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Inflammatory bowel disease (IBD) is increasing in prevalence around the world.1 It can be divided into Crohn’s disease (CD), an inflammatory condition of the entire gastrointestinal tract, or ulcerative colitis, which predominantly affects the large bowel. Advances in therapy, such as anti-integrins, anti IL12/23 and particularly anti-tumour necrosis alpha biologics, have contributed to a decrease in surgical intervention.2 Unfortunately, there is a cohort of patients with a severe phenotype, who are refractory to available therapy and ultimately develop intestinal failure (IF). Risk factors which have been identified for this phenotype include a younger age at diagnosis or at first surgery, ileocolonic and perianal disease, family history, smoking and initial need for corticosteroids.3 4 In fact, a recent study has shown surgical complications (abdominal sepsis) as being the most common cause of IF in patients with CD.4 This may explain why, in combination with the development of targeted biological therapies, a study from a national IF unit found a decrease in the number of patients with IF due to CD directly and an increase in those whose aetiology was from surgical complications.5 A 40-year study from a Danish IF unit showed the number of home parenteral nutrition (HPN) patients due to IBD increased by around 30 patients a decade but reduced as percentage of total cases.6 The accepted definition of IF is “the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth”.7 IF still remains rare, with a prevalence of patients on parenteral nutrition (PN) of between 5 and 20 patients per million7 and around one-third of these patients have CD.3 IF has been defined into three types (table 1).7–9 Many …

Summary Background & aims Prevention of catheter related blood stream infections (CRBSI) and salvage of infected central venous catheters (CVC) are vital to maintaining long term venous access in patients needing home parenteral nutrition (HPN). It remains unclear as to whether patients are best trained for catheter care at home or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC. Furthermore, there is minimal data on the longer term outcome following salvage of infected catheter and limited consensus on agreed protocols for catheter salvage. Method We conducted a retrospective 5-year evaluation of CRBSI occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients were primarily trained to administer PN in hospital; thereafter, patients underwent training at home. Results A total of 134 CRBSI were recorded in 92 patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI) in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)), Klebsiella spp. (16/134 (11.9%)) and methicillin – sensitive Staphylococcus aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to methicillin – resistant (MRSA) infection (1/34), fungal infection (13/34) or clinical instability due to sepsis (20/34). Of the 100 cases where salvage was attempted, 67% were successful. 82.8% of CNS salvage attempts were successful; there was no difference in salvage rates between CNS CRBSIs salvaged with a 10-day (22/26) or 14-day protocol (7/9) (p = 0.4). CRBSI rate, in those cared for by trained home care nurses was the lowest at 0.270 (self care: 0.342 and non-medical carer (e.g. family member): 0.320) (p = 0.03). Conclusion We previously reported a sustained very low CRBSI rate in a large cohort of HPN patients in a national unit; we now further report that this is not influenced by training patients at home rather than in hospital but is influenced by the individual managing the catheter at home. CNS remains the primary cause of CRBSIs and can be successfully salvaged with a reduced duration of antibiotic therapy compared to our previous experience.

Decision-making regarding percutaneous endoscopic gastrostomy (PEG) insertion can be complex both medically and ethically. Thirty-day mortality following (PEG) insertion is an important quality indicator for endoscopy accreditation and for service evaluation. It also forms part of the measures assessed within the 'Getting It Right First Time' programme (GIRFT). We aimed to assess the impact of a newly adopted Feeding Issues MDT (FIMDT) and the clinical application of the Royal Free Gastrostomy Score (RFGS).We adopted a retrospective observational methodology to assess the impact of a feeding issues MDT within our trust. The included study period ran from January 2016 to December 2019 (4 years). This formed part of a quality improvement (QI) project initiated upon receipt of the GIRFT report for our NHS trust. Statistical analysis and QI methodology was used to interpret and present the data.Two hundred and sixty eight PEG insertions occurred during the study period. 188 PEGs were inserted prior to the start of FIMDT and 45 following its inception. On average there were 66 PEGs performed per year. There was no significant difference in age for those undergoing PEG insertion pre (68 years) and post (69 years) FIMDT adoption. Prior to FIMDT those that died within 30 days post PEG were significantly older than those who did not (p 0.001), whilst following FIMDT adoption there was no such difference. Prior to FIMDT the 30-day post PEG mortality was 10.64%, whilst following adoption of the FIMDT the mortality rate fell to 6.6% (p = 0.04). The mean number of procedures performed between a 30-day mortality occurring rose from 7.5 to 13.6. Furthermore, the mean number of days between a 30-day post insertion mortality occurring also rose from a mean of 53.0-111.8, pre and post FIMDT adoption. The Royal Free Gastrostomy Score (RFGS) for those discussed at FIMDT and declined for PEG insertion was significantly higher than those accepted for PEG insertion (p = 0.01). Over the entire study period those who died within 30 days following PEG insertion had a significantly greater RFGS (p 0.0001).In our trust the adoption of a FIMDT has significantly reduced the 30-day mortality for PEG insertion. We have also demonstrated the clinical utility to assess mortality risk of the RFGS when making decisions around patient suitability for PEG insertion.

