BMC Gastroenterology最新文献

Background/aims: The increasing use of biologic therapies for moderate to severe inflammatory bowel disease (IBD) highlights the importance of optimal treatment sequencing, particularly after vedolizumab (VDZ) exposure. Studies comparing the effectiveness of ustekinumab (UST) and antitumor necrosis factor (anti-TNF) agents post-VDZ are limited.

Methods: This retrospective study analyzed VDZ-experienced IBD patients treated with UST or anti-TNF (adalimumab and infliximab) from May 2019 to January 2024. We conducted a comparative analysis of the 52-week treatment persistence between UST and anti-TNF therapies, while also identifying independent predictors that influence 52-week persistence.

Results: The study included 110 participants, with 40 diagnosed with ulcerative colitis (UC) and 70 with Crohn's disease (CD). Demographics were comparable across treatment groups. The primary discontinuation reason for VDZ was secondary non-response. Kaplan-Meier analysis revealed that UST demonstrated superior 52-week persistence in overall IBD, CD and UC patients, compared to anti-TNF. Cox regression analysis also showed UST's superiority in overall IBD (HR: 0.15, 95% CI: 0.05-0.45, p < 0.001), CD (HR: 0.09, 95% CI: 0.01-0.68, p = 0.02), and UC (HR: 0.28, 95% CI: 0.08-0.996, p = 0.049). The independent predictors for 52-week treatment persistence are Crohn's disease (Odds Ratio: 7.151, 95% CI: 1.763-28.995, p = 0.006) and UST treatment (Odds Ratio: 7.912, 95% CI: 1.789-34.992, p = 0.006). Notably, UST required more frequent dosing adjustments than anti-TNF, although both treatments exhibited comparable safety profiles.

Conclusions: UST demonstrated superior 52-week treatment persistence in IBD patients previously treated with VDZ compared to anti-TNF agents, albeit with a need for more frequent dose adjustments.

Background: Current therapies for complex Crohn's perianal fistulas (CPF) have a limited ability to achieve long-term healing. Darvadstrocel (DVS) is an expanded allogeneic adipose-derived mesenchymal stem cell therapy that has demonstrated efficacy in treating complex CPF in clinical trials. There are, however, limited long-term comparative data with standard of care (SoC). The aim of this study was to combine clinical trial data and real-world evidence using statistical methodologies to predict long-term effectiveness of DVS versus SoC in patients with CPF.

Methods: Data were pooled from a clinical trial (ADMIRE-CD) and two retrospective chart review studies (INSPECT and PREFACE). Predictive statistical models extrapolated clinical outcomes beyond observed follow-up using parametric curves, which were implemented into a semi-Markov model to obtain the number of patients in remission. The setting was multinational and multicenter. ADMIRE-CD was conducted in 49 hospitals in 7 European countries and Israel. INSPECT used data from the ADMIRE study. PREFACE involved patients from Belgium, France, Germany, Italy, and Spain. The participants were patients with complex CPF treated with DVS or SoC. Times to remission and relapse (clinical, and clinical plus patient-centric remission) were analyzed. Additionally, the proportion of patients in clinical and patient-centric remission was examined.

Results: In total, 513 patients were included in the analysis (ADMIRE-CD [N = 200] and PREFACE [N = 313]). Patients in ADMIRE-CD and PREFACE were similar in age (median [interquartile range, IQR], 36 [20.0] versus 36 [22.0] years, respectively) and gender (males, 54% and 52%, respectively). The median (IQR) duration of Crohn's disease was 9.4 [11.3] years for patients in ADMIRE-CD and 6.5 [12.9] years for patients in PREFACE. The estimated time to remission was shorter for patients treated with DVS versus SoC. The estimated time to relapse was longer for patients treated with DVS versus SoC. A higher estimated proportion of patients treated with DVS versus SoC had clinical and patient-centric remission at 24 months (48% and 35%, respectively) and 48 months (49% and 32%, respectively).

Conclusion: This novel approach enabled pooled data from a clinical trial and real-world settings to predict long-term effectiveness of DVS versus SoC in patients with complex CPF.

Background: Gastric cancer (GC) remains one of the predominant malignant tumors within the digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective of this study is to delineate the causal relationship between circulating metabolites and GC.

Method: The primary Mendelian randomization (MR) analysis was based on three large GWAS datasets. While the inverse variance weighted served as the primary analysis technique for investigating causal relationships, additional sensitivity analyses were facilitated through methods such as MR-PRESSO, the weighted median, and MR-Egger. Subsequently, replication, meta-analysis, and multivariable MR were executed using another GC GWAS.

Results: The results of this study indicated significant associations between three metabolites 3-methyl-2-oxovalerate (OR 5.8, 95%CI: 1.53-22.05, p = 0.0099), piperine (OR 2.05, 95%CI: 1.13-3.7, p = 0.0175), Phe-Phe dipeptide (OR 0.16, 95%CI: 0.03-0.93, p = 0.0409) and GC.

