A Novel Nomogram Combining Mucus Barrier Index for Predicting Treatment Failures in Ulcerative Colitis

Abstract

Background

Treatment failures (TFs) generally exist in the course of ulcerative colitis (UC), while early reliable predictors of TFs are still lacking. We aimed to generate nomograms for the prediction of TFs.

Methods

In this retrospective case–control study, the endpoint was the occurrence of TFs, which included medically associated treatment failures and surgery-associated treatment failures (colectomy). Clinical features and mucus integrity evident by goblet cells (GCs) number, expression levels of MUC2 and SLC26A3 were enrolled in the univariate analysis. Nomogram performance was evaluated by discrimination and calibration.

Results

We identified 256 UC patients at our center from January 2010 to June 2022. Fourteen variables for TFs and 9 for colectomy were identified by univariate analysis. Five baseline indices were incorporated into the nomogram for the prediction of TFs: area of GCs, age at diagnosis, disease duration, hemoglobin, and Mayo score. The model was presented with decent discrimination (C index of 0.822) and well calibration. In addition, the colectomy predictive nomogram was built using MUC2 intensity, age at onset, and Mayo score with a good discrimination (C index of 0.92).

Conclusion

Nomograms based on comprehensive factors including mucus barrier function were developed to predict TFs in UC patients with great discrimination, which may serve as practical tools aiming to identify high-risk subgroups warrant timely intervention.

Keywords:

• ulcerative colitis
• treatment failure
• nomogram
• mucus barrier

Abbreviations

TFs, treatment failures; UC, ulcerative colitis; GCs, goblet cells; MES, Mayo endoscopic score; ECCO, European Crohn’s and Colitis Organization; FMT, fecal microbiota transplantation; UCEIS, Ulcerative Colitis Endoscopic Index of Severity; mMES, modified MES; IFX, infliximab; CMV, Cytomegalovirus; EBV, Epstein–Barr virus; IHC, immunohistochemistry; AB/PAS, Alcian Blue/Periodic Acid–Schiff; IQR, interquartile range; OR, odds ratios; HR, hazards ratio; CIs, confidence intervals; ROC, Receiver operating characteristic; AIC, Akaike information criterion; DCA, decision curve analysis; CRP, C-reactive protein; AUC, area under curve; PUCAI, Pediatric UC Activity Index.

Data Sharing Statement

We confirmed that the data supporting our ideas are available within the articles or Supplementary Materials except for the original information. The latter can be acquired from the corresponding author based on reasonable request.

Ethics Approval and Informed Consent

This case–control study was conducted with ethical approval from the First Affiliated Hospital of Sun Yat-sen University (No. [2022] 051). Informed consent was obtained from each patient. Our work complied with the Declaration of Helsinki.

Consent for Publication

All study participants provided informed consent, and the study design was approved by the appropriate ethics review board. We confirmed that any details including figures can be published.

Acknowledgments

We thank all collaborators of the multidisciplinary team at the First Affiliated Hospital of Sun Yat-sen University. We are grateful for the public use of the X tile open-source software developed by Yale University.

Author Contributions

All authors made great contribution to this study related to the conception, study design and execution. Data acquisition, analysis and interpretation were operated by each participant. All authors critically drafted, revised and reviewed this article; agreed on the submitted journal and the final version; agreed to be accountable for the contents of this work.

Disclosure

The authors have no conflicts of interests to declare.

Additional information

Funding

This work was supported by the grants from National Natural Science Foundation of China (grant numbers #82070538, #81870374, and #82270555), and Guangdong Science and Technology Department (grant number 2021A1515220107).