Candidacy of adult patients with short bowel syndrome for treatment with glucagon-like peptide-2 analogues: A systematic analysis of a single centre cohort.

BACKGROUND AND AIMS: The glucagon-like peptide-2 (GLP-2) analogue, teduglutide, allows to reduce the intravenous supplementation (IVS) dependency of patients with short bowel syndrome and intestinal failure (SBS-IF). The rate of candidacy of SBS-IF patients for the treatment is unknown. The candidacy for teduglutide treatment of our patient cohort was investigated by a systematic analysis. METHODS: The indications, contraindications, special warnings and precautions for use of teduglutide, listed in the drug monographs and in the phase-III trial protocol were adopted to categorize the patients as non-candidates (NC), potential candidates (PC) or straight candidates (SC) for the treatment. All the SBS-IF adult patients who were cured at our centre were assessed according to their clinical status on January 1st, 2020. RESULTS: Seventy-nine patients were evaluated: 34.2% were NC due to risk of digestive malignancy, recent history of any other cancer, or listing for intestinal transplantation; 30.4% were PC, because of other premalignant conditions, risk of intestinal obstruction, entero-cutaneous fistulas, or severe co-morbidities; 35.4% were SC. The SC group showed the lowest requirement of IVS: the lowest number of days of infusion per week (p = 0.0054), the lowest amount of energy (p = 0.0110) and volume (p = 0.0136). CONCLUSIONS: This systematic analysis allowed a pragmatic categorization of the candidacy of patients with SBS-IF for GLP-2 analogue treatment. The SC group appeared to have the highest probability of a successful response to the treatment. A systematic analysis of SBS-IF patient candidate for GLP-2 analogue therapy would allow a homogeneous patient selection and facilitate the worldwide comparison of the results of clinical practice and research.

Non-interventional, retrospective data of long-term home parenteral nutrition in patients with benign diseases: Analysis of a nurse register (SERECARE).

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of home parenteral nutrition (HPN) service in patients with benign chronic intestinal failure (CIF). METHODS: This was a 10-y retrospective, non-interventional, multicenter study conducted with adult and pediatric patients with CIF who received HPN service. We analyzed data prospectively collected from a dedicated register by HPN nurses. RESULTS: From January 2002 to December 2011 a total of 794 patients (49.7% male, median age 1 y for children and 57 y for adults) were included in the analysis. Over the 10-y period, 723 central venous catheter (CVC) complications occurred, of which 394 were infectious (54.5%), 297 were mechanical (41.1%), and 32 (3.3%) were defined as CVC-related thrombosis. The complication rate was higher in children (1.11 per patient) than in adults (0.70 per patient). During the observation period, the rates of both infectious and mechanical complications showed a global declining trend and ∼75% of patients had neither infectious nor mechanical CVC complications. HPN efficacy was evaluated in 301 patients with a minimum follow-up of 36 mo. Body mass index and Karnofsky score showed that the median growth significantly increased (P < 0.001) over baseline for adults and pediatric patients in the 0 to 2 age range. CONCLUSIONS: The use of a structured register has proved to be a key strategy for monitoring the outcomes of long-term treatment, improving time efficiency, and preventing potential malpractice. To our knowledge, this is the largest survey ever documented; the results were consistent despite the heterogeneity of the centers because of duly applied standard rules and protocols.

Assessment of Intestinal Failure Associated Liver Disease according to different diagnostic criteria.

BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) has been defined using numerous criteria; however the clinical relevance of these criteria has never been compared. We therefore aimed to evaluate the prevalence, incidence, evolution of IFALD diagnosed by different criteria and to assess any clinical features that may be associated with its occurrence. METHODS: A cross sectional (CS) and retrospective study were carried out on adults on home parenteral nutrition (HPN) for chronic intestinal failure (CIF) managed at a single center. Inclusion criteria at CS: age ≥18 years, benign disease. Collected data included: patient demographics, CIF and HPN characteristics, episodes of central venous catheter related bloodstream infection (CRBSI). IFALD was diagnosed by 9 criteria based on liver function tests and liver ultrasound (US) imaging. IFALD diagnoses were categorized as steatosis (2 criteria), cholestasis (3 criteria) or fibrosis (2 criteria) and unclassified (2 criteria). Prevalence was assessed at CS and at starting HPN (baseline, BS). Evolution was assessed as change of IFALD between BS and CS. Incidence was calculated as patients who developed IFALD from BS to CS. RESULTS: A total of 113 patients were included. At CS, IFALD prevalence range in each diagnostic categories was: cholestasis 5-15%; steatosis 17-43%; fibrosis 10-20%; unclassified 7-38%. A 28.5% of patients did not have IFALD according to any criteria. Two cholestasis criteria and one fibrosis criterion were significantly (P < 0.05) associated with a short bowel syndrome as the pathophysiological mechanism of CIF, HPN requirement and the number of CRBSI episodes. At BS, IFALD prevalence range was: cholestasis 13-40%; steatosis 27-90%; fibrosis 2-5%; unclassified 8-75%. The incidence range of IFALD was: cholestasis 0-7%; steatosis 0-39%; fibrosis 7-18%; unclassified 4-9%. IFALD steatosis diagnosed by US was the most frequent diagnosis at both CS prevalence and incidence assessments. Notably, IFALD criteria normalized in various percentages (2-70%), depending on the diagnostic categories, between BS and CS. CONCLUSIONS: This is the first study to systematically demonstrate that the frequency of IFALD varies greatly depending on diagnostic criteria used, confirming the need for a consensus definition to be used between different national and international IF units. IFALD can be present at HPN initiation but may resolve thereafter; further work is required to evaluate the factors associated with improvement.

