Budesonide Induces Favourable Histologic and Symptomatic Recovery in Patients with Non-responsive and Refractory Coeliac Disease When Given in an Open Capsule Format.

INTRODUCTION: Non-responsive coeliac disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous. AIM: To describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD. METHODS: A retrospective cohort study of NRCD and RCD patients who received budesonide for enteropathy despite a strict GFD for over 12 months. Primary outcome was improvement in histology. Symptoms and adverse treatment effects were recorded. RESULTS: 50 patients with NRCD (n = 14; 86% F), RCD type 1 (n = 30; 60% F), and RCD type 2 (n = 6 based on aberrant duodenal T cells; 33% F) were identified. Common RCD symptoms were diarrhoea (68%), fatigue (40%), and weight loss (34%). 16 received closed capsule budesonide (CCB) 9 mg OD and 35 open capsule budesonide (OCB) 3 mg 3 times a day. Complete and partial mucosal healing was significantly higher after OCB compared to CCB (p < 0.001, Mann-Whitney U test). Symptom improvement was also significantly higher after OCB compared to CCB (p = 0.002, Mann-Whitney U test). Side effects were mild and self-limiting and were reported in 25% of both cohorts. CONCLUSION: OCB was well tolerated and associated with improvements in enteropathy (83%) and symptoms (90%) in NRCD and RCD. Our findings support OCB as the preferred 1st-line therapy for NRCD and RCD type 1.

Different Patterns of Care and Survival Outcomes in Transplant-Centre Managed Patients with Early-Stage HCC: Real-World Data from an Australian Multi-Centre Cohort Study.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

Beyond the heart: Noncardiac chest pain.

BACKGROUND: Noncardiac chest pain (NCCP) is a diagnosis usually made after cardiac investigations have failed to demonstrate a specific diagnosis to explain either a single episode or recurrent episodes of chest pain. OBJECTIVE: The aim of this article is to describe the major causes and management of NCCP, with a focus on gastrointestinal conditions. DISCUSSION: Despite its generally benign prognosis, NCCP is a cause of significant morbidity and can be responsible for a high personal cost and healthcare burden. NCCP is commonly associated with gastrointestinal conditions, including gastro-oesophageal reflux disease and oesophageal spasm. However, the differential diagnosis extends to musculoskeletal, neurological and psychiatric conditions, and the broad range of causes of the syndrome, which are not mutually exclusive, means that clinicians need to remain vigilant for changes in clinical pattern.