Bo-Lin Yang

Perianal fistulizing Crohn’s disease (PFCD) is a severe and complex manifestation associated with high morbidity and limited treatment durability. Ustekinumab is a monoclonal antibody targeting the interleukin-12/23 pathway, which is involved in the pathogenesis of PFCD. Evidence from post hoc analyses and real-world studies has shown the therapeutic potential of ustekinumab in both anti-tumor necrosis factor-experienced and selected biologic-naïve patients with PFCD. Preliminary evidence has indicated that the treatment effect may be improved when used in combination with surgical interventions such as seton placement or sphincter-preserving procedures. Adjunctive antibiotics during induction and early monitoring of clinical and radiologic response may further enhance outcomes. While ustekinumab is increasingly being incorporated into multidisciplinary PFCD management, prospective fistula-specific trials are needed to clarify its optimal positioning. Future research should also focus on predictive biomarkers and treatment algorithms to support personalized and durable care.

Background: Crohn’s disease (CD) management lacks biomarkers that precisely reflect immune activity. Prolactin (PRL) has immunomodulatory functions, but its role in CD is unclear. Aim: To investigate serum PRL changes in CD patients and evaluate its potential as a biomarker for disease activity and treatment response. Methods: In a prospective cohort study, serum PRL levels were analyzed in 185 CD patients and 58 healthy controls, and correlated with clinical markers (CRP, FC). Results: Serum PRL levels were significantly higher in CD patients versus controls (p<0.001). Higher baseline PRL levels correlated with a greater reduction in CRP after treatment. The study population had no previous reproductive history. Conclusion: Elevated serum PRL may serve as a supplementary biomarker reflecting immune dysregulation and disease activity in CD, particularly in this cohort enriched with severe, perianal-dominant disease. Its role in evaluating therapeutic effectiveness warrants further investigation.

Background: Our earlier studies identified that non-SMC condensin I complex subunit D2 (NCAPD2) induces inflammation through the IKK/NF-κB pathway in ulcerative colitis. However, its role in the development of Crohn’s disease (CD) and the specific molecular mechanism still need to be further studied. Methods: NCAPD2 expression in clinical ileal CD mucosa vs normal mucosa was examined, alongside its correlation with CD patients’ clinical characteristics via their medical records. The biological function and molecular mechanism of NCAPD2 in CD were explored using a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD mouse model, along with immunofluorescence, western blot, quantitative real-time PCR, immunohistochemistry, hematoxylin and eosin staining, and cell functional analysis. Results: NCAPD2 was overexpressed in CD tissues and significantly correlated with disease activity in CD patients (P = .016). In a TNBS-induced CD mouse model, NCAPD2 knockdown inhibited the development of TNBS-induced intestinal inflammation in mice. In addition, we found that NCAPD2 inhibited autophagy. Mechanistically, NCAPD2 promoted the phosphorylation of mammalian target of the rapamycin (mTOR) and its direct effector S6K and downregulated the expression of autophagy-related proteins Beclin1, LC3II, and Atg5. In addition, NCAPD2 activates the NF-κB signaling pathway, and the downstream inflammatory factors are continuously released, leading to the persistence of inflammation. Conclusions: Our results show that NCAPD2 suppresses autophagy and worsens intestinal inflammation by modulating mTOR signaling and impacting the NF-κB pathway, suggesting a critical role in CD progression. Targeting NCAPD2 could be a promising therapeutic approach to stop CD advancement.

Background: Teduglutide, the first glucagon-like peptide 2 analogue, has been demonstrated to facilitate the absorption of gut nutrient and lessen the need for parenteral assistance in patients with Short Bowel Syndrome (SBS). However, its adverse drug events (AEs) are primarily documented in clinical trials, with a deficit in real-world data. This study evaluates the AEs profile of teduglutide based on Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data.Method: A disproportionality analysis of FAERS data from Quarter 1 (Q1) 2013 to Quarter 3 (Q3) 2023 was conducted to examine the association between teduglutide and adverse events, employing Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) methods.Results: Out of 13,809,302 reports in the FAERS database, 10,114 reports identified teduglutide as the “primary suspect” in AEs identification. During the dosing observation period, the median occurrence of adverse events was 393 days (interquartile range [IQR] 97–996 days). Teduglutide-associated AEs occurred in 27 System Organ Classes (SOC), of which renal and urinary disorders is not mentioned in the specification. Based on the four algorithms, a total of 260 major disproportionality preferred terms (PTs) were filtered out, including previously unreported AEs including weight decreased (n = 805), vascular device infection (n = 683), dehydration (n = 596) and nephrolithiasis (n = 146).Conclusion: Our findings corroborate the AEs listed in the teduglutide prescribing information and additionally unveil new adverse reaction signals such as nephrolithiasis. These discoveries could aid in clinical monitoring and risk identification for teduglutide.

Background and Aims: Fecal incontinence (FI) is a common complaint that greatly affects the quality of life of patients with Crohn’s disease (CD) and is associated with the clinical characteristics of CD. We aimed to identify risk factors related to FI and construct a risk prediction model for FI in patients with CD. Methods: This retrospective study included 600 Chinese patients with CD from 4 IBD centers between June 2016 and October 2021. The patients were assigned to the training (n = 480) and testing cohorts (n = 120). Two nomograms were developed based on the logistic regression and Cox regression models to predict the risk factors for FI in patients with CD. The discriminatory ability and accuracy of the nomograms were evaluated using the receiver operating characteristic (ROC) curves and the area under the ROC curves (AUCs). Additionally, the Kaplan-Meier survival curve was also used further to validate the clinical efficacy of the Cox regression model. Results: The overall prevalence of FI was 22.3% (n = 134 of 600). In the logistic regression model, age at diagnosis (odds ratio [OR], 1.032; P = .033), penetrating behavior of disease (OR, 3.529; P = .008) and Perianal Disease Activity Index score >4 (OR, 3.068; P < .001) were independent risk factors for FI. In the Cox regression model, age at diagnosis (hazard ratio [HR], 1.027; P = .018), Montreal P classification (HR, 2.608; P = .011), and Perianal Disease Activity Index score >4 (HR, 2.190; P = .001) were independent predictors of the prevalence of FI over time. Two nomograms were developed to facilitate risk score calculation, and they showed good discrimination ability according to AUCs. Conclusions: In this study, we identified 4 risk factors related to the prevalence of FI and developed 2 models to effectively predict the risk scores of FI in CD patients, helping to delay the course of FI and improve the prognosis with timely intervention.

