Prognostic models for predicting postoperative recurrence in Crohn's disease: a systematic review and critical appraisal.

Background and Aims: Prophylaxis of postoperative recurrence is an intractable problem for clinicians and patients with Crohn's disease. Prognostic models are effective tools for patient stratification and personalised management. This systematic review aimed to provide an overview and critically appraise the existing models for predicting postoperative recurrence of Crohn's disease. Methods: Systematic retrieval was performed using PubMed and Web of Science in January 2022. Original articles on prognostic models for predicting postoperative recurrence of Crohn's disease were included in the analysis. The risk of bias was assessed using the Prediction Model Risk of Bias Assessment (PROBAST) tool. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; number CRD42022311737). Results: In total, 1948 articles were screened, of which 15 were ultimately considered. Twelve studies developed 15 new prognostic models for Crohn's disease and the other three validated the performance of three existing models. Seven models utilised regression algorithms, six utilised scoring indices, and five utilised machine learning. The area under the receiver operating characteristic curve of the models ranged from 0.51 to 0.97. Six models showed good discrimination, with an area under the receiver operating characteristic curve of >0.80. All models were determined to have a high risk of bias in modelling or analysis, while they were at low risk of applicability concerns. Conclusions: Prognostic models have great potential for facilitating the assessment of postoperative recurrence risk in patients with Crohn's disease. Existing prognostic models require further validation regarding their reliability and applicability. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311737.

Serum amyloid protein A in inflammatory bowel disease: from bench to bedside.

Inflammatory bowel diseases (IBD) is featured by gastrointestinal inflammation and a disease course with alternating recurrence and remission. The global burden caused by IBD has significantly boosted in recent years, necessitating treatment optimization. Serum amyloid A (SAA) is a class of 104 amino acid conservative acute-phase proteins, which is essential in immune-mediated inflammatory processes, like IBD. The SAA monomeric structure is composed of four α-helical regions and a C-terminal amorphous tail. Its disordered structure enables multiple bindings to different ligands and permits multiple functions. It has been proven that SAA has dual roles in the inflammatory process. SAA stimulates the pro-inflammatory cytokine expression and promotes the pathogenic differentiation of TH17 cells. In addition, SAA can remove toxic lipids produced during inflammatory responses and membrane debris from dead cells, redirect HDL, and recycle cholesterol for tissue repair. In IBD, SAA acts on gut epithelium barriers, induces T-cell differentiation, and promotes phagocytosis of Gram-negative bacteria. Owing to the tight connection between SAA and IBD, several clinical studies have taken SAA for a biomarker for diagnosis, assessing disease activity, and predicting prognosis in IBD. Furthermore, 5-MER peptide, a drug specifically targeting SAA, has shown anti-inflammatory effects in some SAA-dependent animal models, providing novel insights into the therapeutic targets of IBD.

Neutrophil-to-lymphocyte ratio for predicting postoperative recurrence in Crohn's disease patients with isolated anastomotic lesions.

Background: Patients with isolated anastomotic lesions (iAL) are common in postoperative Crohn's disease (CD) and have heterogeneous prognosis. Objectives: To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in CD patients with iAL. Design: A bicenter retrospective cohort study. Methods: CD patients who received ileocolonic resection from 2013 and 2020 and had a modified Rutgeerts score of i2a were recruited. NLR was determined within 1 week around the initial endoscopy after ileocolectomy. The primary outcome was clinical recurrence. Kaplan-Meier method and Cox hazard regression analysis were utilized to assess the association between candidate variables and outcomes of interest. Results: In total, 411 postoperative CD patients were preliminarily reviewed and 83 patients were eligible. In total, 36 (48.6%) patients experienced clinical recurrence with a median follow-up time of 16.3 (interquartile range, 9.7-26.3) months. NLR > 2.45 and age at surgery >45 years had higher cumulative incidence of clinical recurrence in the Kaplan-Meier analysis. After adjusted for potential confounders, NLR > 2.45 was the only independent risk factor for clinical recurrence, with an adjusted hazard ratio (HR) of 2.88 [95% confidence interval (CI), 1.39-6.00; p = 0.005]. Furthermore, a risk score based on NLR and age at surgery were built to further stratify patients. Compared to those who scored 0, patients with a score of 1 and 2 had an adjusted HR of 2.48 (95% CI, 1.22-5.02) and 6.97 (95% CI, 2.19-22.16) for developing clinical recurrence, respectively. Conclusions: NLR is a promising prognostic biomarker for CD patients with iAL. The utilization of NLR and the risk score to stratify patients may facilitate the personalized management in patients with iAL.

