British Society of Gastroenterology guidelines on sedation in gastrointestinal endoscopy.

Over 2.5 million gastrointestinal endoscopic procedures are carried out in the United Kingdom (UK) every year. Procedures are carried out with local anaesthetic r with sedation. Sedation is commonly used for gastrointestinal endoscopy, but the type and amount of sedation administered is influenced by the complexity and nature of the procedure and patient factors. The elective and emergency nature of endoscopy procedures and local resources also have a significant impact on the delivery of sedation. In the UK, the vast majority of sedated procedures are carried out using benzodiazepines, with or without opiates, whereas deeper sedation using propofol or general anaesthetic requires the involvement of an anaesthetic team. Patients undergoing gastrointestinal endoscopy need to have good understanding of the options for sedation, including the option for no sedation and alternatives, balancing the intended aims of the procedure and reducing the risk of complications. These guidelines were commissioned by the British Society of Gastroenterology (BSG) Endoscopy Committee with input from major stakeholders, to provide a detailed update, incorporating recent advances in sedation for gastrointestinal endoscopy.This guideline covers aspects from pre-assessment of the elective 'well' patient to patients with significant comorbidity requiring emergency procedures. Types of sedation are discussed, procedure and room requirements and the recovery period, providing guidance to enhance safety and minimise complications. These guidelines are intended to inform practising clinicians and all staff involved in the delivery of gastrointestinal endoscopy with an expectation that this guideline will be revised in 5-years' time.

The PIG-A gene mutation assay in human biomonitoring and disease.

The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene can lead to loss of membrane-bound GPI anchors, which can be enumerated via corresponding GPI-anchored proteins (e.g., CD55) using flow cytometry. The studies published to date by different research groups demonstrate a remarkable consistency in PIG-A mutant frequencies. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9-5.56 × 10-6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy, and occupational exposures, including lead, have been shown to increase mutant levels. Future applications of this test include identifying new harmful agents and establishing new exposure limits. This mutational monitoring approach may also identify individuals at higher risk of cancer development. In addition, identifying protective agents that could mitigate these effects may reduce baseline somatic mutation levels and such behaviors can be encouraged. Further technological progress is required including establishing underlying mechanisms of GPI anchor loss, protocol standardization, and the development of cryopreservation methods to improve GPI-anchor stability over time. If successful, this assay has the potential be widely employed, for example, in rural and low-income countries. Here, we review the current literature on PIG-A mutation in humans and discuss the potential role of this assay in human biomonitoring and disease detection.

Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study.

Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10-6 (95% CI 4.777-10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10-6 (95% CI 1.39-5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.

Eosinophilic oesophagitis: improving diagnosis and therapy - reducing the burden of repeated endoscopy.

Eosinophilic oesophagitis is now being diagnosed more often, although there continues to be a significant delay in the recognition of the condition in primary care, and among patients presenting with food bolus obstruction to other specialities like Ears, Nose and Throat and Accident & Emergency. The diagnosis requires endoscopy and biopsy, with six biopsies taken from at least two different areas of the oesophagus. The diagnostic threshold is > 15 eosinophils/high power field or 0.3 mm2. Dietary management although effective is often difficult to carry out due to poor adherence by patients and the need for a specialist dietitian and repeated biopsies. Orodispersible budesonide is very effective for inducing remission and maintaining it long term, with fewer biopsies. Newer targeted biological agents are promising in the treatment of patients who have not responded to conventional treatments. Dilatation of strictures in this condition is safe.

Transnasal endoscopy: moving from endoscopy to the clinical outpatient-blue sky thinking in oesophageal testing.

