Martyn Dibb

Central Venous Catheter Salvage in Home Parenteral Nutrition Catheter-Related Bloodstream Infections Long-Term Safety and Efficacy Data

BACKGROUND 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSIONS This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol.

Body Mass Index and Smoking Affect Thioguanine Nucleotide Levels in Inflammatory Bowel Disease

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 Crohns disease and 55 [42%] ulcerative colitis. BMI, smoking, and TPMT levels were associated with 6-TGN levels in multivariable analysis. Every 5kg/m(2) 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.

OC-034 Salvage of central venous catheters in HPN catheter-related blood stream infections is safe and effective: 18 years experience from a national centre

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.

Radiation enteritis leading to intestinal failure: 1994 patient-years of experience in a national referral centre

Background/Objectives: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.Subjects/Methods: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).Results: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%.Conclusions: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.

Home Parenteral Nutrition: Vascular Access and Related Complications

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.

Long-term outcome of patients with systemic sclerosis requiring home parenteral nutrition

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.

Validation of a Simple 0 to 10 Numerical Score (IBD-10) of Patient-reported Inflammatory Bowel Disease Activity for Routine Clinical Use.

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 Crohns 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 <7 correlated with treatment escalation. Conclusions:The IBD-10 score correlates well with more complex clinical activity indices. Correlation was less strong for CD than for UC, possibly reflecting a weaker link in CD between stool frequency and the patient perspective of disease activity. The IBD-10 score could readily be used in routine clinical practice.

PWE-078 Mean Corpuscular Volume But Not Lymphocyte Count Is A Predictor Of Thiopurine Dose Adequacy And Toxicity

Introduction The thiopurines, azathioprine (AZA) and mercaptopurine (MP), commonly used in the treatment of inflammatory bowel diseases (IBD), are typically dosed according to patient’s body weight. A previous meta-analysis showed higher remission rates in patients with “therapeutic” levels of 6-thioguanine (6-TGN), but weight based dosing correlates poorly with 6-TGN levels (1). 6-TGN testing is not universally available, results are not available immediately and repeated measurements are necessary to ensure dose adequacy and adherence to therapy. Proxy measures such as mean corpuscular volume (MCV) and lymphocyte count (LC) have been advocated as markers of dose adequacy. We aimed to analyse the relationship between 6-TGN levels, MCV, LC and other putative surrogate markers of therapeutic 6-TGN levels. Methods This retrospective study was conducted at the Royal Liverpool University Hospital. All patients who had concurrent measurements of 6-TGN and full blood count were included in the analysis. 6-TGN levels were classed as sub-therapeutic (<230), therapeutic (230–450) or supra-therapeutic (>450). The association between 6-TGN, patient demographics, MCV, LC and other putative surrogate markers was estimated using a multivariable linear regression model for continuous 6-TGN and a proportional odds logistic regression model for the ordered 6TGN levels. All results were declared statistically significant if p < 0.05. Results A total of 106 patients (48 male, 58 female) were included and contributed 133 measurements. Of these patients 58 (55%) had Crohn’s disease and 47 (44%) had ulcerative colitis. The mean azathioprine dose was 123.5 mg (SD 73.8) or 1.70 mg/kg (SD 0.67). After adjusting for other variables, a one unit increase in MCV, was associated with a 10.88 unit increase in 6TGN levels, Figure 1 (95% CI: 7.63 and 14.014, p < 0.0001) and a one unit increase in ALT was associated with a 2.67 unit decrease in 6TGN levels (95% CI: 0.36 to 4.97 p = 0.0237). There was no correlation between LC, NC, WCC or ALKPHOS and 6-TGN levels. Conclusion MCV and 6-TGN nucleotide levels increase together. If 6-TGN levels are not available, MCV can be used as a crude but imperfect surrogate marker of dose adequacy and toxicity. Reference Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006;130:1047–53 Disclosure of Interest None Declared.

Anaemia in inflammatory bowel disease

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.

Su1306 Central Venous Catheter Salvage in HPN Catheter-Related Blood Stream Infections Safety and Efficacy Data From a National Centre

Background/aim: Nonalcoholic fatty liver disease (NAFLD) is considered to be the most common liver disorder in western countries, with a rising prevalence. NAFLD is strongly associated with the presence and severity of obesity, but there is to date no convincing medical therapy. Thus, weight reduction is still the first-line therapy for NAFLD patients. The aim of this study was to evaluate the efficacy of Optifast 52, a commercial interdisciplinary weight loss program, with special emphasis on the adipokines leptin and adiponectin in NAFLD patients. Methods: A total of 72 participants with a BMI of higher than 30 kg/m2 were included. Participants attended weekly over the course of 52 weeks for medical assessment, physical activity, dietary counseling and psychological support. Laboratory values were determined and bioelectrical impedance analyses (BIA) of body composition performed at baseline, and after 26 and 49 weeks. Assessment of NAFLD was carried out using noninvasive parameters: the NAFLD fibrosis score and the BARD score. Results: Of the 72 participants, 42 completed the Optifast program. Initial weight was reduced significantly from 121.1(± 24)kg to 96.3(± 21.9)kg (p=0.0005). Thus, BMI fell from 41.3(± 6.9)kg/m2 to 32.8(± 6.5)kg/m2 and fat mass was reduced from an initial 54.5(± 13.3)kg to 35(± 13.2)kg. The AST/ALT ratio improved with weight loss from 1.17(± 0.5) to 0.83(± 0.26). At baseline, 69% of patients were found to have a pathological AST/ALT ratio, compared to only 24.1% at week 49. The NAFLD score improved from -0.11(± 1.3) to -1.1(± 1.3) on study completion, where a score of -1,455 indicates that liver fibrosis can be excluded. Thus, at the beginning of the study, 14.3% of participants were at low risk of fibrosis, while 28.6% were at high risk. This changed to 39.3% and 3.6% at week 49, respectively. The BARD score improved significantly from 3.5(± 0.87) (baseline) to 2.6(± 1.1) (week 49), coincidentally with an improvement of the leptin/adiponectin ratio from initial 1.16(±0.96) to 0.31(±0.25) (p=0.0005). Conclusion: These data clearly demonstrate the Optifast 52 interdisciplinary weight reduction program to effectively reduce not only liver parameters, but also scores for estimating NAFLD in obese patients. There is evidence in these data that especially the combination of weight reduction through diet and activity has a positive impact on the leptin/adiponectin ratio. As long as no medication is available for this purpose, weight reduction in the form of an interdisciplinary weight management program is therefore a suitable therapy for NAFLD.