Mark Hvistendahl

Home Parenteral Nutrition in Adult Patients With Chronic Intestinal Failure The Evolution Over 4 Decades in a Tertiary Referral Center

Background/Aims: In Denmark, the public healthcare system ensures patients with intestinal failure (IF) the same rights for a life-saving treatment as patients with other organ failures. This study reports the epidemiological data from the largest Danish IF center. As one of the pioneering centers in treating IF with home parenteral nutrition (HPN), this study documents the HPN evolution and describes the demographics and outcome in one of the world’s largest single-center cohorts. Methods: We included patients with IF discharged with HPN from 1970–2010. Data were extracted according to European Society for Clinical Nutrition and Metabolism classifications from the Copenhagen IF database. Results: Over the decades, we observed an exponential increase in the number of HPN patients. The 508 patients with IF collectively received HPN for 1751 years. While receiving HPN, 211 patients with IF (42%) died. Only 24 deaths were HPN related: sepsis (n = 10), liver disease (n = 12), central venous thrombosis (n = 1), and a complicated catheter placement (n = 1). The HPN-related mortality was as low as 0.014 deaths/HPN year. In the first decade, HPN was mainly provided to younger, intestinally resected adult patients with IF with inflammatory bowel disease (IBD), but numerically, they were subsequently outnumbered by elderly patients with IF with cancer or complications from non-IBD, noncancer abdominal surgery. Despite these demographic changes, the HPN-related mortality has decreased in the past decade. Conclusion: Evolving from being a rare, experimental treatment in the 1970s, HPN at present is safe with a low treatment-related mortality in the experienced center, despite HPN being more widely used in a more elderly population.

Home Parenteral Nutrition in Adult Patients With Chronic Intestinal Failure: Catheter-Related Complications Over 4 Decades at the Main Danish Tertiary Referral Center

BACKGROUND/AIMS Catheter-related complications (CRCs) cause mortality and morbidity in patients dependent on parenteral support at home (HPN) due to intestinal failure (IF). This study describes the incidences of CRCs in an adult IF cohort over 40 years. It illustrates the evolution and consequences of CRCs, their association to demographic characteristics, and potential risk factors in an effort to provide the rationale for preventive precautions to the relevant patients with IF at risk. METHODS All patients with IF discharged with HPN from 1970-2010 were included. Patient and treatment characteristics were extracted from the Copenhagen IF database. The incidences were given per 1000 central venous catheter (CVC) days. RESULTS The 1715 CRCs occurred in 70% of the 508 patients with IF (56% of the 2191 CVCs). The incidence of catheter-related bloodstream infections (CRBSIs) was 1.43. Higher age, HPN administration by community home nurses, and prior CRBSIs significantly raised the hazard for CRBSIs. In the 1970s, catheters were generally replaced following CRBSIs, whereas catheter salvage was the norm in the 2000s. The incidences of mechanical complications, tunnel infections, and catheter-related venous thromboses were 0.80, 0.25, and 0.11, respectively. The overall CRC incidence was 2.58, decreasing the first 3 decades but peaking in the last (2.84). The deaths related to CRCs were low (0.018). CONCLUSION Even in an experienced IF center of excellence, the incidence of CRCs increased over the 4 decades. This increase could be explained by the expansion of the indication of HPN to a more elderly and frail patient population.

A Single-Center, Adult Chronic Intestinal Failure Cohort Analyzed According to the ESPEN-Endorsed Recommendations, Definitions, and Classifications.

