Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center.

BACKGROUND: Parenteral nutrition (PN) is the main treatment for intestinal failure. OBJECTIVE: We aimed to review the indications for home parenteral nutrition (HPN) in children and describe the outcome over a 14-y period from a single center. DESIGN: We conducted a retrospective study that included all children who were referred to our institution and discharged while receiving HPN between 1 January 2000 and 31 December 2013. The indications for HPN were divided into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs). We compared our results to a previous study that was performed in our unit from 1980 to 2000 and included 302 patients. RESULTS: A total of 251 patients were included: 217 (86%) had a PDD. The mean ± SD age at HPN onset was 0.7 ± 0.3 y, with a mean duration of 1.9 ± 0.4 y. The indications for HPN were short bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%), and other digestive diseases (3%). By 31 December 2013, 52% of children were weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10% died mostly because of immune deficiency. The major complications of HPN were catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort). An increased rate of CRBSIs was observed compared with our previous study, but we saw a decreasing trend since 2012. No noteworthy deceleration of growth was observed in SBS children 6 mo after weaning off HPN. CONCLUSIONS: SBS was the major indication for HPN in our cohort. IFALD and CRBSIs were potentially life-threatening problems. Nevertheless, complication rates were low, and deaths resulted mostly from the underlying disease.

Weaning Off Prognosis Factors of Home Parenteral Nutrition for Children With Primary Digestive Disease.

OBJECTIVES: The aim of the present study was to describe the indications for home parenteral nutrition (HPN) in children with primary digestive diseases and to identify factors associated with weaning off. METHODS: All the children initially discharged on HPN between January 1, 2000, and December 31, 2009, for chronic intestinal failure (IF) were included. The associations between clinical factors and weaning off of HPN were assessed using a multivariable Cox regression model. RESULTS: Among the 151 children (boys = 58%) included in this study, 98 (65%) presented with short bowel syndrome (SBS), 17 (11%) with digestive neuromuscular disorders, 14 (9%) with mucosal diseases, 13 (9%) with inflammatory bowel disease, and 9 (6%) with other primary digestive diseases. The probability of survival was ∼100%. At the end of the follow-up, the probability for weaning off of HPN was 0.73 (95% confidence interval 0.54-0.84) but varied according to the underlying cause of IF (for example, SBS and inflammatory bowel disease had a better prognosis). The median time until weaning off was 21 months (95% confidence interval 18-38 months). Unfavourable prognostic factors for weaning off of HPN included a bowel remnant of <40 cm, the presence of <50% of the colon, and daily lipid intakes >1.5 g · kg · day. Underlying disease was also associated with weaning off. CONCLUSIONS: HPN is a safe therapeutic option for children with chronic IF requiring long-term nutritional management. Prognostic factors for weaning off of HPN were identified, and they highlight the relevance of SBS anatomy and parenteral nutrition caloric intake. The outcome of children on HPN was primarily dependent on the underlying disease.

[A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hematopoietic stem cell transplantation in adults: a cross-reflection on our organizations]. / Modèle de coopération médico-pharmaceutique comme contributeur au succès du conditionnement de la greffe allogénique de cellules souches hématopoïétiques chez l'adulte : un regard croisé sur nos organisations.

Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure for many hematological malignancies and some benign and congenital diseases. Busulfan, proposed in its injectable form, has quickly become a mainstay of pharmacological and myeloablative (or non-myeloablative) conditioning. This is following the outbreak in 2010 of a multicenter international clinical phase II trial, we tested the robustness and reliability of our organization in a complex model of organization and multifactorial partnership. In this type "BuCy2" protocol based on a classical treatment duration of 4 consecutive days, the administration of IV busulfan is given in one single daily infusion instead of the conventional 16 infusions, while keeping the same total dose. Under these conditions, the treatment is totally secured using a therapeutic drug monitoring of busulfan, applied in real-time. The process is technically complex and requires the very close cooperation of the teams involved. A strength, weakness, opportunity and threat (SWOT) analysis has been constructed; it fully supports continuous quality improvement to the triple benefit of the nursing chain, the patients and their environment. Several critical points were identified and corrected. The experiment strongly contributes to the safety and security of the medication circuit at the hospital and, improves the performance of allo-SCT. It also contributes to the protection of all actors in the health field and their working environment via a well-functioning quality management system.

A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition.