Conclusion: The present study provides evidence supporting a causal relationship between these three circulating metabolites and GC risk. Elevated levels of 3-methyl-2-oxovalerate and piperine may increase the risk of GC, while Phe-Phe dipeptide may have a protective effect. By integrating genomics and metabolomics, we offer a novel perspective on the biological mechanisms underlying GC. Such insights have the potential to enhance strategies for the screening, prevention, and treatment of GC.

Background: With 20-40% of patients who have inflammatory bowel disease (IBD) not responding to therapy, resource use and costs can be high. We performed a descriptive analysis of health-care data for IBD management in the National Health Service to explore potential areas for improvement.

Methods: In this exploratory study, we analysed real-world data from the Discover dataset for adults with a diagnosis of incident IBD recorded in northwest London, UK, between 31 March, 2016, and 31 March, 2020. We compared mean visit numbers and primary and secondary care costs per patient to examine resource use and costs for active disease versus remission.

Results: We included 7,733 patients (5,872 with ulcerative colitis [UC], 1,427 with Crohn's disease [CD], and 434 with codes for both [termed IBD-undefined in this study]). Remission was recorded in 19,218 (82%) of 23,488 observations for UC, 4,686 (82%) of 5,708 for CD, and 1,122 (65%) for IBD-undefined observations. Health-care resource use was significantly higher with active disease in all settings except primary care for UC. Total health-care costs were greater with active disease than remission for all diagnoses (all p < 0.0001). The main driver of costs was inpatient hospital care among those with active disease; elective inpatient costs were high among patients with UC and IBD-undefined in remission.

Conclusions: Higher health-care resource use and costs were observed with active disease, which underscores the importance of early induction and maintenance of remission in UC and CD. Updated strategies that incorporate treat to target may offer cost benefits by the offsetting of biologic drug costs with a reduction in costly inpatient hospital stays.

Trial registration: This trial was not registered as it used pseudonymised retrospective data.

Background: Open surgical debridement was the main treatment option for infected pancreatic necrosis (IPN). However, it was associated with significant trauma, leading to a higher mortality rate. With the development of minimally invasive surgery, the step-up treatment principle centered around minimally invasive intervention, significantly reducing the incidence of complications and mortality rates among IPN patients. However, few studies have reported the efficacy of laparoscopic retroperitoneal pancreatic necrosectomy (LRPN), a new minimally invasive debridement technique, in IPN patients with duodenal fistula (DF)-a severe complication of IPN. Therefore, we analyzed the effectiveness and safety of LRPN for treating IPN with DF and discussed the impact of DF on patient prognosis.

Methods: We retrospectively examined patients diagnosed with IPN between 2018 and 2023. The patients were divided into two groups based on the presence or absence of DF. Clinical characteristics, treatment strategies, clinical outcomes, and follow-up information were analyzed. A 1:1 propensity score-matching (PSM) method was used to assess differences in outcome indicators more accurately.

Results: A total of 197 patients were examined. After PSM, no significant differences were observed between the two groups in in-hospital mortality rate, incidence of single organ failure, rate of postoperative severe complications (Clavien-Dindo Classification ≥ 3), and intensive care unit stay (P > 0.05). However, the incidence of multiorgan failure, gastrointestinal bleeding, number of percutaneous catheter drainage (PCD) procedures, surgery cases, hospital stay, and hospitalization costs were higher in the DF group (P < 0.05). Of these patients, 71.6% (n = 141) were treated with PCD + LRPN, with a conversion rate of 6.38% to open surgery. A higher proportion of patients in the non-DF group showed improved clinical outcomes solely with PCD (22.6% vs. 2.4%, P < 0.05), whereas a higher proportion of patients in the DF group underwent PCD + LRPN (88.1% vs. 67.1%, P < 0.05). Both groups showed a significant reduction in the Sequential Organ Failure Assessment score 72 h postoperatively.

Conclusions: For patients with IPN and DF, the LRPN-centered step-up strategy was safe and effective. DF prolongs hospital stay and increases hospitalization costs for patients.

Background: High red meat consumption is a main modifiable risk factor for colorectal cancer mortality (CRC), but its attributable disease burden remains unclear in China. We aimed to analyze the temporal trends in CRC deaths and disability-adjusted life years (DALYs) attributable to high red meat consumption in China from 1990 to 2021 and to predict the disease burden in the next 15 years.

Methods: Data was obtained from the Global Burden of Disease (GBD) 2021 study. The Joinpoint regression model was used to calculate the annual percentage change (APC) and the average annual percentage change (AAPC). In addition, the age-period-cohort (APC) model was employed to explore the effects of age, period, and cohort on CRC mortality. The autoregressive integrated moving average (ARIMA) model was utilized to predict the disease burden in 2022-2036. We also compared the CRC burden attributed to high red meat in China with 204 countries worldwide.

Results: The results showed that the number of CRC deaths in China due to high red meat consumption increased nearly 2.5 times, from 17,608 (95% UI: -3 to 36,613) in 1990 to 43,580 (95% UI: -16 to 92,083) in 2021. Male CRC deaths exhibited a more pronounced increase, rising from 9,800 in 1990 to 27,600 in 2021. Additionally, the number of DALYs increased from 518,213 (95% UI: -105,107 to 1,074,174) in 1990 to 1,091,788 (95% UI: -509 to 2,295,779) in 2021. Joinpoint regression analysis confirmed that the AAPC in ASDR and ASMR was - 0.20 (95% CI: -0.40 ∼ 0.00) and - 0.30 (95% CI: -0.40 ~ -0.10). When age, period, and cohort effects were examined as the reference group, the risk of CRC was found to increase with age. However, women experienced a marked decline in both period and cohort effects compared to men.

