John N Plevris

The University of Edinburgh | UoE · Division of Health Sciences

Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are a ected remains uncl...

Background and aims: Cells are known to respond to nanoscale features thus our aim was to assess phenotypic morphology of HepaRGs cultured on 2D-nanopatterned polymer slides (NPS) for the optimisation of prototype LiverBioChips for pre-clinical drug-screening. Methods: NPS were manufactured using electron-beam lithography and injection moulding. S...

Organotypic liver culture models for hepatotoxicity studies that mimic in vivo hepatic functionality could help facilitate improved strategies for early safety risk assessment during drug development. Interspecies differences in drug sensitivity and mechanistic profiles, low predictive capacity, and limitations of conventional monocultures of human...

Background and aims: Small-bowel bleeding is the primary indication for capsule endoscopy (CE). Many experts advocate a "watch-and-wait" policy in negative CE. This meta-analysis examines the odds of re-bleeding after negative index CE, and the impact on long-term follow-up. Methods: A comprehensive literature search identified papers examining...

Background and aims: Fecal calprotectin is a well-established marker of mucosal inflammation. Although the correlation of elevated calprotectin levels with colonic inflammation has been confirmed repeatedly, it is less established for the small bowel. The aim of the current study was to assess the diagnostic accuracy of calprotectin for the predict...

Objective In May 2021 we implemented a locally developed gastric ulcer protocol. Patients with low Edinburgh Gastric Ulcer Scores (EGUS) and benign biopsy results at index oesophagogastroduodenoscopy (OGD1) were recommended to not undergo follow-up OGD (OGD2). We aimed to validate the EGUS and identify any gastric cancer diagnoses since protocol ad...

Objective Small-bowel capsule endoscopy (SBCE) is being used with increasing frequency. It is important, however, to ensure that the frail elderly in particular are undergoing investigations which have a positive impact on their ongoing management. We aimed to determine the SBCE rate in the elderly, the clinical outcomes, and if clinical frailty ma...

Sharing retrospectively acquired data is essential for both clinical research and training. Synthetic Data Generation (SDG), using Artificial Intelligence (AI) models, can overcome privacy barriers in sharing clinical data, enabling advancements in medical diagnostics. This study focuses on the clinical evaluation of medical SDG, with a proof-of-co...

BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic lipid accumulation, causes inflammation and oxidative stress accompanied by cell damage and fibrosis. Liver injury (LI) is also frequently reported in patients hospitalised with coronavirus disease 2019 (COVID-19), while pre-existing MASLD increase...

Introduction Upper gastrointestinal (GI) bleeding accounts for 75% of bleeding from the GI tract and is a common reason for presentation to acute hospitals. However, many hospitals in the U.I. do not have a 24 hour on-call GI bleeding service and instead this is centralised in tertiary centres. NHS Lothian provides healthcare for a population of al...

Pilot of a Quantitative Faecal Immunochemical Test.pdf (could not be inserted)

Introduction Small bowel capsule endoscopy (SBCE) is often used in elderly patients as it is non-invasive and does not require sedation. It is important however, to ensure that the frail elderly in particular are undergoing investigations which have a positive impact on their ongoing management. We aimed to determine the SBCE rate in the elderly, t...

Introduction We audited intravenous (IV) iron prescribing in Gastroenterology inpatients to assess whether patients received follow-up doses as outpatients to complete their calculated total iron requirement. We have used this information to change prescribing practice within our trust. Methods Electronic inpatient prescribing data for ferric carb...

Objective We aimed to investigate the clinical utility of follow-up oesophagogastroduodenoscopy (OGD2) in patients with severe oesophagitis (Los Angeles grades C or D) through evaluating the yield of Barrett’s oesophagus (BO), cancer, dysplasia and strictures. Second, we aimed to determine if the Clinical Frailty Scale (CFS) may be used to identify...

Introduction In this study we aimed to investigate the clinical utility of follow-up oesophagogastroduodenoscopy (OGD2) in clinically frail patients (according to the Clinical Frailty Scale) with severe oesophagitis through evaluating, by Los Angeles (LA) grade, the yield of Barrett’s oesophagus (BO), cancer, dysplasia and strictures. Methods Pati...

Introduction The British Society of Gastroenterology guidelines on the management of suspected acute upper gastrointestinal bleeding (AUGIB) recommend that endoscopy (OGD) is performed within 24 hours of presentation. However, certain hospital sites in the UK have no provision for therapeutic endoscopy and the optimal AUGIB scoring system for inter...

