Search

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagenesis and Genomics Society.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

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 mm 2 . 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: The sensitivity of endoscopic ultrasound (EUS) in staging gastro-oesophageal cancers (GOCs) has been widely studied. However, the economic evidence of EUS staging in the management of patients with GOCs is scarce. This review aimed to examine all economic evidence (not limited to randomised controlled trials) of the use of EUS staging in the management of GOCs patients, and to offer a review of economic evidence on the costs, benefits (in terms of GOCs patients' health-related quality of life), and economic implications of the use of EUS in staging GOCs patients., Methods: The protocol was registered prospectively with PROSPERO (CRD42016043700; http://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?ID=CRD42016043700 ). MEDLINE (ovid), EMBASE (ovid), The Cochrane Collaboration Register and Library (including the British National Health Service Economic Evaluation Database), CINAHL (EBSCOhost) and Web of Science (Core Collection) as well as reference lists were systematically searched for studies conducted between 1996 and 2018 (search update 28/04/2018). Two authors independently screened the identified articles, assessed study quality, and extracted data. Study characteristics of the included articles, including incremental cost-effectiveness ratios, when available, were summarised narratively., Results: Of the 197 articles retrieved, six studies met the inclusion criteria: three economic studies and three economic modelling studies. Of the three economic studies, one was a cost-effectiveness analysis and two were cost analyses. Of the three economic modelling studies, one was a cost-effectiveness analysis and two were cost-minimisation analyses. Both of the cost-effectiveness analyses reported that use of EUS as an additional staging technique provided, on average, more QALYs (0.0019-0.1969 more QALYs) and saved costs (by £1969-£3364 per patient, 2017 price year) compared to staging strategy without EUS. Of the six studies, only one included GOCs participants and the other five included oesophageal cancer participants., Conclusions: The data available suggest use of EUS as a complementary staging technique to other staging techniques for GOCs appears to be cost saving and offers greater QALYs. Nevertheless, future studies are necessary because the economic evidence around this EUS staging intervention for GOCs is far from robust. More health economic research and good quality data are needed to judge the economic benefits of EUS staging for GOCs., Prospero Registration Number: CRD42016043700 .

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mirtazapine is a commonly used drug indicated for the treatment of severe depression. It works as a presynaptic α 2 -adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission, and it is metabolized by the p450 cytochrome oxidase system. There is evidence within the literature to suggest a link between antidepressants and increased liver enzymes, although case reports demonstrating a link between mirtazapine specifically and steatosis are sparse. Here, we present a case of mirtazapine-induced steatosis in a 48-year-old office worker. She presented with painless jaundice of 2 days duration and generalized lethargy and peripheral edema present for 3 weeks beforehand. Extensive investigations were undertaken to identify the cause of her jaundice but no biochemical, blood-borne, or anatomical cause could be found. Mirtazapine was subsequently stopped, and her liver function, both clinically and biochemically, improved rapidly. She made a full recovery after discontinuation of her mirtazapine.
.

The management of diabetes during terminal illness is complex, with lack of agreement and consensus among physicians and multidisciplinary teams. Despite the plethora of guidelines available for the management of diabetes, there exists no agreed, evidence-based strategy for managing diabetes during terminal illness and at the end of life. A number of physiological factors may influence glycaemic control during terminal illness. These include anorexia, cachexia, malabsorption, renal and hepatic failure. Furthermore, controversy exists on the frequency of blood glucose monitoring, the optimum blood glucose range and how to achieve this. We review the factors influencing blood glucose during terminal illness and provide a suggested approach to managing patients with type 1 and type 2 diabetes during the early and late stages of terminal illness.

Peritoneal disease accounts for just under a third of all malignant mesothelioma. Its insidious onset means that diagnosis is often made at an advanced stage, however, new therapeutic techniques are starting to lead to improved outcomes.

The aim of this study was to investigate the effect of a moderate degree of hypoxia on coronary vascular permeability to various lipophobic solutes. Using the multiple indicator dilution method the permeability-surface area (PS) products were determined for 125I-albumin, 125I-insulin and 57Co-cyanocobalamin in perfused rat hearts (flow approximately 10 ml.min-1.g-1) either with well-oxygenated (pO2 approximately 96 kPa) or hypoxic (pO2 approximately 45 kPa) solutions. The PS products for albumin, insulin and cyanocobalamin during the well-oxygenated equilibration period were 0.20 +/- 0.03, 0.29 +/- 0.06 and 2.0 +/- 0.3 ml.min-1.g-1 (mean +/- SE), respectively, relative to 131I-gamma-globulin. The PS products for these solutes 15 min after the induction of hypoxia were 1.3 +/- 0.3, 0.8 +/- 0.1 (p < 0.05) and 2.1 +/- 0.2 (p < 0.05), respectively. In hearts perfused with well-oxygenated solution for 75 min, the PS products for these solutes remained stable throughout the period of the study. Electron-microscopic examination of hypoxic tissues showed the presence of endothelial gaps of approximately 1 micron which were underlined by an intact basal lamina. We conclude that a moderate degree of hypoxia produces a large increase in permeability of albumin and insulin but has no effect on the PS products for cyanocobalamin and that the endothelial gaps are the likely mechanism of the observed increase in permeability.

