Introduction

5-HT3 receptor antagonists are a second line treatment for irritable bowel syndrome with predominant diarrhoea (IBS-D), but there is no evidence on their efficacy for functional diarrhoea (FDr) (Savarino, 2022). Randomized controlled trials show that ondansetron seems to be effective in treating IBS symptoms (Garsed 2014, Gunn 2023), but real-life data are lacking.

Aims & Methods

Our aim was to study the clinical response to ondansetron in patients with IBS-D or FDr in a real-life setting. A retrospective analysis on consecutive patients (December 2014 – February 2024) meeting criteria for IBS-D or FDr according to Rome III criteria was conducted in a single Neurogastroenterology outpatient clinic. Only patients prescribed with ondansetron were included. A standardized template was used to collect clinical data and patient-reported response to treatment. Ondansetron was prescribed at initial dosage of 4mg 1 tablet every other day with the possibility of increasing the dosage up to 6 tablets/daily. Clinical response was defined as (i) an improvement in the number of bowel movements per day vs baseline and (ii) firmer stool consistency (Bristol stool form types 3 and 4, ‘normal’).

Results

Ninety-four patients (female 68.1%, mean age 45 ±15 years old) were included. Among them, 77 (82%) were diagnosed with IBS-D and 17 (18%) with FDr. The mean follow-up duration was 19.1 months (SD±16.71). Seventy patients (74.5%) achieved a clinical response to ondansetron. Response was maintained with ondansetron at a mean dosage of 2.5 tablets/daily (SD±1.5) for a mean follow-up duration of 23.5±17 months. There was no significant difference between the number of IBS-D and FDr patients who responded to ondansetron (table 1). Patients with IBS-D reported a significantly higher improvement in abdominal pain vs baseline (p<0.01, table 1). Twenty-four patients (25.5%) did not respond to ondansetron. Adverse events were significantly higher in non-responders compared to responders (p=0.02, table 1).

Table 1. Main characteristics of responders and non-responders at baseline and post-treatment

Conclusion

This is the first real-life study assessing the response to ondansetron in IBS-D or FDr patients showing long-term reduction in the frequency of bowel movements, improvement in faecal consistency, and reduction in abdominal pain. Our data suggest that ondansetron can be used in FDr patients.

References

1. Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J. 2022 Jul;10(6):556-584.
2. Garsed K, Chernova J, Hastings M, Lam C, Marciani L, Singh G, Henry A, Hall I, Whorwell P, Spiller R. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014 Oct;63(10):1617-25.
3. Gunn D, Topan R, Barnard L, Fried R, Holloway I, Brindle R, Corsetti M, Scott M, Farmer A, Kapur K, Sanders D, Eugenicos M, Trudgill N, Whorwell P, Mclaughlin J, Akbar A, Houghton L, Dinning PG, Aziz Q, Ford AC, Farrin AJ, Spiller R. Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial. Aliment Pharmacol Ther. 2023 Jun;57(11):1258-1271.

Introduction

Controversy still remains regarding the appropriate tools to investigate symptoms’ severity in Eosinophilic esophagitis (EoE). It is, indeed, recognized that the behavioral adaptation strategies implemented by EoE patients may overshadow the effective burden of dysphagia at presentation. On the other hand, it has also been reported that EoE patients are at higher risk of developing Avoidant restrictive food intake disorder (ARFID) in both pediatric and adult settings, calling for the need of assessing their eating patterns [1]. Given this background, the Eosinophilic Esophagitis Score Activity Index (EEsAI) has been specifically developed to evaluate the severity of dysphagia and eating behaviors in EoE patients [2]. To date, this standardized tool has never been explored in an Italian EoE population.

Aims & Methods

This was a prospective study involving consecutive EoE patients referred to our tertiary center from March 2022. The EEsAI was translated and adapted to an Italian cultural context by replacing “grits” with “porridge”, “dry rice” with “boiled rice” and “omelet and mash” instead of “pudding and jelly”. All patients underwent the EEsAI questionnaire at baseline and after each therapy modification, independently from histological remission. The EEsAI score ranges between 0-100 and consists of two domains: (1) the Visual Dysphagia Question (VDQ) that explores the difficulty in swallowing 8 different food consistencies [meat, mashed potato, boiled rice, hamburger, soft bread, porridge, raw vegetables, fries; range 0-3 for each food] and (2) the Avoidance, Modification and Slowly eating (AMS) score, which measures the behavioral modifications implemented in a 7-day recall period. Data are presented as mean±SD.

