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Background and aims Capsule endoscopy (CE) interpretation requires the review of many thousands of images, with lesions often limited to just a few frames. In this study we aim to determine whether lesion detection declines according to the number of capsule videos read. Methods 32 participants, 16 of which were novices (NR) and 16 experienced (ER) capsule readers took part in this prospective evaluation study. Participants read six capsule cases with a variety of lesions, in a randomly assigned order during a single sitting. Psychomotor Vigilance Tests and Fatigue Scores were recorded prior to commencing and then after every two capsules read. Changes in lesion detection and measures of fatigue were assessed across the duration of the study. Results Mean agreement with the predefined lesions was 48.3% (SD:16.1), and 21.3% (SD:15.1) for the experienced and novice readers respectively. Lesion detection declined amongst experienced reader after the first study (p = 0.01), but remained stable after subsequent capsules read, while NR accuracy was unaffected by capsule numbers read. Objective measures of fatigue did not correlate with reading accuracy. Conclusion This study demonstrates that reader accuracy declines after reading just one capsule study. Subjective and objective measures of fatigue were not sufficient to predict the onset of the effects of fatigue.

Background Small-bowel capsule endoscopy is advocated and repeat upper gastrointestinal (GI) endoscopy should be considered for evaluation of recurrent or refractory iron deficiency anemia (IDA). A new device that allows magnetic steering of the capsule around the stomach (magnetically assisted capsule endoscopy [MACE]), followed by passive small-bowel examination might satisfy both requirements in a single procedure. Methods In this prospective cohort study, MACE and esophagogastroduodenoscopy (EGD) were performed in patients with recurrent or refractory IDA. Comparisons of total (upper GI and small bowel) and upper GI diagnostic yields, gastric mucosal visibility, and patient comfort scores were the primary end points. Results 49 patients were recruited (median age 64 years; 39 % male). Combined upper and small-bowel examination using the new capsule yielded more pathology than EGD alone (113 vs. 52; P Conclusion Combined examination of the upper GI tract and small bowel using the MACE capsule detected more pathology than EGD alone in patients with recurrent or refractory IDA. MACE also had a higher diagnostic yield than EGD in the upper GI tract and was better tolerated by patients.

Introduction Confirmed (visual) passage of an intact Agile (Medtronic Ltd) patency device (which contains a radiofrequency (RF) tag), absence of an RF signal or failure to identify the patency device on radiological imaging 30 hours post-ingestion predicts safe capsule endoscopy. [Hererrias et al., Gastrointest Endosc 2008] Premature dissolution of the device would give false reassurance that capsule endoscopy could be performed safely. Methods Retrospective review of 2017 patency capsule database. Results RF scan was performed on 490 patients 30 hours after swallowing an Agile patency device and, if an RF signal was present, patients went for a scout film and, where indicated, limited CT scan. Premature dissolution occurred in four cases (0.8%). All had normal colonoscopies and symptoms of Crohn’s disease (two of whom had abnormal, one normal and one no prior small bowel imaging). In two, the scout films were reported normal, but a persistent RF signal prompted re-examination of the films and the identification of the RF tags. In the two later cases, the RF tag alone or with adjacent high density material (consistent with barium) was recognised as demonstrating premature dissolution. Conclusions This is the first report of premature dissolution of the Agile patency device which occurred in about 1:100 cases. If the RF signal remains 30 hours post ingestion, care should be taken to look for the RF device on radiological imaging when the intact patency device (see figure 1) is not evident. The tags may be confused with surgical clips, IUCDs, metallic items of clothing and jewellery.

Introduction Guidelines support endoscopic assessment of mucosal healing in Crohn’s disease before a change in therapy. [Gomollon, J Crohn’s Colitis 2016] A recent study has shown that the PillCam Crohn’s (PCC, Medtronic, Dublin, Ireland) has a better diagnostic yield than ileocolonoscopy [Leighton, Gastrointest Endosc 2017] and that colon capsule (for which the same bowel preparation is used) is better tolerated [Ojidu, European J Gastroenterol Hepatol, in press]. We report the first experience of PCC in routine clinical practice. Methods Data was collected prospectively in Sheffield and South Tyneside hospitals. Montreal classification was used (ileal:L1; colonic: L2; ileocolonic: L3; upper GI: L4; B1: non-stricturing/penetrating; B2: stricturing; B3: penetrating). All patients passed an Agile patency capsule (Medtronic). Results Eighteen patients (median age 35 years, 38.9% male, known Crohn’s in 83%) had PCC. Indications were: symptom assessment (77.8%), assess response to treatment (11.1%), consideration of stepping down therapy (16.7%). Patients with established Crohn’s had L1 (53.3%), L2 (13.3%), and L3 disease (33.3%) which was uncomplicated (40%), stricturing (46.7%) and penetrating (13.3%). Patients were on medical treatment in 73.3%. PCC changed staging of disease in 33% of cases (L1 to L3 n=1, B2 to B1 n=3 and B1 to B2 n=1). One of three patients with suspected Crohn’s disease subsequently had endoscopic confirmation (L3 B1). PCC was normal (5/18), revealed L1 disease alone (8/18), L2 disease alone (1/18) and L3 disease (5/18). There were three incomplete procedures, all with an otherwise normal visualised colon. No capsule retentions occurred. Follow up data was available in 11 patients. Of eight patients with symptoms, five had active disease and three no or minimal activity. Of the five, three had a step-up in treatment, one had adalimumab temporarily suspended due to a perianal abscess and management continues to be discussed in one patient on maximal medical therapy. Other causes of symptoms were sought in the patients with inactive disease. Three patients had no symptoms, one had active disease and a step up in treatment, two had no or minimal activity of whom one continued therapy due to poor prognostic factors and one was already on no treatment (PCC being performed to provide supportive evidence of a diagnosis made in childhood). No patient known to have Crohn’s has been referred for further small bowel imaging or colonoscopy. Conclusion PCC provides a single visit assessment of both small and large bowel which was useful in guiding patient management without complications.

