Introduction

Current guidelines suggest upper and lower GI endoscopy to investigate iron deficiency anaemia (IDA) because of a perceived low risk of small bowel pathology. We aimed to identify the Bleeding Location In The Gastrointestinal Tract (BLITGIT) in patients with IDA.

Aims & Methods

Patients referred to three centres (Sheffield, Hong Kong and Szekesfehervar, Hungary) for the investigation of IDA underwent small bowel (SB) capsule endoscopy (Navicam, AnX Robotica, Plano, US) in the week prior to upper and lower gastrointestinal endoscopy. All lesions were described using terms selected from a predetermined diagnostic list and according to the perceived likelihood of bleeding (P0: unlikely; P1: suspected; P2: likely. Saurin et al., Endoscopy 2003).

Results

Gastroscopy pathology (P1/P2)	Small bowel pathology (P1/P2)	Colon pathology (P1/P2)
Oesophagitis- 2 Oesophageal ulcer- 1 Oesophageal varices- 2 Gastric erosions- 9 Gastric ulcer- 5 Gastric polyp with blood- 1 Gastric antral vascular ectasia -2 Portal hypertensive gastropathy – 1 Duodenal ulcer- 3	Angioectasia- 23 Erosion - 18 Ulcers- 16 Polyp with eroded surface- 1 Fresh blood- 3 Portal hypertensive enteropathy- 1	Haemorrhoids- 15 Colorectal cancer- 3 Ulcerative colitis- 2 Diverticulitis-2 NSAID induced Ulcers- 1 Angioectasia- 2 Radiation proctitis- 2

Table-1: Number of patients with P1/P2 pathology identified at gastroscopy, SB capsule and colonoscopy.

92 patients (median age 61 years (IQR 45-72); 54.3% male) had a median haemoglobin of 107.5 g/L (IQR 93.2-121.7), ferritin 8(IQR 8- 18) and iron 3.8(IQR 3.8- 6.4). Completion rates for gastroscopy, colonoscopy and capsule endoscopy were 98.9%, 95.6% and 84.7% respectively. Diagnostic yield of P1/P2 lesions by SB capsule (48.9%) was higher than gastroscopy (27.1%) and colonoscopy (29.3%; p=0.003). On multivariant analysis there was no correlation between age, haemoglobin level, symptoms or medication on pathology. A few patients had more than one P1/P2 lesions. Three patients had colorectal cancer and two patients had a new diagnosis of ulcerative colitis.

Conclusion

The diagnostic yield in the small bowel is higher as compared to the upper and lower GI tract and examination should be considered routinely.

Introduction

Eosinophilic esophagitis (EoE), a chronic, progressive, type 2 inflammatory disease. Dupilumab is a fully human monoclonal antibody that blocks interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation.

Aims & Methods

The aim of this analysis was to assess the impact of dupilumab on caregiver-reported EoE symptoms in children aged 1 to <12 years with active EoE in the placebo-controlled Part A of the Phase 3 EoE KIDS trial (NCT04394351). This analysis was conducted in children randomized to dupilumab higher-exposure or placebo. The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) version 2.0 (caregiver version) comprises 20 items (items scored 0–4; higher scores indicate greater burden) assessing frequency (11 questions) and severity (9 questions) of symptoms and adaptive behaviors, containing 4 subdomains: dysphagia, nausea/vomiting, gastroesophageal reflux disease, and pain. PEESSv2.0 was evaluated at baseline and Week 16 in EoE KIDS; total, frequency, severity, domain (all scored 0–100), and individual item scores were compared in patients treated with dupilumab higher-exposure or placebo. Reported p-values are nominal.

Results

Baseline characteristics were similar in dupilumab higher-exposure (n=37) and placebo (n=34) groups; baseline mean PEESSv2.0 total scores were 38.0 and 38.3, respectively. At Week 16, PEESSv2.0 total was reduced with dupilumab higher-exposure vs placebo (least squares [LS] mean change [95% confidence interval (CI)] -19.86 [-24.98, -14.74] vs -11.83 [-17.61, -6.05]; LS mean difference [95% CI] -8.03 [-15.39, -0.67], p<0.05). At Week 16, all domain subscores were at least numerically reduced with dupilumab higher-exposure vs placebo with nominal significance observed in LS mean scores for frequency (-22.47 vs -11.88 [p<0.01]), dysphagia (-23.38 vs -13.76 [p<0.05]), and nausea/vomiting (-29.08 vs -15.30 [p<0.05]) domains.

