Introduction

The BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a cone-shaped transparent plastic cap attached by a adhesive tape to the tip of the endoscope and allows optical and tactile feedback during stricture dilation. In 2021, our group published on a one-time esophageal stricture dilation using the first version of BougieCap in 50 adults with EoE and were able to show its efficacy and safety. However, one BougieCap got detached during endoscopy. Ovesco recently released an upgraded BougieCap (version 2.0) that is characterized by the following features: 1) improved adhesive power of the tape; 2) gradual dilation over two millimeters per cap; 3) improved fit of the connecting part of the cap with the endoscope. As of yet, the technical feasibility, safety and clinical effectiveness of BougieCap version 2.0 for stricture dilation in adult EoE patients is unknown.

Aims & Methods

EoE patients prospectively included in the Swiss EoE Cohort were dilated with BougieCap 2.0 in case of the presence of esophageal strictures and stricture-related symptoms. Symptoms were assessed before and two weeks after a single dilation session using the validated EEsAI PRO tool (range 0-100 points). This is an investigator-initiated study. None of the authors has financial ties with Ovesco Endoscopy AG.

Results

Fourty two patients (76.2% male, median age 40 years (IQR 31-54 years), median disease duration 5 years (IQR 4-8 years), median diagnostic delay of 4 years (IQR 3-5 years), 57.2% treated with swallowed topical corticosteroids, 19.1% with proton pump inhibitors, 9.5% without anti-eosinophil therapy, 7.1% with elimination diet, 4.8% treated with dupilumab, 2.4% treated with benralizumab) were evaluated. Endoscopic bougienage was technically successful in 100%. A stricture diameter of <10mm was found in 14.3% of patients. Strictures were located in 38.1% in the proximal esophagus, in 57.4% in the distal esophagus, and in 4.8% in both proximal and distal esophagus. Median esophageal diameter increased from 12 mm (IQR 12-13) to 14mm (IQR 14-16, p<0.001). Median EEsAI PRO dropped from 35 points (IQR 27-42) to 0 (IQR 0-12, p<0.001) at 2 weeks post dilation. There was no bleeding necessitating endoscopic intervention. Temporary post-dilational thoracic pain was reported by 33.3% of patients. No esophageal perforation was observed and no BougieCap got detached. One BougieCap was used in 66.7% of dilations whereas two BougieCaps were used in 33.3% of procedures. Median esophageal peak eosinophil count was 10/hpf (IQR 0-24).

Conclusion

In adults with EoE, endoscopic treatment of esophageal strictures using the upgraded BougieCap version 2.0 is technically feasible, safe and offers symptomatic improvement in the short term.

Introduction

Patients with eosinophilic oesophagitis often experience diagnostic delays. Untreated eosinophilic oesophagitis may result in fibrosis and stricture formation, leading to morbidity and impaired quality of life. Early diagnosis and treatment can potentially prevent these outcomes and reduce emergency admissions with food bolus obstruction. The reasons for these delays have not been examined in primary care previously. This study quantifies the time to eosinophilic oesophagitis diagnosis and examines factors associated with diagnostic delays.

Aims & Methods

A retrospective cohort study of incident eosinophilic oesophagitis patients between 1st Jan 2006 and 31st Dec 2022 was undertaken using Clinical Practice Research Datalink (CPRD AURUM) linked to hospital admission data in Hospital Episode Statistics. Patients were followed from first proton pump inhibitor (PPI) prescription or presentation with eosinophilic oesophagitis related symptoms (food bolus obstruction or dysphagia) identified from SNOMED CT codes for primary care and ICD-10 codes for secondary care to diagnosis. The association between patient level factors and time to eosinophilic oesophagitis diagnosis was examined using a Robust Poisson regression model.

