Royal Hallamshire Hospital Research Articles

Transglutaminase 6 antibodies in gluten neuropathy

BackgroundTG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies). MethodsThis was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy. ResultsTwenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy. ConclusionsWe found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.

Reassessing the value of gastroscopy for the investigation of dyspepsia

ObjectiveTo evaluate the diagnostic yield of investigating dyspepsia with oesophagogastroduodenoscopy (OGD) with or without mucosal biopsy.DesignRetrospective service evaluation study.SettingTwo teaching hospitals: The Royal Hallamshire Hospital and Northern General Hospital, Sheffield...

Diagnostic accuracy and cost analysis of the Alere™ i Influenza A&B near-patient test using throat swabs

Clinical diagnostic sensitivity alone is inadequate in the diagnosis of influenza. Polymerase chain reaction (PCR) testing is sensitive but the inherent delays in result availability potentially prolong time to isolation and treatment. Until recently no near-patient test (NPT) has demonstrated adequate sensitivity for routine clinical use. To evaluate diagnostic accuracy, time to result availability, clinical impact, and cost consequences of Alere™ i Influenza A&B NPT (Alere Inc., Waltham, MA, USA) using off-label throat swabs. Prospective, multi-centre [four UK National Health Service (NHS) hospitals], diagnostic accuracy cohort study with cost modelling. Throat swab samples from suspected influenza patients were tested for influenza using the reference standard of PCR; a second throat swab was tested using NPT. A total of 827 participants were recruited; 589 were suitable for analysis: sensitivity was 75.8% [95% confidence interval (CI): 67.0-84.6]; specificity was 96.8% (95% CI: 95.2-98.3). Sensitivity varied between Sheffield (Northern General Hospital: 82.1%; Royal Hallamshire Hospital: 83.3%) and other sites (Doncaster Royal Infirmary: 71.4%; Newcastle's Royal Victoria Infirmary: 50.0%) whereas specificity was high (92-100%). Positive predictive value (PPV) was 81.2% (95% CI: 72.9-89.5) with negative predictive value 95.6% (95% CI: 93.9-97.4) with observed prevalence of 15.4%. Median time to result for PCR was 1.1 days (on-site laboratories) and 5.2 days (remote laboratories). Isolation findings: 75% influenza positive not isolated; 69% of isolated participants did not have influenza. For a cohort of 1000 participants, annual estimated non-diagnostic cost savings with NPT are £215,040. This first prospective study of the Alere i NPT using throat swabs demonstrates high specificity, high PPV during seasonal epidemics, and rapid result availability which could lead to substantial cost savings.

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre

Background and aims: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs.Method: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes.Results: Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis.There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131–166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048).Conclusion: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.

Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

AimsTo determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune...

Inhibitor development in haemophilia.

HaemophiliaVolume 23, Issue S1 p. 3-3 Foreword Inhibitor development in haemophilia F. Peyvandi, F. Peyvandi flora.peyvandi@unimi.it Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, ItalySearch for more papers by this authorM. Makris, M. Makris m.makris@sheffield.ac.uk Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United KingdomSearch for more papers by this author F. Peyvandi, F. Peyvandi flora.peyvandi@unimi.it Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, ItalySearch for more papers by this authorM. Makris, M. Makris m.makris@sheffield.ac.uk Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United KingdomSearch for more papers by this author First published: 19 December 2016 https://doi.org/10.1111/hae.13145Citations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume23, IssueS1Special Issue: New Findings on Inhibitor Development: from Registries to Clinical StudiesJanuary 2017Pages 3-3 RelatedInformation

Ian Bruce Sneddon (1915-1987).

Ian Bruce Sneddon (1915-1987).

PATHOLOGICAL INTRUSIVE MEMORIES: DÉJÀ VU, FLASHBACKS AND OTHER PHENOMENA

Professor Markus Reuber MD PhD FRCP I am a Professor of Clinical Neurology and Honorary Consultant at the University of Sheffield and the Royal Hallamshire Hospital in Sheffield, United Kingdom....

