Alpesh Patel

CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis.

This study investigates the role of CD4+CD25+ regulatory T cells during the clinical course of juvenile idiopathic arthritis (JIA). Persistent oligoarticular JIA (pers-OA JIA) is a subtype of JIA with a relatively benign, self-remitting course while extended oligoarticular JIA (ext-OA JIA) is a subtype with a much less favorable prognosis. Our data show that patients with pers-OA JIA display a significantly higher frequency of CD4+CD25bright T cells with concomitant higher levels of mRNA FoxP3 in the peripheral blood than ext-OA JIA patients. Furthermore, while numbers of synovial fluid (SF) CD4+CD25bright T cells were equal in both patient groups, pers-OA JIA patients displayed a higher frequency of CD4+CD25int T cells and therefore of CD4+CD25total in the SF than ext-OA JIA patients. Analysis of FoxP3 mRNA levels revealed a high expression in SF CD4+CD25bright T cells of both patient groups and also significant expression of FoxP3 mRNA in the CD4+CD25int T cell population. The CD4+CD25bright cells of both patient groups and the CD4+CD25int cells of pers-OA JIA patients were able to suppress responses of CD25neg cells in vitro. A markedly higher expression of CTLA-4, glucocorticoid-induced TNFR, and HLA-DR on SF CD4+CD25bright T regulatory (Treg) cells compared with their peripheral counterparts suggests that the CD4+CD25+ Treg cells may undergo maturation in the joint. In correlation with this mature phenotype, the SF CD4+CD25bright T cells showed an increased regulatory capacity in vitro compared with peripheral blood CD4+CD25bright T cells. These data suggest that CD4+CD25bright Treg cells play a role in determining the patient’s fate toward either a favorable or unfavorable clinical course of disease.

Meta-analysis suggests antibiotic prophylaxis is not warranted in low-risk patients undergoing laparoscopic cholecystectomy.

Although laparoscopic cholecystectomy is associated with a low incidence of wound infection antibiotic prophylaxis is still commonly used in low-risk patients undergoing this procedure. A review of the available evidence on infective complications in laparoscopic surgery concluded that antibiotic prophylaxis could be omitted1. A meta-analysis was performed to assess whether antibiotic prophylaxis reduced the risk of wound infection and other septic complications.

Modelling of a metal-containing hepcidin

Hepcidin was originally identified as a liver-expressed antimicrobial peptide but further studies have shown that it also has a key role in iron homeostasis. The NMR structure of the synthetic peptides reveal a distorted beta-sheet containing 4 disulphide bridges, with an unusual vicinal disulphide bridge which has been suggested to be functionally significant. In this study, we report the presence of co-purified iron with the urine-purified 20 and 25 residue hepcidins. Since the published structure does not allow metal binding, the interaction of hepcidin with metals was investigated for other possible structural conformations by threading its primary sequence onto existing 3D folds. Several alignments were obtained and the best scores were used to build a 3D model of hepcidin containing one atom of iron. The new 3D structure, that contains only reduced Cys residues, is completely different from the solved structure of the synthetic peptide. Although the model presented here shows only one metal bound to the peptide, the binding of several metal atoms cannot be excluded from such a short flexible peptide. The co-purification of iron with both peptides, together with our 3D model, suggest a conformational polymorphism for hepcidin, reminiscent of the iron regulatory proteins IRPs.

Extraction of retained gallstones from an abscess cavity: a percutaneous endoscopic technique.

A novel technique to retrieve spilled gallstones in an abscess cavity with the use of minimally invasive techniques is described.

PTH-088 Non Invasive Monitoring Of Fatty Livers In Morbidly Obese Patients: Preliminary Evaluation With Acoustic Radiation Force Impulse Imaging