Results

2300 eosinophilic oesophagitis patients were studied (67.7% male; age 38 (IQR 30-49)). Median time to diagnosis was 3.6 years (IQR 0.5-8.7). 80.7% patients had a PPI prescription record in primary care prior to eosinophilic oesophagitis diagnosis with a time to eosinophilic oesophagitis diagnosis of 4.9 years (IQR 1.5- 9.7). Factors associated with more than 3 years to diagnosis included: female sex (adjusted risk ratio 1.18, 95% CI 1.10-1.27); smoking (1.11, 1.01-1.23); compared with baseline of elective endoscopy, urgent endoscopy for dysphagia (1.35, 1.18-1.54), urgent endoscopy for food bolus obstruction (1.26, 1.13-1.41), dysphagia presentation in primary care (1.16, 1.08-1.25), food bolus obstruction presentation in primary care (1.11,1.00-1.23) and PPI prescription in primary care (3.08, 2.58-3.67). 77% of patients had PPI treatment prescribed after eosinophilic oesophagitis diagnosis. 21% patients with no history of asthma or chronic obstructive pulmonary disease were prescribed a steroid inhaler (presumably swallowed) after eosinophilic oesophagitis diagnosis.

Conclusion

Longer time to eosinophilic oesophagitis diagnosis was associated with being female, smoking, food bolus obstruction and dysphagia presentations in primary or secondary care and particularly PPI prescriptions in primary care.

Introduction

Janus Kinase (JAK) inhibitors are licensed for the treatment of ulcerative colitis with the benefits of a fast onset of action and a short half-life.[i] This makes them a potential treatment option for patients hospitalised with UC, including those previously treated with, or unsuitable for, infliximab or cyclosporine. There is currently limited published evidence in this setting, drawn from small case series.

Aims & Methods

We performed a retrospective analysis of data collected at 14 sites in the United Kingdom, including both tertiary IBD centres (n=10) and general hospitals (n=4) between January 2019 to January 2024. We included patients who were hospitalised due to active UC and commenced a JAK inhibitor for that indication during the same admission. Baseline data included disease duration and extent, prior exposure to advanced therapies, clinical and endoscopic assessments of disease activity and laboratory parameters. We reviewed treatments administered during the same admission, including corticosteroids and advanced therapies.
Coprimary endpoints were colectomy rate at 30 days and 12 months. 12 week, 6 month and 12month persistence data was collected. Adverse outcomes and treatment persistence at the same time points were also recorded.

Results

80 patients (filgotinib (n=15), tofacitinib (n=25) and Upadacitinib (n=40) were included, with a minimum of 12 weeks follow-up. 43/80 (54%) were male, mean age was 37±14, mean admission albumin 35 and CRP 52. Extent of disease was E1 1/80 (1%), E2 31/80 (39%) and E3 48/80 (60%).
63/80 (79%) of patients had prior anti-TNF exposure (infliximab 47/80 (59%), including 13/80 (16%) of whom had received it as a previous rescue therapy). 31/80 (39%) were on prednisolone at admission.
50/80 (63%) had a baseline endoscopic assessment within 72 hours of admission, of which 34/50 (68%) had severe (Mayo 3) endoscopic activity.
During admission, prior to JAK inhibitor administration, treatments given included IV hydrocortisone (93%), methylprednisolone (5%), infliximab (4%) and cyclosporine (1%).
Colectomy rates were 8% and 14% at day 30 and week 12 respectively. In patients for whom 12-month follow-up data were available, 5/34 (15%) had undergone a colectomy at that timepoint.
There was one recorded herpes zoster infection and no recorded thromboses or major adverse cardiovascular events.

Table 1. JAK Inhibitor & Treatment Persistence

Conclusion

JAK inhibitors appear to offer a valuable treatment option for patients hospitalised with active UC. This appears to be the case even in patients with prior anti-TNF exposure. 86% of patients avoided colectomy at 12 weeks, with a similar proportion colectomy-free at 12-months. The risk of adverse events was small. Our study is, to our knowledge, the largest dataset examining the initiation of JAK inhibitors for those hospitalised with UC.

