United European Gastroenterology Journal最新文献

Background and aims: Beta-blockers are successfully used to treat hemangioma and may decrease the proliferation of cancer cells. We hypothesized that individuals with colorectal polyps may also benefit from beta-blocker initiation.

Methods: Individuals diagnosed with their first colorectal polyp 2006-2016 in the nationwide Swedish ESPRESSO histopathology cohort aged 45-79 years without CRC were eligible. We excluded individuals with previous indications for beta-blocker (cerebrovascular disease, heart failure, aortic aneurysms, myocardial infarction) and individuals with contraindications for preventive beta-blocker initiation (COPD, dementia, liver cirrhosis, Charlson score > 5 or metastatic cancer). Using duplication and inverse probability weighting, we emulated a target trial of beta-blocker initiation within 2 years of the first polyp diagnosis. Main outcomes were incident CRC, CRC mortality, and all-cause mortality until 2019.

Results: In total, 30,399 individuals met our inclusion criteria and were followed for a median of 8 years. Beta-blockers were initiated in 2083 (6.9%) eligible individuals. The 10-year cumulative incidence in initiators versus non-initiators was 5.8% versus 8.6% for CRC incidence, 0.9% versus 1.1% for CRC mortality. The corresponding fully adjusted hazard ratios (HRs) were 0.87 (95% confidence interval, 95% CI: 0.85-0.89) and 0.96 (0.83-1.09). CRC mortality was significantly reduced in women HR 0.78 (0.68-0.99) but not in men HR = 1.14 (0.80-4.46). Cumulative CRC mortality was 0.6% in initiating women versus. 1.1% in non-initiating women.

Conclusion: Beta-blocker initiation within 2 years of polyp diagnosis was linked to a lower CRC incidence for all subgroups, and a lower CRC mortality in women, indicating that beta-blocker initiation may improve long-term outcomes in this high-risk population.

Background: Perinuclear-antineutrophil cytoplasmic antibodies (pANCA) have been identified in familial ulcerative colitis (UC), but the mechanism underlying their expression remains elusive. We assessed the role of genetic predisposition, environmental factors and systemic subclinical inflammation in the development of pANCA in a twin cohort with UC.

Methods: A total of 48 twin pairs (Leuven, Belgium n = 4, Maastricht, The Netherlands n = 6 and Örebro, Sweden n = 38) with UC were included. Among these, 18 were monozygotic (3 concordant and 15 discordant for UC) and 30 were dizygotic (1 concordant and 29 discordant for UC). P-ANCA was detected through standardised ELISA, an indirect immunofluorescence assay and DNase treatment. In addition to high sensitivity C-reactive protein (hs-CRP), 92 inflammatory protein markers were measured in serum by proximity extension assay.

Result: Perinuclear-ANCA was present in 15/52 (29%) of UC twins vs. 4/44 (9%) healthy twin siblings (p = 0.02). No agreement in the presence of pANCA or their levels was observed between twin siblings in monozygotic pairs discordant for UC [intraclass correlation coefficient (ICC) = 0.09] or dizygotic pairs (ICC = -0.20). Female sex was associated with an increased likelihood of pANCA (odds ratio, OR 5.25; 95% confidence interval, CI 1.36-20.30) and higher ANCA levels (ratio of geometric means 1.86; 95% CI 1.18-2.93). Active smoking was associated with lower concentrations of ANCA (ratio of geometric means 0.31; 95% CI 0.14-0.68) and potentially reduced the likelihood of pANCA (OR 0.20; 95% CI 0.03-1.34) in twins with UC but not in their healthy siblings. In healthy twin siblings, significant correlations between ANCA levels and hs-CRP, CDCP1, IL17 A, CXCL9 and IL5 (correlation coefficients 0.36-0.41, p-values < 0.05) were observed.

Conclusion: Female sex and tobacco smoking outweighed genetics regarding the generation and levels of pANCA and ANCA antibodies. The correlations between ANCA levels and inflammatory markers in healthy twin siblings suggest that pANCA may result from subclinical inflammation.

Background and aims: The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) is a Europe-wide network for centers of excellence in the management of rare liver diseases. We aimed to evaluate the current diagnostic and therapeutic trends of primary biliary cholangitis (PBC).