Non-alcoholic fatty liver disease (NAFLD) has been identified as a predictor of liver injury in patients hospitalised with coronavirus disease 2019 (COVID-19) and there are emerging reports of COVID-19-associated cholangiopathies, highlighting the requirement for further study of the principal mechanisms underlying liver injury.Our study aimed to (...

Introduction A local ‘gastric ulcer follow-up’ protocol was developed, externally validated and implemented locally in May 2021. Under the local protocol, patients with low ulcer risk scores based on ulcer size, location and patient age with benign biopsy results at index oesophagogastroduodenoscopy (OGD1), are not offered endoscopic follow-up to c...

The gut–liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell lin...

Background and study aim: Meckel`s Diverticulum (MD) may remain silent or be associated with complications like gastrointestinal (GI) bleeding. The main aim of this study was to evaluate indicative small bowel capsule endoscopy (SBCE) findings and the secondary aim to describe clinical presentation in patients with MD. Patients and methods: This...

Schizophrenia is a severe mental illness which can have a devastating impact on an individual’s quality of life. Comorbidities are high amongst patients and life expectancy is approximately 15 years less than the general population. Despite the well-known increased mortality, little is known about the impact of gastrointestinal and liver disease on...

Introduction: Schizophrenia is a severe mental illness which can have a devastating impact on all aspects of an individual’s life. Substance misuse (in particular alcohol), risk of suicide, and high rates of often poorly controlled physical health conditions, have resulted in patients having a life expectancy which is reduced by approximately 15 ye...

Introduction: Patients with Los Angeles (LA) grades C and D reflux oesophagitis are collectively considered to suffer from severe forms of oesophagitis. We aimed to determine if there are differences in clinical outcomes between those with grade C and grade D oesophagitis at index oesophago-gastro-duodenoscopy (OGD1). Methods: Patients in NHS Loth...

Diagnostic unsedated transnasal endoscopy (uTNE) has been proven to be a safe and well-tolerated procedure. Although its utilization in the United Kingdom (UK) is increasing, it is currently available in only a few centers. Through consideration of recent studies, we aimed to perform an updated review of the technological advances in uTNE, consider...

Background and Aims Human breath contains numerous volatile compounds which reflect metabolic activity. Electronic nose (eNose) technology can distinguish non-alcoholic fatty liver disease (NAFLD) from healthy with reasonable confidence.1 2 We hypothesised that breath prints obtained from eNose could identify patient subgroups at higher risk for pr...

The Edinburgh Dysphagia Score (EDS) was previously developed to identify patients referred to secondary care with dysphagia, who were most likely to have oesophageal cancer. The aim of this study was to use the EDS prospectively during the COVID pandemic to risk stratify patients to either urgent or routine investigation of dysphagia. Between 1st A...

Background Intra-hepatocyte triglyceride accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD). Little is known of the role of lipid droplets in the pathogenesis of this increasingly common condition. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been suggested as a potential treatment for NAFLD. Within this study we e...

Objective Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score. Design/method All patients in National Heal...

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypert...

Introduction Capsule endoscopy (CE) is well established the investigation of small-bowel (SB) pathology. We compared the use of double-headed (DH) capsules, to conventional single-headed (SH), in a real-world patient cohort in the first multicentre British study. Methods Over 9 months, patients referred for routine SBCE at 4 tertiary referral cent...

Background and aim Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. Materials a...

Background and Aims Capsule endoscopy (CE) is a visual modality; hence, diagnosis relies on image quality. We studied the contribution of image parameters to visualization quality and their effect on diagnostic certainty of small bowel (SB) lesions. Methods Five clear CE images of common SB pathology – two vascular lesions, two inflammatory, one p...

Upper gastrointestinal (UGI) tract pathology is common worldwide. With recent advancements in robotics, innovative diagnostic and treatment devices have been developed and several translational attempts made. This review paper aims to provide a highly pictorial critical review of robotic gastroscopes, so that clinicians and researchers can obtain a...

Background: Conventional colonoscopy (CC) allows access for colonic investigation and intervention; in the small group in whom CC is unsuccessful alternative imaging is often sufficient. There remains a subset, however, requiring full colonic visualisation or intervention. Balloon-assisted colonoscopy (BAC) gives a further option when access is di...

Background and study aims This study aimed to establish 5-year survival of patients diagnosed with bleeding small bowel (SB) angioectasia, with the hypothesis that many will suffer deaths relating to comorbidity rather than gastrointestinaI bleeding. Patients and methods SB capsule endoscopy (SBCE) procedures, performed for suspected SB bleeding or...