References

[i] Agrawal M, Kim ES, Colombel J-F. JAK inhibitors safety in ulcerative colitis: practical implications. Journal of Crohn's and Colitis. 2020;14(Supplement_2):S755-S60.

Introduction

Eosinophilic oesophagitis is a condition characterised by symptoms of dysphagia and/or food impaction in adults, with oesophageal histology showing a peak eosinophil count of >15 eosinophils/high power field (or >15 eosinophils/0.3mm2 or >60 eosinophils / mm2), and the absence of other causes¹. Recent BSG guidelines for the management of Eosinophilic oesophagitis (EOE) in adults recommend repeat endoscopy to ensure histological remission on treatment. This can require multiple procedures that are unpleasant for patients and are resource intensive. Capsule sponge is a minimally invasive oesophageal cell sampling technology that has been used in >15000 patients with Reflux symptoms and Barrett’s oesophagus. To date it has not been used in adults with EOE in clinical practice. The COSIE study is a pragmatic prospective ongoing study of adults with non-stenotic EOE to evaluate capsule sponge in routine clinical practice.

Aims & Methods

All adult patients attending a monthly dedicated EOE clinic May 2023 to April 2024 in a non-specialist hospital, were screened by a single consultant, Patients were offered capsule sponge and same day gastroscopy at least 8 weeks after starting or changing therapy or after three weeks from first diagnostic gastroscopy to monitor disease response and activity. The Endosign device was used in all patients. The Dysphagia Symptom Questionnaire, cytological and histological eosinophil count and Endoscopic reference score (EREFS) were measured as part of the ongoing study. Qualitative outcomes including success rate of swallowing, satisfactory cell sample (sufficient squamous cells), evidence of sponge reaching the stomach (columnar cells seen), complications and patient feedback and test preference were collected patient satisfaction questionnaire was collected after the procedure on the same day . All sponge cytology were processed by CYTED laboratories and endoscopic histology as part of normal clinical practice.

Results

138 patients with EOE attended the clinic between May 2023 and April 2024. 77 patients identified as suitable, 41/53 (75%) agreed to take part. 12/53 (25%) declined to take part in the study when our research nurse contacted them and 24 are awaiting testing. 31/41 (75.6%) were male and 10 (24.4%) females. Median age observed was 50 years, standard deviation 14.58, minimum was 19 years old and maximum age recorded was 72 years. Of the 41 patients who attempted to swallow capsule sponge 5 (12%) failed to swallow after 2 attempts. There have been no complications and no sponge detachments. 36 /41 (87.8%) agreed to same day gastroscopy. On same day gastroscopy examination, 20/ 36(55.5%) had minor grade I or II visible abrasions. No mucosal tears were evident. There was evidence of the capsule sponge reaching the stomach in 29/32 (90.6%). Adequate squamous cytological specimen were produced in 32/32 (100%). 36 (87.8%) patients found test acceptable of which 28/37 (75.6%) of those who expressed a preference preferred capsule sponge to gastroscopy.

Conclusion

The preliminary results show that capsule sponge is feasible to use in routine clinical practice and can be used safely to sample the oesophagus in non-stenotic EOE, providing sufficient samples. It is well tolerated and patients preferred capsule sponge to gastroscopy. Ongoing work will assess clinical effectiveness and management outcomes, comparative eosinophil counts and will contribute to a multicentre QUBIE (QUantitative Biomarker Identification for Eosinophilic oesophagitis) study to evaluate potential biomarkers in EOE.

References

Dhar A, Haboubi HN, Attwood SE, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut 2022;71:1459-1487.

Introduction

Hepatocellular carcinoma (HCC) is an end stage liver disease with increasing morbidity and mortality worldwide. Development of the disease is dependent on various genetic, dietary and environmental factors. While alcohol-related liver disease (ALD/MetALD) remains a major contributor, metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly relevant in clinical practice. There is increasing evidence for the role of bacteria, for instance, such as Bifidobacterium and Blautia, which were considered protective, while Streptococcus has been associated with disease progression. However, little is known about the alteration of microRNAs (miRNAs) in liver diseases and its interrelationship with microbial environment in view of etiological factors.