Functional lipidomics in patients on home parenteral nutrition: Effect of lipid emulsions.

AIM: To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions. METHODS: A cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition (HPN), receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion (IVLE) (OO-IVLE; n = 15), a soybean- medium-chain triacylglycerol-olive-fish oil-based IVLE (SMOF-IVLE; n = 8) or HPN without IVLE (No-IVLE; n = 8) and 42 healthy controls (HCs). The inclusion criteria were: duration of HPN ≥ 3 mo, current HPN admixtures ≥ 2 mo and HPN infusions ≥ 2/wk. Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion. The functional lipidomics panel included: the red blood cell (RBC) fatty acid (FA) profile, molecular biomarkers [membrane fluidity: saturated/monounsaturated FA ratio = saturated fatty acid (SFA)/monounsaturated fatty acid (MUFA) index; inflammatory risk: n-6/n-3 polyunsaturated fatty acid (PUFA) ratio = n-6/n-3 index; cardiovascular risk: sum of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) = n-3 index; free radical stress: sum of FA trans isomers = %trans index] and FA pathway enzyme activity estimate (delta-9-desaturase = D9D; delta-6-desaturase = D6D; delta-5-desaturase = D5D; elongase = ELO). Statistics were carried out using nonparametric tests. The amount of each FA was calculated as a percentage of the total FA content (relative%). RESULTS: In the OO-IVLE group, the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE (r = 0.540, P = 0.043). In the SMOF-IVLE cohort, the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOF-IVLE (r = 0.751, P = 0.044) and the number of HPN infusions per week (r = 0.753; P = 0.046), respectively. The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages (P < 0.001). The RBC membrane linoleic acid content was lower, and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs. Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE (r = 0.716; P = 0.007) and the SMOF-IVLE (r = 0.732; P = 0.053) groups. The estimated activity of D9D was higher in all the HPN groups than in the HCs (P < 0.001). The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs (P = 0.013). The SFA/MUFA ratio was lower in all the HPN groups than in the HCs (P < 0.001). The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups (P < 0.001). The %trans index did not differ among the four groups. CONCLUSION: The FA profile of IVLEs significantly influenced the cell membrane functional lipidomics. The amount of glucose in the HPN may play a relevant role, mediated by the insulin regulation of the FA pathway enzyme activities.

Iodine nutrition in adults on long-term home parenteral nutrition.

OBJECTIVE: The aim of this study was to evaluate iodine nutrition in adults on long-term home parenteral nutrition (HPN) and to compare it with iodine supplemented with PN, categorized as below or according to the European Society for Clinical Nutrition and Metabolism guidelines (ESPEN-GL) recommendation. METHODS: Iodine nutrition was evaluated retrospectively in 31 stable adults on long-term HPN. We analyzed urinary iodine concentration (UIC) and serum thyroid-stimulating hormone (TSH). A median UIC value ≥100 µg/L was considered indicative of adequate iodine intake, a value between 50 and 100 was indicative of moderate iodine deficiency, and a value <50 µg/L was indicative of overt iodine deficiency. RESULTS: PN iodine amount was according to ESPEN-GL in 26% of patients and lower in 19%; 55% did not receive iodine with PN. The median UIC was 63 µg/L (95% confidence interval [CI], 26-99 µg/L) in the whole group of patients, 56 µg/L (95% CI, 24-100) in the group including patients who did not receive any PN iodine supplementation and those who received PN iodine supply lower than the ESPEN-GL recommendation, and slightly higher (77 µg/L) in eight patients with PN iodine supply according to the ESPEN-GL (P = 0.42). TSH was normal in 74% of patients, increased in 23%, and reduced in 3%. Results did not change when patients with reduced glomerular filtration rate were excluded from the analysis. CONCLUSIONS: The analyzed patients on long-term HPN had a low iodine intake as shown by low median UIC level, as did the group of patients who received PN iodine supplementation according to ESPEN-GL. A condition of subclinical hypothyroidism was observed in a small percentage of patients.

Renal function in patients on long-term home parenteral nutrition and in intestinal transplant recipients.

OBJECTIVE: A decrease of renal function was described in patients on long-term home parenteral nutrition (HPN) for benign intestinal failure. The risk for chronic renal failure (CRF) due to frequent episodes of dehydration despite optimal HPN, is an indication for intestinal transplantation (ITx). ITx is the solid organ transplant at highest risk for developing CRF. The aim of this study was to compare the prevalence and the probability of CRF occurring in adults on HPN and after ITx. METHODS: A cross-sectional and retrospective follow-up study was carried out in 2011. Renal function was evaluated at cross-sectional and at time of starting HPN or ITx, by serum creatinine concentration (mg/dL) and estimated glomerular filtration rate (eGFR), according to the Modification of Diet in Renal Disease equation (mL·min·1.73 m2). CRF was defined as eGFR <60. Duration of follow up was from time of starting treatment to time of cross-sectional. RESULTS: We enrolled 33 patients on HPN and 22 who had undergone ITx. The frequency of CRF was 6% in the HPN group and 9% in the ITx group (P = 0.67) at start of treatment, and 21% and 54%, respectively (P = 0.01) at the time of the cross-sectional evaluation. During the follow-up, the annual decline of eGFR was 2.8% and 14.5%, respectively (P = 0.02). The 5-y probability of maintaining an eGFR ≥60 was 84% in the HPN group and 44% in the ITx group (P < 0.001). CONCLUSIONS: The decrease of renal function and the risk for developing CRF are greater after ITx than during HPN. The risk for CRF on HPN, as a criterion for ITx, should be revised.