Results

40 EoE patients (32M, 31±11 ys) were studied. 26 patients (65% of the population, 23M; 30±12 ys) achieved histological remission: 7 patients (27%; 24±11ys) on proton pump inhibitors, 14 (54%; 31.5±15ys) on topical steroids and 5 patients (19%; 21±11ys) with Interleukin 4 receptor α antibody. The total VDQ questionnaire subscores significantly differ between active and inactive esophagitis (2.6±2.3 vs 1.2±1.4 p=0.01), with a significant difference in the difficulty to swallow boiled rice and hamburger (0.7±1 vs 0.1±0.3; p=0.01 and 0.9±0.9 vs 0.3±0.7; p=0.005, respectively). On the other hand, no difference was observed for all the other food consistencies. Mirroring this, the pre-post treatment total EEsAI scores significantly differ (30±24 vs 16±19 p=0.01). Interestingly, despite the improved severity of dysphagia, no significant differences were observed in Avoidance behavior (0.4±1.1 vs 0.4±0.8), Modification (0.3±1 vs 0.4±1.3), Slow eating (0.8±2 vs 0.6±1.9) and total AMS subscore (2.3±2.3 vs 2±2; all p=NS). Overall, avoidance behaviors were retained in 27% of EoE patients who achieved clinical and histological remission.

Conclusion

EoE patients show a significant improvement in dysphagia severity after histological remission, as measured by the VDQ item. However, this is not paralleled by an improvement in eating behaviors and avoidance strategies. This implies that patients, once established an abnormal eating pattern, avoid to adjust these behaviors, even following resolution of symptoms and histological activity. Properly evaluating eating patterns in EoE patients in clinical practice, through the standardized EEsAI questionnaire is crucial to promptly identify and correct abnormal eating patterns in EoE patients.

References

1. Ketchem CJ, Dellon ES. Avoidant Restrictive Food Intake Disorder in Adults With Eosinophilic Esophagitis. Gastro Hep Adv. 2022;1(1):52-54. doi:10.1016/j.gastha.2021.09.004
2. Schoepfer AM, Straumann A, Panczak R, et al. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology. 2014;147(6):1255-66.e21. doi:10.1053/j.gastro.2014.08.028

Introduction

Accurate estimation of cancer risk in patients with Barrett’s esophagus (BE) and low-grade dysplasia (LGD) or indefinite for dysplasia (ID) is difficult, leading to potential under- and over-treatment. We aimed to evaluate the utility of machine learning (ML) and copy number alterations (CNAs) assessed by shallow whole genome sequencing (sWGS) on standard formalin-fixed paraffin-embedded (FFPE) samples for precise risk stratification in this group of BE patients.

Aims & Methods

We conducted a retrospective analysis on a cohort of 164 BE patients encompassing 990 tissue samples with sWGS (~0.4X) data from 2001-2018. These included 215 samples with LGD or ID from 64 patients, of which 38 progressed to high-grade dysplasia (HGD) or cancer at later timepoints (P), and 26 who did not progress (NP). CNAs were quantified using QDNASeq, and outlier bins were determined by Tukey's fences. Subsequently, the CNAs of 64 esophageal cancer driver genes were compared between P and NP groups using t-tests and ranked by p-values. A random forest (RF) ML model was developed on the CNAs of the 64 genes, employing nested 5-fold cross-validation split by patients and iterated 100 times to mitigate bias. The model's performance was compared against routine p53 immunohistochemistry (IHC), a decision tree that incorporates p53 followed by the ML model, and the current ESGE clinical guideline recommending treatment after LGD is identified in two endoscopies. Both the model and model+p53 were assessed across 100 test sets derived from the cross-validation. The guideline's performance was evaluated using a historical extended cohort comprising 253 LGD patients, of which 32 progressed, and underwent at least one surveillance endoscopy after LGD diagnosis and before HGD/cancer diagnosis. According to the guideline, two occurrences of LGD result in a positive prediction.

Results

Significant variance was observed in the distribution of relative CNAs across genomic bins between P- and NP-LGD/ID samples, with the proportions of outliers at 2.15% (95% CI: 1.88%, 2.42%) vs. 1.35% (95% CI: 1.26%, 1.44%). The most divergent genes included TP53, ABCB1, MET, BRAF, and SIN3A, exhibiting higher CNAs in progressed samples. Among the 215 samples, the RF model achieved an average sensitivity of 73.4% and specificity of 80.2%. Of these, 160 samples were tested for p53 IHC staining, where p53 alone showed a sensitivity of 22.1% and specificity of 100%, and a combined analysis of p53 and model increased the sensitivity of model alone (81.5% vs. 78.1%, p<0.001) while maintaining the same specificity at 78.9%. As a benchmark, the performance of the current ESGE guideline on biopsy diagnosed LGD patients demonstrated a sensitivity of 75.0% and specificity of 59.6%.