Purpose of review The aim of this review is to give up-to-date information on intestinal failure-associated liver disease (IFALD) and how its investigation and management has evolved. Despite advances in treatment for patients with intestinal failure, IFALD remains a significant cause of mortality. Recent findings Liver biopsy remains as the gold standard for the diagnosis of IFALD, but its invasive nature has prompted assessment of noninvasive techniques. Risk factors for IFALD are both nonnutritional (e.g. sepsis) and nutritional. Strict protocols for the prevention of central venous catheter infections in patients with intestinal failure are well established, as is the optimization of the constituents of parenteral nutrition. Further research comparing the available lipid emulsions has become available. Novel approaches at maximizing intestinal absorption are discussed including glucagon-like peptide-2 analogues, as well as surgical approaches. Summary Although there are data on the novel investigative and therapeutic strategies for managing IFALD, further study is required to identify a suitable noninvasive technique for earlier diagnosis and then monitoring of IFALD. Further data are also required on the impact of novel therapies aimed at improving absorption and reducing parenteral nutrition load on IFALD occurrence and progression.

INTRODUCTION:Antitumour necrosis factor (TNF) agents and vedolizumab are used to treat ulcerative colitis (UC) but the response is variable and there is little data on comparative effectiveness. Apart from previous exposure to anti-TNF agents, predictors of response have not been identified. We aimed to (i) compare the efficacy of anti-TNF agents and vedolizumab in UC and (ii) investigate the utility of clinical and biochemical parameters in predicting response. PATIENTS AND METHODS:Patients commencing any biological therapy for ambulant UC were included. Disease activity was monitored serially with the Simple Clinical Colitis Activity Index for up to 12 months. We compared the efficacy of anti-TNF agents and vedolizumab for induction and maintenance of response and remission on an intention-to-treat basis. We examined the utility of faecal calprotectin (FC) and early normalization of FC to predict response. RESULTS:Ninety-seven patients commencing anti-TNF and 42 commencing vedolizumab therapy were included. Vedolizumab-treated patients had significantly greater previous anti-TNF therapy exposure and a lower baseline FC. Response, remission and steroid-free remission rates were comparable between both groups at 6 weeks, 6 and 12 months. Clinical remission but not steroid-free remission at 12 months was higher in the vedolizumab group. There was a significant reduction in the Simple Clinical Colitis Activity Index and FC at 6 weeks, 6 and 12 months compared with baseline in both groups. Baseline FC and early normalization did not predict response at 6 and 12 months. CONCLUSION:The efficacy of anti-TNF and vedolizumab in UC appear comparable. We could not identify any predictors of response and remission.

BACKGROUND Various physician- and patient-reported instruments exist for quantification of disease activity in inflammatory bowel diseases (IBD) but none are widely used in routine clinical practice. A simple patient-reported outcome measure might help inform clinical decision making. We evaluated a patient-reported 0 to 10 score of IBD activity (IBD-10) by correlation with conventional multicomponent activity indices. METHODS A single-center prospective cross-sectional study was conducted in ambulant patients with IBD. Patients were asked to verbally rate the control of Crohn's disease (CD) or ulcerative colitis (UC) on a numerical scale from 0 to 10, with 10 indicating perfect control. Disease activity was assessed using Harvey-Bradshaw index for CD and simple clinical colitis activity index for UC. RESULTS A total of 405 patients were included, of whom 209 (52%) had CD and 196 (48%) had UC. The median age was 41 (interquartile range, 27-55) years. IBD-10 correlated well with Harvey-Bradshaw Index (rs = -0.69, P < 0.001) and simple clinical colitis activity index (rs = -0.79, P < 0.001). An IBD-10 score of ≥7 predicted remission (defined by Harvey-Bradshaw index/simple clinical colitis activity index) with 90% sensitivity (95% confidence interval [CI], 86-94) and 75% specificity (95% CI, 67-82). The discriminatory ability of IBD-10 for remission was better for UC (area under the receiver operating characteristic curve, 0.93; 95% CI, 0.89-0.97) than for CD (area under the receiver operating characteristic curve, 0.86; 95% CI, 0.81-0.91; P = 0.035). An IBD-10 score of

Active Crohn's disease (CD) often co-exists with malnutrition and requires input from the inflammatory bowel disease multidisciplinary team in order to assess, prevent and treat the complications of both malnutrition and active disease. Three forms of nutrition therapy are available: enteral nutrition, parental nutrition and diet modification. This article will discuss the arguments for and against the use of each form of nutritional management in CD patients in order to empower health professionals caring for this patient population to initiate early nutritional support upon admission to hospital.

