Therapeutic Advances in Gastroenterology最新文献

Background: Inflammatory bowel disease (IBD) is characterized by periods of remission and relapses, and treatment is based on phenotype, risk factors, and disease severity. Treatments include 5-aminosalicylates (5-ASA), thiopurines, methotrexate, calcineurin inhibitors, corticosteroids (CS), biological therapy (BxT), and, more recently, small molecules.

Objective: To determine the baseline demographics and clinical characteristics, treatment patterns, and disease status of patients in Mexico with a history of moderate/severe IBD returning for hospital follow-up (Index Day).

Design: This was a non-interventional, cross-sectional study.

Methods: Socio-demographics, clinical characteristics, and prescribed treatments were collected from a retrospective review (3 years) of each patient's medical records.

Results: A total of 326 patients with a diagnosis of moderate/severe IBD at least 6 months before the Index Day were included in the analysis: 95 patients (29.2%) had Crohn's disease (CD) and 231 (70.9%) ulcerative colitis (UC). In the CD group, 45.3% (n = 43) had a Harvey Bradshaw Index score ⩾8 or Crohn's Disease Activity Index ⩾220; 10 patients had a B1-non-stenosing, non-penetrating phenotype and 17 had stenosis (B2). In the UC group, 18.2% (n = 42) had moderate/severe disease and the most frequent presentation was pancolitis (n = 56). Regarding treatment over the previous 3 years: for CD, 62 (65.3%) received CS and 20.0% (n = 19) were CS-dependent; 30.5% received 5-ASA + IMS; 27.4% BxT + IMS; and 38.9% 5-ASA + IMS + BxT. In the case of UC, 74.9% (n = 173) received CS and 32.9% (n = 76) were CS-dependent; 64.5% received 5-ASA + IMS; 2.2% BxT + IMS; and 31.6% 5-ASA + IMS + BxT.

Conclusion: In Mexico, 45.3% of CD patients and 18.1% with UC presented with moderate/severe disease activity. Conventional therapy was used to treat the majority of patients, and the availability of more advanced therapies and a personalized treatment approach is needed to improve clinical outcomes in the future.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as HDAC inhibitors (HDACis) and analyze the role of HDAC inhibition in alleviating IBD along with its mechanism, as well as clinical potential of HDACis in IBD treatment.

Background: Endoscopic submucosal dissection (ESD) is a representative treatment modality for early gastric neoplasms. However, the learning curve for beginners performing ESD using a multibending endoscope has not been introduced.

Objective: This study aimed to evaluate the learning curves of operators undergoing intensive training using a multibending endoscope.

Design: This was a retrospective single center study.

Methods: We retrospectively analyzed data of over 1500 consecutive gastric ESDs performed by two operators using a multibending endoscope. A change-point analysis with 50 cases of moving average speeds was used to determine the new target resection speed. Cumulative sum (CUSUM) analysis was used to identify the cases required for proficiency in ESD. Risk-adjusted CUSUM (RA-CUSUM) analysis was performed for each operator after adjusting for confounding factors influencing the resection speed.

Results: In total, 1491 cases were enrolled, with early gastric cancer accounting for 43.2% (n = 644). Overall, the en bloc resection, R0 resection, and curability rates were 97.7%, 96.0%, and 92.3%, respectively. The mean resection speed was 19.8 cm²/h. Because both operators surpassed the commonly used benchmark resection speed of 9 cm²/h in the first 50-case block, we established a new target benchmark of 17.9 cm²/h in the change-point analysis. CUSUM analysis indicated that performing 166 cases overall was required to achieve the benchmark, with the 2 operators needing 153 and 69 cases to meet this target speed after RA-CUSUM analysis.

Conclusion: Using a multibending endoscope for gastric ESD can help beginners achieve safe and excellent outcomes. These findings will serve as a useful guide for beginners attempting to use a multibending endoscope.

Background: Dietary fatty acids (FA) are crucial to the pathophysiology of inflammatory bowel disease (IBD), influencing systemic and gut inflammatory responses. Dietary FA intake influences the fatty acid profiles of vital cell membranes, which might be a source of inflammatory mediators. Despite their significance, research on dietary FA subtypes and their effects on inflammation and oxidative stress in IBD is limited.

Objective: We investigated the association between dietary FA intake, the erythrocyte membrane FA composition (EMFA), and inflammation and oxidative stress markers in patients with mild-moderate luminal Crohn's Disease (CD) participating in the CD Therapeutic Dietary Intervention (CD-TDI).

Design: A cross-sectional analysis was performed on 24 participants (13 CD-TDI, 11 habitual diet controls) from a 13-week randomized controlled trial assessing the efficacy of CD-TDI in inducing clinical and biomarker remission in CD.

Methods: EMFA was analyzed using direct-injection gas chromatography, and dietary FA intake was assessed using the ASA 24-h Dietary Assessment Tool^®.

