Therapeutic Advances in Gastroenterology最新文献

Background: Crohn's disease (CD) exhibits variability in colorectal cancer (CRC) incidence and prognostic factors due to diverse clinical and behavioral characteristics, presenting inconsistencies between Western and Eastern patients.

Objectives: This study compared clinical characteristics between CD patients with CRC from the US and Korean tertiary referral centers and defined the prognostic factors related to mortality.

Design: Retrospective study.

Methods: We reviewed the electronic medical records of 236 adult CD patients with colorectal adenocarcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona (N = 200) and Asan Medical Center in Korea (N = 36) between January 1989 and August 2022.

Results: Asan patients had a younger age, shorter CD duration, more colonic involvement (L2 plus L3), penetrating behavior, perianal fistula, and shorter biological treatment duration before CRC diagnosis than Mayo patients. Furthermore, despite significant differences in body mass index, smoking status, primary sclerosing cholangitis, immunomodulators, CRC diagnosis period, clinical presentation, CRC location, surgery, and some histopathological details between the two groups, overall survival was not statistically different (p value, 0.29, log-rank test). Advanced age (adjusted hazard ratio (aHR), 1.03 per year; 95% confidence interval (CI), 1.01-1.04; p value, <0.01), unresectable CRC (aHR, 5.02; 95% CI, 2.49-10.12; p value, <0.01), and advanced CRC stage (aHR, 1.45 per stage; 95% CI, 1.07-1.97; p value, 0.02) were significantly associated with increased risk of death. CD remission at CRC diagnosis (aHR, 0.26; 95% CI, 0.08-0.91; p value, 0.04), CRC diagnosis period of 2011-2022 (aHR relative to 1989-2000, 0.46; 95% CI, 0.25-0.87; p value, 0.02), and CRC diagnosis by surveillance (aHR, 0.56; 95% CI, 0.32-0.98; p value, 0.04) were significantly associated with decreased risk of death.

Conclusion: Notably, some clinical features of CD with CRC differed between Asan and Mayo patients; however, overall survival was not different. CD remission, CRC surveillance, and more recent diagnosis of CRC were associated with a reduced risk of death.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for the minimally invasive management of biliary and pancreatic disorders. Under certain indications, performing ERCP without delay during the weekend can be important for improving outcomes.

Objectives: To compare the outcomes of ERCP performed on weekends and holidays with those of regular weekday ERCPs.

Design: Propensity score match analysis of the data from the Hungarian ERCP Registry.

Methods: A total of 116 ERCPs were performed during weekends or holidays, and 3144 during weekday working hours. The analyses were performed on 1:2 propensity-matched groups (116 weekend and 232 weekday cases).

Results: Weekend ERCPs were mostly performed for acute cholangitis and acute biliary pancreatitis (70% of cases), whereas in the weekday group, only 32% of cases were performed for these indications. No significant difference was found between weekday and weekend ERCPs in terms of the rates of successful (91.38% vs 93.1%, p = 0.565) and difficult (33.62% vs 36.64%, p = 0.511) biliary cannulations. We found no significant differences in the number of adverse events (bleeding, post-ERCP pancreatitis, and 30-day mortality) in ERCPs performed during weekends or weekdays. Moreover, no significant differences in the aforementioned outcomes were detected between the propensity-matched groups.

Conclusion: In this propensity-matched study, no significant differences were found in the outcomes of weekend and weekday ERCPs.

Interest in artificial intelligence (AI) applications for ulcerative colitis (UC) has grown tremendously in recent years. In the past 5 years, there have been over 80 studies focused on machine learning (ML) tools to address a wide range of clinical problems in UC, including diagnosis, prognosis, identification of new UC biomarkers, monitoring of disease activity, and prediction of complications. AI classifiers such as random forest, support vector machines, neural networks, and logistic regression models have been used to model UC clinical outcomes using molecular (transcriptomic) and clinical (electronic health record and laboratory) datasets with relatively high performance (accuracy, sensitivity, and specificity). Application of ML algorithms such as computer vision, guided image filtering, and convolutional neural networks have also been utilized to analyze large and high-dimensional imaging datasets such as endoscopic, histologic, and radiological images for UC diagnosis and prediction of complications (post-surgical complications, colorectal cancer). Incorporation of these ML tools to guide and optimize UC clinical practice is promising but will require large, high-quality validation studies that overcome the risk of bias as well as consider cost-effectiveness compared to standard of care.