Background Response to the anti-tumour necrosis factor (TNF) agents and the anti-integrin-α4β7 antibody, vedolizumab, in ulcerative colitis (UC) is variable. There are few clinical predictors of long term efficacy to biological therapy apart from prior exposure to anti-TNF therapy. Identification of readily available clinical and biochemical predictors will enable better utilization of these expensive drugs. We sought to evaluate the role of clinical factors and faecal calprotectin prior to initiation of therapy in predicting steroid free remission at 1 year. Methods The case records of all patients who commenced biological therapy for UC were examined. Baseline clinical factors including disease extent, duration, smoking status, body mass index, concurrent immunomodulatory or steroid therapy and biochemical factors including C-reactive protein and faecal calprotectin were recorded. Patients with acute severe colitis were excluded. Remission was defined as simple clinical colitis activity index of Results A total of 150 patients commenced biological therapy during the study period (2014–2017). Eighteen patients (12%) were excluded from the final analysis (Adverse reactions, N=5, 3.3%, Surgery, N=6, 8%, and data unavailable, N=7, 4.6%). After exclusion, a total of 98 patients commenced anti-TNF therapy (37 infliximab, 14 golimumab and 12 adalimumab) and 34 commenced vedolizumab. Twenty-three (23.5%) of the anti-TNF treated and 16 (47%) of vedolizumab treated patients were in steroid free remission at 12 months. Forty-seven patients had extensive colitis and 4 patients were active smokers. A baseline calprotectin of >500 µg/g was associated with a lower probability of remission to vedolizumab (OR 0.23, 95% CI 0.05 to 0.98, P Conclusions A raised basal calprotectin was associated with a lower probability of steroid free clinical remission with both anti-TNF and anti-integrin biological therapy in UC. None of the other clinical variables including BMI at baseline predicted steroid free clinical remission at 1 year.

Introduction The response to the anti-integrin-α 4 β 7 antibody, vedolizumab, is variable in both Crohn’s disease and ulcerative colitis. Apart from prior exposure to anti-TNF agents, there are very few clinical predictors of response to vedolizumab therapy. Previous studies have shown that clinical and biological variables such as body mass index (BMI), baseline disease activity and concurrent immunosuppression influence response to anti-TNF agents but such data are not available for vedolizumab. We sought to evaluate the role of clinical and biological variables as predictors of response to vedolizumab. Methods We conducted a retrospective single centre retrospective cohort study of all patients commencing vedolizumab therapy. Clinical response was defined as a reduction of 3 points from baseline for Harvey-Bradshaw index (HBI) and 2 points for simple clinical colitis activity index (SCCAI). Clinical remission was defined as HBI Results A total of 95 patients commenced vedolizumab therapy during the study period (2014–17). Of these, 11 patients (11.5%) had recently commenced therapy and a further 20 patients (21%) were excluded (Surgery, n=4, adverse reaction, n=4, primary non-response, n=5 and insufficient data, n=7). Of these, 64 patients had disease activity data at 6 months and 45 patients at 12 months. The pooled steroid free remission rates at 6 and 12 months were 45% and 32% respectively. Baseline clinical factors including BMI, smoking status, concurrent immunomodulatory or steroid therapy were not associated with steroid free remission at 6 and 12 months. Prior anti-TNF failure did not influence clinical remission at 6 months (OR 0.7, 95% CI 0.26–1.88, p=0.4) or 12 months (OR 1.24, 95% CI 0.44–3.46, p=0.6). Patients with UC were more likely to be in steroid free remission at 6 (OR 2.45, 95% CI 0.89–6.74, p=0.08) and 12 months (OR 3.5, 95% CI 1.2–10.6, p=0.02). Neither baseline calprotectin nor a reduction in calprotectin at 2 months predicted steroid free remission at 6 or 12 months. Conclusions In a mixed IBD cohort treated with vedolizumab, patients with UC were more likely to be in steroid free remission at 6 and 12 months. None of the other clinical and biological variables were associated with steroid free remission.

Summary Background & aims Patients with systemic sclerosis may develop intestinal failure requiring home parenteral nutrition. However, few outcome data have been reported. This study aimed to review the outcome of patients with systemic sclerosis receiving home parenteral nutrition. Methods Records of all patients with systemic sclerosis who commenced home parenteral nutrition, at a national intestinal failure unit were retrospectively reviewed. Disease characteristics, survival and outcome data were evaluated. Results Twenty five patients (20% male; median age: 55 years) were included over a 22-year period (37,200 central venous catheter days). All patients had small intestinal involvement. Prior to home parenteral nutrition, 16 failed enteral feeding. Nine patients were trained to self-administer their home parenteral nutrition; carers/relatives were trained for the remainder. Cumulative survivals on home parenteral nutrition at 2, 5 and 10 years were 75%, 37%, and 23%. Sixteen patients died from causes unrelated to home parenteral nutrition. Two patients were weaned off home parenteral nutrition. Seven patients survive on home parenteral nutrition (median: 41 months; range 9–178). Central venous catheter-related complications were low; these included occlusion (0.70 episodes per 1000 central venous catheter days), sepsis (0.19 episodes per 1000 central venous catheter days) and central venous thrombosis (0.11 episodes per 1000 central venous catheter days). Conclusions This is the longest, largest reported series of patients with systemic sclerosis receiving home parenteral nutrition. It shows that home parenteral nutrition can be used safely and effectively in patients with very severe systemic sclerosis-related gastrointestinal involvement.