Results: The CD-TDI group showed a significant increase in dietary n-3 polyunsaturated fatty acids (PUFA) at Week 13 (p = 0.04) compared to no changes in the control group. Participants on the CD-TDI also demonstrated a significant reduction in total fat, saturated fat, and arachidonic acid (AA) (p < 0.01). EMFA analysis revealed lower percentages of AA (p = 0.03) in the CD-TDI group. Positive correlations were observed between C-reactive protein, fecal calprotectin, and dietary stearic acid (p < 0.05). Inverse correlations were found between malondialdehyde (MDA) and the Mediterranean Diet Score (r = -0.67) as well as MDA and the intake of whole fruit, legumes, and nuts/seeds (r > -0.50).

Conclusion: The CD-TDI significantly increased dietary n-3 PUFA intake, reduced pro-inflammatory n-6 PUFA (AA), and improved markers of oxidative stress, supporting its potential in CD management. The cell membrane fatty acid profile might be a therapeutic target in CD.

Trial registration: NCT04596566.

Background: Inflammatory bowel disease (IBD) is a chronic condition requiring lifelong management and frequent interactions with healthcare providers. Digital health tools have the potential to enhance disease management by providing real-time data and improving care coordination. Despite their potential, there is limited evidence on patient perspectives regarding barriers and facilitators to the adoption of these tools.

Objectives: To explore patient perspectives on the barriers and facilitators associated with using digital health tools for IBD self-management, focusing on the adoption of a tool called MyIBDToolkit.

Design: This study employed a qualitative description approach to gather detailed insights into patient experiences.

Methods: Participants with a confirmed IBD diagnosis were recruited from clinics in Alberta, Canada. Data were collected via virtual semi-structured interviews conducted between June and July 2024. Thematic analysis was used to identify key themes, and member checking ensured the credibility of the findings.

Results: Eighteen interviews were conducted, reaching thematic saturation. Participants viewed MyIBDToolkit as beneficial for enhancing disease monitoring and care coordination. However, concerns about data entry burden, privacy, and engagement emerged as significant barriers. Variability in healthcare provider use of the tool was another critical concern.

Conclusion: While digital health tools such as MyIBDToolkit have the potential to improve IBD self-management, addressing barriers such as usability, privacy, and sustainability is crucial. Incorporating patient feedback during the design process can enhance the effectiveness and acceptability of these tools in chronic disease management.

Background: As an uncommon serological pattern, the effect of hepatitis B e antigen/anti-hepatitis B e (HBeAg/anti-HBe) coexistence on peginterferon-α (Peg-IFN-α) therapy in patients with chronic hepatitis B (CHB) remains unknown. Moreover, Peg-IFN-α is clinically limited due to several side effects. It is of significant value to early identify the favored population for Peg-IFN-α therapy in CHB patients.

Objectives: This study aimed to analyze the impact of HBeAg/anti-HBe coexistence on the effectiveness of Peg-IFN-α and to construct a nomogram for predicting the occurrence of HBeAg seroconversion in treatment-naïve CHB patients with Peg-IFN-α therapy.

Design: Retrospective, case-control study of treatment-naïve CHB patients with Peg-IFN-α at a tertiary care center.

Methods: Data from HBeAg-positive treatment-naïve CHB patients were retrospectively analyzed. Clinical characteristics of the HBeAg/anti-HBe coexistence group were compared with those of the anti-HBe-negative group. In addition, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for HBeAg seroconversion. The nomogram for the prediction of HBeAg seroconversion was constructed and evaluated.

Results: A total of 140 HBeAg-positive CHB patients were enrolled. Patients with HBeAg/anti-HBe coexistence accounted for 11.4% of HBeAg-positive patients, and their hepatitis B surface antigen (HBsAg) and HBeAg levels were significantly lower than those of anti-HBe negative patients, but the HBeAg seroconversion rate was higher after Peg-IFN-α treatment. As revealed by multivariate logistic analysis, HBeAg/anti-HBe coexistence, baseline HBsAg, baseline HBeAg, and alanine aminotransferase ratio at baseline were independent correlates of HBeAg seroconversion. The nomogram model constructed based on these four independent correlates demonstrated good discrimination (area under the curve = 0.866), calibration, and clinical adaptability.

Conclusion: HBeAg/anti-HBe coexistence is associated with a higher HBeAg seroconversion rate, and the nomogram model constructed based on HBeAg/anti-HBe coexistence performs well in predicting HBeAg seroconversion in treatment-naïve CHB patients treated with Peg-IFN-α therapy.

Background: The comparable evaluation of computed tomography enterography (CTE), enteroscopy, and intestinal ultrasound in small bowel Crohn's disease (CD) is imprecise.

Objectives: The purpose of this study was to analyze the findings of enteroscopy, CTE, and intestinal ultrasound to determine the advantages and disadvantages of each method for the evaluation of small bowel CD.

Design: It was a single-center, observational, retrospective study.

