Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.

Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

1: ESGE recommends in patients with acute upper gastrointestinal hemorrhage (UGIH) the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Patients with GBS ≤ 1 are at very low risk of rebleeding, mortality within 30 days, or needing hospital-based intervention and can be safely managed as outpatients with outpatient endoscopy.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in patients with acute UGIH who are taking low-dose aspirin as monotherapy for secondary cardiovascular prophylaxis, aspirin should not be interrupted. If for any reason it is interrupted, aspirin should be re-started as soon as possible, preferably within 3-5 days.Strong recommendation, moderate quality evidence. 3: ESGE recommends that following hemodynamic resuscitation, early (≤ 24 hours) upper gastrointestinal (GI) endoscopy should be performed. Strong recommendation, high quality evidence. 4: ESGE does not recommend urgent (≤ 12 hours) upper GI endoscopy since as compared to early endoscopy, patient outcomes are not improved. Strong recommendation, high quality evidence. 5: ESGE recommends for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. 6: ESGE recommends for patients with an ulcer with a nonbleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy, or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, high quality evidence. 7 : ESGE suggests that in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic spray/powder or cap-mounted clip should be considered. Weak recommendation, low quality evidence. 8: ESGE recommends that for patients with clinical evidence of recurrent peptic ulcer hemorrhage, use of a cap-mounted clip should be considered. In the case of failure of this second attempt at endoscopic hemostasis, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after failed TAE. Strong recommendation, moderate quality evidence. 9: ESGE recommends high dose proton pump inhibitor (PPI) therapy for patients who receive endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endoscopically. (A): PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g., 80 mg then 8 mg/hour) for 72 hours post endoscopy. (B): High dose PPI therapies given as intravenous bolus dosing (twice-daily) or in oral formulation (twice-daily) can be considered as alternative regimens.Strong recommendation, high quality evidence. 10: ESGE recommends that in patients who require ongoing anticoagulation therapy following acute NVUGIH (e. g., peptic ulcer hemorrhage), anticoagulation should be resumed as soon as the bleeding has been controlled, preferably within or soon after 7 days of the bleeding event, based on thromboembolic risk. The rapid onset of action of direct oral anticoagulants (DOACS), as compared to vitamin K antagonists (VKAs), must be considered in this context.Strong recommendation, low quality evidence.

Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology.

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.

Diagnostic yield from symptomatic lower gastrointestinal endoscopy in the UK: A British Society of Gastroenterology analysis using data from the National Endoscopy Database.

BACKGROUND: The value of lower gastrointestinal endoscopy (LGIE; colonoscopy or sigmoidoscopy) relates to its ability to detect clinically relevant findings, predominantly cancers, preneoplastic polyps or inflammatory bowel disease. There are concerns that many LGIEs are performed on low-risk patients with limited benefit. AIMS: To determine the diagnostic outcomes of LGIE for common symptoms. METHODS: We performed a cross-sectional study of diagnostic LGIE between March 2019 and February 2020 using the UK National Endoscopy Database. We used mixed-effects logistic regression models, incorporating random (endoscopist) and fixed (symptoms, patient age, and sex) effects upon two dependent variables (large polyp [≥10 mm] and cancer diagnosis). Adjusted positive predictive values (aPPVs) were calculated. RESULTS: We analysed 384,510 LGIEs; 33.2% were performed on patients aged under 50 and 53.6% on women. Regarding colonoscopies, the unadjusted PPV for cancer was 1.5% (95% CI: 1.4-1.5); higher for men than women (1.9% vs. 1.1%, p < 0.01). The PPV for large polyps was 3.2% (95% CI: 3.1-3.2). The highest colonoscopy cancer aPPVs were in the over 50s (1.9%) and in those with rectal bleeding (2.5%) or anaemia (2.1%). Cancer aPPVs for other symptoms were <1% despite representing 54.3% of activity. In patients under 50, aPPVs were 0.4% for cancer and 1.6% for large polyps. Results were similar for sigmoidoscopy. CONCLUSIONS: Most colonoscopies were performed on patients with low-risk symptoms, where cancer risk was similar to the general population. Cancer and large polyp yield was highest in elderly patients with rectal bleeding or anaemia, although still fell short of FIT-based screening yields.

Comments on recent community water fluoridation studies.

Water fluoridation is a public health measure to reduce levels of dental caries in populations. A report of the recently completed CATFISH study has been published. This was the first UK evaluation of fluoridation introduction for many years; it was carefully designed and executed and is welcomed. The purpose of this article is to highlight the 180-page report of the study and comment on some aspects to aid interpretation of the findings. Significant features were that two cohorts, from birth and from five years, were followed for six years in a fluoridated and a non-fluoridated area, and clinical and cost analyses were reported. Areas of the report which deserve comment are: a) interruption of fluoridation for a year for half the children in the intervention area and its effect; b) clinical results were reported as absolute reduction in caries prevalence, with the preventive fraction for caries severity downplayed; c) the power of the study was diminished by an unexpected lower caries increment; and d) control for differences in diet was not possible. Nevertheless, this major UK study showed clinical and cost benefits of water fluoridation. The risk of cessation of water fluoridation is highlighted in examples of three recently published studies.

Variation in exposure to endoscopic haemostasis for acute upper gastrointestinal bleeding during UK gastroenterology training.

