Systematic review on management of high-output enterostomy in children: An urgent call for evidence.

OBJECTIVES/BACKGROUND: High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output enterostomy in children is mostly based on personal experience. This systematic review aims to clarify the evidence-based therapeutic approach of high-output enterostomy in children. METHODS: A systematic review was performed using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published until March 20, 2023, following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The study population comprised children (i.e., age <18 years) with high-output enterostomy (i.e., jejuno-, ileo-, and/or colostomy), regardless of underlying aetiology. Interventions comprised any (non)pharmacological and/or surgical treatment. Interventions were compared with each other, placebos, and/or no interventions. Primary outcome was reduction of enterostomy output. Secondary outcomes were morbidity, mortality, quality of life, associated healthcare costs, and adverse events. RESULTS: The literature search identified 4278 original articles of which 366 were screened on full text, revealing that none of the articles met the inclusion criteria. CONCLUSION: This first systematic review on management of high-output enterostomy in children revealed that any evidence on the primary and secondary outcomes is lacking. There is an urgent need for evidence on conservative treatment strategies including fluid restrictions, dietary advices, oral rehydration solution, chyme re-infusion, and pharmacological and surgical treatments of high-output enterostomy in children, aiming to reduce the risk for short- and long-term complications. Till more evidence is available, a systematic and multidisciplinary step-up approach is needed. Therefore, a therapeutic work-up is proposed that could guide the care.

The Impact of Teduglutide on Real-Life Health Care Costs in Children with Short Bowel Syndrome.

OBJECTIVES: To analyze the real-life health care costs of home parenteral nutrition (HPN) in children with short bowel syndrome with intestinal failure (SBS-IF) before and after treatment with teduglutide, and to compare those with costs of children with SBS-IF not treated with teduglutide. STUDY DESIGN: All consecutive children with SBS-IF on HPN treated with subcutaneous teduglutide starting from 2018 through 2020 in a tertiary French referral center were retrospectively included. These patients were matched to children with SBS-IF on HPN followed during the same 3-year period who were eligible for the teduglutide but were not treated. HPN direct medical costs included home-care charges, HPN bags, hospital admissions, and teduglutide. A comparison of costs before/after treatment and between patients treated/not treated was performed. RESULTS: Sixty children were included: 30 (50%) were treated with teduglutide and 30 (50%) were untreated. In the treated group, the median total costs of HPN significantly decreased after 1 (P < .001) and 2 years of treatment (P < .001) from 59 454 euros/year/patient to 43 885 euros/year/patient and 34 973 euros/year/patient, respectively. When we compared patients treated and not treated, the total HPN costs/year/patient were similar at baseline (P = .6) but were significantly lower in the teduglutide-treated group after 1 (P = .006) and 2 years of treatment (P < .001). When we added the cost of teduglutide into the analysis, the total cost increased significantly in the treated group and remained much greater even after modeling a reduction in the cost of the drug to one-third the present cost and PN weaning (P < .001). CONCLUSIONS: Treatment with teduglutide is associated with a significant reduction in the annual costs of HPN but still remains expensive because of the drug itself. Finding cost-saving strategies is essential.

Predicting Factors of Protracted Intestinal Failure in Children with Gastroschisis.

OBJECTIVE: To identify prenatal and neonatal predictors of short bowel syndrome-related intestinal failure (SBS-IF) in gastroschisis. STUDY DESIGN: This retrospective study included all patients with gastroschisis born between 2000 and 2017 who were enrolled in our home parenteral nutrition program, and all patients with gastroschisis born in our institution who survived 2 weeks, during the same time period. Prenatal ultrasound features, neonatal status, anatomic features, oral feeding, and parenteral nutrition dependency were analyzed. RESULTS: Among 180 patients, 35 required long-term parenteral nutrition (SBS-IF group) and 145 acquired full oral feeding within 6 months (oral feeding group). The mean follow-up was 7.9 years (IQR, 1.6-17.5 years) and 5.0 years (IQR, 0.1-18.2 years), respectively. Both bowel matting (OR, 14.23; 1.07-16.7; P = .039) and secondarily diagnosed atresia or stenosis (OR, 17.78; 3.13-100.98; P = .001) were independent postnatal predictors of SBS-IF. Eighteen children (51% of the SBS-IF group) were still dependent on artificial nutrition at the last follow-up. patients with SBS-IF who achieved full oral feeding had a median residual small-bowel length of 74 cm (IQR, 51-160 cm) vs 44 cm (IQR, 10-105 cm) for those still dependent on artificial nutrition (P = .02). An initial residual small bowel length of more than 50 cm was the best predictive cut-off for nutritional autonomy, with a sensitivity of 67% and a specificity of 100%. CONCLUSIONS: Bowel matting, complex gastroschisis, and secondary intestinal obstruction were associated with SBS-IF in gastroschisis. For patients with SBS-IF, a small bowel length of more than 50 cm was predictive of secondary nutritional autonomy.