PWE-030 High definition (hd) endoscopy but not i-scan significantly increases the detection of markers of coeliac disease: a multicentre uk study: Abstract PWE-030 Table 1

<h3>Introduction</h3> Coeliac disease (CD) remains underdiagnosed. Many patients with CD have undergone a previous endoscopy where the opportunity to make a diagnosis was missed. Clinicians may rely on endoscopic markers of CD to guide biopsy but they lack sensitivity. A routine duodenal biopsy approach may solve this problem but it is expensive. Methods to improve the detection of CD at endoscopy to guide biopsy would seem advantageous. I-Scan, a digital enhancement technique, has shown promising results. However, only one, single centre study has been performed. This was an uncontrolled, unblinded trial in high prevalence population (35% CD). We aimed to assess the utility of I-Scan in a lower prevalence population in a randomised controlled trial <h3>Method</h3> Patients from 2 UK hospitals (Royal Hallamshire Hospital, Sheffield and St. Mary’s Hospital, London) were randomised into 2 groups: Group 1 standard HD white light endoscopy (WLE) and Group 2 WLE plus I-Scan. Patients were compared to a standard non-HD WLE control group, Group 3. All patients received at least 4 duodenal biopsies. Coeliac serology was performed concurrently. The presence of endoscopic markers of CD, scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vascularity was noted and compared to VA on histology as the gold standard <h3>Results</h3> 700 patients (63% female, mean age 51.7) were recruited (201 into Group 1, 199 in Group 2 and 300 into Group 3). In total 130 (18.5%) new diagnoses of CD were made (19 in Group 1, 22 in Group 2 and 89 in Group 3). In new CD cases, endoscopic markers of CD were seen in 80.5% in the HD groups compared to 41.6% in Group 3 (p &lt; 0.0001). In Group 2, I-Scan appeared to enhance changes in 18% of new CD cases. However there was no significant difference in sensitivity between Group 1 (89.5%) and Group 2 (72.7%) (p = 0.2). Full sensitivity and specificity analysis is shown in Table 1. The severity of VA was analysed for missed cases. There was no significant difference in the distribution of VA severity across the 3 groups (p = 0.6). The use of HD/I-Scan did not prevent total VA being missed <h3>Conclusion</h3> HD endoscopy significantly increases the detection of the endoscopic markers of CD (p &lt; 0.0001). However although I-scan appears to enhance the changes of villous atrophy it does not significantly increase the detection of markers (p = 0.2) <h3>Disclosure of interest</h3> None Declared.

Increased Detection of Celiac Disease With Measurement of Deamidated Gliadin Peptide Antibody Before Endoscopy