Methods: The differences in localization of disease lesions, mucosal inflammation, and transmural inflammation between enteroscopy, CTE, and intestinal ultrasound for evaluation of small bowel CD were compared.

Results: A total of 198 patients with small bowel CD were included in the analysis. CTE and intestinal ultrasound had a lower detection rate of upper intestinal lesions compared with enteroscopy (p < 0.05). Enteroscopy was better than CTE and intestinal ultrasound in the detection of stenosis (p < 0.001), and the assessment of fistula by CTE was better than that by enteroscopy and intestinal ultrasound (p < 0.05). Enteroscopy, CTE, and intestinal ultrasound differed in the assessment of inflammatory activity, and the agreement of the three methods was poor (all intra-class correlation coefficient <0.75).

Conclusion: Enteroscopy is superior to CTE and intestinal ultrasound for the assessment of upper intestinal CD lesions. Enteroscopy, CTE, and intestinal ultrasound were not consistent in evaluating inflammatory activity, and the three methods may need to be combined for an accurate assessment.

Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.

Background: Linaclotide, a guanylate cyclase-C agonist, is indicated for irritable bowel syndrome with constipation (IBS-C). However, real-world data on the safety and patient-reported outcomes (PROs) of linaclotide are scarce in Chinese patients with IBS-C.

Objectives: To assess the real-world safety and PROs of linaclotide in the Chinese IBS-C population.

Design: Multicenter, prospective observational study.

Methods: Adults with IBS-C who had taken or planned to take at least one dose of linaclotide 290 μg were enrolled and followed up for 3 months. Face-to-face visits were conducted at baseline (V1), Week 4 ± 7 days (V2), and Week 12 ± 7 days (V3). Primary endpoints included the incidences of adverse events (AEs), AEs by severity, adverse drug reactions (ADRs), serious AEs (SAEs), and AEs leading to treatment interruption, discontinuation, and death. Secondary endpoints included mean treatment satisfaction at V2 and V3, and mean overall Irritable Bowel Syndrome-Quality of Life (IBS-QoL) at V2.

Results: Out of 3000 enrolled patients, 2963 took at least one dose of linaclotide and were analyzed. Overall, 712 patients (24.0%) reported 1095 AEs, which were mostly mild (89.9%). Diarrhea, reported in 297 out of the 2963 patients analyzed (10.0%), was the most common AE. No severe diarrhea was reported. Totally, 319 patients (10.8%) reported ADRs. Forty-six patients (1.6%) reported 50 SAEs and two cases were considered related to linaclotide treatment. Fifty-one (1.7%) and 70 patients (2.4%) interrupted and discontinued treatment due to AEs, respectively. One patient died of hepatic cancer, which was considered unrelated to linaclotide treatment. During the follow-up, the mean (±SD) treatment satisfaction increased numerically and continuously (V1, 2.8 ± 1.3 (n = 1721); V2, 3.5 ± 1.1 (n = 1705); V3, 3.9 ± 1.0 (n = 833)). The mean (±SD) overall IBS-QoL increased numerically from 73.2 ± 16.6 (n = 1924) at V1 to 80.2 ± 15.5 (n = 1738) at V2.

Conclusion: In the Chinese real-world setting, linaclotide was safe and well tolerated in patients with IBS-C. Numerically, there are trends toward improvement in PROs with linaclotide treatment.

Background: Coeliac disease (CeD) is a chronic immune-mediated disease triggered by exposure to dietary gluten in genetically predisposed individuals. The burden of CeD on patients and the healthcare system remains poorly evaluated in Germany.

Objectives: To assess the healthcare resource utilisation (HCRU) and costs of diagnosed CeD patients in a German claims database.

Design: A retrospective CeD case-control study was conducted using German claims data between 2017 and 2021.

Methods: CeD diagnosis was defined by at least one inpatient or two outpatient diagnostic codes (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM) K90.0) within four quarters (irrespective of calendar year) for CeD during the study period. Controls (non-CeD patients) were matched in a ratio of 5:1 by age, Charlson Comorbidity Index, sex and region. HCRU (hospitalisations, outpatient visits, medication use, sick leaves) and healthcare costs (outpatient services, inpatient services, outpatient pharmaceuticals, sick leaves and aids and remedies) were compared between CeD patients and controls.

Results: From the 3,352,188 patients with continuous enrolment during the study period (2017-2021), 8258 (0.25%) patients were identified as having a CeD diagnosis. The mean number of hospitalisations and outpatient visits within 5 years was 1.8- and 1.5-fold higher among matched CeD patients (n = 8243) compared to their controls (n = 41,215), resulting in an excess healthcare cost of €5251. Inpatient expenses were the main cost driver and accounted for 31.5% of total incremental costs.

Conclusion: The current study showed that CeD patients have considerably higher HCRU and related costs compared to matched controls. Our findings suggest the need for improved treatment options for CeD patients in addition to a gluten-free diet.