Outcome of Total Colonic Aganglionosis Involving the Small Bowel Depends on Bowel Length, Liver Disease, and Enterocolitis.

OBJECTIVES: Total colonic aganglionosis involving the small bowel is a rare form of Hirschsprung disease. We aim to analyse the long-term outcomes, digestive autonomy, and complications, to suggest recommendations for prevention and treatment. METHODS: All patients born between 2000 and 2015 followed in our centre were retrospectively included. We analysed the length of aganglionosis, surgical procedures, growth, duration of parenteral nutrition (PN), enterocolitis, liver disease, intestinal transplantation. RESULTS: Twenty-five patients were followed for a median of 10.9 years. Fifteen patients had less than 80 cm of ganglionic small bowel (SB) with a median of 20 cm. Ten patients had more than 80 cm of ganglionic sB with a median of 115 cm. The median PN duration was significantly shorter for patients with more than 80 cm: 0.9 versus 7.5 years in those with less than 80 cm (P  < 0.001). No patient with less than 80 cm was weaned off PN, except 1 who underwent intestinal transplantation. Ten patients with less than 80 cm develop enterocolitis on the excluded segment, leading to emergency entero-colectomy in 5. Liver disease was more frequent in patients with less than 80 cm (11 vs 0). Three patients required combined liver-intestine transplantation; 2 underwent an isolated intestinal transplantation. CONCLUSIONS: Digestive autonomy was possible in most patients with more than 80 cm of ganglionic SB. The more severe complication was enterocolitis. Liver disease compromised long-term survival without transplantation. Both complications should be prevented by early diversion and enterectomy of the whole aganglionic segment. Follow-up in or together with a multidisciplinary intestinal rehabilitation centre is suggested.

Results of an International Survey on Feeding Management in Infants With Short Bowel Syndrome-Associated Intestinal Failure.

OBJECTIVES: Short bowel syndrome (SBS) is a complex and rare condition (incidence 1200/100,000 live births) that requires a multidisciplinary team approach to management. In January 2019, the first European Reference Network on Rare and Inherited Congenital Anomalies (ERNICA) Intestinal Failure (IF) workshop was held. Several questions about the strategies used in managing IF associated with SBS were devised. The aim of our study was to collect data on the enteral feeding strategies adopted by the ERNICA centres. METHODS: A questionnaire (36 questions) about strategies used to introduce enteral nutrition post-operatively and start complementary food/solids in infants with SBS associated IF was developed and sent to 24 centres in 15 countries that participated in the ERNICA-IF workshop. The answers were collated and compared with the literature. RESULTS: There was a 100% response rate. In infants, enteral nutrition was introduced as soon as possible, ideally within 24-48 hours post-small intestinal surgical resection. In 10 of 24 centres, bolus feeding was used, in nine continuous, and in five a combination of both. Twenty-three centres used mothers' own milk as the first choice of feed with extensively hydrolysed feed, amino acid-based feed, donor human milk or standard preterm/term formula as the second choice. Although 22 centres introduced complementary/solid food by 6 months of age, food choice varied greatly between centres and appeared to be culturally based. CONCLUSIONS: There is diversity in post-surgical enteral feeding strategies among centres in Europe. Further multi-centre studies could help to increase evidence-based medicine and management on this topic.