Conclusion

Dupilumab higher-exposure led to improvement in PEESSv2.0 total score vs placebo at Week 16 in EoE KIDS. Frequency, dysphagia, and nausea/vomiting domains were improved with nominal significance, though all domains were improved numerically with dupilumab vs placebo.

Disclosure

Rothenberg ME: Allakos, AstraZeneca, BMS, Celldex, ClostraBio, EnZen Therapeutics, GSK, Guidepoint, Pfizer, PulmOne, Regeneron Pharmaceuticals Inc., Revolo Biotherapeutics, Sanofi, Santa Ana Bio, Serpin Pharma, Spoon Guru, and Uniquitybio – consultant; Allakos, Celldex, ClostraBio, EnZen Therapeutics, PulmOne, Santa Ana Bio, Serpin Pharma, Spoon Guru, and Uniquitybio – equity interest; Receives royalties from Mapi Research Trust (for PEESSv2), Teva Pharmaceuticals (for reslizumab), and UpToDate; and is the inventor of patents owned by Cincinnati Children’s Hospital.
Oliva S: Celgene/Receptos/BMS, Medtronic, Ocean Pharma, Sanofi/Regeneron – advisory board; Medtronic, Sanofi/Regeneron – speaker fees.
Ashok D: Sanofi – speaker fees.
Xia C, Durrani S, Radwan A, Thomas R: Regeneron Pharmaceuticals Inc. – employees and shareholders.
Pela T, Jacob-Nara J, Tilton ST: Sanofi – employee, may hold stock and/or stock options in the company.

Introduction

Small intestinal bacterial overgrowth (SIBO) is a commonly diagnosed finding in diverse conditions ranging from DGBI to GI motility, connective tissue and neurodegenerative disorders (1). A wide spectrum of signs and symptoms have been attributed to SIBO (1,2). Diagnosis is achieved either by direct culture of duodenal aspirate or indirectly, by demonstrating exhaled fermentation gases with ingested sugars, such as glucose or lactulose (3,4). In the breath tests used for carbohydrate intolerances, the symptoms provoked are at least as important for the diagnostic interpretation as the measured gas concentrations. However, the symptoms generated during SIBO breath tests are neither evaluated nor mentioned in most testing guidelines. SIBO exists in asymptomatic populations and the association with symptoms remains uncertain (1,2).

Aims & Methods

We examined the acute relationship between breath gases and the symptoms generated during glucose breath tests in DGBI. A standardised breath test with glucose (50g in 150ml water) was performed after a 24-hour low-FODMAP diet and >8-hour fast. Exhaled hydrogen and methane concentrations were measured and symptom assessments (composite symptom index score, SI used for intolerance breath tests)(5) were performed every 15 minutes for 2 hours in 790 male (30%) and female patients of average age 40.0 years referred to our gastroenterology practice with DGBI (Rome 4 criteria). Breath gas concentration thresholds of >20ppm and >10ppm above baseline were considered positive tests for hydrogen and methane, respectively.

Results

Overall, 59 (7.5%) and 111 (14.1%) DGBI patients were SIBO positive using the hydrogen and methane thresholds, respectively. The composite SI was positive in 208 (26.3%) of patients. The most common individual symptoms were fullness, nausea, tiredness, headache (each in >30% of patients), followed by bloating, flatulence, abdominal cramps or pain, GORD and problems concentrating (each in 20-30% of patients). A positive SI with a negative hydrogen test was seen in 151 (19.1%) of DGBI patients, in 108 (13.0%) with a negative methane test and in 55 (7.0%) with both negative hydrogen and methane tests. A negative SI occurred in 2.4% of patients if either of the gas tests was positive.

Conclusion

During the glucose SIBO breath test, positive gas results and evoked symptoms are closely associated. However, glucose frequently provokes symptoms in DGBI patients with negative hydrogen and/or methane breath test results. This may be due to a discrepancy between breath and intestinal gases, production of gases beyond hydrogen and methane, or the induction of symptoms by glucose or its metabolites via alternative mechanisms.

References

1. Quigley EMM, et al. Expert Review. Gastroenterology 2020;159:1526-1532.
2. Bushyhead D, et al. Gastroenterology 2022;163:593-607.
3. Losurdo G, et al. J Neurogastroenterol Motil 2020;26:16-28.
4. Tansel A, et al. Clin Transl Gastroenterol 2023;14:e00567.
5. Wilder-Smith CH, et al. Aliment Pharmacol Ther 2013;37:1074-83.