Background/Aims: The objective of this study was to describe a clinically well-defined, single-center, intestinal failure (IF) cohort based on a template of definitions and classifications endorsed by the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods: A cross-sectional, retrospective, adult IF cohort, receiving parenteral support (PS), was extracted from the Copenhagen IF database at the tertiary IF center, Copenhagen University Hospital, Rigshospitalet, Denmark. Results: Rigshospitalet provided PS to 188 adult patients with IF on December 31, 2011. Six patients received only fluids and electrolytes, while 97% required parenteral energy (17 ± 12 kcal/kg/d). Although 92% of the cohort had undergone intestinal resection, only 53% were classified as patients with short bowel syndrome (SBS) according to the pathophysiological classification. In the remaining cohort, patients were distributed as 5% with intestinal fistula, 12% with intestinal dysmotility, 5% with mechanical obstruction, and 14% with mucosal diseases. Twelve percent had a combination of pathophysiological causes. The patients with SBS (n = 100) were subdivided according to bowel anatomy into group 1 (jejuno/ileostomy, n = 82), group 2 (jejuno-colonic-anastomosis, n = 16), and group 3 (jejuno-ileo-colonic-anastomosis, n = 2). When evaluating the cohort requirements for PS using the ESPEN chronic IF classification based on the need for fluid volume and energy, 53% of the patients with IF were distributed in the maximum categories. Conclusion: The orphan condition of IF with its large patient heterogeneity mandates establishment of uniform definitions and a harmonization of classifications. As illustrated, the ESPEN-endorsed definitions and classifications are well designed and may serve as a common uniform template to facilitate both intra- and intercenter comparisons between reference centers and thus outcome results.

Su2095 Survival and Cause-Specific Mortality in an Intestinal Failure Cohort Depending on Home Parenteral Nutrition (HPN) in a Referral Centre From 1970 to 2010

G A A b st ra ct s enhanced microbial fermentation of dietary fiber and dysregulation of choline metabolism. The OPLS-DA model constructed based on samples collected post DI (R2X=30.7%, Q2Y= 0.37) showed higher concentrations of glutamate and 6-aminosalicylic acid in AA compared with AF. Microbial data acquired using HITChip was integrated with fecal profiles using OPLS. At the phylum level, 2 out of 22 identified phyla were significantly correlated with fecal profiles, which are Cyanobacteria and uncultured Mollicutes significantly correlating with fecal glutamate and valerate. By statistically integrating the fecal metabonome and the 130 microbial genus, Bacteroides vulgates et rel. and Bacteroides plebeius et rel. were observed to be correlated with choline, whereas Uncultured Clostridiales II was correlated with pyroglutamate. Uncultured Mollicutes, Eubacterium siraeum et rel and Aneurinibacillus demonstrated similar metabolic activity. Conclusions: These findings indicate that after only two-weeks of a dietary exchange diet, the fecal metabolic profile is significantly altered and that these metabolic changes are closely associated with alterations in the structure and function of the gut microbial network.

Glepaglutide, a long-acting glucagon-like peptide-2 analog, alters postprandial intestinal hormone levels but not glucose homeostasis in patients with short bowel syndrome

HORMONE LEVELS BUT NOT GLUCOSE HOMEOSTASIS IN PATIENTS WITH SHORT BOWEL SYNDROME R. M. Naimi1, 2, M. Hvistendahl1, J. J. Holst3, B. Hartmann3, M. B. Hansen4, P. B. Jeppesen1 1. Department of Medical Gastroenterology, Rigshospitalet, Copenhagen, 2. Clinical Development, Zealand Pharma, Glostrup, 3. Novo Nordisk Foundation, Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 4. Research & Development, Zealand Pharma, Glostrup, Denmark

Fasting and Postprandial Plasma Citrulline and the Correlation to Intestinal Function Evaluated by 72-Hour Metabolic Balance Studies in Short Bowel Jejunostomy Patients With Intestinal Failure.