Methods: Prospective data of PBC cases diagnosed from 2017 to March 2024 were extracted from the R-LIVER registry of ERN-RARE LIVER. Cases without two follow-ups within 24 months were excluded from the treatment analysis. Biochemical response according to Toronto criteria and normalization of alkaline phosphatase (ALP) values after 12 months of Ursodeoxycholic Acid (UDCA) were evaluated.

Results: This study included 327 incident cases from six centers. Median age was 56 years, 89.3% were female. At the time of diagnosis, median values of ALP were 1.37 x ULN, and median bilirubin was 0.49 x ULN. Transient elastography (TE) was performed in 230 patients (70.3%) at baseline; median liver stiffness was 6.2 kPa. Out of 316 subjects, treatment with UDCA was started in 312 patients (98.7%); 246 (85.1%) achieved ALP values < 1.67 x ULN at 12 months. Normalization of ALP values occurred in 143 subjects (49.5%) at 12 months. Among 43 patients with inadequate response, 18 (41.9%) were treated with second-line therapies, and had worse liver biochemistry at baseline.

Conclusion: In the current era, patients with PBC are diagnosed at an early stage using non-invasive methods and are almost all treated with UDCA. The biochemical response rate is 85.1%, but the use of second-line therapies for inadequate responders remains suboptimal.

Background and aims: Acute necrotising pancreatitis carries high mortality, especially if infected necrosis occurs. While percutaneous drainage may be required when internal drainage is not feasible, reliable guidelines for managing percutaneous drains are lacking. This study aimed to assess the common practice of percutaneous drainage therapy for infected pancreatic necrosis.

Methods: This retrospective study among 29 tertiary care centres included all patients hospitalised for necrotising acute pancreatitis from 01/2016 until 12/2022 with at least one percutaneous drain. The length of hospital stay was the primary endpoint, with mortality as the secondary endpoint. Between-group comparisons were conducted using the ratio of restricted mean survival time (RMST) after adjusting for confounders.

Results: 585 patients (67% male) from 29 tertiary care centres in 15 countries in Europe, Canada and Bolivia were included in the analysis. Length of hospitalisation or mortality did not differ between the flushed (n = 398) and non-flushed groups (RMST ratio 1.04, p-value = 0.42 and RMST ratio 1.05, p-value = 0.1 respectively). Mortality was significantly lower in those patients who received a combination of percutaneous and internal drains (dual-modality drainage, n = 243) as compared to those who received percutaneous drains only (RMST ratio 1.05, p-value = 0.01). Flushing with antibiotics as compared to saline was not associated with shorter length of hospital stay or lower mortality (RMST ratio 0.98, p-value = 0.78 and 0.97, p-value = 0.48 respectively).

Conclusions: This study reveals notable differences in therapeutic concepts and flushing management for percutaneous drains. While flushing itself was not associated with a shorter length of hospitalisation or lower in-hospital mortality, a lower mortality was observed when internal and percutaneous drainage were used in combination.

Clinical trial registration: The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) under the registration number DRKS00032231.

Background: Few data are available on the impact of primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD).

Objective: We conducted a retrospective study using TriNetX to compare the outcomes of patients with IBD and those with concomitant IBD and PSC.

Methods: All patients with a confirmed diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis with or without PSC were eligible. One-to-one propensity score matching was employed to balance demographic parameters, comorbid conditions, and IBD medications between cohort 1 (IBD) and cohort 2 (IBD and concomitant PSC). The primary endpoint was a composite endpoint including the risk of mortality, hospitalization, and surgery. Risks were expressed as Hazard Ratio (HR) with a 95% confidence interval (CI).