Background: COVID-19 has severely affected UK endoscopy services with an estimate 86% loss of activity during the first wave. Subsequent delays in diagnostic and surveillance procedures highlight the need for novel solutions to tackle the resultant backlog. Transnasal endoscopy (TNE) provides an attractive option compared with conventional upper gastrointestinal endoscopy given its limited use of space, no sedation and reduced nursing resources. Our experience: We describe piloting and then establishing an outpatient model TNE service in the pandemic era and the implications on resource allocation, training and workforce. We also discuss our experiences and outline ways in which services can evolve to undertake more complex endoscopic diagnostic and therapeutic work. Over 90% of patients describe no discomfort and those who have previously experienced conventional transoral endoscopy preferred the transnasal approach. We describe a low complication rate (0.8%) comprising two episodes of mild epistaxis. The average procedure duration was reasonable (9.9±5.0 min) with full adherence to Joint Advisory Group quality standards. All biopsies assessed were deemed sufficient for diagnosis including those for surveillance procedures. Discussion: TNE can offer a safe, tolerable, high-quality service outside of a conventional endoscopy setting. Expanding procedural capacity without impacting on the current endoscopy footprint has great potential in recovering endoscopy services following the COVID-19 pandemic. Looking forward, TNE has potential to be used both within the endoscopy suite as part of therapeutic procedures, or outside of the endoscopy unit in outpatient clinics, community hospitals, or mobile units and to achieve this in a more sustainable and environmentally friendly way.

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.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

Comparison of an e-learning package with lecture-based teaching in the management of supraventricular tachycardia (SVT): a randomised controlled study.

INTRODUCTION: To compare the impact of an e-learning package with theoretical teaching on the ability of both graduate and undergraduate medical students to learn the management of supraventricular tachycardia. METHODS: We conducted a randomised, controlled, study at two Welsh medical schools. Participants were graduate-entry and undergraduate medical students, who were randomised (in a 1:1 ratio) to either 1 hour of training using an e-learning package or an hour of lecture-based teaching. The outcome was a comparison, within each group and between groups, of median scores achieved in assessments of knowledge through completion of preintervention, immediate post intervention and 2 weeks postintervention questionnaires. RESULTS: Of the 97 participants available for randomisation, 47 underwent teaching using the e-learning package and 50 were taught in the lecture group. Median scores were higher in the e-learning package group than the lecture group, though this difference was not statistically significant (4.00 vs 3.00; p=0.08) immediately after intervention. At 2 weeks post intervention, median scores in the e-learning package group were significantly higher than the median scores in the lecture group (4.00 vs 3.00; p=0.002). This was despite a subanalysis of the results demonstrating that subjects in the lecture group reported having seen more cases compared with those in the e-learning group (32 vs 13; p=0.002). Further, there was a significant fall in score over 2 weeks in the group receiving lecture-based teaching, but no such decrease in those using the e-learning package. CONCLUSION: E-learning seems to be the preferred method of learning and the method that confers longer retention time for both postgraduate and undergraduate medical students.

Endoscopy findings in patients on dual antiplatelet therapy following percutaneous coronary intervention.

PURPOSE OF STUDY: This study examines the associations between dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) and gastrointestinal bleeding (GIB), to explore possible predictors of outcomes. STUDY DESIGN: Retrospective analysis of 3342 patients who underwent PCI between 1 August 2011 and 31 December 2018 in a single centre was carried out. Oesophagogastroduodenoscopies (OGDs) for patients 12 months post-PCI were analysed. RESULTS: Blood loss occurred in 2% of all (3342) patients post-PCI within 12 months. 128 patients (63% male, mean age (SD) of 69.8 (10) years) who had PCI subsequently underwent an OGD within 12 months of the index PCI procedure. GIB occurred within the first 30 days of DAPT in 36% (n=13/36) of cases. There were no thrombotic events associated with cessation of one antiplatelet agent. Increased age, haemoglobin (Hb) ≤109 g/L and Glasgow-Blatchford score ≥8 were associated with increased 12-month mortality. An Hb drop of ≥30 g/L was a sensitive and specific marker for significant pathology and evidence of bleeding on OGD (sensitivity=0.83, specificity=0.81). CONCLUSIONS: GIB bleeding occurred infrequently in the patients post-PCI on DAPT. Risk assessment scores (such as Glasgow-Blatchford and Rockall scores) are useful tools to assess the urgency of OGD and need for endoscopic therapy.