BACKGROUND: SMOFlipid 20% is an intravenous lipid emulsion (ILE) containing soybean oil, medium-chain triglycerides, olive oil, and fish oil developed to provide energy, essential fatty acids (FAs), and long-chain ω-3 FAs as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy and safety of this new ILE in pediatric patients receiving home parenteral nutrition (HPN) compared with soybean oil emulsion (SOE). METHODS: This single-center, randomized, double-blind study included 28 children on HPN allocated to receive either SMOFlipid 20% (n = 15) or a standard SOE (Intralipid 20%, n = 13). ILE was administered 4 to 5 times per week (goal dose, 2.0 g/kg/d) within a parenteral nutrition regimen. Assessments, including safety and efficacy parameters, were performed on day 0 and after the last study infusion (day 29). Lipid peroxidation was determined by measurement of thiobarbituric acid reactive substances (TBARS). RESULTS: There were no significant differences in laboratory safety parameters, including liver enzymes, between the groups on day 29. The mean ± standard deviation changes in the total bilirubin concentration between the initial and final values (day 29 to day 0) were significantly different between groups: SMOFlipid group -1.5 ± 2.4 µmol/L vs SOE group 2.3 ± 3.5 µmol/L, P < .01; 95% confidence interval [CI], -6.2 to -1.4). In plasma and red blood cell (RBC) phospholipids, the ω-3 FAs C20:5ω-3 (eicosapentaenoic acid) and + C22:6ω-3 (docosahexaenoic acid) increased significantly in the SMOFlipid group on day 29. The ω-3:ω-6 FA ratio was significantly elevated with SMOFlipid 20% compared with SOE group (plasma, day 29: 0.15 ± 0.06 vs 0.07 ± 0.02, P < .01, 95% CI, 0.04-0.11; and RBC, day 29: 0.23 ± 0.07 vs 0.14 ± 0.04, P < .01, 95% CI, 0.04-0.13). Plasma α-tocopherol concentration increased significantly more with SMOFlipid 20% (15.7 ± 15.9 vs 5.4 ± 15.2 µmol/L, P < .05; 95% CI, -2.1 to 22.6). The low-density lipoprotein-TBARS concentrations were not significantly different between both groups, indicating that lipid peroxidation did not differ between groups. CONCLUSIONS: SMOFlipid 20%, which contains 15% fish oil, was safe and well tolerated, decreased plasma bilirubin, and increased ω-3 FA and α-tocopherol status without changing lipid peroxidation.

Effect of recombinant human growth hormone on intestinal absorption and body composition in children with short bowel syndrome.

This prospective study aimed to establish the effect of recombinant human growth hormone (rhGH) on intestinal function in children with short bowel syndrome (SBS). Eight children with neonatal SBS were included. All were dependent on parenteral nutrition (PN) for >3 years (range, 3.8-11.6 years), with PN providing >50% of recommended dietary allowance for age (range, 50%-65%). The subjects received rhGH (Humatrope) 0.13 mg/kg/d subcutaneously over a 12-week period. The follow-up was continued over a 12-month period after rhGH discontinuation. Clinical and biological assessments were performed at baseline, at the end of the treatment period, and 12 months after the end of treatment. No side effects related to rhGH were observed. PN requirements were decreased in all children during the course of rhGH treatment. Between baseline and the end of treatment, significant increases were observed in concentrations (mean ± standard deviation) of serum insulin-like growth factor 1 (103.1 ± 49.9 µg/L vs 153.5 ± 82.2 µg/L; P < .01), serum insulin-like growth factor-binding protein 3 (1.7 ± 0.6 mg/L vs 2.5 ± 0.9 mg/L; P < .001), and plasma citrulline (16.5 ± 14.8 µmol/L vs 25.2 ± 18.3 µmol/L; P < .05). A median 54% increase in enteral intake (range, 10%-244%) was observed (P < .001) and net energy balance improved significantly (P < .002). It was necessary for 6 children to be maintained on PN or restarted after discontinuation of rhGH treatment, and they remained on PN until the end of the follow-up period. A 12-week high-dose rhGH treatment allowed patients to decrease PN, but only 2 patients could be definitively weaned from PN. Indications and cost-effectiveness of rhGH treatment for SBS pediatric patients need further evaluation.

Some new insights in intestinal failure-associated liver disease.

PURPOSE OF REVIEW: To point new insights in the cholestasis that is a complication of both intestinal failure and parenteral nutrition. View on liver disease has recently evolved with the onset of fish oil-based intravenous lipid emulsions (ILE). RECENT FINDINGS: Focused on the role of ILE in causing liver disease. Reversal of cholestasis was recently achieved in infants with short bowel syndrome, by replacing the 'reference' soybean oil-based ILE by fish oil-based ILE. SUMMARY: It is likely that this reversal involves several factors such as the change in n-6: n-3 ratio, the reduction in phytosterol load, the increased provision of alpha-tocopherol as antioxidant agent. Alternative issue might be based on the use of a new generation of ILE aiming to provide n-3 and to reduce n-6 fatty acids load while enhancing alpha-tocopherol intake. New data are based on the use of an ILE containing a balanced proportion of four types of oil as a physical mixture of 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil with amounts of alpha-tocopherol calculated according to the number of double bonds. This new emulsion was reported to be beneficial in reversing or preventing liver disease.

Long-term outcome of children receiving home parenteral nutrition: a 20-year single-center experience in 302 patients.