Results: A total of 398,980 IBD patients were analyzed (cohort 1: 395,874 and cohort 2: 3106). After propensity-score-matching, 3007 patients from each group were included (mean age 48.1 ± 19.4 years, female 40%, UC 75% CD 24.8%). Approximately 1%-2% of patients were treated with advanced therapies. Cohort 2 patients had a higher risk of experiencing the composite endpoint compared to cohort 1 group (HR:1.32, 95%CI:1.23-1.42). Similarly, a higher risk of hospitalization and mortality was identified in subjects with IBD and concomitant PSC (HR:1.32, 95% CI: 1.22-1.43 and HR: 1.69, 95%CI: 1.46-1.96). Both CD and UC patients with concomitant PSC had a higher risk of achieving the composite endpoint (HR: 1.18, 95%CI: 1.02-1.37 and HR: 1.29, 95%CI: 1.18-1.40). An increased risk of mortality and hospitalization was found both in patients with CD (HR: 2.16, 95%CI:1.58-2.95, and 1.20, 95%CI:1.03-1.41) and UC (HR: 1.87, 95%CI: 1.57-2.22 and HR: 1.27, 95%CI:1.16-1.40) and concomitant PSC.

Conclusion: In this administrative study of patients with IBD and PSC, concomitant PSC was associated with an increased risk of mortality and hospitalization.

Background: The incidence of pancreatic ductal adenocarcinoma (PDAC) is lower in females than males (19.0 vs. 20.2 for 100,000 individuals in Europe). This disparity is commonly attributed to differences in exposure to lifestyle risk factors such as smoking and alcohol consumption; however, hormonal activity may also play a role.

Objective: This study aimed to comprehensively examine the role of hormone exposure and reproductive factors in males and females in PDAC susceptibility.

Methods: We analyzed 816 PDAC cases and 302,645 controls from the UK Biobank prospective cohort. Twenty hormone-related variables and a polygenic risk score (PRS) were examined in females and males using epidemiological methods and machine learning algorithms.

Results: Oral contraceptives (OC) use increased PDAC risk (OR = 2.17 (95% CI: 1.70-2.80), p = 8.16 × 10^-10), while each full-term pregnancy decreased it (OR = 0.83 (95% CI: 0.76-0.90), p = 2.60 × 10^-5). In males increased level of sex hormone-binding globulin (SHBG) was associated with a decreased risk (OR = 0.98, 95% CI: 0.97-0.98, p = 7.38 × 10^-10). The machine learning model performed well in both sexes, with AUCs of 0.95 and 0.92, specificity of 0.86 and 0.92 and sensitivity of 0.90 and 0.81 for females and males, respectively. The use of an explainer identified age and the PRS as significant features for both sexes, with additional factors such as age at menopause and OC use for females, and SHBG concentration in blood for males.

Conclusion: We observed a consistent protective effect of the factors that decrease-the exposure to menstrual cycle related hormones. Additionally, exogenous hormones increase due to long exposure to OC and HRT increases the risk of the disease. Therefore, our result suggests that it is more important to which hormones an individual is exposed compared to the overall increase or decrease in exposure.

Background: Ileal pouch-anal anastomosis (IPAA) is the preferred intervention for ulcerative colitis (UC) patients whose medical treatment fails. Acute severe ulcerative colitis (ASUC) can precipitate the need for urgent surgery, potentially influencing post-IPAA outcomes.

Objective: This study details the incidence, disease course, and treatment of pouchitis and pouch failure in a population-based cohort of UC patients following IPAA construction.

Methods: We included all UC patients who underwent IPAA construction within two administrative regions in Denmark between November 1993 and April 2021 in a population-based cohort. Data spanning from diagnosis to January 2023 were manually extracted from electronic patient records and analyzed.

Results: Among 233 patients, 118 (50.6%) experienced 519 pouchitis events. 437 (84.2%) had intermittent pouchitis, 60 (11.6%) had chronic antibiotic-dependent pouchitis, and 22 (4.2%) had chronic antibiotic-refractory pouchitis. There was no significant difference in the incidence of pouchitis between patients who underwent urgent surgery due to ASUC and those who underwent non-urgent surgery. Antibiotics were used in 89.6% of cases, with ciprofloxacin and metronidazole being the most common treatment. Thirty-two (13.7%) patients experienced 36 pouch failures, 6.9% experienced permanent pouch failure, with 8.3% of failures attributed to pouchitis.

Conclusion: Half of the patients with IPAA experienced at least one episode of pouchitis. ASUC did not appear to increase the risk of pouchitis. The overall incidence of pouch failure was low, with pouchitis contributing to a minority of failures.