Effects of Modified Crohn’s Disease Exclusion Diet as Adjunctive Therapy on Clinical Remission and Nutrition in Pediatric Crohn’s Disease: A Real-World Study from China

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study “Effects on Effects of Modified Crohn's Disease Exclusion Diet as Adjunctive Therapy on Clinical Remission and Nutrition in Pediatric Crohn's Disease: A Real-World Study from China” (children-3887361) is a prospective study. The study aims to compare the synergistic induction of remission, as well as the effects on physical growth and nutritional indicators, of the Modified Crohn's Disease Exclusion Diet (CDED) and Exclusive Enteral Nutrition (EEN) when used as adjunctive therapies alongside infliximab for children with Crohn's disease (CD). The study addresses several important issues, such as malnutrition in children with Crohn's disease and the role of nutrition as a factor improving patients’ quality of life and enhancing treatment efficacy when combined with other therapeutic approaches. These contributions are relevant and necessary for the advancement of knowledge on Crohn's disease treatment. However, some aspects of the manuscript need to be supplemented and clarified for better interpretation of the results.

The manuscript structure is coherent and clear, and the language used in the manuscript is appropriate and clear, facilitating reading and interpretation of the results.

Tables and descriptions of results are generally readable enough to allow a full understanding and interpretation of the article. However, in the “Materials and Methods” section, it would be useful to include a schematic representation of the study design and participant recruitment described in this section.

The greatest concerns arise in the description of nutritional therapy methods in section 2.2 (lines 126 and 136):

1. There is no information on whether patients were hospitalised for all 2 stages of the diet – this information is important for assessing adherence to the diet, and consequently its effectiveness.
2. Lines 134–136: There is no information on which body weight of the child was used to calculate caloric requirements (ideal or current body weight), nor how the physical activity level was determined.
3. It is unclear whether children with body weights outside the normal range were included in the study, and if so, how their daily energy intake was determined.

The discussion is clear and comprehensive, and the drawn conclusions are consistent. Most of the cited sources are not older than 10 years. Self-citations are present but not overused. The topic is original, well-defined, and expands current knowledge about Crohn's disease, and the results may significantly contribute to improving patient well-being in the future.

Author Response

please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for submitting the manuscript "Effects of Modified Crohn's Disease Exclusion Diet as Adjunctive Therapy on Clinical Remission and Nutrition in Pediatric Crohn's Disease: A Real-World Study from China”. The paper addresses a clinically relevant and topic, however, there are some points that need to be addressed:

Abstract

• Consider adding sentence or two as an introduction
• please specify if only newly diagnosed patients were included or all patients on infliximab therapy
• were there any patients in infliximab therapy who were not on CDED or EEN
• were there any significant differences between the groups regarding BMI and calprotectin levels at the starting point and were there any significant differences in CDED group between starting point and weeks 6 and 12.

1.Introduction

- line 56 – children – first letter does not have to be capitalized

3.Results

3.1. General information and demographic characteristics

- what was the total number of newly diagnoses CD patients during the observed period, how many children were eligible for the study study in total and how many were excluded? How many children did not accept or did not adhere to the dietary regimens? Consider providing a flow-chart

Table 3 and Table 4 and Table 5:

- why are some results in bold?

- please correct typos (put one blank before parenthesis, put blank after commas)

3.3. Comparison of physical growth indicators between the two groups of children after treatment

- were there any significant differences between physical growth indicators between baseline results and results at week 6 and 12 (for each group)

3.4. Comparison of serum nutritional and inflammatory markers between the two groups of children after treatment

- consider also showing baseline values

4.Discussion

- Regarding „In this study, the clinical remission rate after 12 weeks of CDED combined with TNF therapy reached 94.7%, the remission rate for EEN combined with TNF therapy was 84.6%, suggesting that the efficacy of nutritional therapy combined with TNF therapy may be superior to that of TNF monotherapy.“ – based on presented results one cannot say that nutritional therapy combined with TNF therapy may be superior to that of TNF monotherapy. However, consider comparing children on infliximab monotherapy with presented groups.