BACKGROUND Fasting plasma citrulline (p-citrulline) is a marker of functional enterocyte mass. However, the optimal timing of measurement in relation to meals has yet to be clarified. Furthermore, p-citrulline has been proposed to be a surrogate marker for small bowel length and intestinal absorption parameters in short bowel syndrome patients with intestinal failure (SBS-IF). MATERIALS AND METHODS Eight patients with SBS-IF and 8 healthy controls (HCs) were given a standardized mixed test meal, and p-citrulline was measured 15 minutes before and 60, 120, and 180 minutes after completion of the meal. The patients with SBS-IF had their intestinal absorption of wet weight, energy, macronutrients, and electrolytes measured in relation to 72-hour metabolic balance studies. We investigated the possible correlations between p-citrulline and short bowel length, absorptive parameters, and the dependence on parenteral support (PS). RESULTS In the patients with SBS-IF, we found a 12% (P = .041) reduction in postprandial citrulline levels after 180 minutes. In the HCs, there was a 13% postprandial reduction at 60 minutes (P = .018). No significant correlations between fasting p-citrulline and bowel length, bowel absorptive function, or the dependence on PS were found. Even when excluding 2 patients in whom the intestinal absorption was adjacent to the intestinal insufficiency borderlines, these correlations were not significant. CONCLUSION Based on findings in this small study, the optimal timing of p-citrulline measurement is on fasting samples. However, p-citrulline seems insufficiently discriminative to serve as a valid biomarker of bowel length, bowel absorptive function, or dependence on PS in patients with SBS-IF.

577 A Potential Association Between Remnant Bowel Anatomy and the Incidence of Catheter-Related Blood-Stream Infections (CRBSIS) in Adult Intestinal Failure (IF) Patients Depending in Home Parenteral Nutrition(HPN)

Patients with intestinal failure (IF) depend on parenteral support through a central line for survival, but are challenged by the risk of catheter-related bloodstream infections (CRBSIs). Employing the Copenhagen HPN database, we investigated the association between the remaining bowel anatomy and the incidence and infectious species in CRBSIs with the aim of identifying risk factors. Methods: The CopenhagenHPNdatabase is based on a retrospective annually review of all charts from adult patients, who have received HPN from Rigshospitalet, Denmark. The diagnosis of a CRBSI required clinical signs of a systemic infection and positive blood cultures, with the exclusion of other causes of infections. Results: From 1970 to 2010, 510 IF patients were discharged with HPN, in total contributing to 1745 HPN years. In 256 of the IF patients 873 CRBSI were detected: 595 mono-bacteraemia, 140 polybacteraemia, 85 fungemia and 49 combinations of bacteraemia and Candidemia. The species of bacteraemia and Candidemia were determined in 869 CRBSIs, while 4 positive cultures were recorded without species. The cohort were divided into three groups according to remain bowel anatomy (-colon, +colon and no-surgical). The overall incidence of CRBSIs in HPN were 1.37 per 1000 HPN days. In the group without colon, the incidence of CRBSIs were 1.54 per 1000 HPN days. The median remaining small intestine was 125 cm, and the median age at complication was 57.8 years. The group were subdivided dependent on the remaining small intestine ( 200cm) with minor variations in incidence (1.59, 1.69, 1.42 and 1.60 per 1000 HPN days). The CRBSI incidence in IF patients with remaining colon was 0.92 per 1000 HPN days. The median small intestine was 100 cm, and the patients had a median of 70.5% of remaining colon. The median age at complication in this group was 49.1 years. The colon-group was first split into two: less/ above 50% remaining colon with CBRSI incidences of 0.42 and 1.06 per 1000 HPN days. Staphylococcus spp were detected in 55 % of blood cultures in IF patients with colon, while only seen in 30 % in IF patients without remaining colon. In the no colon group enterobacteriaceae were more frequent (50 %) with the exception of IF patients with < 50 cm small intestine (24 %). Candidemia were detected in 14 % of the cultures from IF patients without colon, while only 6.8 % in IF patients with colon. Conclusion: The CRBSI incidence rate in IF patients without colon is almost two fold higher compared to IF patients with remaining colon. Most frequently IF patients with a colon had bacteraemia with Staphylococci, while CRBSI in patients without a colon as frequently were caused by enterobacteriaceae. Candidemia was most frequently seen in patients without colon. The role of remaining bowel on the incidence of CRBSI needs further investigation. Tabel 1: Incidence of CRBSIs in HPN years and 1000 HPN days.