Objectives: Small bowel (SB) endoscopic healing has not been well explored in patients with Crohn’s disease (CD). This study aimed to assess the clinical utility of SB endoscopic mucosal and histological healing in patients with CD. Methods: In total, 99 patients with CD in clinical–serological remission were retrospectively followed after they underwent colonoscopy and double-balloon enteroscopy. Time until clinical relapse (CD activity index of >150 with an increase of >70 points) and serological relapse (abnormal elevation of C-reactive protein levels) constituted the primary endpoints. Results: Of the 99 patients, 75 (74.7%) exhibited colonoscopic healing and 43 (43.4%) exhibited SB endoscopic healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 8 (18.6%), 11 (25.6%), 11 (25.6%), and 2 (4.6%) patients, respectively. Of the 43 patients who exhibited SB endoscopic healing, 21 (48.8%) achieved histological healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 4 (19.0%), 7 (33.3%), 7 (33.3%), and 1 (4.8%) patient, respectively. There was no statistically significant difference in the number of patients who relapsed, were hospitalized, or underwent surgery between those who exhibited histological healing and those who did not. Conclusion: A substantial number of patients who were in clinical–serological remission did not undergo SB endoscopic healing, and the lesions increased their risk of clinical relapse. Thus, endoscopic healing may be of greater clinical value than histological healing when evaluating the remission of patients with CD.

Background: Ligasure hemorrhoidectomy for thrombosed external hemorrhoids in pregnancy has been rarely studied. Objective: The purpose of this article is to study the efficacy and safety of Ligasure hemorrhoidectomy comparing with conservative treatment for thrombosed external hemorrhoids in pregnancy. Design: This was a retrospective cohort study. Setting: The patients were treated at a tertiary referral center in China. Patients: 94 pregnant patients hospitalized for thrombosed external hemorrhoids from September 2020 to December 2021. Interventions: Ligasure hemorrhoidectomy treatment or conservative treatment according to the patient’s wishes. Main outcome measures: Symptom relief, recurrence and satisfaction of thrombosed external hemorrhoids in pregnancy with different interventions. Results: There were no differences between groups in maternal age, gestational age, body mass index, parity, constipation and a prior history of thrombosed external hemorrhoids. The pain scores were less in surgical group than in conservative group in post-treatment days 1 and 7. Time to return to normal activities was shorter in surgical group than in conservative group (6.51 vs. 13.52 days, P < 0.001). Post-treatment complications were mild in surgical group and there were no significant differences concerning the rate of abortion, preterm birth, cesarean delivery and weight of fetus. Recurrence rate was significantly lower in surgical group (8.57% vs. 30.43%, P = 0.017). The patient satisfaction scores were significantly higher in surgical group than in conservative group (Z = − 2.979, P = 0.003). Limitations: This was a retrospective study with a limited number of patients, the data was obtained from only one center. Conclusions: Comparing with conservative treatment, Ligasure hemorrhoidectomy for TEH in pregnancy results in more rapid pain relief, shorter time to return to normal activities, lower incidence of recurrence, and better patient satisfaction. This type of surgery has low and mild postoperative complications, is not attended by any risk to the mother or her fetus.

Objective: Abdominoperineal resection (APR) is currently established as a standard treatment regimen for fistula-associated anal adenocarcinoma (FAAA), however, the efficacy of chemoradiotherapy (CRT) remains unclear. The aim of this study is to evaluate the role of CRT in patients with FAAA treated with APR through single-center experience and literature review.Methods: A retrospective review was performed on patients with FAAA consecutive treated in our institution from 2005 to 2022. In addition, a systematic literature search was performed using PubMed and MEDLINE. All patients with FAAA who received APR in our institution and reported in the literature were included and divided into three categories for statistical analysis: APR alone (APR group), neoadjuvant therapy combined APR (CRT+APR group), and APR combined postoperative therapy (APR+CRT group).Results: Fifteen patients with FAAA were identified from our retrospective charts review. At a median follow-up time of 18 months, the recurrence-free survival rate was 53.3% and the survival rate was 73.3%. Eight patients underwent APR and 6 received postoperative chemotherapy. Among them, one died, one developed recurrence and the remaining six patients were alive with disease free. We found 37 publications describing 62 patients with FAAA treated with APR. Clinical data from these articles were analyzed together with the 8 cases in our institution. The overall survival rates were 94.1%, 70.8%, and 38.5% at 1-, 3-, 5-years respectively. Combining (neo)adjuvant therapy did not appear to improve outcomes in FAAA treated with APR (CRT+APR vs. APR, p=0.977; APR+CRT vs. APR, p=0.351). Lymph node involvement was shown to be significantly associated with poor outcomes by multivariate analysis (p=0.020).Conclusions: For patients with FAAA without lymph node involvement, APR is adequate to control disease and the addition of CRT does not appear to prolong survival.