Quality of life in long term survivors of pediatric intestinal transplantation compared with liver transplantation and home parenteral nutrition: A prospective single-center pilot study.

Health-related quality of life (HRQOL) after intestinal transplantation (IT) is important, as many psychological troubles have been reported in these patients on the long term. Our aim was to assess and compare HRQOL of patients after IT to patients after liver transplantation (LT) or on home parenteral nutrition (HPN) for intestinal failure. A cross-sectional study included patients and their parents between 10 and 18 years of age, on HPN for more than 2 years, or who underwent IT or LT, with a graft survival longer than 2 years. Quality of life was explored by Child Health Questionnaire. Thirteen children-parents dyads after IT, 10 after LT, and eight children on HPN completed the survey. Patients were a median age of 14 years old, a median of 10 years post-transplantation or on HPN. Patients after IT scored lower than patients after LT or on HPN in "social limitations due to behavioral difficulties" and in "behavior." They scored higher than those on HPN in "global health." Parents of children after IT scored lower than those after LT in many domains. No relevant correlation with clinical data was found. Our study showed the multi-level impact of IT on quality of life of patients and their parents. It highlights the importance of a regular psychological follow-up for patients, but also of a psychological support for families. Helping the patients to overcome the difficulties at adolescence may improve their mental health in adulthood.

Beyond 10 years, with or without an intestinal graft: Present and future?

Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m2 . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.

Experience of Using a Semielemental Formula for Home Enteral Nutrition in Children: A Multicenter Cross-sectional Study.

OBJECTIVES: The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product. METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events. RESULTS: We recruited 136 patients ages 9.8 ±â€Š4.4 years at baseline. Mean body mass index z score was -1.0 ±â€Š1.8; mean height z score was -1.1 ±â€Š1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children. CONCLUSIONS: This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.

Intravenous lipid emulsions in pediatric patients with intestinal failure.

The incidence of cholestatic liver disease (CLD) in pediatric patients suffering intestinal failure (IF) is not well established. Due to persistent portal inflammation, about 20% of these patients will progress to end-stage intestinal failure associated liver disease (IFALD) leading to liver transplant or death. PURPOSE OF REVIEW: Premature babies as well as infants with short bowel syndrome (SBS) and repeated sepsis (catheter or small intestinal bacterial overgrowth related) are at risk of developing CLD. Clinical data in SBS infants focused on intravenous lipid emulsion (ILE) as an important factor of CLD. RECENT FINDINGS: Compared to the last generation of composite ILE containing fish oil (FO), soybean oil (SO) based ILE, have marked differences in term of oil source, omega-3 fatty acids (FAs) composition, vitamin E (α-tocopherols) and plant sterols contents, that may explain CLD and CLD reversal. Randomized controlled trials and meta-analysis allow the following recommendations. SUMMARY: In pediatric patients with developing or established CLD or IFALD, potential causes should be explored and pure SO ILE should be avoided. A reduction of the ILE dosage and/or the use of the new composite FO based ILE, may be recommended along with the treatment and management of other risk factors. The 10% pure FO ILE should not be used as a sole provision of IV lipids in paediatric patients on total PN but can only serve as a short-term rescue treatment.

[NUTRITIONAL STATUS ASSESSMENT IN PATIENTS WITH CYSTIC FIBROSIS]. / Prise en charge nutritionnelle de la mucoviscidose.

Prognosis of cystic fibrosis has been largely modified over the past 30 years. Optimization of nutrition is one of the most important contributing factors of this improvement. Nutritional defect result from the conjunction of loss of calories, maldigestion, hypercatabolism and insufficient intake. Pancreatic opotherapy and ADEK vitamin administration is mandatory in pancreatic insufficient patients. Nutritional status must be evaluated at each clinics to detect nutritional defect as early as possible. Nutritional intake must be hypercaloric, normalipidic and adapted to the tastes of the patient. The clinician must be aware of at risk nutritional period: first year of life, puberty, infectious exacerbation, respiratory worsening and diabetes, In neonatal screened babies, recovery of birth weight percentile must be targeted at 6 months, and for the height must be in accordance to genetic height at 2 years. In all cases it is mandatory to treat denutrition by oral supplementation and if necessay enteral nutrition.