Introduction: Optimal levels of the thiopurine metabolite, 6-thioguanine nucleotides [6-TGN] correlate with remission of inflammatory bowel disease [IBD]. Apart from variations in the thiopurine methyl transferase [TPMT] gene, little is known about other predictors of 6-TGN levels. Obesity adversely affects response to infliximab and adalimumab and clinical course in IBD, but little is known about the interaction of thiopurines and obesity. We investigated the relationship between body mass index [BMI] and 6-TGN levels and sought to examine other predictors of 6-TGN levels. Methods: This retrospective cohort study included patients with concurrent measurements of 6-TGN and BMI. The association between 6-TGN and clinical variables including BMI was estimated using a multivariable linear regression model. Results: Of 132 observations, 77 [58%] had Crohn’s disease and 55 [42%] ulcerative colitis. BMI, smoking, and TPMT levels were associated with 6-TGN levels in multivariable analysis. Every 5kg/m2 increase in BMI was associated with an 8% decrease in 6-TGN (0.92; 95% confidence interval [CI] 0.87–0.98; p = 0.009). Smokers had higher 6-TGN levels in comparison with non-/ex-smokers [1.43; 95% CI 1.02–2.02; p = 0.041]. Patients with intermediate TPMT had higher 6-TGN compared to those with normal levels [2.13; 95% CI 1.62–2.80; p < 0.001]. Obese patients were more likely to have sub-therapeutic 6-TGN levels and a higher methyl mercaptopurine nucleotide [MMPN/TGN] ratio despite a similar dose of thiopurines. Conclusions: Active smoking and intermediate TPMT values were associated with higher 6-TGN levels but increasing BMI resulted in lower 6-TGN and higher MMPN levels. This may explain the worse outcome that has been reported previously in obese IBD subjects.

Patients with chronic intestinal failure are dependent on parenteral nutrition (PN) to maintain health and preserve life. Maintaining safe vascular access is vital to prevent life-threatening complications such as catheter-related bloodstream infection or central venous occlusion. Dedicated central venous catheters with rigorous catheter care aseptic protocols are vital in obtaining good long-term outcomes that allow continuation of PN over many years. Good catheter care requires an experienced multidisciplinary team using appropriate vascular devices, trained to identify and aggressively treat catheter-related bloodstream infections, catheter occlusions, and catheter-related thrombosis. Consideration must also be given to evolving strategies to prevent recurrent infections, including prophylactic central venous catheter locks.

Malnutrition can be characterized as the condition that develops as a result of inadequate or unbalanced intake of nutrients, vitamins and minerals or their impaired assimilation or utilization. This can result from undernutrition, a lack of uptake or intake of nutrition or overnutrition, which results from the overconsumption of nutrients and food, leading to adverse health effects and poor clinical outcomes.

Chronic radiation enteritis (RE) has been reported in up to 20% of patients receiving pelvic radiotherapy and can lead to intestinal failure (IF), accounting for 3.9% of new registrants for home parenteral nutrition (HPN) in the UK annually. Our aim is to report nutritional and survival outcomes for patients with RE referred to a national IF unit. A retrospective study of all new admissions over a 13-year period at the Intestinal Failure Centre, Manchester, UK. Data are presented as median (range). Twenty-three (3.8%) of 611 patients were admitted with IF secondary to RE. The primary site of malignancy was genitourinary in 17 (74%) patients. Radiotherapy was administered 9.5 (1–42) years previously. Patients underwent 2 (1–5) laparotomies prior to intestinal failure unit (IFU) admission. Twelve (52%) patients were admitted with intestinal obstruction and 11 (48%) with intractable weight loss and/or high output fistulae/stomas. Additional conditions contributing to IF were noted in 11 (48%) patients. Twenty-two (96%) patients had 2 (1–5) laparotomies prior to IFU referral. At discharge, 5 (22%) patients resumed oral diet without the need for artificial nutrition support, 3 (13%) required enteral feeding and 13 (56%) commenced HPN. The 10-year survival of the patient cohort was 48.2%. Surgical intervention is infrequently required, whereas the majority of patients with IF secondary to RE require long-term HPN. The judicious use of surgery in selected patients, coupled with an aggressive medical strategy to detect and treat contributing factors, and optimal enteral feeding may allow a modest proportion of patients with IF secondary to RE to achieve independence from PN.

Background: The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been shown to be overexpressed in a variety of different tumour types. Methods: We have used a combination of RT–PCR, western blotting, tissue microarrays and metadata analysis of microarray data to study whether the FOXM1-PLK1 regulatory axis is upregulated and operational in oesophageal adenocarcinoma. Results: FOXM1 and PLK1 are expressed in oesophageal adenocarcinoma-derived cell lines and demonstrate cross-regulatory interactions. Importantly, we also demonstrate the concomitant overexpression of FOXM1 and PLK1 in a large proportion of oesophageal adenocarcinoma samples. This co-association was extended to the additional FOXM1 target genes CCNB1, AURKB and CKS1. In a cohort of patients who subsequently underwent surgery, the expression of several FOXM1 target genes was prognostic for overall survival. Conclusions: FOXM1 and its target gene PLK1 are commonly overexpressed in oesophageal adenocarcinomas and this association can be extended to other FOXM1 target genes, providing potentially important biomarkers for predicting post-surgery disease survival.