Complex fistulizing perianal disease is a disabling manifestation of inflammatory bowel disease (IBD), seriously compromising patients 'quality of life'. The success rate of available treatments is quite low, and nearly half of the patients will develop chronically active fistulas or experience fistula recurrence. Mesenchymal stem cell therapy has shown interesting results, but the complexity and the cost of production limit its widespread use. This study aims to report the results of the innovative use of autologous emulsified adipose-derived stromal vascular fraction tissue for treating complex fistulizing perianal disease. From March 2021 to March 2022, 10 patients underwent a two-step procedure: (1) examination under anaesthesia, with loose seton drainage and 4 weeks later and (2) curettage of the fistulous tract, internal fistula closure and an injection of autologous emulsified adipose-derived stromal vascular fraction tissue harvested from the subcutaneous layer of the patient's hip. Clinical and radiological (through magnetic resonance imaging) healing were assessed at 6 months. We included five patients affected by Crohn's disease, three by ulcerative colitis and two by indeterminate colitis. All patients were on concomitant biological therapy (50% on Infliximab). One patient required a re-treatment for a relapse and two different fistulas were separately treated in another one. Out of 12 total procedures performed, clinical healing was achieved in 10 cases (83%), while radiological healing in 6 patients (50%). No adverse events were recorded. Autologous emulsified adipose-derived stromal vascular fraction tissue can represent an effective, safe and cheap add-on therapy for patients with complex perianal fistulas in IBDs.

Objectives: Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling.

Design: Online questionnaire circulated via three tertiary IBD centres and Crohn's Colitis Australia.

Methods: Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated.

Results: There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn's disease and ulcerative colitis demonstrated a good fit. In Crohn's disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn's disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis.

Conclusion: In Crohn's disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn's disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority.

[This corrects the article DOI: 10.1177/17562848241265782.].

Objectives: Stenting of the malignant hilar biliary obstruction (MHBO) area for bile drainage is challenging. Bilateral stenting techniques of stent-in-stent (SIS) and stent-by-stent (SBS) have shown promising results. This study evaluates the efficacy of different stenting methods for MHBO.

Design: A meta-analysis was performed to determine the efficacy of SIS and SBS stenting strategies for MHBO.

Data sources and methods: Medical databases such as PubMed, Web of Science, Embase, and Scopus, were searched up to August 2023. We selected eligible studies reporting the data on technical and clinical success, adverse events, and incidence of re-obstruction (RO) of SBS and SIS groups in MHBO patients. We compared the outcomes of SBS and SIS groups.

Results: A total of 9 studies comparing the data of 545 patients (268 in the SBS group and 277 in the SIS stenting group) were analyzed. There was no significant difference (p > 0.05) in the odds ratio (OR) of Re-obstruction (RO) 0.87 (95% confidence interval (95% CI) 0.6-1.25), technical success 0.58 (95% CI 0.16-2.11), clinical success 1.13 (95% CI 0.62-2.07), and adverse events 1.53 (95% CI 0.88-2.64). The mean difference in procedure time was -12.25 min (95% CI -18.39, -6.12), and the hazard ratio of stent patency was 1.22 (95% CI 1.01-1.47), favoring SBS, with high heterogeneity (I ² = 94%). There was no significant difference in HR for survival 1.05 (95% CI 0.95-1.16) with high heterogeneity (I ² = 84%).

Conclusion: Compared with SIS, SBS showed better stent patency with comparable technical and clinical success and adverse events.

Prospero registration: The registration number for this study on PROSPERO is CRD42024523230.

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown.

Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator.

Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale.

Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test.

Results: The most commonly used drugs at inclusion were Humira^® (436/941, 46.3%), Amgevita^® (177/941, 18.8%) and Hulio^® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma^® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects.

Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

Background: The risk of serious infection and active tuberculosis in patients with inflammatory bowel disease (IBD) has not been concurrently evaluated based on the use of anti-tumor necrosis factor (TNF)-α agents versus non-anti-TNF biologics (vedolizumab/ustekinumab) in the Korean population.

Objectives: We compared the risk of serious infection and active tuberculosis in Korean patients with IBD treated with non-anti-TNF biologics (vedolizumab/ustekinumab) or anti-TNF-α agents.

Design: This study was a population-based cohort analysis of nationwide administrative claims data.

Methods: Health Insurance Review and Assessment Service claims data (representing 97% of the South Korean population) from between January 2007 and February 2021 were reviewed, and adults with IBD who initiated vedolizumab/ustekinumab or anti-TNF-α treatment (n = 6123) between 2017 and 2020 were enrolled. Intergroup differences in the risk of serious infection requiring hospitalization/emergency department visits or active tuberculosis during the follow-up period were analyzed.

Results: In the patients treated with anti-TNF-α agents or vedolizumab/ustekinumab during a mean follow-up of 1.55 ± 1.05 and 0.84 ± 0.69 years, the incidence rates of serious infection were 9.43/100 and 6.87/100 person-years, respectively. Multivariable analysis showed no significant intergroup difference in the risk of serious infection with vedolizumab/ustekinumab or anti-TNF-α treatment; the adjusted relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.81 (95% confidence interval 0.46-1.44, p = 0.478). Among patients treated with anti-TNF-α agents and vedolizumab/ustekinumab, the incidence rates of active tuberculosis were 0.87 and 0.37 per 100 person-years, respectively. The relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.31 (95% confidence interval 0.07-1.26, p = 0.101). In a subset analysis comparing vedolizumab and ustekinumab with anti-TNF-α agents, similar results were observed.

Conclusion: In Korean patients with IBD, non-anti-TNF biologics (vedolizumab/ustekinumab) tended to be associated with a lower risk of serious infection or active tuberculosis than anti-TNF-α agents.

Background: Biologic agents have demonstrated efficacy in treating ulcerative colitis (UC); however, treatment failure to tumor necrosis factor inhibitors (TNFi) is common in the real world. Data on preferential sequencing in clinical practice after failure remain limited.

Objectives: This study aimed to evaluate real-world outcomes of patients cycling to TNFis or switching to non-TNFi biologics following first-line failure with TNFis.

Design: Retrospective cohort study in Germany.

Methods: Adult patients with UC were identified using administrative claims data from 1 May 2014 to 30 June 2022 provided by a statutory sickness fund. Patients newly initiating first-line therapy with TNFis and then switching to another agent were identified. Patients were defined as within-class switched (WCS), if they cycled to another TNFi, or outside-class switchers (OCS), if they switched to a non-TNFi biologic [ustekinumab (UST) or vedolizumab (VDZ)] and followed from index (switch date) to death, insurance end, or study end on 30 June 2022. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline characteristics between groups, and weighted Cox regression models were used to compare primary (time to discontinuation and second treatment switch) and secondary outcomes (corticosteroid-free drug survival).

Results: We identified 166 patients initiating TNFis and switching to a subsequent treatment (mean age: 42.9 years, 49.4% female). Following IPTW, there were 71 and 76 patients in the WCS and OCS groups, respectively. Compared to OCS, WCS were more likely to discontinue the new therapy [hazard ratio (HR), 1.82, 95% confidence interval (CI), 1.14-2.89, p = 0.012], and switch a second time (HR, 3.46, 95% CI, 1.89-6.36, p < 0.001). Moreover, WCS showed an increased likelihood of initiating prolonged corticosteroid therapy (HR, 1.42, 95% CI, 0.77-2.59, p = 0.260); however, the results were not significant.

Conclusion: Following first-line TNFi failure, this study suggests that real-world outcomes among patients with UC are less favorable when cycling to another TNFi, compared to switching to a non-TNFi such as UST or VDZ.