INTRODUCTION: Gastroenterologists are typically expected to be competent in endoscopic haemostasis for acute upper gastrointestinal bleeding (AUGIB), with the Certificate of Completion of Training (CCT) often heralding the onset of participation in on-call AUGIB rotas. We analysed the volume of haemostasis experience recorded by gastroenterology CCT holders on the Joint Advisory Group on Gastrointestinal Endoscopy Training System (JETS) e-portfolio, the UK electronic portfolio for endoscopy, and assessed for variations in exposure to haemostasis. METHODS: UK gastroenterologists awarded CCT between April 2014 and April 2017 were retrospectively identified from the specialist register. Credentials were cross-referenced with JETS to retrieve AUGIB haemostasis procedures prior to CCT. Procedures were collated according to variceal versus non-variceal therapies and compared across training deaneries. RESULTS: Over the 3-year study period, 241 gastroenterologists were awarded CCT. 232 JETS e-portfolio users were included for analysis. In total, 12 932 haemostasis procedures were recorded, corresponding to a median of 42 (IQR 21-71) per gastroenterologist. Exposure to non-variceal modalities (median 28, IQR 15-52) was more frequent than variceal therapies (median 11, IQR 5-22; p<0.001). By procedure, adrenaline injection (median 12, IQR 6-23) and variceal band ligation (median 10, IQR 5-20) were most commonly recorded, whereas sclerotherapy experience was rare (median 0, IQR 0-1). Exposure to haemostasis did not differ by year of CCT (p=0.130) but varied significantly by deanery (p<0.001), with median procedures ranging from 20-126. CONCLUSION: Exposure to AUGIB haemostasis during UK gastroenterology training varied across deaneries and procedural modalities which should prompt urgent locoregional review of access and delivery of training. Endoscopy departments should ensure the availability of supportive provisions in haemostasis (i.e. training/upskilling, supervision, mentorship) during the early post-CCT period.

The biochemical and clinical penetrance of individuals diagnosed with genetic haemochromatosis by predictive genetic testing.

BACKGROUND: HFE-related genetic haemochromatosis (GH) is the commonest inherited genetic disorder in Caucasian populations with approximately one in 180 of individuals in the west of Scotland homozygous for the common C282Y mutation. The clinical diagnosis of GH, however, remains relatively uncommon - suggesting either under diagnosis or low clinical penetrance. AIM: We aimed to assess the biochemical and clinical penetrance of GH in first-degree relatives of patients with known GH, who subsequently themselves screened positive for the common GH mutations. METHODS: Individuals were identified from two large teaching hospitals in North Glasgow from July 1997 to July 2005 diagnosed with GH after predictive genetic testing after a relative was found to have GH. Details of patient history, biochemistry and known comorbidity at diagnosis and results of related further investigations were collected. RESULTS: Sixty-three individuals were identified, 31 (49%) of whom were males. Fifty-five individuals (87%) were C282Y homozygous and the remaining eight were compound heterozygotes for C282Y and H63D. All 31 male patients were found to have evidence of iron overload as opposed to 63% of females. Elevated liver enzyme levels were encountered in 15 patients (24%). All except one had evidence of iron overload. Four individuals underwent a liver biopsy, two of whom had hepatic fibrosis. Four patients were found to be diabetic. A full clinical history was obtained from 54 of 63 individuals, 38 (70%) of whom were entirely asymptomatic. Thirteen individuals complained of joint pains and a further nine complained of fatigue. CONCLUSION: This study suggests that although biochemical penetrance of GH is high, the clinical penetrance is low.

Abnormal liver function tests following bone marrow transplantation: aetiology and role of liver biopsy.

INTRODUCTION: Liver dysfunction is common in bone marrow transplant recipients. Common causes are graft-versus-host disease, drugs, veno-occlusive disease, sepsis and iron overload. We studied the prevalence and aetiology of abnormal liver function tests following bone marrow transplantation and the role of liver biopsy. METHODS: All allogeneic and autologous bone marrow transplantations undertaken in our institution over a 2-year period were studied. Subsequent liver function tests, the use and timing of liver biopsy and the final cause of liver dysfunction were determined in each case. RESULTS: We studied 121 patients (58 allogeneic, 63 autologous). Abnormal liver function tests were found in 52% of bone marrow transplant recipients (72% allogeneic and 33% autologous; P = 0.015). The most common causes of liver dysfunction were graft-versus-host disease, drugs and iron overload in the allogeneic group, and drugs and sepsis in the autologous group. Nineteen patients (16%; 18 allogeneic) underwent liver biopsy. The majority of liver biopsies were carried out in the late post-transplant period to exclude or confirm graft-versus-host disease, although only one case was confirmed. Sixteen of the 19 patients who underwent biopsy had significant hepatic iron overload, but no biopsy revealed evidence of fibrosis or cirrhosis. CONCLUSION: Liver dysfunction following bone marrow transplantation is common and most diagnoses can be ascertained without resorting to liver biopsy. In our series, hepatic iron overload was the most common finding in those who underwent liver biopsy.

A dental risk management protocol for electroconvulsive therapy.

This article describes the results of an evaluation of a system to use trained junior psychiatric doctors to perform the pre-ECT oral assessment. All junior doctors were given a 1-hour training session in making oral assessments, and their ability to diagnose was tested by dental follow-up visits to patients they had assessed. Seventy-one patients were seen by both doctor and dentist, and the sensitivity for doctors ranged between 92% for the presence of dentures or removable bridges to 8% for the presence of teeth vulnerable to fracture. Where the doctors made a positive diagnosis, these were not always correct; the positive predictive value ranging from 92% for dentures or removable bridges to 25% for teeth vulnerable to fracture. It is concluded that the use of trained doctors is better than no assessment but falls short of that provided by a dentist with experience of psychiatric patients undergoing ECT.