Aims & Methods

This study aimed to elucidate gastrointestinal miRNA alterations and explore their relationship with microbiome composition in patients with different stages of liver disease in terms of disease etiology. Multi-omics analyses were performed in a subset of well characterized patients (n=59) with liver disease and healthy controls. Systematic characterization included clinical, laboratory, demographic and imaging characterization and dietary preferences. Patients subclassification included fibrosis stage (no fibrosis, fibrosis, liver cirrhosis(LC)) and etiology (MetALD/ALD vs. MASLD). Fecal miRNAs were extracted using the Qiagen miRNeasy Kit and profiled via Agilent miRNA microarray. Microbiome analyses were performed amplifying the V1-V2 region of the 16S rRNA gene following Illumina sequencing.

Results

For miRNA analysis stringent criteria were applied to identify high quality miRNA targets. From approximately 4,000 candidates filtering resulted in selection of 202 high-quality miRNAs with reliably measurable concentrations. 28 of these miRNAs showed significantly positive alterations in concentration in patients with liver disease and 7 miRNAs significant negative alterations. Specifically, miR-642a-3p, miR-5006, miR-6781, and miR-6849 were elevated in feces in patients with LC. In contrast, miR-6869, miR-4467, and miR-5001 were present in lower concentration in LC patients. Notably, miR-4467 also showed strong negative associations with liver-specific laboratory markers, including gamma-glutamyl transferase (GGT) (r=-0.34; p=0.026) and M65, a marker of apoptosis (r=-0.42; p=0.005). Cross-sectional comparison of miRNA and microbiome data revealed miRNA alterations associated with specific microbial signatures. MiR-6795-5p, which was associated with liver stiffness (r = 0.39, p = 0.01), also correlated positively with the abundance of Streptococcus, a genus linked to disease progression (r=0.29; p=0.047). Conversely, miR-6869, miR-4467, and miR-5001 showed positive correlations with the potentially protective genera Blautia and Bifidobacterium (miR-6869: r_{Bifidobacterium}=0.35; p_{Bifidobacterium}=0.012; r_Blautia=0.37; p_Blautia=0.008; miR-4467: r_Blautia=0.41; p_Blautia=0.002; miR-5001: r_Blautia=0.38; p_Blautia=0.006).

Conclusion

Multi-omics analysis reveals distinct alterations in fecal miRNAs and gut microbiota across different stages of liver disease. Changes in microbial composition were associated with shifts in miRNA profiles, suggesting a functional link in maintaining intestinal homeostasis. These findings highlight the potential of integrated microbiome–miRNA signatures as novel diagnostic and therapeutic targets. Further studies are warranted to validate these associations and explore their clinical applications.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a widespread chronic liver condition closely associated with obesity, insulin resistance, and dyslipidemia. Recent evidence points to gut microbiota dysbiosis as a key player in MASLD pathogenesis, affecting intestinal barrier function and systemic inflammation.

Aims & Methods

The aim was to investigate gut microbiota composition in patients with MASLD and assess its association with disease progression and gut barrier dysfunction. A total of 152 MASLD patients and 150 matched controls without liver pathology were examined. Diagnosis was confirmed by ultrasound and steatometry, alongside assessment of cardiometabolic risk factors. Gut microbiota composition was analyzed using real-time PCR, focusing on Bacteroidetes, Firmicutes, and Actinobacteria. Hydrogen breath testing was used to diagnose small intestinal bacterial overgrowth (SIBO), and the presence of Akkermansia muciniphila was evaluated as a marker of gut barrier integrity.

