Therapeutic Advances in Gastroenterology最新文献

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial.

Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.

Design: Cross-sectional study.

Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed.

Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort.

Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.

Background: Diverticular disease (DD) represents a common gastrointestinal condition that poses a heavy burden on healthcare systems worldwide. A high degree of uncertainty surrounds the therapeutic approaches for the control of symptoms in patients with symptomatic uncomplicated diverticular disease (SUDD) and primary and secondary prevention of diverticulitis and its consequences.

Objectives: To review the current knowledge and discuss the unmet needs regarding the management of SUDD and the prevention of acute diverticulitis.

Eligibility criteria: Randomized trials, observational studies, and systematic reviews on lifestyle/dietary interventions and medical treatment (rifaximin, mesalazine, and probiotics) of SUDD or prevention of acute diverticulitis.

Sources of evidence: The literature search was performed from inception to April 2023, without language restriction, following the modified Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) reporting guidelines. References of the papers selected were checked to identify additional papers of potential interest. The final list of references was evaluated by a panel of experts, who were asked to check for any lack of relevant studies.

Charting methods: Information on patient population, study design, intervention, control group, duration of the observation, and outcomes assessed was collected by two authors independently.

Results: The review shows a high degree of uncertainty about therapeutic interventions, both dietary/lifestyle and pharmacological, in patients with SUDD, because of the scarcity and weakness of existing evidence. Available studies are generally of low quality, heterogeneous, and outdated, precluding the possibility to draw robust conclusions. Similarly, acute diverticulitis prevention has been seldom investigated, and there is a substantial lack of evidence supporting the role of dietary/lifestyle or pharmacological approaches to reduce the risk of diverticulitis.

Conclusion: The lack of robust evidence regarding therapeutic options for gastrointestinal symptoms in SUDD patients and for primary and secondary prevention of acute diverticulitis remains an important unmet need in the management of DD.

Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis.

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment.

Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs).

Design: Meta-analysis of RCTs.

Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions.

Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66-3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary.

Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design.

Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621).

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs.

Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities.

Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings.

Data sources and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps.

Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise.

Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.

Background: Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAI), and ELIAKIM. Recent advances in artificial intelligence (AI) have made it possible to automatically select the most relevant frames in CE.

Objectives: In this proof-of-concept study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation.

Design: Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAI, and ELIAKIM scores were calculated.

Methods: We developed a convolutional neural network-based automated score consisting of the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence-generated score (AIS).

Results: A total of 61 patients were included. The median LS was 225 (0-6006), CECDAI was 6 (0-33), ELIAKIM was 4 (0-38), and SB_AIS was 0.5659 (0-29.45). We found a strong correlation between SB_AIS and LS, CECDAI, and ELIAKIM scores (Spearman's r = 0.751, r = 0.707, r = 0.655, p = 0.001). We found a strong correlation between LS and ELIAKIM (r = 0.768, p = 0.001) and a very strong correlation between CECDAI and LS (r = 0.854, p = 0.001) and CECDAI and ELIAKIM scores (r = 0.827, p = 0.001).

Conclusion: Our study showed that the AI-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining of a CE score that may accurately correlate with prognostic factors and aid in the management and treatment of CD patients.

Introduction: Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations.

Aim: To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], Clostridioides difficile infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug.

Methods: A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching.

Results: We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); p = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); p = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects.

Conclusion: The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.

Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce fecal products for patients with rCDI at their treatment sites, and the American Gastroenterology Association has a National Registry focused on long-term safety of administering fecal microbiota products. The science behind the licensing of fecal microbiota, live-jslm, a consortium of fecal anaerobes found in stool augmented with strains of Bacteroidetes and fecal microbiota spores, live-brpk, a mixture of 50 species of purified Firmicutes spores is reviewed. Both products appear to be safe in clinical trials and effective in reducing rCDI episodes by mechanisms established for FMT, including normalization of α- and β-diversity of the microbiome and by increasing fecal secondary bile acids. The different makeup of the two LBPs suggests that rCDI responds to a variety of engrafting microbiota which explains why nearly all donors in FMT of rCDI are generally effective. Fecal microbiota, live-jslm has also been shown to successfully treat rCDI in elderly patients with advanced comorbidities. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning.

Background: Inflammatory bowel diseases (IBDs) have a peak incidence between the second and fourth decades of life and can affect women's reproductive life.

Objectives: Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition.

Design: Cross-sectional study.

Methods: Women with IBD followed at our IBD Unit and a group of healthy controls were enrolled. Data on reproductive life were collected using a dedicated questionnaire.

Results: The study included 457 women, of whom 228 had IBD, and 229 age-matched healthy controls. No differences were found in the use of contraceptives, infertility, and endometriosis. The risk of spontaneous and voluntary abortions was significantly higher in IBD patients than in healthy controls [odds ratio (OR) 2 and 3.62, respectively]. The risk of obstetrical complications in the IBD population was more than six times higher in patients who experienced disease reactivations during pregnancy than in those with persistent remission [OR 6.9, 95% confidence interval (CI) 1.51-31.28]. Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, 95% CI 0.22-0.91).

Conclusion: Our study underlines the negative impact of IBD on women's reproductive life, supporting the need for proactive preconception counseling.