Widespread gaps in the quality of care for primary biliary cholangitis in UK.

OBJECTIVE: Primary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines. DESIGN: Data were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ2 analysis for variation in performance between trusts. RESULTS: 790 patients' medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297). CONCLUSION: Our findings identify a broad-based deficiency in 'real-world' PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.

Obesity management for the gastroenterologist.

Obesity has reached epidemic levels in the United Kingdom. Obesity is associated with important gastrointestinal and hepatic complications which are common and can present sooner than cardiometabolic disease but often the underlying obesity remains untreated. Given that gastroenterologists and hepatologists will be at the forefront of obesity management we present an overview encompassing obesity pathophysiology, medical and surgical treatment options as well as the role of endobariatrics and the gut microbiome.

To scan or not to scan - D-dimers and computed tomography pulmonary angiography in the era of COVID-19.

The COVID-19 pandemic has had many ramifications on healthcare delivery and practice. As part of this, utilising biomarkers to risk stratify patients has become increasingly popular. During the COVID-19 pandemic the use of D-dimer has increased due to the evidence of COVID-19 induced thrombo-embolic disease. We evaluated the use of D-dimer on all hospital admissions during the peak of the pandemic and evaluated its sensitivity in diagnosing pulmonary embolic disease (PE). Patients without COVID-19 infection were as likely to have evidence of PE as their COVID-positive counterparts. However, the sensitivity of a D-dimer was higher in COVID-positive patients at a lower D-dimer level (>1,500 µg/L, sensitivity 81%, specificity 70%) than in those without clinical, immunological or radiological evidence of COVID-19 infection (D-dimer >2,000 µg/L, sensitivity 80%, specificity 76%). These data suggest higher D-dimer thresholds should be considered for the exclusion of pulmonary emboli.

Incidence, pattern and severity of abnormal liver blood tests among hospitalised patients with SARS-COV2 (COVID-19) in South Wales.

INTRODUCTION: SARS-CoV-2 (COVID-19) is a novel coronavirus that emerged in Wuhan, China in late 2019 and since become a global pandemic. As such, its clinical behaviour is a subject of much interest. Initial reports suggested a significant proportion of patients have abnormal liver blood tests. Gwent has experienced one of the highest incidences of COVID-19 infection in the UK, which itself has among the highest COVID-19 impacts worldwide. METHOD: We set out to report the incidence, clinical pattern and severity of liver blood test abnormalities in hospitalised patients with confirmed COVID-19 in our institution over a 3-week period. Data on clinical outcomes such as admission to intensive therapy unit (ITU), hospital discharge and mortality were recorded. RESULTS: 318 hospitalised COVID-19 positive had liver blood tests available for analysis. Ninety-seven patients (31%) had one or more abnormal liver blood tests and were abnormal admission in 64%. Liver tests were predominantly cholestatic (72%) in contrast to other studies to date. Male gender and abnormal liver blood tests were associated with ITU admission. CONCLUSIONS: Almost one-third of admissions with COVID-19 have abnormal LBTs which are typically mild and are associated with male gender. Importantly, we have identified that cholestatic patterns dominate but were not clearly associated with ITU admission or death.

Dietary and lifestyle factors effect erythrocyte PIG-A mutant frequency in humans.