Development and validation of a non-invasive biomarker-based model to identify endoscopic recurrences of Crohn's disease.

Background: Endoscopic recurrence is common in postoperative patients with Crohn's disease (CD). Monitoring endoscopic recurrence is important for selecting an appropriate treatment to prevent the development of postoperative disease. The aim of this study was to develop and validate a diagnostic model to identify endoscopic recurrence. Methods: This was a retrospective cohort study recruiting postoperative CD patients who underwent endoscopy at the First Affiliated Hospital, Sun Yat-sen University from January 2016 to June 2020. Endoscopic recurrence was defined as Rutgeerts score > i1. Thirty non-invasive biomarkers, including C-reactive protein, erythrocyte sedimentation rate, vitamin D, complete blood count, and biochemical blood indices, were used as candidate predictors to build a multivariate logistic regression diagnostic model. The predictive ability of the diagnostic models was assessed by receiving the area under the characteristic curve (AUC) and calibration plots, and internal validation was performed by the bootstrap method. Results: Two hundred and nineteen eligible patients were included in this study, and 135 (61.6%) patients had a postoperative endoscopic recurrence. The final diagnostic model included eight biomarkers with an AUC (95% confidence interval (CI)) of 0.796 (0.737-0.855) to identify endoscopic recurrence. The AUC, sensitivity, and specificity of this diagnostic model were 0.781 (0.780-0.782), 0.647 (0.643-0.651) and 0.811 (0.807-0.815), respectively, by internal validation. In addition, the diagnostic model exhibited good calibrability with calibration slope, calibration-in-the-large ('mean calibration') and Brier scores of 1.00, 0.00, and 0.175, respectively. Conclusion: This non-invasive biomarker-based diagnostic model has an excellent ability to identify endoscopic recurrence in patients with CD. Application of the model to clinical practice to monitor postoperative patients may be helpful for patient management.

Metabolomics facilitate the personalized management in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterized by chronic relapsing inflammation and mucosal lesions. Reliable biomarkers for monitoring disease activity, predicting therapeutic response, and disease relapse are needed in the personalized management of IBD. Given the alterations in metabolomic profiles observed in patients with IBD, metabolomics, a new and developing technique for the qualitative and quantitative study of small metabolite molecules, offers another possibility for identifying candidate markers and promising predictive models. With increasing research on metabolomics, it is gradually considered that metabolomics will play a significant role in the management of IBD. In this review, we summarize the role of metabolomics in the assessment of disease activity, including endoscopic activity and histological activity, prediction of therapeutic response, prediction of relapse, and other aspects concerning disease management in IBD. Furthermore, we describe the limitations of metabolomics and highlight some solutions.

Prealbumin and Retinol-Binding Protein 4: The Promising Inflammatory Biomarkers for Identifying Endoscopic Remission in Crohn's Disease.

OBJECTIVE: Endoscopic remission is the primary therapeutic target and associated with clinical outcome in Crohn's disease (CD). Non-invasive and accurate biomarkers are important in monitoring endoscopic remission frequently. Our study aimed at investigating the predictive capacity of prealbumin and retinol-binding protein 4 (RBP4) for identifying endoscopic remission. METHODS: From June 2018 to December 2020, 515 endoscopy procedures (332 in the training cohort and 183 in the validation cohort) were enrolled in this multicentre retrospective cohort study. Blood samples were collected for prealbumin or RBP4 testing with 7 days before the endoscopy. A simple Endoscopic Score for CD (SES-CD) was performed to evaluate endoscopic activity and defined endoscopic remission. The area under receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value and negative predictive value were performed to assess the predictive capacity of the biomarkers. RESULTS: Serum concentration of prealbumin and RBP4 was demonstrated to be higher in patients with endoscopic remission and significantly negatively correlated with SES-CD in the training cohort. The AUROC of prealbumin and specificity of prealbumin and RBP4 were larger than that of C-reactive protein in the training cohort and the validation cohort. The model combining prealbumin and faecal calprotectin had the largest AUROC (0.842 [95% CI: 0.775-0.908]). Furthermore, in both cohorts, prealbumin had a larger AUROC than C-reactive protein for identifying endoscopic remission in patients with anti-tumour necrosis factor therapy. CONCLUSION: Prealbumin and RBP4 were promising biomarkers for identifying endoscopic remission, especially in patients with anti-tumour necrosis factor therapy.