Celiac disease is underdiagnosed. Many patients are examined by endoscopy, but celiac disease is missed or not detected. We evaluated the accuracy of finger prick-based point-of-care tests in the detection of celiac disease and developed an algorithm for diagnosis. We performed a prospective study of 2 groups of patients with celiac disease evaluated at the Royal Hallamshire Hospital in Sheffield (United Kingdom) from March 2013 through February 2014. In group 1, patients at high risk of celiac disease who tested positive for endomysial antibody (n = 55) were evaluated using the Biocard test (BHR Pharmaceuticals, Nuneaton, UK) and the Celiac Quick Test (Biohit Healthcare UK, Ellesmere Port, UK), which measure antibodies to tissue transglutaminase (anti-tTG), and the Simtomax test (Tillotts Pharma, Rheinfelden, Switzerland), which measures deamidated gliadin peptide antibodies (DGP). Patients in group 2 (508 consecutive patients who underwent an endoscopy examination for any indication) received the DGP test, and also were evaluated using a diagnostic algorithm that incorporated results from the DGP test and data on symptoms. In both groups, point-of-care tests were taken at the time of endoscopy and results were compared with results from histologic analyses of duodenal biopsy specimens from all patients. In group 1, the DGP test identified patients with celiac disease with 94.4% sensitivity, the Celiac Quick Test identified patients with 77.8% sensitivity (P = .03 vs the DGP test), and the Biocard test identified patients with 72.2% sensitivity (P = .008 vs the DGP test). In group 2, the DGP test identified patients with celiac disease with 92.7% sensitivity (95% confidence interval, 83.0-97.3), 85.2% specificity (95% confidence interval, 81.5-88.3), a positive predictive value of 49.2% (95% confidence interval, 40.3-58.2), and a negative predictive value of 98.7% (95% confidence interval, 96.8-99.5). Measurement of serum anti-tTG identified patients with celiac disease with 91.2% sensitivity (95% confidence interval, 81.1-96.4), 87.5% specificity (95% confidence interval, 84.0-90.4), a positive predictive value of 53.0% (95% confidence interval, 43.6-62.2), and a negative predictive value of 98.5% (95% confidence interval, 96.5-99.4). The algorithm identified patients with celiac disease with 98.5% sensitivity; its use could reduce duodenal biopsies by 35%. In a prospective study, a test for DGP identified patients with celiac disease with similar levels of sensitivity and specificity as standard serologic analysis of anti-tTG. Use of the DGP test before endoscopy could increase the accuracy of the diagnosis of celiac disease. Further studies, in lower-prevalence populations, are required to assess the impact of the test in clinical practice.

Lessons from my first week as a doctor

Will Sapwell started work as a foundation year 1 doctor this August. He describes the lessons learnt during his first week at the National Centre for Pulmonary Hypertension at the Royal Hallamshire Hospital in Sheffield

Rethinking Dietary Approaches for Brain Health

David Perlmutter: The major thesis of Grain Brain is that both carbohydrates and glucose are detrimental to brain health. Well-respected and peer-reviewed journals have published reports that higher levels of blood glucose are specifically damaging and detrimental to the brain in general, and more specifically, to the hippocampus, which mediates memory function. A recent article in Neurology reported that elevations of blood glucose and glycated hemoglobin [HbA1c] translate into two things: memory compromise and shrinkage of the hippocampus.2 Another recent article in The New England Journal of Medicine demonstrated that even mild elevations of blood sugar translate dramatically into an increased risk for developing dementia.3 It is a profound correlation to recognize that even subtle elevations of blood glucose—well below levels to be considered diabetic—may already be damaging the brain. If we understand that elevated blood glucose and glycation of proteins relate to an increased risk for cognitive dysfunction, as well as brain shrinkage, what should a dietary evaluation look like? A study in the Journal of Alzheimer’s Disease, demonstrated that individuals who consumed higher amounts of carbohydrates in their diets had about an 89% increased risk for developing dementia, in contrast to people whose diets were highest in fat and whose risk was reduced by 44%.4 We live with this notion that a calorie is a calorie, but, at least in terms of brain health—and I believe for the rest of the body as well—there are very big differences between our sources of calories in terms of the impact on our health. Carbohydrate calories, which elevate blood glucose, are dramatically more detrimental to human physiology—and specifically to human health—than are calories derived from healthful sources of fat. The diet that I recommend—high in fat and low in carbohydrates—has simply been what we have eaten for a million years, so it has a bit of a track record. The notion that this is a revolutionary new diet has to be put into context. In reality, the diet that people are now consuming, which is dreadfully high in carbohydrates and low in fat, as our governmental institutions are recommending, is the biggest challenge to human physiology that we have ever experienced, and this is very, very worrisome. In terms of gluten consumption, we have come a long way from our understanding that celiac disease exists, and we now recognize that, according to top researchers, non-celiac gluten sensitivity also exists, which may affect 30% of humanity. Marios Hadjivassiliou [MD, department of neurology, Royal Hallamshire Hospital, Sheffield, United Kingdom] has said, so poetically, that gluten sensitivity may at times be a pure neurologic disease that is basically extraintestinal, and that we do not need to have intestinal issues to define gluten sensitivity. In fact, we are now seeing literature that points the finger clearly at gluten sensitivity as a culprit in a variety of neurologic problems, including depression, cognitive dysfunction, seizures, and even headaches. According to the work of Alessio Fasano [MD, chief of pediatric gastroenterology and nutrition at MassGeneral Hospital for Children, Boston, Massachusetts], gluten stimulates the production of zonulin, and zonulin makes the bowel hyperpermeable, which allows proteins access to the bloodstream, where they might normally have been excluded.5 More importantly, what Dr. Fasano’s research has revealed is that the same mechanism is involved—gluten-stimulating zonulin—in increasing the permeability of the blood–brain barrier. While clinicians may be concerned about patients having leaky bowels, I can promise that having a leaky brain is certainly of much more concern. What is so compelling about Dr. Fasano’s work is that, according to Rethinking Dietary Approaches for Brain Health