It is well understood that poor diet and lifestyle choices can increase the risk of cancer. It is also well documented that cancer is a disease of DNA mutations, with mutations in key genes driving carcinogenesis. Measuring these mutations in a minimally invasive way may be informative as to which exposures are harmful and thus allow us to introduce primary preventative measures, in a bid to reduce cancer incidences. Here, we have measured mutations in the phosphatidylinositol glycan class A (PIG-A) gene in erythrocytes from healthy volunteers (n = 156) and from non-cancer patients attending the local endoscopy department (n = 144). The X-linked PIG-A gene encodes an enzyme involved in glycosylphosphatidylinositol (GPI) anchor synthesis. A silencing mutation in which leads to the absence of GPI anchors on the extracellular surface which can be rapidly assessed using flow cytometry. The background level of PIG-A mutant erythrocytes was 2.95 (95% CI: 2.59-3.67) mutant cells (10-6). Older age increased mutant cell frequency (P < 0.001). There was no difference in mutant cell levels between males and females (P = 0.463) or smokers and non-smokers (P = 0.186). In the endoscopy group, aspirin users had lower mutant frequencies (P = 0.001). Further information on diet and exercise was available for the endoscopy patient group alone, where those with a higher health promotion index score had lower mutant frequencies (P = 0.011). Higher dietary intake of vegetables reduced mutant cell levels (P = 0.022). Participants who exercised for at least 1 h a week appeared to have reduced mutant frequencies than those who did not exercise, although this was not statistically significant (P = 0.099). This low background level of mutant erythrocytes in a population makes this assay an attractive tool to monitor exposures such as those associated with lifestyles and diet, as demonstrated here.

Adult obesity complications: challenges and clinical impact.

The complications associated with adult obesity are overwhelming national healthcare systems. No country has yet implemented a successful population-level strategy to reverse the rising trends of obesity. This article presents epidemiological data on the complications of adult obesity and discusses some of the challenges associated with managing this disease at a population and individual level.

Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode.

A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient's mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid.

G-Eye: ocular manifestations of gastrointestinal disease.

Extraintestinal manifestations of gastrointestinal disease can form an important aspect of the diagnosis, monitoring and management in these diseases. Ocular manifestations in particular are often disregarded and can, albeit rarely, present as an emergency.

Aortic stenosis and anemia with an update on approaches to managing angiodysplasia in 2018.

Angiodyplasia and aortic stenosis are both conditions that are highly prevalent in elderly people and can often co-exist. Recent studies suggest that this association is related to subtle alterations in plasma coagulation factors. The von Willebrand factor is the strongest link between aortic stenosis and bleeding associated with gastrointestinal angiodysplasia. With an ageing population, the disease burden of aortic stenosis and its association with angiodysplasia of the bowel makes this an incredibly underdiagnosed yet important condition. Clinicians should be aware of this association when dealing with elderly patients presenting either with unexplained anemia, gastrointestinal bleeding or with aortic stenosis. A high index of suspicion and appropriate diagnostic techniques followed by appropriate and prompt treatment could be life-saving. No clear guidelines exist on management but surgical aortic valve replacement is thought to offer the best hope for long-term resolution of bleeding. With a growing number of technological armamentarium in the management of such patients, especially with the advent of transcatheter aortic valve implantation, new options can be offered even to elderly patients with comorbidities for whom conventional surgery would have been impossible.

Slumped posture on chest X-ray-association with mortality and length of hospital stay in older hospitalised patients.

INTRODUCTION: frail, older patients are occasionally incapable of keeping their head out of the field of view of a chest radiograph (CXR) resulting in a 'slumpogram'. This study aims to explore a possible link between a slumped appearance on a CXR; mortality and length of hospital stay. METHODS: the CXRs of patients aged over 65 admitted to a Health Board with a catchment area of approximately 300,000 were investigated in a retrospective analysis of all CXRs taken during the first week of January 2015. Slumped patients were compared to age matched controls. The degree of slumping was measured by the number of ribs covered and the MA/C factor (the shortest distance between the angle of the mandible and a line drawn between the heads of both acromion divided by the length of the patient's clavicle). Outcomes investigated included length of hospital stay and 18-month mortality. RESULTS: 806 CXRs were viewed with 53 slumped patients and 53 matched controls identified. In all patients aged over 65 there was a statistically significant correlation between the length of stay and the number of ribs covered by the patients' head (P = 0.038). The MA/C factor was also associated with length of stay (P = 0.025). In patients over 80 there was a significant association between the number of ribs covered and death (P = 0.015). CONCLUSION: a slumped CXR may be associated with longer hospitalisation or death. The results of this small study require further revalidation but if true could help inform clinical decision making.