- regarding „However, it is worth noting that compared with the 6-week mark, the clinical remission rate in the EEN plus infliximab group showed a decreasing trend at 12 weeks, while the clinical remission rate in the CDED plus infliximab group was higher at 12 weeks.“ – were the differences statistically significant? Consider adding this analysis to the results

- the suggestion that „… that the CDED group may be more effective in reducing intestinal inflammation than the EEN group and may exhibit a more stable trend toward maintaining clinical remission.“ is not supported by the results. Consider presenting calprotectin levels and differences between groups also at baseline.

References

- reference formatting is inconsistent

- references 2, 3, 4, 5, 6, 7, 9, 10, 11, 13, 14, 22, 23, 24, 25, 26, 27, 30, 31, 32, 33 are not cited correctly

- references 3 and 29 are the same

- please correct the typos

Author Response

please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for submitting the revised manuscript "Effects of Modified Crohn's Disease Exclusion Diet as Adjunctive Therapy on Clinical Remission and Nutrition in Pediatric Crohn's Disease: A Real-World Study from China” and thank you for answering the comments. However, there are some points that need to be addressed:

Abstract

- 6/26 is 23% and in the results, it is said 6/25 – what is correct?

3.Results

3.3. Comparison of physical growth indicators between the two groups of children after treatment

- Table 4 is not presented clearly, it is too busy. There is no need to repeat baseline data 2 times (two columns can be removed)

4.Discussion

- regarding “At 12 weeks, the endoscopic remission rate for CDED combined with TNF was 47.1%, while the endoscopic remission rate for EEN combined with TNF was 24.0%.” – please put the p value within the sentence – although it is mentioned later in the text that the difference is not statistically significant, data presented as such can be misleading

- the suggestion that „… that the CDED group may be more effective in reducing intestinal inflammation than the EEN group and may exhibit a more stable trend toward maintaining clinical remission.“ is not supported by the results. Consider presenting calprotectin levels and differences between groups also at baseline.

References

- reference formatting is still not consistent

- what does J. stand for in all references

- the name of the journal should be abbreviated

Author Response

Responses to reviewer comments

 

We sincerely thank the reviewers for their continued time and expertise in reviewing our revised manuscripts. The additional input provided has been invaluable in helping us further refine our work. We've carefully addressed every question raised in the latest round of feedback, with detailed point-by-point responses provided below. Thank you again for this opportunity to improve our work.

 

Point-by-point responses to the author's comments and suggestions

 

Thank you for submitting the revised manuscript "Effects of a modified Crohn's disease elimination diet as an adjunctive therapy on clinical remission and nutrition in pediatric Crohn's disease: a real-world study from China" and thank you for your comment responses. However, there are a few key points to address:

abstract

- 6/26 is 23%, and in the result, say 6/25 – what is correct?

Re: Thank you for your meticulous attention to detail. The number "6/26" mentioned in the abstract is a clerical error, as clarified in the results section: 1 out of 26 patients did not undergo a scheduled follow-up endoscopy. Thus, the total number of patients evaluated for effectiveness is 25. Therefore, the accurate calculation of the effective rate is 6/25 (24%). We corrected this in the revised manuscript

3. Results

3.3. Comparison of physical growth indicators between the two groups after treatment

- Table 4 is not clearly presented and is too busy. No need to duplicate baseline data 2 times (two columns can be deleted)

Re: Thank you very much for your valuable feedback on the desktop. The current duplication of information in Table 4 does impair the clarity and readability of Table 4. We completely agree with your assessment. Duplicating baseline data makes the table appear cluttered and unnecessary. Based on your suggestion, we modified the table to remove duplicate baseline data columns and keep only the data for comparisons between groups after treatment.