Conclusion

Our findings affirm the utility of ML and CNAs in predicting progression in BE patients with LGD or ID. Incorporating p53 followed by ML can further improve the performance. Molecular biomarkers would allow anticipation of intervention in high-risk cases and reduction of overtreatment in low-risk cases.

Disclosure

Nothing to disclosure.

Introduction

Artificial intelligence (AI) algorithms aid endoscopists in detecting and characterizing colonic polyps in clinical practise and lead to an improved adenoma detection rate. AI may also support therapeutic procedures by detecting and marking anatomical structures during complex procedures like endoscopic submucosal dissection (ESD) ¹. However, a possible effect of AI on the intraprocedural blood vessel detection rate during third space endoscopy remains unclear.

Aims & Methods

This study aimed at evaluating the impact of a newly developped AI algorithm for real time intraprocedural vessel detection on the vessel detection performance of endoscopists during ESD. To this end, 5470 single images from 59 full length third space endsocopy videos were annotated for submucosal blood vessels. Together with 179681 additional unlabeled images this dataset was utilized for the training of a DeepLabV3+ neural network. The trained algorithm detected and marked submucosal blood vessels on the endoscopic image in real time. Consequently, a video test consisting of 101 video clips with 200 predefined blood vessels was used for the evaluation of the algorithm alone, as well as 19 endoscopists with and without AI support.

Results

The algorithm showed a vessel detection rate (VDR) of 93.5% and a median vessel detection time (VDT) of 0.3 sec. AI support was associated with an elevation of endoscopists‘ VDR from 56.4% to 72.4% (p<0.001). VDT decreased from 6.7 to 5.2 sec with AI support (p<0.001). False positive detections were measured on 4.5% of single frames. They had a significantly shorter duration than true positive findings (0.7 vs. 6.0 sec, p<0.001).

Conclusion

AI support led to increased VDR and reduced VDT of endoscopists. False positive findings were easily distinguishable from true positives by their short duration. Future research may elucidate a possible effect of AI on clinical parameters like intraprocedural complication rates or procedure times.

References

1. Ebigbo A, Mendel R, Scheppach MW, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut 2022.

Introduction

Metabolic associated steatosis liver disease (MASLD) is the new nomenclature of non-alcoholic fatty liver diseases (NAFLD) which highlights its crucial effect on the cardiometabolic risk factors that lead to the development and progression to liver diseases. Recently SGLT2 inhibitors have been identified to reduce hepatic steatosis in patients with T2DM with MASLD

Aims & Methods

Our aim was to assess the effect of SGLT2 inhibitors on hepatic steatosis in patients with T2DM and MASLD, we enrolled 30 diabetic adults with hepatic steatosis on ultrasound confirmed and quantified by baseline magnetic resonance proton density fat fraction (MRI-PDFF) they started SGLT2 inhibitors added to the standard of care treatment for 6 months and assessment of the percentage change of hepatic steatosis with done by repeat MR-PDFF.

Results

There were statistically significant decreases in the mean body weight and BMI after treatment (86.7Kg, 33.313 Kg/m²) respectively compared to their levels before treatment (90.367kg, 35.144 Kg/m²) respectively, P <0.001. Moreover, the mean serum fasting blood sugar and alanine transaminase decreased significantly after treatment (209.267, 22.633) compared to levels before treatment (220.566, 28.03) (P= 0.017, P=0.03) respectively. Regarding hepatic steatosis there was a statistically significant decrease in the mean MRI-PDFF measurement for hepatic steatosis after treatment (13.297 ±7.15) compared to the mean levels before treatment (15.288 ± 8.72) with a mean difference (-1.9911, P = 0.006) of about 13.16% decrease of steatosis

Conclusion

Addition of SGLT2 inhibitors to the standard treatment in type 2 diabetic patients with MASLD could reduce the hepatic steatosis significantly after 6 months of treatment associated with decrease in body weight, BMI, fasting blood sugar. Thus, the therapeutic use of SGLT2 inhibitors is valuable in type 2 diabetic patients associated with MASLD

Introduction

Confocal laser endomicroscopy (CLE) enables real-time microscopic visualization of the duodenal mucosa during upper endoscopy and has shown acute food-triggered disruption of the epithelial barrier in the duodenum of irritable bowel syndrome (IBS) patients. While this technique offers novel scientific insights, image interpretation is subjective and agreement rates between observers are unknown.