Pediatric Intestinal Failure Associated Eating Disorder: An Overview of the Importance of Oral Feeding in a Population at Risk for Feeding Difficulties.

Achieving feeding skills and food acceptance is a multi-layered process. In pediatric intestinal failure (PIF), oral feeding is important for feeding skills development, physiologic adaptation, quality of life and the prevention of eating disorders. In PIF, risk factors for feeding difficulties are common and early data suggests that feeding difficulties are prevalent. There is a unique paradigm for the feeding challenges in PIF. Conventional definitions of eating disorders have limited application in this context. A pediatric intestinal failure associated eating disorder (IFAED) definition that includes feeding/eating skills dysfunction, psychosocial dysfunction, and the influence on weaning nutrition support is proposed.

Transition from pediatric to adult care in patients with chronic intestinal failure on home parenteral nutrition: How to do it right?

BACKGROUND: Life expectancy of children with chronic intestinal failure (CIF) on home parenteral nutrition has greatly improved. Children are now able to grow into adulthood which requires transfer from pediatric to adult health care. A guideline for structured transition is lacking and the demand for a more standardized care for this patient group is necessary. Therefore, we investigated the perceptions of health care professionals from various disciplines working in this specific field, concerning effective interventions regarding transition to adult health care. AIM: To create a standardized protocol which provides practical guidance for health care professionals in order to bridge the gap between pediatric and adult health care and to facilitate successful transition of children with chronic intestinal failure. METHODS: A survey consisting of 20 interventions for transition was sent out to members of the Intestinal Failure working group of European Reference Network for Rare Inherited Congenital (gastrointestinal and digestive) Anomalies (ERNICA) and the Network of Intestinal Failure and Intestinal Transplant in Europe (NITE) group - European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) healthcare professionals in 48 medical centers in various countries. Next to 20 interventions, an open-ended question to fill in any other suggestion with respect to most effective intervention was included. Interventions scoring higher than 80% by the participants were included in the protocol. Interventions scoring between 50% and 80% and other own suggestions were discussed during a consensus meeting and included when consensus, defined as unanimous agreement, was reached. Interventions scoring as effective by < 50% of participants were excluded directly. RESULTS: A total of 80 healthcare professionals from 33 medical centers (participation rate 69%) participated. The protocol consisted of modifiable components expected to be targets of interventions. The most important key outcomes of the survey were: 1) assessment of patient's transition readiness and provision of knowledge to the patient by the pediatric team, 2) involvement of parents in the transition process, and 3) collaboration between the pediatric and adult chronic intestinal failure team. In addition it is advised that the transition process should start 1-2 years before transfer. A nurse specialist working in both services should form a bridge. All interventions must be tailor-made and based on the maturity of the patient. CONCLUSION: This study provides a protocol describing transition of children with chronic intestinal failure from pediatric to adult care. This international protocol will serve as practical guidance for pediatric chronic intestinal failure which will provide a more structured, optimal transition process. It is advised to use this protocol as a formal checklist that can be placed in the patient's chart to review and track the transition process by CIF team members. Future research investigating transition readiness of CIF patients is needed.

An innovative educational program for adolescents on home parenteral nutrition for the "transition" to adulthood.