Introduction Repeat upper gastrointestinal (GI) examination and small bowel capsule endoscopy should be considered in iron deficiency anaemia (IDA) when recurrent/refractory. Magnetically assisted capsule endoscopy (MACE) using a handheld magnet to steer the MiroCam Navi (Intromedic Ltd., Korea) capsule around the stomach followed by passive small bowel transit might satisfy both requirements as a single procedure. Methods MACE was performed in patients with recurrent/refractory IDA who were due gastroscopy (OGD). Total (upper GI and small bowel) and upper GI diagnostic yields and patient tolerance of the two modalities were compared. Assuming a diagnostic yield of 25% and 55% for OGD and small bowel capsule endoscopy (SBCE) respectively in recurrent/refractory IDA, 41 patients were needed to achieve 80% power and 5% two-sided significance. McNemar’s test was used to measure differences in paired proportions. To allow for withdrawal, 50 patients were recruited. MACE mucosal visualisation was also assessed. Results OGD was performed within 2 days (IQR=13) of MACE in 49 patients (one failed to attend for OGD; median age 64 years (IQR=13), 39% male). Combined upper and mid-gut examination using MACE and passive SBCE yielded pathology in more patients than OGD alone (32 vs 6 (CI, 0.37 to 0.69); p Conclusions Combined upper GI and small bowel examination with the MiroCam Navi yields more pathology than OGD alone in patients with recurrent/refractory IDA. MACE also has better diagnostic yield than OGD in the upper GI tract and was better tolerated.

AIM To test the feasibility and performance of a novel upper gastrointestinal (GI) capsule endoscope using a nurse-led protocol. METHODS We conducted a prospective cohort analysis of patients who declined gastroscopy (oesophagogastroduodenoscopy, OGD) but who consented to upper GI capsule endoscopy. Patients swallowed the upper GI capsule following ingestion of 1 liter of water (containing simethicone). A series of positional changes were used to exploit the effects of water flow and move the upper GI capsule from one gravity-dependent area to another using a nurse-led protocol. Capsule transit time, video reading time, mucosal visualisation, pathology detection and patient tolerance was evaluated. RESULTS Fifty patients were included in the study. The mean capsule transit times in the oesophagus and stomach were 28 s and 68 min respectively. Visualisation of the following major anatomical landmarks was achieved (graded 1-5: Poor to excellent): Oesophagus, 4.8 (± 0.5); gastro-oesophageal junction (GOJ), 4.8 (± 0.8); cardia, 4.8 (± 0.8); fundus, 3.8 (± 1.2); body, 4.5 (± 1); antrum, 4.5 (± 1); pylorus, 4.7 (± 0.8); duodenal bulb, 4.7 (± 0.7); second part of the duodenum (D2), 4.7 (± 1). The upper GI capsule reached D2 in 64% of patients. The mean video reading time was 48 min with standard playback mode and 20 min using Quickview (P = 0.0001). No pathology was missed using Quickview. Procedural tolerance was excellent. No complications were seen with the upper GI capsule. CONCLUSION The upper GI capsule achieved excellent views of the upper GI tract. Future studies should compare the diagnostic accuracy between upper GI capsule and OGD.