Summary Background Home parenteral nutrition (HPN) is the mainstay of treatment for patients with Type 3 intestinal failure (IF), however long term data on mortality and nutritional outcomes are limited. Objectives To assess the long-term survival and requirements for ongoing HPN in patients receiving treatment at a UK national referral centre for intestinal failure. Methods Patients with IF who received HPN for more than 3 months at this Intestinal Failure Unit between 1978 and 2011 had their clinical records reviewed. SPSS 20 was utilised to perform Cox regression analysis and generate Kaplan Meier curves, with the aim of identifying factors associated with death and the continued need for HPN. Results Case notes from 545 patients were reviewed. Overall survival (OS) in patients without malignancy at commencement of IF was 93%, 71%, 59% and 28% at 1, 5, 10 and 20 years after starting treatment. Crohn's disease, mesenteric ischaemia and chronic intestinal pseudo-obstruction were associated with a better OS than scleroderma and radiation enteritis on multivariate analysis. Older age at onset of IF was associated with poor OS, while shorter small bowel length or central line sepsis was not. 15% (25/170) of deaths were due to complications of HPN (central line sepsis = 10, IF-associated liver disease = 15). Continued HPN dependence in survivors was 83%, 63%, 59% and 53% at 1, 5, 10 and 15 years, respectively. Among the 153 patients without malignancy who achieved nutritional independence from HPN, 77 (50.3%) did so after surgical reconstruction of the alimentary tract (HPN duration mean 19 months, range 3–126 months). 76 patients (49.7%) weaned from HPN without undergoing surgical reconstruction. Conclusion This is the largest reported data set on long-term survival and dependence on HPN and will inform the indications, benefits and risks of treatment in disease specific groups. A significant proportion of patients achieved nutritional autonomy without surgical intervention.

Catheter-related bloodstream infections (CRBSIs) are a serious complication in the provision of home parenteral nutrition (HPN). Antibiotic salvage of central venous catheters (CVCs) in CRBSI is recommended; however, this is based on limited reports. We assessed the efficacy of antibiotic salvage of CRBSIs in HPN patients.All confirmed CRBSIs occurring in patients receiving HPN in a national intestinal failure unit (IFU), between 1993 and 2011, were analyzed. A standardized protocol involving antibiotic and urokinase CVC locks and systemic antibiotics was used.In total, 588 patients were identified with a total of 2134 HPN years, and 297 CRBSIs occurred in 137 patients (65 single and 72 multiple CRBSIs). The overall rate of CRBSI in all patients was 0.38 per 1000 catheter days. Most (87.9%) infections were attributable to a single microorganism. In total, 72.5% (180/248) of CRBSIs were salvaged when attempted (coagulase-negative staphylococcus, 79.8% [103/129], Staphylococcus aureus, 56.7% [17/30]; polymicrobial infections, 67.7% [21/30]; and miscellaneous, 66.1% [39/59]). CVC salvage was not attempted in 49 episodes because of life-threatening sepsis (n = 18), fungal infection (n = 7), catheter problems (n = 20), and CVC tunnel infection (n = 4). Overall, the CVC was removed in 33.7% (100/297) of cases. There were 5 deaths in patients admitted to the IFU for management of the CRBSI (2 severe sepsis at presentation, 3 metastatic infection).This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol.

Anaemia is a common manifestation in inflammatory bowel disease (IBD) and impairs quality of life. Anaemia in IBD is typically caused by iron deficiency or anaemia of chronic disease. Treatment of iron deficiency with oral iron may lead to gastrointestinal intolerance though this may be related to the dose of iron replacement. New intravenous formulations have emerged which allow safe, rapid and effective correction of iron deficiency in IBD. In this article, we provide a review on the topic and cover recent progress in the field for the practicing gastroenterologist.

Introduction Immunogenicity is a common problem associated with anti-tumour necrosis factor (TNF) therapy and is often associated with loss of clinical response. Concomitant immunomodulatory therapy reduces the rate of anti-drug antibody (ADA) formation with infliximab and is associated with better outcomes. 1 However, the impact of immunomodulator initiation specifically to reverse established ADA has not been adequately investigated. Current guidelines recommend switching of anti-TNF agent or class switch in the presence of ADA titre >9 u/ml. However, outcomes with further biologics are poor and reversal of ADA may be preferable. We report the successful reversal of very high titre ADA with immunomodulator initiation. Methods This was a retrospective study of patients with established ADA on infliximab or adalimumab monotherapy, in whom an immunomodulator was commenced. Levels of ADA and trough levels of drug were monitored by ELISA (Theradiag). Results Four patients were included (3 Crohn’s disease and 1 ulcerative colitis), of which two patients were receiving infliximab and 2 adalimumab. There were 3 males and 1 female with a mean age of 50 years (SD ±17.6). All patients had initial titres of ADA > 200 ng/ml for infliximab and >160 ng/ml for adalimumab, with undetectable trough levels ( Conclusion In patients undergoing monotherapy with anti-TNF treatment who develop ADA, the addition of an immunomodulator agent has the potential to reverse even high antibody titres and regain clinical response. This strategy is particularly useful as the risk of ADA with a subsequent anti-TNF is higher in patients with ADA to one anti-TNF agent[2]. References 1 Ruffolo C, Scarpa M, Bassi N. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 363 :1086–8. doi:10.1056/NEJMoa0904492 2 Frederiksen MT, Ainsworth MA, Brynskov J, Thomsen OO, Bendtzen K SC. Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD. Inflamm Bowel Dis 2014; 20 :1714–21. Disclosure of Interest None Declared