Background Analysis of volatile organic compounds (VOCs) in exhaled breath, ‘volatomics’, provides opportunities for non-invasive biomarker discovery and novel mechanistic insights into a variety of diseases. Aim The purpose of this pilot study was to compare breath VOCs in an initial cohort of non-alcoholic fatty liver disease (NAFLD) patients an...

A novel strain of coronoviridae (SARS-CoV-2) was reported in Wuhan China in December 2019. Initially, infection presented with a broad spectrum of symptoms which typically included muscle aches, fever, dry cough, and shortness of breath. SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract. However, there i...

Fully differentiated HepaRG™ cells are the hepatic cell line of choice for in vitro work in toxicology and drug trials. They are derived from a hepatoblast-like progenitor (HepaRG™-P) that differentiate into a co-culture of hepatocyte-like and cholangiocyte-like cells in the presence of differentiation-inducing chemical dimethylsulfoxide (DMSO). Th...

Gene expression analysis by quantitative real-time polymerase chain reaction (RT-qPCR) is routinely used in biomedical studies. The reproducibility and reliability of the data fundamentally depends on experimental design and data interpretation. Despite the wide application of this assay, there is significant variation in the validation process of...

There are a variety of end-point assays and techniques available to monitor hepatic cell cultures and study toxicity within in vitro models. These commonly focus on one aspect of cell metabolism and are often destructive to cells. Impedance-based cellular assays (IBCAs) assess biological functions of cell populations in real-time by measuring elect...

Background In the medical literature, the nomenclature and descriptions (ND) of small bowel (SB) ulcerative and inflammatory (U-I) lesions in capsule endoscopy (CE) are scarce and inconsistent. Inter-observer variability in interpreting these findings remains a major limitation in the assessment of the severity of mucosal lesions, which can impact...

Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000–2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the firs...

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...

Introduction Capsule endoscopy (CE) is a well-established mode of investigation for small bowel (SB) pathology. This study examines the potential benefits of using double-headed capsules compared to conventional single-headed ones in a real-world cohort of patients referred for CE. We present initial results from the first multicentre British study...

Introduction Capsule endoscopy (CE) is the prime mode of investigation for small bowel (SB) pathology. It relies heavily on image quality, which is commonly affected by poor preparation. Currently, there is no widely-accepted method for quantifying visualisation quality. We studied the contribution of various image parameters to visualisation quali...

Introduction Drug induced liver injury accounts for approximately one half of all acute liver failure cases, with Paracetamol (APAP) being one of the most reported hepatotoxins [1]. We used an in vitro approach to model APAP transport from gut to liver where metabolic products (NAPQI) can cause hepatocellular damage. Investigating the mechanisms of...

Background: Angioectasias are a prominent cause of small bowel (SB) bleeding frequently identified during capsule endoscopy (CE). Subsequent management depends upon grade/severity and location. There is increasing evidence that the location of SB angioectasias is not random. We aimed to map the distribution of SB angioectasias, and assess whether t...

A 78-year-old man attended for outpatient capsule endoscopy, to investigate a recent history of unexplained small bowel bleeding. His previous medical history included an abdominal aortic aneurysm repair 6 years ago. Soon after capsule ingestion, he experienced sudden onset abdominal pain and collapsed on hospital grounds. He was rapidly transferre...

Objectives: This study aims to review the utility of repeat capsule endoscopy (CE) with on-going concern of small bowel (SB) bleeding following initial SB investigation with CE. Materials and methods: A specifically designed database of CE examinations performed over 13 years, with hospital records, was retrospectively interrogated for patients und...

Capsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations...

Background and study aims Nomenclature and descriptions of small bowel (SB) vascular lesions in capsule endoscopy (CE) are scarce in the medical literature. They are mostly based on the reader's opinion and thus differ between experts, with a potential negative impact on clinical care, teaching and research regarding SBCE. Our aim was to better def...

Chlorpromazine (CPZ) is a neuroleptic drug and prototype compound used to study intrahepatic cholestasis. The exact mechanisms of CPZ induced cholestasis remain unclear. Rat hepatocytes, or a sandwich culture of rat and human hepatocytes, have been the most commonly used models for studying CPZ toxicity in vitro. However, to better predict outcomes...

Introduction: This review presents noteworthy advances in clinical and experimental Capsule Endoscopy (CE), focusing on the progress that has been reported over the last five years since our previous review on the subject. Areas covered: This study presents the commercially available CE platforms, as well as the advances made in optimizing the diag...

We congratulate Boeckmans et al., on their comprehensive review of current models of non-alcoholic fatty liver disease (NAFLD) presented ‘Human based systems: Mechanistic NASH modelling just around the corner?’ (1). NAFLD affects a large number of people worldwide and despite advances in our knowledge of the condition, further research is needed to...