measured during the follow-up period. The timing of systemic steroid
and/or biologic therapy initiation might impact the surgery rate and survival. Were these factors
analyzed as time-dependent covariates by the authors? The hazard ratio (HR) could differ based
on the analysis approach.