Therapeutic Advances in Gastroenterology最新文献

Background: Dietary therapy may potentially reduce inflammation and promote mucosal healing in patients with Crohn's disease and is associated with fewer side effects and lower cost compared to medical therapy. Recently the Crohn's disease exclusion diet (CDED) has been developed to reduce exposure to individualized dietary components which negatively affect the intestine in patients with Crohn's disease.

Objectives: This systematic review aimed to explore the effectiveness of CDED in Crohn's disease patients.

Design: A systematic review.

Data sources and methods: A systematic search was performed on the PubMed, EBSCOhost, Cochrane library, OVID, Embase, Scopus, and CINHAL to identify relevant clinical trials published from 1 January 2014 to 31 August 2022.

Results: A total of 1120 studies were identified and 7 studies were finally included in the analysis. The study was reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement.

Conclusion: Our findings suggested that the use of CDED seemed to be effective for induction and maintenance of remission in children and adults with mild to moderate Crohn's disease. However, heterogeneity and limitations existed among the studies included. Further investigation in the form of well-designed randomized clinical trials is needed to validate the present findings.

Registration: PROSPERO registration number CRD42022335453.

Background: Patients with inflammatory bowel disease (IBD) have an attenuated serologic response to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of severe COVID-19.

Objectives: To evaluate SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients.

Design: A systematic literature search and meta-analysis was performed.

Data sources and methods: The search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and CINAHIL. The articles were independently screened and selected by two reviewers. A random-effects model was used to calculate the pooled relative risk for breakthrough infections in vaccinated IBD patients and controls.

Results: A total of 16 studies were included, with study periods ranging from January 2020 to October 2021 and follow-up time from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in vaccinated IBD patients. The disease course of COVID-19 was generally mild, with low hospitalization and mortality rates (0-8.7% and 0-4.3%, respectively). Vaccinated IBD patients had a significantly lower relative risk of breakthrough infection rate compared to unvaccinated controls (risk ratio: 0.07, 95% CI: 0.03-0.18). No difference was observed between IBD patients and non-IBD controls, and between partially and fully vaccinated IBD patients. The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. Most studies showed no impact from immunosuppressive treatment, anti-tumour necrosis factor alpha or corticosteroids and other biologics; one study reported higher rates for patients treated with infliximab versus vedolizumab.

Conclusion: Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time.

Registration: The protocol was published in the PROSPERO database (CRD42021292853).

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce.

Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time.

Design: A comprehensive literature review and time-trend analysis.

Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model.

Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910).

Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.

Background: While the detrimental impact of negative emotions on the clinical course of inflammatory bowel disease (IBD) and quality of life has been extensively investigated, evidence for a potential impact of positive emotions is scarce.

Objectives: We aim to analyse contributing factors of positive affect and their predictive value for disease course in IBD patients.

Design: In this retrospective cohort study, epidemiological, psychosocial and IBD disease characteristics of Swiss IBD cohort study patients were analysed longitudinally.

Methods: Epidemiological, psychosocial and disease characteristics were extracted from the database of the Swiss IBD cohort study. Participants' positive emotions were assessed cross-sectionally with the seven-item Marburg questionnaire (range 1-6) addressing positive affect in different aspects of daily life. Predictors of positive emotions were identified by linear regression. The quantitative longitudinal impact of positive emotions on the further disease course was analysed using a multivariable Cox proportional hazards model.

Results: Among 702 IBD patients, those reporting more positive emotions were found to have significantly less intense medical treatment, less pain and fewer depressive symptoms (p < 0.05). A higher percentage of variability in positive emotions was explained by pain (36%) and depressive symptoms (13%) than by epidemiological characteristics (0.3%), or characteristics of IBD and its treatment (2.4%). Patients with higher levels of positive emotions (score > 3.5) experienced longer flare-free survival, also after adjusting for confounders (adjusted hazard ratio: 0.39, p < 0.05).

Conclusions: The absence of pain and depressive symptoms were the strongest drivers for high positive affect. Higher scores of positive affect were associated with longer disease-free survival in IBD patients.

Over the last 2 years the lives of millions have changed because of the emergence of Coronavirus disease 2019 (COVID-19). Patients living with inflammatory bowel disease (IBD) represent a sizable population with their own sets of challenges to providers in the wake of so much uncertainty. The Centers for Disease Control considers immunocompromised individuals at higher risk of infection and complications from COVID-19. Early in the pandemic, the specific risks for IBD patients were unclear as guidance was based on expert opinion regarding the management of IBD during a COVID-19 era. Fortunately, after considerable work in the field, the overwhelming evidence suggests that IBD patients as a whole do not appear to be at increased risk for more severe disease from COVID-19. Certain risk factors such as age, steroids, comorbidities, combination immunomodulatory therapy, and IBD disease activity have been associated with worse outcomes. Most IBD medications are low risk, with the exception of immunomodulator monotherapy and combination therapy with thiopurine and anti-TNF. Vaccination remains safe and effective for all IBD patients, although additional booster doses may be necessary, particularly in patients taking anti-TNF agents.

