Improved diagnosis of coeliac disease has increased incidence and therefore burden on the health care system. There are no quality outcome measures (QOM) in use nationally to assess hospital management of this condition. This study applied QOM devised by the East of England paediatric gastroenterology network to 99 patients reviewed at two tertiary hospitals in the Network, to assess the quality of care provided by nurse led and doctor led care models. The average performance across all QOM was 96.2% at Addenbrooke’s Hospital (AH), and 98.7% at Norfolk and Norwich Hospital (NNUH), whilst 95% (n = 18) of QOM were met. Patient satisfaction was high at both sites (uptake of questionnaire 53 of 99 patients in the study). The study showed a comparably high level of care delivered by both a nurse and doctor led service. Our quality assessment tools could be applied in the future by other centres to measure standards of care.
The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances, especially in regenerative medicine, are currently hampered by the lack of knowledge concerning human hepatic cell development. Here, we addressed this limitation by describing the developmental trajectories of different cell types comprising the human fetal liver at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional maturation of hepatocytes, with non-parenchymal cells playing critical, supportive roles during organogenesis. We utilised this information to derive bipotential hepatoblast organoids and then exploited this novel model system to validate the importance of key signalling pathways and developmental cues. Furthermore, these insights into hepatic maturation enabled the identification of stage-specific transcription factors to improve the functionality of hepatocyte-like cells generated from human pluripotent stem cells. Thus, our study establishes a new platform to investigate the basic mechanisms of human liver development and to produce cell types for clinical applications.
Gastrointestinal endoscopy is an invasive procedure used to diagnose and/or treat diseases of the gut. As with any invasive procedure, there is a small risk for complications, and it is therefore important that due consideration be taken when reviewing the indications for endoscopy, particularly in children. Despite this, there remains a wide variation nationally in clinical practice among paediatric gastroenterologists. In the absence of a standard, we critically reviewed current endoscopy practice at Addenbrooke's Hospital with the aim of creating robust measures that could be used to achieve and maintain an efficient, high-quality paediatric endoscopy service. Specifically, we assessed the proportion of referred patients undergoing endoscopy and the clinical outcomes of these procedures.A retrospective list of new clinic patients who had undergone endoscopy within 3 months of their appointment was obtained, dating from 1 January 2011 to 31 December 2011. Individual electronic medical records (eMR) records were reviewed for the type of endoscopy, indications, interval to procedure, histology findings, diagnoses, and impact on management.Out of the 674 children seen at clinic over the year, 17% (n=114) went on to have an endoscopic procedure; half of these patients underwent both upper endoscopy (i.e., oesophagogastroduodenoscopy) and colonoscopy. Out of the children who underwent colonoscopy, 43% (n=25) were confirmed to have inflammatory bowel disease.Our results provide a useful initial reference point against which other tertiary units can assess their own practice, with all striving to provide appropriate, efficient and cost-effective endoscopy services for children.
Damage to the heart muscle often leads to chronic arrhythmia and heart failure. This is because the muscle of the adult human heart does not functionally regenerate after injury and is replaced by fibrous non-contractile and non-conductive scar tissue. However, the heart muscle of some vertebrates and developing mammals is capable of regeneration which restores the muscular function of the damaged tissue. Evidence suggests that the epicardium plays a crucial role in orchestrating this successful regenerative response in animals like the zebrafish and that epicardium cells are active in developmental stages of life. However, in adult humans the epicardium is putatively quiescent.
Objectives
We hypothesise that the difference in the regenerative capacity of human adult and foetal myocardium may be explained in part by differences in the epicardium and reactivation of these molecular processes lost in adult epicardium may lead to effective myocardial regeneration. Using single-cell RNA sequencing, our aim was to capture the regenerative epicardial signalling present in the foetal epicardium that may be absent in adult hearts.
Methods
Heart sections from 7 human embryos between 8 and 12 weeks of gestation were dissociated and sequenced with scRNA-seq. ScRNA-seq data from 5 human adult hearts between 55 and 75 years old were acquired from the Heart Cell Atlas. Data were integrated and epicardial cells in all samples were identified using supervised classification and canonical markers.