Aims & Methods

We aimed to assess the agreement rate between assessors regarding acute food induced mucosal changes visualized by CLE in IBS. To this end we performed a multicentric, international post-hoc evaluation of CLE recordings. CLE sequences from three centers were blindly assessed. Five investigators from the three participating centers blindly assessed all videos both in real-time and in slow-motion in a random order, including some duplicates.
Mucosa was considered altered if fluorescein leakage AND “cell shedding” were simultaneously present. Outcomes of the global assessment were assessed using the binary outcome “altered” vs. “unaltered”. Agreement was quantified using Fleiss’ kappa for >2 assessors and Cohens’ kappa for 2 assessors – both are reported as κ.

Results

A total of 124 video sequences (94572 frames, 197 minutes of real-time recording) were reviewed. Intraindividual agreement rate was between 90 and 100% (κ=0.74-1.00). Overall interobserver agreement rate for all assessors and all videos was 86% (κ=0.69). Agreement rates were not higher when videos were assessed in slow-motion (81%, κ=0.58). Among the 3 centers, agreement between all blinded assessors and real-time assessment by the endoscopist ranged from 78% (κ=0.55) to 86% (κ=0.67). A total of 63 videos were judged the same by all assessors (100% agreement) – here agreement rates with the endoscopist were 97% (κ=0.91). Using these videos as reference, a cutoff of 2 altered spots in a recording of 5 spots showed a sensitivity and specificity of 100% for the presence or absence of alterations.

Conclusion

We report here for the first time the interobserver agreement rates of acute food induced mucosal alterations as visualized on CLE. The agreement rates were substantial overall – both among blinded assessors and between blinded assessors and real-time judgement by the endoscopist. Slow-motion revision did not increase agreement rates. A cutoff of 2/5 spots was ideal for the detection of acute mucosal alterations.

Introduction

The available evidence on the epidemiology of acute pancreatitis (AP) is primarily based on older studies conducted in other countries, limiting its applicability to local settings. This study aims to provide updated data on the clinical characteristics and outcomes of patients with AP in our region thereby improving understanding and management of the disease.

Aims & Methods

A retrospective analysis was conducted on a prospective database comprising a cohort of 526 patients with acute pancreatitis (AP), consecutively included between March 2017 and June 2019 at a tertiary care hospital. Systematic laboratory testing was performed at admission and again at 48 hours. Clinical management followed standard practice guidelines, including routine abdominal ultrasound after admission and abdominal CT scan in cases of diagnostic uncertainty, clinical deterioration, or lack of improvement. Diagnosis and classification were based on the revised 2012 Atlanta classification.

Results

The most frequent etiology of AP in our setting was biliary lithiasis (65.9%), followed by idiopathic (15.4%) and alcohol-related causes (8.4%). Severe AP accounted for 9% of cases, while 14.3% were classified as moderately severe. Up to 20.2% of patients developed local complications; however, only 4.9% presented with pancreatic necrosis. SIRS was observed in 18.7% of patients at admission, decreasing to 8.7% at 48 hours. Only 3.7% of patients required ICU admission (Table 1). Factors such as smoking, ERCP, antibiotic therapy, acute cholangitis, and SIRS showed significant differences across different etiological groups.

Conclusion

Acute pancreatitis (AP) is a common condition that imposes a significant healthcare burden. Determining the etiology of AP at admission is important not only from an epidemiological standpoint but also due to its profound implications for patient prognosis.
Contrary to what has been reported in the literature, the second most frequent cause of AP in our cohort was idiopathic, surpassing alcohol-related cases. In line with other studies, we observed significant differences between biliary and alcohol-related etiologies regarding smoking habits, development of acute cholangitis, need for ERCP, and use of antibiotic therapy. Patients with alcohol-related AP were significantly more likely to present with SIRS at admission. However, we did not find statistically significant differences in other key clinical outcomes, although patients with alcohol-related AP appeared to have a higher, but not statistically significant, risk of developing local complications, pancreatic necrosis, and SIRS at 48 hours.
This study highlights the importance of tailoring management strategies according to etiology to optimize clinical outcomes.

References

1. Wang, G. J., Gao, C. F., Wei, D., Wang, C., & Ding, S. Q. (2009). Acute pancreatitis: etiology and common pathogenesis. World journal of gastroenterology, 15(12), 1427–1430.
2. Petrov, M. S., & Yadav, D. (2019). Global epidemiology and holistic prevention of pancreatitis. Nature reviews. Gastroenterology & hepatology, 16(3), 175–184.
3. Iannuzzi, J. P., King, J. A., Leong, J. H., Quan, J., Windsor, J. W., Tanyingoh, D., Coward, S., Forbes, N., Heitman, S. J., Shaheen, A. A., Swain, M., Buie, M., Underwood, F. E., & Kaplan, G. G. (2022). Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology, 162(1), 122–134.