Facing with an increasing demand for transition to adult care management, our home parenteral nutrition (HPN) team designed an adolescent therapeutic educational program (ATEP) specifically intended for adolescents on long-term HPN. The aim of this study was to report on the first sessions of this program. Methods: The ATEP is designed in three sessions of five consecutive days, during school holidays over the year. It includes group sessions on catheter handling, disconnecting and connecting the PN and catheter dressing, dealing with unforeseen events (e.g., fever or catheter injury), but also sessions with psychologist, social worker, sports teacher, fashion specialist, meeting with adults who received HPN since childhood. Specific course for the accompanying parents were also provided. Six months after the last session, a 3-day trip to the attraction park "le Futuroscope," Poitiers, France, was organized without any parental presence. Results: After 3 ATEP courses, a total of 16 adolescents have been enrolled. They were aged between 13 and 17 years (median 14 IQR: 14-16.25). All were on long term HPN started during the neonatal period except for four who started PN at a median age of 10 years old (IQR: 1-10). At the time of the ATEP, their median PNDI was 105% (IQR: 95.5-120.8) while receiving a median of six infusions per week (IQR: 5-7). Thirteen received Taurolidine lock procedure. After the ATEP, 11 adolescents could be considered as fully autonomous, 4 as partially autonomous and one failed to gain any autonomy. Course evaluation by adolescents or parents was good to excellent. Conclusion: Through the holistic and multiprofessional approach of this training and the group cohesion, the adolescents were not only able to handle catheter care and PN connections but were able to understand and accept better their illness and project themselves into their own future.

Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

BACKGROUND: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. METHODS: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. RESULTS: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. CONCLUSIONS: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. TYPE OF STUDY: Clinical consensus statement. LEVEL OF EVIDENCE: 3a.

Long-term treatment with teduglutide: a 48-week open-label single-center clinical trial in children with short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) is the main cause of intestinal failure in children. OBJECTIVES: This single-center study evaluated the safety and efficacy of teduglutide in pediatric patients with SBS-associated intestinal failure (SBS-IF). METHODS: Children with SBS followed at our center with ≥2 y on parenteral nutrition (PN) and with small bowel length <80 cm who had reached a plateau were consecutively included in the study. At baseline, participants underwent a clinical assessment including a 3-d stool balance analysis, which was repeated at the end of the study. Teduglutide was administered subcutaneously 0.05 mg/kg/d for 48 wk. PN dependence was expressed as the PN dependency index (PNDI), which is the ratio PN non-protein energy intake/REE. Safety endpoints included treatment-emergent adverse events and growth parameters. RESULTS: Median age at inclusion was 9.4 y (range: 5-16). The median residual SB length was 26 cm (IQR: 12-40). At baseline, the median PNDI was 94% (IQR: 74-119), (median PN intake: 38.9 calories/kg/d, IQR: 26.1-48.6). At week 24, 24 (96%) children experienced a reduction of >20% of PN requirements with a median PNDI = 50% (IQR: 38-81), (PN intake: 23.5 calories/kg/d IQR: 14.6-26.2), P < 0.01. At week 48, 8 children (32%) were weaned completely off PN. Plasma citrulline increased from 14 µmol/L (IQR: 8-21) at baseline to 29 µmol/L (IQR: 17-54) at week 48 (P < 0.001). Weight, height, and BMI z-scores remained stable. The median total energy absorption rate increased from 59% (IQR: 46-76) at baseline to 73% (IQR: 58-81) at week 48 (P = 0.0222). Fasting and postprandial endogenous GLP-2 concentrations increased at weeks 24 and 48 compared with baseline. Mild abdominal pain at the early phase of treatment, stoma changes, and redness at the injection site were commonly reported. CONCLUSIONS: Increased intestinal absorption and PN dependency reduction were observed with teduglutide treatment in children with SBS-IF. TRIAL REGISTRATION: ClinicalTrials.gov NCT03562130. https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.

Development of a core outcome set for pediatric chronic intestinal failure.

BACKGROUND: In research on pediatric chronic intestinal failure, heterogeneity in reported definitions and outcomes exists. This leads to a risk of reporting bias and impossibility of evidence synthesis. Also, reported outcomes should be relevant to both healthcare providers and patients and their parents. Therefore, the aim of this study is to create a core outcome set (COS) to be used in studies on pediatric chronic intestinal failure. METHODS: Candidate outcomes were selected from a recent systematic review. A three-round Delphi study among key stakeholders and a consensus meeting with an expert panel were undertaken to achieve consensus on the COS. RESULTS: Seventy-two stakeholders (79%) completed all three rounds of the Delphi process. Ninety-eight outcomes were assessed, and five new outcomes were added after the first round. Ten outcomes were included in the final COS: weaning from parenteral nutrition, growth, mortality, central line-related infection, central line longevity, sepsis not related to central line infection, central line-related thrombosis, intestinal failure-associated liver disease, (serious) adverse events, and health-related quality of life. CONCLUSION: This pediatric chronic intestinal failure COS consists of 10 outcomes important for all key stakeholders. Usage of this set in future research should minimize outcome heterogeneity and enhance the value of evidence synthesis. This will lead to better management in this field of rare gastrointestinal conditions.