BACKGROUND: More information is needed regarding the prognosis of children receiving home parenteral nutrition (HPN). This article describes 20-year outcome data in children receiving HPN and provides separate profiles for the major pediatric diagnostic subgroups. PATIENTS AND METHODS: This retrospective study included children who started receiving HPN between January 1, 1980, and December 31, 1999, in a single pediatric HPN center. RESULTS: A total of 302 children were recruited, 230 (76%) with primary digestive disorders and 72 (24%) with nonprimary digestive disorders. Median age at HPN onset was 1.5 years. Median duration of HPN was 1.3 years. By January 1, 2000, 54% had weaned from HPN, 26% were still receiving HPN, 16% had died, and 4% had undergone intestinal transplantation. The survival probabilities at 2, 5, 10, and 15 years were 97%, 89%, 81%, and 72%, respectively. The likelihood and cause of death depended on the underlying diagnosis. Nine percent of children with primary digestive disorders died, 24% from their primary disease and 48% from liver disease or sepsis. Children with intractable diarrhea of infancy had the highest mortality rate (25%) and the highest incidence of liver disease (48%; P = 0.0002). Thirty-eight percent of children with primary nondigestive diseases died, 94% from their primary disease and 6% from liver disease or sepsis. CONCLUSIONS: Outcome and survival of children receiving HPN are mainly determined by their underlying diagnosis. Nearly all children with primary digestive disease survive if referred early to an expert center.

Enterocyte metabolism during early adaptation after extensive intestinal resection in a rat model.

OBJECTIVE: A better knowledge of intestinal adaptation after resection is required to improve the nutritional support that is given to patients. The aim of this study was to understand the metabolic changes underlying early adaptation after massive intestinal resection. METHODS: Rats were assigned to either 80% intestinal resection or transection. All animals received the same intragastric nutrition. On day 8, plasma glutamine turnover was measured. Substrate use was determined on isolated enterocytes that were incubated in the presence of D-[U-(14)C] glucose (2 mmol/L), L-[U-(14)C] glutamine (2 mmol/L), L-[U-(14)C] arginine (1 mmol/L), or L-[1-(14)C] ornithine (1 mmol/L). RESULTS: Plasma glutamine turnover was similar in both groups. The rate of enterocyte glutamine use was significantly increased in the resection group, although the maximal glutaminase activity was unchanged. Glutathione generation was enhanced 3-fold in remnant intestine as compared with transected intestine (P <.05). L-ornithine decarboxylation was increased markedly in resected animals (P <.05), without any detectable change of maximal ornithine decarboxylase activity. CONCLUSION: The early phase of intestinal adaptation after resection induces changes in enterocyte glutamine and ornithine metabolism that may be related, in part, to increased de novo polyamine synthesis. This observation suggests that a supplementation of artificial nutrition by nutrients that lead to the generation of trophic agents may be of potential interest.

Endothelial function and mechanical properties of the common carotid artery in children on parenteral nutrition.

Intravenous administration of nutrition mixtures induces endothelial damage and arterial wall remodeling in animal models. To study endothelial function and common carotid artery mechanical properties in children receiving parenteral nutrition, we used noninvasive ultrasonic measurements in 18 children on parenteral nutrition and 18 controls. No difference appeared in the geometry of the common carotid artery (intima media thickness, systolic and diastolic diameters) between the patients on parenteral nutrition and the controls. The incremental elastic modulus was significantly higher in the patients on parenteral nutrition (1.8 +/- 0.4 versus 1.4 +/- 0.5 4 mm Hg x 10(3), p < 0.05) reflecting alteration of the elastic properties of the arterial wall independent of the vessel geometry. The flow-mediated dilatation of the brachial artery was significantly lower in the patients on parenteral nutrition (6 +/- 3 versus 8 +/- 3%, p < 0.05), whereas the dilatation after glyceryl trinitrate administration was similar (22 +/- 9 versus 25 +/- 9%). Children on parenteral nutrition exhibit endothelial dysfunction and altered stiffness of the common carotid artery. The noninvasive methods used in this study may prove useful for objectively determining the effects of various preventive methods.

Luminal fermentation and colonocyte metabolism in a rat model of enteral nutrition.

Large intestinal fermentation and nutrient metabolism in colonocytes were investigated in a rat model of enteral feeding. Male Wistar rats (240-280 g) were submitted to 7 or 14 days of treatment: intragastric feeding (elemental formula) versus oral feeding (isocaloric and isonitrogenous diet, containing 5% purified cellulose) in the control group. Fermentation products and bacterial populations were analyzed in cecal contents. Colonic cells were isolated and tested for their capacities to metabolize [1-(14)C] butyrate and [U-(14)C]glutamine. After 7 days of enteral nutrition, short-chain fatty acid concentrations represented 52% of those measured in the control group, but colonocyte metabolism remained unchanged. After 14 days of enteral nutrition, short-chain fatty acid concentrations were still decreasing, although bacterial counts remained unchanged. In parallel, ammonia and lactate concentrations were significantly increased. The capacities to utilize butyrate and glutamine in colonocytes were only slightly affected. However, there was a dramatic increase in the ratio of beta-OH-butyrate to acetoacetate fluxes, suggesting a more reduced redox mitochondrial state associated with enteral feeding.

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition.

BACKGROUND: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. METHODS: Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. RESULTS: The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). CONCLUSIONS: Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.