Introduction Liver biopsy remains the gold standard for diagnosing non-alcoholic steatohepatitis (NASH). But with a variability of 10–20% and a mortality rate of 0.01%, non invasive techniques of monitoring change in liver morphology have been sought after. Acoustic radiation force impulse imaging (ARFI) is a promising innovation that combines ultrasound imaging and elastography to measure liver stiffness which correlates well with liver fibrosis. Morbidly obese patients are at a risk of developing NASH or Non Alcoholic Fatty Liver Disease (NAFLD) and weight loss helps improve liver steatosis. Very low calorie diets (VLCD) help in weight reduction and are known to shrink the liver. Our aim was to assess the role of ARFI in assessing and monitoring the change in liver architecture in a cohort of morbidly obese patients in response to VLCD. Methods A cohort of non-diabetic morbidly obese patients at risk for NASH was selected for this study (clinical trial no: NCT01950052). Liver volume was estimated with the help of a standardised ultrasound protocol while liver fibrosis was analysed with ARFI. After randomisation, a very low calorie diet (800 kcal) was given to one group while the rest were controls. Four weeks later, ARFI was repeated and all patients underwent a laparoscopic roux-en-y gastric bypass. A liver biopsy was taken during surgery from the same liver segment as the ARFI measurements. The liver histology was evaluated according to the NASH Clinical Research Network Scoring System by two blinded pathologists. Steatosis, fibrosis and NAFLD activity scores were correlated with ARFI scores. Results Liver volume shrank by 21.5% in the diet arm (n = 10) compared to 2% (p < 0.05) in the control arm (n = 14) in 4 weeks. The ARFI scores were similar in the diet and control group [median 2.92 (1.1–3.8) m/s vs. 3.22 (1.54–3.65) m/s, p = 0.7], p = 0.7] at recruitment and at the time of the biopsy 4 weeks later [2.16 (1.19–3.68) m/s vs. 2.83 (1.5–3.48) m/s, p = 0.3]. ARFI demonstrated a drop in values in the diet group (p = 0.1) but this was not significant. Similarly, liver biopsy at surgery confirmed a trend of lower levels of steatosis in the diet group (27 vs. 42%, p = 0.12). The ARFI scores did not correlate with the steatosis grade (p = 0.8), or NAFLD score (p = 0.48). Conclusion Low calorie diets shrink liver volumes but ARFI could not detect any change in liver stiffness. ARFI does not appear to correlate with liver steatosis and may not be ideally suited for short term monitoring of successful treatment of NASH. However its role in long term monitoring needs further evaluation. Disclosure of Interest None Declared.

OC-012 Endobarrier: A Bridge To Surgery In Morbidly Obese Patients?

Introduction Bariatric surgery is the best available intervention for weight reduction in morbidly obese patients. Although outcomes are not quite comparable to surgery, an endoscopically implanted device called the Endobarrier (Endoscopic duodenojejunal bypass liner) can lead to significant weight loss and improvement of glycaemic control when compared to either dietary caloric restriction or sham procedures. Surgery may be complicated in high-risk groups like patients with poorly controlled diabetes, multiple co-morbidities or a body mass index (BMI) >50 kg/m2. We aimed to analyse the effect of an Endobarrier as an effective risk reducing tool in such high-risk patients prior to surgery. Methods All patients who underwent an Endobarrier insertion between January and October, 2013 were analysed. This included patients with poorly controlled diabetes, patients with a BMI >50 kg/m2 or those who were at a high risk of peri-operative complications based on obesity surgery mortality risk score (OSMRS: normal score 1–5). Patient outcomes which included length of stay, complications, weight loss, and impact on glycaemic control were prospectively observed. Results The Endobarrier was inserted in 18 patients (13 M) with median age of 53 years (range 32–68), median weight 159 kg (range 102–237), median BMI 54 kg/m2 (range 37–70.4) and a median OSMRS of 4 (mortality risk=2.4%). Device insertion was successful in all patients with no early removals required to date. The median length of stay was 1 day (range 1–5). There were no major complications apart from a single case of upper GI bleed 3 months later, which settled conservatively. Median weight over 3–6 months was now reduced to 147 kg (range 77–192) with median weight loss of 16.2 kg (6.9–41 kg) and 20.4 kg (9–47 kg) at 3 and 6 months respectively. Post-procedure, diabetic medication were either decreased (n = 9/11) or no longer required (n = 2/11) in diabetic patients and at 3 months HbA1C levels improved significantly from a median of 8.7 to 6.7% (p = 0.01). Conclusion Endobarrier may be used as a stepping stone to surgery in high risk patients by safely and effectively reducing weight and improving glycaemic control. Disclosure of Interest None Declared.