Patients Who Avoid Wheat and Gluten: Is That Health or Lifestyle?

In a New York restaurant, a celiac patient requesting a gluten-free menu was asked by the server if the diet was for health or for lifestyle. This increasingly common exchange exemplifies the clinical conundrum clinicians face regarding the use of a gluten-free diet (GFD). Although humankind has likely existed in some form for 2.5 million years, it is only in the last 10,000 years that humans have been exposed to wheat, which was originally cultivated in the Fertile Crescent from *9000 BC to 4000 BC. Thus, wheat and therefore, gluten is a relatively novel component of the human diet. The globalization of wheat production, and subsequently its increased worldwide consumption, has increased the incidence and clinical recognition of gluten-related disorders [1]. The most notable gluten-related disorder is celiac disease (CD), a state of heightened immune response to ingested gluten in genetically susceptible individuals. Initial reports in the 1950s suggested this to be a rare condition affecting 1 in 8,000. Nevertheless, more recently, its prevalence in the United States and elsewhere is 0.71 % or 1 in 141 [2]. The sole effective treatment for CD is lifelong adherence to a strict GFD. More recently, a few case reports and series published in the 1980s described individuals intolerant to gluten, by way of experiencing irritable bowel syndrome (IBS) type symptoms, but in whom CD serologies and small intestinal biopsies were normal. Since the diagnosis or explanation for these symptoms was lacking and possibly dismissed, such patients were unclassifiable and untreatable [3]. Nonetheless, over the last few years, mounting media reports have speculated that the use of a GFD is rapidly growing to the point that it is now a big business, seemingly greatly exceeding the demand predicted from CD subjects alone. This media pressure finally prodded the scientific community into a response, led by an Australian group, who performed a landmark double-blind, randomised, placebo-controlled study reporting that gluten from two slices of bread and one muffin indeed induced gastrointestinal symptoms in subjects without CD [4]. Subsequently, a consensus of experts has introduced the term ‘‘non-celiac gluten sensitivity’’ (NCGS) to describe such subjects [5]. A subsequent flurry of research papers raised the ratio of publications for NCGS:CD from 1:438 to 1:10, to the point that NCGS is considered the new frontier of gluten-related disorders [6]. The pathophysiology of NCGS has not yet been fully elucidated. Whereas the innate and adaptive immune response to gluten is responsible for the manifestations seen in CD, only the innate immune system is seemingly triggered in NCGS. There have been promising reports of altered small bowel intestinal permeability, proliferation of peripheral blood monocytes, the presence of antigliadin antibodies, enhanced cytokine induction, and induction of basophil activation in NCGS, although these findings have not yet been confirmed [6]. Gluten is only one of the complex milieu of nutrients present in wheat, which also contains fructans, which are fermentable, poorly absorbed, short chain carbohydrates, also termed FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). FODMAPS provoke gastrointestinal symptoms in IBS patients through mechanisms involving gut microbiota, gas production, and fermentation [7]. There is also emerging evidence that wheat-amylase trypsin inhibitors are also associated with intestinal symptoms [8]. Since it is unclear which component of wheat-based products is I. Aziz (&) D. S. Sanders Department of Gastroenterology, Room P39, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK e-mail: imran.aziz@sth.nhs.uk