Conclusions: Compared to global levels, the burden in China is heavier. In terms of mortality or DALY standardized rates, Chinese women show a similar downward trend to the overall trend, while Chinese men show a striking upward trend. This study provides valuable insights into enhancing CRC prevention and improving dietary patterns in China.

Background: This study aimed to investigate the association between Metabolic-dysfunction-associated steatotic liver disease(MASLD)and C-reactive protein/lymphocyte ratio (CLR).

Methods: MASLD was defined as a Controlled Attenuation Parameter (CAP ≥ 274dB/m) and CLR = C-reactive protein/lymphocyte. A multifactor linear regression model was used to test the relationship between MASLD and CLR. Smoothed curves and threshold effects analyses were fitted to describe nonlinear relationships. Subgroup analyses and interaction tests were then performed according to gender, prevalence of diabetes, ethnicity, and smoking status.

Results: A total of 1846 participants from the NHANES database were included in this study. In the unadjusted model and model 1 (adjusted for age, sex, and race), CLR was positively associated with MASLD pathogenicity. Unadjusted model (OR = 1.04, 95% CI: 1.02-1.07, P = 0.0017), model 1 (OR = 1.04, 95% CI: 1.01-1.07, P = 0.0056). The results of the fitted smoothed curves showed that CLR and the risk of developing MASLD were nonlinear. Interaction tests and subgroup analyses confirmed that there were no significant interactions between CLR and MASLD causation with gender, race, prevalence of diabetes mellitus, and smoking status(P interaction>0.05).

Conclusions: This study shows that CLR is positively associated with the risk of developing MASLD Targeting CLR levels may be a new approach to treating MASLD.

Background: Although stage I gastric cancer (GC) presents a favorable survival rate, outcomes for patients experiencing recurrence remain poor. This research focuses on assessing the prognosis and identifying risk factors for stage I GC patients, further assessing the necessity of adjuvant chemotherapy (AC).

Methods: The study involved a retrospective analysis of 902 patients with stage I GC who received curative resection from November 2010 to December 2020. Independent prognostic factors were identified using multivariate Cox regression analysis. Kaplan-Meier analysis was employed to compare recurrence-free survival (RFS) and disease-specific survival (DSS) across different groups.

Results: During follow-up, 47 patients (5.2%) experienced recurrence or death, with the 3-, 5-, and 10-year survival rates exceeding 90%. Age ≥ 65 years and pT2 stage were independently associated with decreased RFS, while age ≥ 65 years, pT2 stage, and tumor diameter ≥ 5 cm was significantly associated with decreased DSS. Patients with an increasing number of risk factors exhibited lower 5-year RFS [97.4% (risk factors = 0) vs. 91.3% (risk factors = 1) vs. 85.0% (risk factors = 2) vs. 63.6% (risk factors = 3); P < 0.001] and DSS [97.5% (risk factors = 0) vs. 92.7% (risk factors = 1) vs. 85.1% (risk factors = 2) vs. 72.9% (risk factors = 3); P < 0.001]. The AC group had lower DSS for patients without risk factors than the non-AC group. However, there was no significant difference in survival outcomes among patients with risk factors between the AC and non-AC groups.

Conclusion: Stage I GC patients exhibited excellent long-term outcomes post-curative resection. Independent prognostic factors included age, pT stage, and tumor diameter. AC failed to provide any additional survival advantage for these patients.

Background and purpose: Esophageal and gastric varices hemorrhage (EGVH) is a life-threatening condition with the 6-week mortality rate of 15-25%. Up to 60% of patients with EGVH may experience rebleeding with a mortality rate of 33%. The existing scoring systems, such as RS scoring system (Rockall score, RS) and GBS scoring system (Glasgow-Blatchford score, GBS), have limitations in predicting the risk of rebleeding. Our study was to construct and validate a novel predictive model for the risk of rebleeding in patients with EGVH and to compare the predictive power of the predictive model with GBS and pRS.

Methods: Data of patients with EGVH was collected in the First Affiliated Hospital of Dalian Medical University from January 2016 to June 2020. Binary logistic and stepwise regression was performed to construct a predictive model. We compared the predictive power of the new predictive model to the GBS and pRS scoring systems.

Results: Clinical data from a total of 265 patients with EGVH was collected. Six factors including systolic blood pressure, transfusion requirement, CA199, platelet count, upper esophageal varices and severity of esophageal varices were included in our new predictive model. The AUCs of the specificity of the predictive model, GBS and pRS are 0.82, 0.60 and 0.56.

Conclusion: This study successfully constructed a predictive model for the risk of rebleeding in patients with EGVH. This predictive model demonstrated higher predictive ability than pRS and GBS scoring systems for assessing rebleeding risk in EGVH patients.