Introduction Concern has been raised as to the risk of malignancy in patients with inflammatory bowel disease related to their exposure to ionising radiation from diagnostic tests. A meta-analysis has reported that 8.8% of patients with inflammatory bowel disease were exposed to potentially harmful levels of diagnostic medical radiation (DMR) (defined as greater than 50 milli-sieverts (mSv)). 1 Patients requiring anti-TNF treatment for management of their disease may be at greatest risk of exposure to diagnostic medical radiation by virtue of their disease activity. AIM To determine the prevalence of exposure to a potentially harmful dose of DMR in patients receiving anti-TNF treatment and to determine predictors of high exposure. Method A retrospective review of patients receiving anti-TNF agents for IBD in a tertiary referral centre between 2005 and 2012 was undertaken. Logistic regression was used to identify predictors of exposure to a potentially harmful cumulative effective dose (CED) of >50 mSv in patients with Crohn’s disease. Variables considered as potential predictors of a harmful CED included elements of the Montreal classification of disease (site and behaviour of disease and presence of perianal disease), age and sex. Results A cohort of 149 patients was identified. The median age was 36 (range 18 to 72 years). 135 patients had Crohn’s disease. 1137 diagnostic procedures associated with exposure to ionising radiation were performed. The median CED was 10.72mSv (Range 0 to 146). 12% of all IBD patients received a potentially harmful CED of >50 mSv. In patients with Crohn’s disease, 9.6% received a CED of > 50mSv. Logistic regression failed to demonstrate a significant association between a CED of > 50mSv and the variables assessed. Abdominal CT scans accounted for 69% of the CED. During the study period the ratio of abdominal MR scans to abdominal CT scans was 1:24 and 2:3 in the first and last quartile of the study period, respectively. Conclusion 12% of IBD patients receiving anti-TNF agents for IBD in a tertiary setting received a potentially harmful dose of ionising radiation from diagnostic imaging. This was largely related to abdominal CT scans. The temporal trend towards a greater use of non-ionising radiation for diagnostic imaging in this group is therefore reassuring. Disclosure of interest None Declared. Reference Chatu et al . Aliment Pharmacol Ther. 2012;35:529

Introduction QUOTE-IBD is a validated patient questionnaire that assesses the quality of health care provision in inflammatory bowel disease (IBD) from the patient’s perspective. 1 A series of questions assess health care within eight domains. Each patient scores elements of their health care according to: 1) The importance of that aspect of health care to them, and 2) Their experience as to how well that aspect of the service is delivered. The QUOTE instrument combines the “Importance” and “Performance” scores to generate a “Quality Impact” (QI) score for each domain (range 0 to 10). A QI of less than 9.0 indicates that there is room for improvement. Patients scored health care provision for specialist clinics and GP attendances separately. Aim To assess the quality of health care provision from the IBD service in a tertiary centre from patients’ perspective. Method The QUOTE-IBD questionnaire was given to consecutive patients in three consecutive IBD clinics. Data were analysed as described by van der Eijk et al . 1 Results 149 consecutive patients were invited to complete the QUOTE-IBD questionnaire with a response rate of 98.7%. 59 patients (40.1%) indicated that they had a diagnosis of Crohn’s disease, and 49 patients (33.3%) a diagnosis of ulcerative colitis (33.3%). 39 patients (26.6%) did not indicate an IBD-subtype. Specialist clinics and GP services had QI scores of > 9.0 for accommodation and cost, with specialist clinics also scoring >9.0 for courtesy. Overall there was a trend for specialist-led clinics to have higher QI scores than GP-based services for IBD care. With the exception of one domain, all QI scores were >8.0. The aspect of health care rated lowest for quality provision was in the domain of provision of information. Subjective feedback supported this latter observation, with requests for information on diet as a common theme. Conclusion Patients attending a tertiary IBD service express a high level of satisfaction with their health care. Feedback indicates areas where there is room for improvement, with provision of information deemed the area requiring greatest focus. (Patient information packs have been developed in partnership with the patient panel.) The QUOTE-IBD tool is a valuable resource to enhance patient-centred improvement in the quality of health care in IBD. Disclosure of interest None Declared. Reference van der Eijk et al . Am J Gastroenterol. 2001;96:3329