Results

MASLD patients demonstrated a significant increase in Firmicutes (50.3%) and Actinobacteria (15.3%) proportions compared to controls, with a higher Firmicutes/Bacteroidetes (F/B) ratio. SIBO was detected in 52% of MASLD patients versus 40.5% in controls (p<0.05). The presence of Akkermansia muciniphila was notably lower in MASLD patients (33%) compared to controls (63%), suggesting impaired gut barrier function. Strong positive correlations were observed between Actinobacteria abundance and the F/B index (r=0.75, p<0.05), while Akkermansia muciniphila presence negatively correlated with MASLD development (r=–0.69, p<0.05).

Conclusion

Gut microbiota dysbiosis, characterized by elevated Firmicutes and Actinobacteria and reduced Akkermansia muciniphila, is closely associated with MASLD pathogenesis. The findings highlight the potential of microbiota-targeted interventions for improving gut barrier function and modifying disease progression in MASLD patients.

Introduction

Thiopurines (TP) (azathioprine AZA, and 6 mercaptopurine 6MP) are immunosuppressive drugs (IS) used in the treatment of chronic inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). The aim of our work is to see if they still have an indication in monotherapy, in the era of biotherapies and small molecules.

Aims & Methods

This is a retrospective analytical study conducted at the Hepato-Gastroenterology and Proctology Department "Medicine B" from January 2012 to July 2022. 740 patients were followed for CD during this period. 407 patients were put on TP. Age, sex, different characteristics of CD, indication for and type of TP treatment, and course of treatment were collected from all patients. SPSS 20.0 software was used for statistical analysis. The khi-2 test was used to compare categorical variables. The binary logistic regression model was used for multivariate analysis.

Results

There were 375 patients followed up for CD on TP monotherapy (92.13%) and 32 on combination therapy (7.86%). The sex ratio was F/H=1.5. The average age was 39.8 years (15-72). The location was ileal in 69 patients (16.95%), colonic in 78 patients (19.16%), ileocolic in 257 patients (63.14%), 6 patients (1.47%) had upper gastrointestinal tract involvement of CD and 3 patients (0.73%) had anal CD. 99 patients (24.32%) had ano-perineal lesions (APL). The phenotype was stenosing in 47 cases (11.54%), fistulizing in 159 cases (39%), stenosing and fistulizing in 60 cases (14.74%) and inflammatory in 141 cases (34.64%). The type of TP used was AZA in 299 patients (73.46%) and 6MP in 108 patients (26.53%). TP was indicated as maintenance treatment in 270 cases (66.33%), as monotherapy in the absence of biotherapy (which was not available before 2016) in fistulizing forms in 105 cases (25.8%), and in case of cortico-dependency in 32 cases (7.86%).
Clinical remission was obtained with monotherapy in 326 cases (86.93%) and with combotherapy in 24 cases (75%), this difference is statistically non-significant p=0.08. Mucosal healing was noted with monotherapy in 124 cases (33%) in patients who performed a control endoscopy, and with combotherapy in 15 cases (46.87%), this difference is statistically not significant p=0.07.
CRP was negatived in monotherapy in 149 patients (39.73%) and in combination therapy in 27 patients (84.37%), this difference is statistically significant p<0.001. Fecal calprotectin was not always available. Among the patients who had it performed (65: 15.97%), it was negative in 18 cases (41.86%) in monotherapy and 3 cases (13.63%) in combination therapy. This difference is statistically significant p=0.015. Metabolite dosing was also rarely available. In cases where this was done (43 cases: 10.56%), 6-TGN was in the therapeutic range only in 14 cases (32.55%) and in 36 cases (83.72%) for 6-MMP, requiring therapeutic adjustment.
In multivariate analysis and adjusting for the different confounding parameters, it was found that only the combination therapy was a predictive factor for mucosal healing [OR=1.8; [0.8 - 3.9]; p=0.01].

Conclusion

The results of this study show that TPs still have a place in the therapeutic arsenal of CD, but that their combination with biotherapy allows more clinical and biological remission and especially mucosal healing.