Khat (Catha Edulis) as a possible cause of autoimmune hepatitis

To investigate the potential role of khat in triggering auto immune hepatitis. Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital. They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria. Six patients were identified. All of them had presented with acute hepatitis on a background of khat. All were male and five of these patients were of Somali origin, while one patient was from Yemen. The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs, immunoglobulin levels and liver histology. The patients were given a score of -4 for khat use due to its potential to cause drug induced liver injury. Five of these patients scored between 10 and 15 points, placing them in the probable group for having autoimmune hepatitis. All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression. One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual. Further studies are needed for confirmation.

A comparison of psychological stress among women with and without reproductive failure

ObjectiveTo determine whether women with recurrent implantation failure (RIF) after in vitro fertilization (IVF), similar to women with recurrent pregnancy loss, have significantly higher stress levels than women without reproductive failure, and to compare stress levels between women with RIF and women with recurrent pregnancy loss. MethodsIn a questionnaire-based study between September 2009 and January 2011, psychological stress was measured among patients attending recurrent pregnancy loss and RIF clinics at the Royal Hallamshire Hospital, Sheffield, UK. Participants completed the Fertility Problem Inventory (FPI), the Perceived Stress Scale (PSS), and the Positive and Negative Affect Schedule (PANAS) on their first visit to their respective clinic. Thirty fertile control women also completed the 3 validated questionnaires. ResultsCompared with the control group, women with RIF and recurrent pregnancy loss had significantly higher scores in the FPI (RIF, P<0.001; recurrent pregnancy loss, P=0.003) and the PANAS negative affect domain (RIF, P=0.004; recurrent pregnancy loss, P=0.001), and lower scores in the PANAS positive affect domain (RIF, P<0.001; recurrent pregnancy loss, P<0.001). Whereas the perceived stress score (PSS) of the recurrent pregnancy loss group was significantly higher than that of the control group (P=0.006), the score of the RIF group was not, although the difference tended toward statistical significance (P=0.058). ConclusionThe study findings confirm the stressful nature of RIF and recurrent pregnancy loss.

PHENYTOIN AND CEREBELLAR ATAXIA: NOT ALL DOWN TO TOXICITY?

IntroductionPhenytoin is an effective anticonvulsant for focal epilepsy with the advantage of single daily administration. Its popularity however is in decline, partly because of perception of adverse effects that include...

Testicular torsion: A comparative audit of operative practices in South Yorkshire

Testicular torsion: A comparative audit of operative practices in South Yorkshire

The development of fibrosis in a novel model of chronic pancreatitis is mediated by complement factor C5

The development of fibrosis in a novel model of chronic pancreatitis is mediated by complement factor C5

PTU-041 Dedicated GI Bleed Services Result in a Significant Difference in Inpatient Mortality: a South Yorkshire Experience

IntroductionAcute upper GI bleeding (AUGIB) is a common gastrointestinal problem associated with significant mortality.1 Whilst numerous factors have been shown to influence mortality in these individuals including co-morbidity and time...

Pancreatic Exocrine Insufficiency (PEI) in chronic pancreatitis (CP) and cystic fibrosis (CF) patients: Combining clinician insights and existing literature to develop a conceptual model to aid in the identification and management of PEI

Pancreatic Exocrine Insufficiency (PEI) in chronic pancreatitis (CP) and cystic fibrosis (CF) patients: Combining clinician insights and existing literature to develop a conceptual model to aid in the identification and management of PEI