A technique has been developed to monitor changes in synovial vascular tone and leakage of macromolecules, two of the cardinal features of inflammation. The technique permits not only quantitative sequential measurements of the leakage of 125I-albumin from the circulation into the synovium, but also semiquantitative continuous monitoring of the leakage changes. It allows simultaneous continuous monitoring of changes in synovial vascular tone as well. Vascular protein leakage was monitored semiquantitatively by measuring the radioactivity of 125I-albumin in synovial perfusate when passed through a flow cell consisting of a plastic tubing coil situated inside the well of a gamma detector. Quantitative measurements were provided by collecting and counting the synovial perfusate for 125I-albumin. Synovial vascular tone was monitored continuously by measurement of the change in joint radiation emitted by in vivo-labelled 99m-Tc erythrocytes. The in vivo labelling procedure yielded an 86% +/- 9% labelling efficiency. The degree of erythrocyte labelling was stable throughout the course of the experiment. Using this technique, the abilities of histamine to induce changes in synovial vascular tone and protein leakage were examined. Intraarticular infusion of 1 ng/mL histamine produced a 61% +/- 24% increase in synovial vascular blood volume, but did not significantly increase 125I-albumin leakage above that produced by Krebs solution alone. Higher concentrations produced a concentration-related increase in the leakage of 125I-albumin, which was not accompanied by appreciable increases in synovial vascular blood volume above the basal line. The simultaneous and continuous monitoring provided by this technique has revealed an apparent dissociation between vascular tone and vascular protein leakage in response to intraarticular histamine.

Adjuvant arthritis in rats was induced by a single subcutaneous injection of Freund adjuvant into a hind paw. The injected paws' mean volume increased continuously by 80 +/- 26% after 6 h (acute local response). The injected paw displayed a biphasic response peaking at day 1-2 decreasing to day 5, then increased to day 14 by 123% while the contralateral non-injected paw showed little increase until day 10 and increased by 42% at day 14. The lateral diameter of both knee-joints also increased biphasically, peaking at day 4, decreasing to day 6, then increasing to day 14 (early and late systemic phase). Mepyramine maleate, 1 mg.kg-1 (i.p.) daily, suppressed only the early systemic phase by 50%. Daily cimetidine hydrochloride, 1 mg.kg -1.day-1, almost completely abolished the inflammatory response in the knee joints up to day 12, while at day 14 the suppression was 71%. The increase in mean paw volume was also suppressed by orally administered cimetidine. Intraperitoneal doses of cimetidine (3.5 mumol.kg-1) totally suppressed paw oedema produced by subplantar injection of histamine (1.8 mM) but had no action on equiactive dose of the specific H1-agonist, 2-pyridylethylamine. Mepyramine at 3.5 mumol.kg-1 or greater produced no more than 50% suppression of the histamine response. A component of both adjuvant and histamine-induced responses thus appears to be histamine H2-receptor mediated.

A single sub-plantar injection of 1% carrageenan in saline produced a bi-phasic paw volume increase, phase 1 plateauing at 0.5-1 h, phase 2 at 3-6 h. Subtraction of the non-specific contralateral paw response produced by saline injection revealed a monophasic carrageenan response. Mepyramine maleate at a dose maximally effective on histamine-induced paw oedema (1 mg X kg-1 i.p.) failed to suppress carrageenan-induced inflammation. Maximally effective doses of cimetidine HCl (1-100 mg X kg-1) suppressed the response by no more than 53%. In animals treated with cimetidine HCl (1 mg X kg-1), pretreatment with indomethacin (2.5 mg X kg-1) further suppressed the mean oedema response by 59% compared with cimetidine alone. The indomethacin dose suppressed mean volume increase by 41%. Mepyramine alone or combined with cimetidine showed no anti-inflammatory activity. Following pretreatment with indomethacin (2.5 mg X kg-1), mepyramine maleate further suppressed the carrageenan oedema by 41% compared with indomethacin alone. While supporting a role for prostanoid formation, or other indomethacin-sensitive mechanisms, the results show that the mechanism of carrageenan-induced rat paw oedema also involves histamine acting largely through H2-receptors, although a role for H1-receptors can not be excluded. The interaction between mepyramine and indomethacin is discussed.