indicator	BMI Z [x±s] [M (P25, P75)]							HAZ [x±s] [M （ pp. 25, 75))]
	baseline	6 weeks after treatment	t/Z	P	12 weeks after treatment	t/Z	P	baseline	6 weeks after treatment	t/Z	P	12 weeks after treatment	t/Z	P
CDED	-1.1±1.7	-0.3±1.3	-3.950	0.001	-0.0±1.3	-2.290	0.034	0.4±1.2	0.3±1.2	1.022	0.320	0.3±1.1	0.710	0.487
ONE	-1.3 (-2.9, -0.8)	-1.1 (-1.9, -0.6)	-1.880	0.060	-0.9 (-1.6, 0.0)	-2.462	0.014	0.1 (-0.9, 0.9)	0.0 (-0.8, 0.7)	-0.606	0.545	0.2 (-0.8, 0.6)	-0.495	0.620

4. Discussion

- Regarding "Endoscopic response rate for CDED plus TNF was 47.1% at 12 weeks, compared to 24.0% for EEN plus TNF" – please put p-value in the sentence – although the difference is not statistically significant, the data presented may be misleading

Re: Thank you for your insightful comment on the introduction of endoscopic remission rates. You make a great point. We agree that presenting a percentage difference without a corresponding p-value directly in a sentence can be misleading for readers, as it may overemphasize the observed numerical difference without the critical context of its statistical significance. Based on your suggestion, we will modify the sentence in the discussion to include a p-value. The revised text reads: "At 12 weeks, the endoscopic response rate of CDED plus TNF was 47.1% compared to 24.0% for EEN plus TNF, with an unstatistically significant difference (P =0.120). "

- Suggest "...... The CDED group may be more effective in reducing intestinal inflammation than the EEN group and may exhibit a more stable trend towards maintaining clinical remission. Calprotectin levels and between-group differences are also considered to be provided at baseline.

Re: Thank you for your critical comment. You are absolutely correct in emphasizing that the original statement goes beyond the available data, especially regarding the "more stable trend" regarding maintaining remission, which was not directly measured in our study. We have completely revised the discussion section to ensure that all conclusions are strictly supported by the results. The key change is the removal of the phrase "and may exhibit a more stable trend towards maintaining clinical remission." The rationale for discussing the rest is now clearly anchored in concrete data. The revised text clearly states: "In addition, at 12 weeks, fecal calprotectin levels were significantly lower in the CDED plus infliximab group than in the EEN plus infliximab group (P = 0.007), starting at comparable baseline levels in both groups (P=0.797). This significant reduction suggests that the CDED regimen may be more effective than the EEN regimen in reducing intestinal inflammation. This revision ensures: This statement is directly related to a significant post-treatment difference in fecal calprotectin (P < 0.05). Include context at comparable baseline levels, thus establishing an effective comparison. Tables 1 and 6 give baseline fecal calprotectin levels and comparisons between the two groups. In addition, Table 6 shows fecal calprotectin levels and differences between the two groups after treatment.

cite

- The reference format is still inconsistent

- J. What is represented in all references

- The journal name should be abbreviated

Thank you for your continued guidance and for pointing out areas for revision. We have thoroughly addressed all key points in your latest feedback: Citation Formatting: We have implemented a unified formatting style across all citations to ensure full consistency. The "J." has been removed. Journal Names: All journal titles now display with the correct standard abbreviations. A revised document incorporating these corrections is attached for your review. We appreciate your meticulous attention to detail. Please feel free to let us know if further improvements are needed.

We are deeply grateful to the reviewers for their exceptional expertise and meticulous attention to detail throughout this round of revisions. Their insightful guidance helped refine key aspects of our manuscript, from ensuring precise data presentation in the Abstract and tables, to enhancing the statistical rigor of our interpretations of the results, and maintaining an appropriate level of scientific caution in our Discussion. The reviewers' patience and unwavering commitment to quality have significantly enhanced the clarity, accuracy, and overall impact of our work. We sincerely thank you for this valuable learning experience and the substantial improvements their feedback has brought to this manuscript.

 

Author Response File: Author Response.pdf