Introduction The development of capsule endoscopy (CE) and enteroscopy have increased the ability to investigate and treat pathology in the small bowel. We have been providing a comprehensive small bowel endoscopy service and we present our data from the last 15 years evaluating demand, diagnostic yield and impact on patient management. Method A retrospective analysis was conducted on patients who underwent CE, push enteroscopy (PE), double balloon enteroscopy (DBE) and intraoperative enteroscopy (IOE) between January 2002 and December 2016. Results A total of 5065 CEs, 569 DBEs, 327 PEs and 22 IOEs were performed over 168 months. Obscure gastrointestinal bleeding (OGB) and anaemia were the most common indications for CE (37.8%), DBE (30%) and IOE (55%). Exclusion of coeliac disease complications (26.6%) was the most common indication for PE. The majority of patients had a CE prior to DBE (83.4%) and IOE (81.8%) (p=0.0001). Fifty percent of patients had a DBE prior to IOE. The demand for CE has plateaued over the past few years compared to the demand for DBE which is rising. The demand for PE has fallen dramatically (p=0.0001). This is also true for IOE and its use is reserved only for lesions beyond the limits of DBE (p=0.0001). In 2016, for every 11 CEs performed, 1 patient underwent a DBE locally. The diagnostic yield for CE, PE, DBE and IOE were 29%, 43.9%, 53.8% and 89.5% respectively (p=0.0001). The diagnostic yield for CE has fallen over the years (p=0.0001). This is perhaps due to the lower threshold for performing CE by the referring clinicians. The diagnostic yield for CE was highest for the indication of OGB (36%) compared to Crohn’s disease (30.0%, p=0.001). This contrasts with the diagnostic yield of DBE which has risen gradually (p=0.0001). Fifteen percent of patients underwent a DBE despite a negative CE. The yield for DBE in this group of patients was only 4.3% (p=0.0001). The rate of therapeutics for DBE, PE and IOE were 29%, 20% and 77% respectively. The majority of therapeutic procedures performed were argon plasma coagulation to angioectasias and polypectomies. The complication rates were 2% for DBE, 0.9% for PE and 13.6% for IOE (p=0.004). Complications following DBE included cardiovascular events (0.2%), respiratory compromise (0.9%), pancreatitis (0.2%) and gastrointestinal bleeding following polypectomy in (0.2%). Conclusion This is one of the largest series to date comparing the clinical utility and yield of all 4 small bowel endoscopic modalities. Enteroscopy has an important role in providing further management directed by CE. In patients with a negative CE, the yield of DBE is low, hence careful patient selection is required to maximise the use of resources. Disclosure of Interest None Declared

The intracellular ileal lipid binding proteins (ILBPs) are involved in the transport and enterohepatic circulation of bile acids. ILBPs from different species show high sequence and structural homology and have been shown to bind multiple bile acid ligands with differing degrees of selectivity and positive co-operativity. Human ILBP binds bile acid derivatives in a well-characterised 2:1 ligand:protein complex, however, we show that the highly homologous rabbit ILBP (82% sequence identity) with seven conservative substitutions preferentially binds multiple conjugated deoxycholate ligands in a novel 3:1 binding mode essentially within the same beta-clam shell structure. We have extended these studies to investigate the role of the alpha-helical capping motif (residues 9-35) in controlling the dimensions of the binding cavity and ligand uptake. Substituting the alpha-helical motif (residues 9-35) with a short Gly-Gly-Ser-Gly linker dramatically affects the protein stability such that under physiological conditions the mutant (Deltaalpha-ILBP) is highly disordered. However, we show that the inability of the mutant to adopt a stable three-dimensional structure under these conditions is no barrier to binding ligands with near-native affinity. These structural modifications not only demonstrate the possibility of strong coupling between ligand binding and protein folding, but result in changes in bile acid selectivity and binding stoichiometry, which we characterise in detail using isothermal calorimetry and mass spectrometry.

Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53 ml/min per 1.73 m(2), PTH 46 pg/ml, FGF23 42 pg/ml, and 25(OH)vitamin D3 53 nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of ⩾40 ml/min per 1.73 m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status.

Substitution of the helix-turn-helix capping motif (residues 9-35) of rabbit I-BABP with a flexible Gly-Gly-Ser-Gly linker results in the loss of stabilizing hydrophobic contacts and renders the beta-clamshell structure of this steroidal bile acid transport protein unfolded. However, in the presence of a bile acid ligand, we observe strong coupling between binding and folding, resulting in an enthalpy-driven high-affinity interaction (K(A) approximately 4 x 10(5) M(-1)) that "rescues" the native state. We investigate the mechanism of induced folding using fluorescence stopped-flow kinetic measurements to distinguish between conformational selection and induced-fit models. We observe both ligand-dependent and -independent kinetic phases which, together with their relative amplitudes, we attribute to an induced-fit "fly casting" type of model in which transient encounter complexes between the ligand and the extended polypeptide chain may act as nucleation sites for folding. An initial fast ligand-dependent kinetic process appears to be consistent with formation of a hydrophobically collapsed intermediate state which slowly rearranges to a nativelike beta-clamshell structure. We show that the intermediate forms at a rate 1000 times slower than the rate of ligand association with wild-type I-BABP, reflecting the large configurational entropic barrier to the coupled binding and folding steps of Deltaalpha-I-BABP. We have provided mechanistic insights into how natively disordered states, now commonly identified in biology, may fold on binding a target substrate or ligand.