Introduction Inflammatory bowel disease (IBD) often requires long term immunosuppressive therapy with thiopurines such as azathioprine (AZA) or mercaptopurine (MP) and anti-tumour necrosis factor (TNF) agents. Despite the variable response to thiopurines and anti-TNF agents, few predictive factors of response have been identified. A lower body mass index (BMI) has been associated with a better outcome for azathioprine therapy, infliximab and adalimumab. Obese IBD patients are more likely to have active disease or be hospitalised. This study examined the association between weight and thiopurine therapy by examining 6-thioguanine nucleotide (6-TGN) levels. Methods We conducted a retrospective analysis of patients who were treated at the Royal Liverpool University Hospital with a thiopurine. The dose of thiopurines was adjusted as tolerated to a maximum of 2.5 mg/kg for AZA and 1.5 mg/kg for MP. Eligible patients had a 6-TGN measurement with their height and weight recorded at the same time. Associations between 6-TGN, BMI, weight, patient demographics and biochemical indices were estimated using a multivariable linear regression model. Body fat index was calculated as described previously. All tests were declared statistically significant if p Results 106 patients (48 male, 58 female) were included and contributed 133 measurements. 55% had Crohn’s disease and 45% had ulcerative colitis. 91% were on AZA and 9% were on MP. After adjustment, a one kilogram increase in weight was associated with a 1.62 unit decrease in 6-TGN levels (95% CI: 0.40 to 2.82, p = 0.0094). Body fat index correlated strongly with weight for both males and females (0.8345 and 0.8860 respectively) and a significant difference was found between BFI for each sex (p Conclusion 6-TGN levels decreased significantly with increasing weight and BMI despite a similar weight based dosing. This may explain the previously noted adverse outcomes in obese IBD subjects and underscores the importance of thiopurine metabolite testing Disclosure of Interest S. Subramanian Speaker bureau with: Speaker honoraria from Warner Chilcott, Shire, MSD, Abbvie and Almirall, Conflict with: Conference support from Abbvie, MSD and Warner Chillcott, S. Poon: None Declared, A. Kneebone: None Declared, R. Asher: None Declared, R. Jackson: None Declared, B. Gregg: None Declared, P. Collins: None Declared, C. Probert: None Declared, M. Dibb: None Declared.

Introduction Home parenteral nutrition (HPN) is an essential treatment modality for patients with Type 3 intestinal failure (IF), but long term data on the factors associated with HPN dependence and survival are limited. Methods Medical records of patients with IF who received HPN for more than 3 months from a national IF Unit between 1978 and 2011 were reviewed. Kaplan–Meier curves and Cox regression analysis were performed to identify factors associated with HPN dependence and poor prognosis. Results Case notes of 547 patients were reviewed. The overall probability of survival was 89%, 67%, 58% and 27% at 1, 5, 10 and 20 years after starting treatment. Multivariate analysis demonstrated an association between diagnosis and survival; Crohn9s disease, mesenteric ischaemia and pseudo-obstruction were associated with a better outcome. There was also an association with increasing age at IF diagnosis and poor outcome. There was no association between small bowel length or the occurrence of catheter-related infection and survival. 14.7% (25/170) of deaths were related to HPN complications. Line sepsis and IF-associated liver disease were considered to be the cause of death in 10 and 15 patients respectively (mean survival of these patients: 67 months (range 6–223); 32% within the first 2 years of treatment). Continued HPN dependence in survivors was 83%, 63%, 59% and 53% at 1, 5, 10 and 15 years respectively. 80% of those who achieved nutritional independence from HPN did so within the first 7 years of treatment. Surgical reconstruction resulted in a shorter period of HPN dependence than adaptation and/or medical therapies (19.8 vs 32.8 months respectively) p=0.008. On multivariate analysis, mechanism of IF was significantly associated with the likelihood of HPN independence: patients with gastro-intestinal dysmotility or malabsorption were less likely to achieve HPN independence, whereas those with short bowel syndrome with or without enterocutaneous fistula were more likely achieve HPN independence. Of the latter group, patients with a small bowel length >150 cm were 3.5× more likely to achieve nutritional independence compared to those with Conclusion This is the largest reported long-term experience of survival and dependence on HPN and will inform future decisions about evolving alternative therapies for type 3 IF, such as small bowel transplantation and lengthening. Nutritional autonomy can be achieved in a significant proportion of patients through adaptation, medical treatment of underlying disease and/or surgical reconstruction. Competing interests None declared.

Introduction Catheter-related blood stream infections (CRBSI) are a serious and life-threatening complication in the provision of HPN. European guidelines recommend antibiotic salvage of central venous catheters (CVCs) with CRBSI, wherever possible, to minimise repeated catheter replacement and preserve venous access, but this is based on limited reported evidence. 1 Methods Data were analysed from a prospectively-maintained register of all confirmed CRBSIs occurring in patients on HPN since January 1993 to December 2011, managed in a National Intestinal Failure Unit (IFU). Diagnosis of a CRBSI was based on quantitative and qualitative assessment of central and peripheral blood cultures and pour plates. Treatment was commenced according a standardised protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration. Results A total of 299 CRBSIs occurred in 138 patients (66 single CRBSI, 72 multiple CRBSI) with 377 patients having no catheter infections. The mean number of catheter days prior to developing an infection was 712 (range 5–6128). This represents an overall rate of infection in all patients of 0.39 per 1000 catheter days. A single microorganism caused 87.9% of infections, most commonly coagulase negative staphylococcus (CNS; 49.5% cases). Overall catheter salvage was achieved in 62.2% (intention to treat) of all patients presenting with CRBSIs (Coagulase negative staphylococcus 70.5% (105/149), MRSA 36.4% (4/11), polymicrobial infections 58.3% (21/36), other Staphylococcus aureus 48.3% (14/29) and miscellaneous 56.8% (42/74)). Line salvage was not attempted in 46 patients because of life-threatening sepsis (n=18), fungal line infection (n=7), mechanical catheter problems (eg, co-existing line fracture; n=18) and tunnel line infection (n=3). The catheter was removed in 37.7% (95/299) of cases. There were five deaths in patients admitted to the IFU for management of the CRBSI. Conclusion This is the largest reported series of catheter salvage in CRBSIs and demonstrates that catheter salvage according to a standardised protocol is a safe and effective strategy to preserve essential venous access in patients dependent on HPN. Competing interests None declared. Reference 1. Pittiruti M , Hamilton H, Biffi R, et al. ESPEN guidelines on parenteral nutrition: central venous catheters (access, care, diagnosis, and therapy of complications). Clin Nutr 2009; 28 :365–77.