Results
We compared the markers expressed in foetal and adult mesothelial epicardial cells and identified foetal, adult and stage-independent epicardial signatures. Among these were a number of pro-angiogenic factors specific to the foetal epicardium, including a group of WNT-signalling secreted factors, WNT2B, SFRP2 and SFRP5. Gene Ontology suggested a shift towards immune response of the epicardial cells during maturation. Additionally, an epicardial cluster with fibroblast-like markers was found only in the foetal heart (96 % foetal). We examined organ-wide influences of epicardial signalling by mapping the potential ligand receptor interactions from the epicardial-derived secreted factors to receptors upregulated in other heart cell clusters. This revealed the prospective influence of reactivating foetal epicardial pathways for heart regeneration. Lastly, we demonstrated that epicardium derived from human embryonic stem cells exhibits some of these lost regenerative pathways, promoting their value as a model and as therapeutic agents.
Conclusions
We have shown that the adult epicardium has major differences to the foetal epicardium. Firstly, a set of epicardium-specific angiogenic pathways are absent from the adult epicardium and secondly, foetal hearts contain another epicardial cell type that is not present in the adult heart. Recapitulating both the missing epicardial signals and the synergy between the foetal epicardial cell types may be essential for developing effective regenerative stem cell therapy.
Although strictures are the most common complication of inflammatory bowel disease their natural history is not known. Strictures reflect sites of intense active inflammation as well as fibrosis. There are very few data on whether drug therapy has any impact on their progression, but recent preliminary data suggest that anti-TNF therapy may improve stricture-related symptoms and the need for surgery.1 We have assessed the outcomes of patients with an IBD-associated stricture. Patients diagnosed with their IBD-related first stricture between 2011 and 2016, and who had a minimum of 12 months follow-up, were identified from radiology and clinical records. Magnetic resonance enterography (MRE) scans were reviewed by a single experienced radiologist and the Magnetic Resonance Index of Activity (MaRIA) score calculated. Drug therapy and the need for endoscopic dilatation, hospitalisation, and surgery were recorded. 207 patients (98% Crohn’s disease, 2% ulcerative colitis) with one or more strictures were included. Median follow-up for those patients not requiring surgical intervention was 45 months. 176 (85%) had ileal or small bowel strictures and 122 (59%) had undergone previous surgery for their disease. Following diagnosis 68 (33%) required intestinal surgery and 42 (20%) underwent endoscopic stricture dilatation; the remainder had drug therapy only. The median time to surgery was 6 months. Fifty-six patients (27%) were on anti-TNF therapy at stricture diagnosis. The factors associated with increased risk for bowel surgery were hospitalisation at time of stricture diagnosis (p = 0.006), elevated CRP ( ≥10 mg/l) (p = 0.011), and MRE features of inflammation including T2 wall hyper-enhancement (p = 0.02), mesenteric oedema (p = 0.03), higher stricture specific MaRIA score (p = 0.003), stricture length >10 cm (p = 0.01) and proximal luminal dilatation >3 cm (p = 0.008). Previous surgery was associated with a reduced risk of surgery (p = 0.015). There was no difference in the need for stricture surgery between those who were on anti-TNF therapy at stricture diagnosis and those who were not (p = 0.895). Drug therapy was changed following stricture diagnosis in only a minority, with 24 (16%) commencing anti-TNF therapy within 3 months. To our knowledge this is the first assessment of the outcome of IBD patients with strictures. Strictures are associated with major morbidity and the use of health-care resources. Strictures associated with active inflammation, both biochemically and on MRE imaging, have a greater risk of requiring surgery. This suggests that intense anti-inflammatory therapy, titrated to control inflammation, may improve prognosis; this now needs to be studied prospectively. 1. Bouhnik Y, Carbonnel F, et al. Efficacy of adalimumab in patients with Crohn’s disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study. Gut, 2017.
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