Background: Previous studies have identified useful endoscopic ultrasonography (EUS) features to predict the malignant potential of gastrointestinal stromal tumors (GISTs). However, the results of the studies were not consistent. Artificial intelligence (AI) has shown promising results in medicine.

Objectives: We aimed to build a risk stratification EUS-AI model to predict the malignancy potential of GISTs.

Design: This was a retrospective study with external validation.

Methods: We developed two models using EUS images from two hospitals to predict the GIST risk category. Model 1 was the four-category risk EUS-AI model, and Model 2 was the two-category risk EUS-AI model. The diagnostic performance of the models was validated with external cohorts.

Results: A total of 1320 images (880 were very low-risk, 269 were low-risk, 68 were intermediate-risk, and 103 were high-risk) were finally chosen for building the models and test sets, and a total of 656 images (211 were very low-risk, 266 were low-risk, 88 were intermediate-risk, and 91 were high-risk) were chosen for external validation. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the four-category risk EUS-AI model in the external validation sets by tumor were 74.50%, 55.00%, 79.05%, 53.49%, and 81.63%, respectively. The accuracy, sensitivity, specificity, PPV, and NPV for the two-category risk EUS-AI model for the prediction of very low-risk GISTs in the external validation sets by tumor were 86.25%, 94.44%, 79.55%, 79.07%, and 94.59%, respectively.

Conclusion: We developed a EUS-AI model for the risk stratification of GISTs with promising results, which may complement current clinical practice in the management of GISTs.

Registration: The study has been registered in the Chinese Clinical Trial Registry (No. ChiCTR2100051191).

Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower.

Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs).

Design: A systematic review and meta-analysis was conducted.

Data sources and methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs).

Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71-85%). There was significant heterogeneity among studies with an I² of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60-82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p < 0.0001).

Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies.

Bacterial translocation is a pathological process involving migration of pathogenic bacteria across the intestinal barrier to enter the systemic circulation and gain access to distant organs. This phenomenon has been linked to a diverse range of diseases including inflammatory bowel disease, pancreatitis, and cancer. The intestinal barrier is an innate structure that maintains intestinal homeostasis. Pathogenic infections and dysbiosis can disrupt the integrity of the intestinal barrier, increasing its permeability, and thereby facilitating pathogen translocation. As translocation represents an essential step in pathogenesis, a clear understanding of how barrier integrity is disrupted and how this disruption facilitates bacterial translocation could identify new routes to effective prophylaxis and therapy. In this comprehensive review, we provide an in-depth analysis of bacterial translocation and intestinal barrier function. We discuss currently understood mechanisms of bacterial-enterocyte interactions, with a focus on tight junctions and endocytosis. We also discuss the emerging concept of bidirectional communication between the intestinal microbiota and other body systems. The intestinal tract has established 'axes' with various organs. Among our regulatory systems, the nervous, immune, and endocrine systems have been shown to play pivotal roles in barrier regulation. A mechanistic understanding of intestinal barrier regulation is crucial for the development of personalized management strategies for patients with bacterial translocation-related disorders. Advancing our knowledge of barrier regulation will pave the way for future research in this field and novel clinical intervention strategies.

Pancreatic ductal adenocarcinoma (PDA) is highly aggressive and has few treatment options. To personalize therapy, it is critical to delineate molecular subtypes and understand inter- and intra-tumoral heterogeneity. Germline testing for hereditary genetic abnormalities is recommended for all patients with PDA and somatic molecular testing is recommended for all patients with locally advanced or metastatic disease. KRAS mutations are present in 90% of PDA, while 10% are KRAS wild type and are potentially targetable with epidermal growth factor receptor blockade. KRAS^G12C inhibitors have shown activity in G12C-mutated cancers, and novel G12D and pan-RAS inhibitors are in clinical trials. DNA damage repair abnormalities, germline or somatic, occur in 5-10% of patients and are likely to benefit from DNA damaging agents and maintenance therapy with poly-ADP ribose polymerase inhibitors. Fewer than 1% of PDA harbor microsatellite instability high status and are susceptible to immune checkpoint blockade. Albeit very rare, occurring in <1% of patients with KRAS wild-type PDAs, BRAF V600E mutations, RET and NTRK fusions are targetable with cancer agnostic Food and Drug Administration-approved therapies. Genetic, epigenetic, and tumor microenvironment targets continue to be identified at an unprecedented pace, enabling PDA patients to be matched to targeted and immune therapeutics, including antibody-drug conjugates, and genetically engineered chimeric antigen receptor or T-cell receptor - T-cell therapies. In this review, we highlight clinically relevant molecular alterations and focus on targeted strategies that can improve patient outcomes through precision medicine.

Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.