INTRODUCTION: Screening for LTB is mandatory before starting therapy with Tumor Necrosis Factor (TNF) alpha inhibitors. Recently, a whole blood interferon gamma assay (QuantiFERON®) emerged as additional test for screening of LTB usually consisting of tuberculin skin test (TST) and chest X-ray. However, in patients with immunosuppression (IS) both tests might show limitations. AIMS & METHODS: We aimed to compare results from QuantiFERON®, TST and chest X-ray in consecutive IBD patients with or without IS with the indication of anti TNF alpha therapy. Signs indicative of LTB from chest x-ray included granuloma, bihilar lymphadenopathy and pleura scarring. TST was assessed positive if induration ≥5mm appeared after 48-72h of intracutan application of tuberculin /2 units in 0,1ml/ in immunosuppressed and ≥10mm in all other IBD patients. QuantiFERON® was positive if quantitative measurement indicated ≥ 0,35 U/ml. In pts under IS type, dose, and duration of therapy were obtained. RESULTS: In 145 patients all three tests for LTB were performed. QuantiFERON® test failed on samples from 15/145 (10.3%) patients, resulting in 130/145 (89.7%) patients on whom results from all 3 screening tests were available. There were 109 pts (75.2%) with and 36 (24.8%) without IS. Seventy-six patients (52.4%) were under maintenance AZA/6-MP, 49 (33.7%) under steroids ≥10mg daily for ≥ 2weeks and 16 subjects (11%) received infliximab within a median of 8 (6-16) weeks previously. The impact of IS therapy on TST and QuantiFERON® is shown in the table. The median TST induration was 2.11 mm (±5.2) for the entire study population, 2.07 mm (±5) in pts with and 2.22mm in pts without IS (±5.7) (p=0.882), respectively. Among subjects with positive TST median induration was 12.5 mm (±5.3) in IS patients (n=17) and 16mm (±2.4) in pts without IS (n=5, p=0.058). There was a higher rate of positive QuantiFERON® results in patients without IS (p=0.036). CONCLUSION: Our results reveal significant influence of IS on single TST and QuantiFERON® results in IBD patients undergoing screening for LTB and suggest an underestimation of the actual rate of LTB. Therefore, LTB screening might be best performed before IS treatment.

Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world. Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle. A large international effort has led to the development of a large number of inhibitors, which target cell cycle kinases, including cyclin-dependent kinases, Aurora kinases and polo-like kinase. Initial phase I/II trials in solid tumors have often demonstrated only modest clinical benefits of monotherapy. This may relate in part to a failure to identify the patient populations that will gain the most clinical benefit. Newer compounds lacking the side effect profile of first-generation compounds may show utility as adjunctive treatments targeted to an individual’s predicted response to treatment.

BackgroundGastric cancers present late in life with advanced disease and carry a poor prognosis. Polo-like Kinase 1 (PLK1) is a mitotic kinase with regulatory functions during G2/M and mitosis in the cell cycle. In mammalian cells, there is an intricate co-regulatory relationship between PLK1 and the forkhead transcription factor FOXM1. It has been demonstrated that individually either PLK1 or FOXM1 expression predicts poorer survival. However, the co-expression of both of these markers in gastric adenocarcinomas has not been reported previously.MethodsWe aimed to assess the expression of PLK1 and FOXM1 in Gastric adenocarcinomas in a Western Population, to examine whether there is a relationship of PLK1 to FOXM1 in cancer samples. We assess both the protein and mRNA expression in this patient population by Tissue Microarray immunohistochemistry and RT-PCR.ResultsImmunohistochemistry was performed on biopsy samples from 79 patients with gastric cancer. Paired normal controls were available in 47 patients. FOXM1 expression was significantly associated with gastric adenocarcinoma (p = 0.001). PLK1 and FOXM1 co-expression was demonstrated in 6/8 (75 %) tumours when analysed by RT-PCR. FOXM1 is overexpressed in a large proportion of gastric carcinomas at the protein level and FOXM1 and PLK1 are concomitantly overexpressed at the mRNA level in this cancer type.ConclusionsThis study has demonstrated that FOXM1 and its target gene PLK1 are coordinately overexpressed in a proportion of gastric adenocarcinomas. This suggests that chemotherapeutic treatments that target this pathway may be of clinical utility.