Erythrocyte fatty acid membrane composition in children on long-term parenteral nutrition enriched with ω-3 fatty acids.

BACKGROUND: Composite lipid emulsions containing soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%) (SMOF) are now widely used. OBJECTIVES: We aimed to evaluate the tolerance, the efficiency, and the erythrocyte fatty acid (FA) profile for children on long-term home parenteral nutrition (HPN) receiving a composite fish oil-based emulsion (FOLE). METHODS: At baseline, children (n = 46) with severe intestinal failure highly dependent on parenteral nutrition (PN) for ≥1 y were included in the study when they had received the composite FOLE for >6 mo. Out of this baseline group, only 25 children remained highly PN-dependent (SMOF1, n = 25) and could be assessed a second time, 2.4 y later (SMOF2, n = 25). An independent control group ("weaned off PN" group; n = 24) included children who had been weaned off PN for >2 y (median: 4 y). RBC-FA composition was established by GC-MS. Growth parameters, plasma citrulline, conjugated bilirubin, FA profiles, and the Holman ratio (20:3ω-9/20:4ω-6) were compared between groups. RESULTS: No difference for growth parameters, citrulline, and bilirubin was observed between the SMOF groups after 2.4 y (0.2 < P < 0.8). The weaned-off group did not differ from the SMOF groups for growth parameters (0.2 < P < 0.4) but citrulline was higher (P < 0.0001) and conjugated bilirubin lower (P < 0.01). The composite FOLE induced higher proportions of EPA (20:5n-3) (8.4% ± 2.9%) and DHA (22:6n-3) (11.7% ± 2.2%) than what was observed in weaned-off children (0.8% ± 0.4% and 6.6% ± 2.3%, respectively) but lower proportions of arachidonic acid (20:4n-6). However, the Holman ratio did not vary between groups (P = 0.9), whereas the PUFA concentrations varied widely. CONCLUSIONS: Long-term use of the composite FOLE was well tolerated in HPN-dependent children. The RBC-FA profile alterations were consistent with the ω-3 PUFA-enriched composition of this emulsion without evidence of essential FA deficiency.

Chylopericardium or contamination by injectable lipid emulsion? / « Mets la main sur mon cœur, Et vois comme il se trouble ¼ ­ un pseudo-chylopéricarde ?

Effusions can show some surprises. We document the case of a fourteen-month-old male patient with short-bowel syndrome, hospitalized in a cardiology unit, receiving a chronic parenteral nutrition by a Broviac® catheter. The patient presented several thrombosis following iterative catheter replacements. In parallel with superior vena cava plasty, a right intra-atrial Broviac® catheter was placed in the absence of other peripheral venous accesses. This device has a cutaneous exit site to allow for infusion of a hyperosmolar lipid emulsion. Seven days later, a milky liquid was secreted from pericardial/mediastinal redon. A gel lipoprotein electrophoresis of the fluid suggested a preliminary diagnosis of chylopericardium. However, biochemical testing of certain analytes evoked a parenteral nutrition-related pericardial effusion and a possible pseudochyloperitoneum caused by the shearing of a migrated Broviac® in pericardium. The patient, on a fat-free diet, was admitted to the ICU to drain the effusion and reposition the catheter, with success. In the light of new datas on the interference of parenteral lipid emulsions with the lipoproteins gel electrophoresis, we will try to determine whether the apparent presence of chylomicrons in the gel would be the sign of a lesion of the lymphatic system, or rather the result of a contamination by artificial chylomicron in the lipid emulsion, if not the sign of contaminated blood. In our article, we highlight several considerations in identifying and confirming cases of pericardial effusion, such as chylopericardium and parenteral nutrition-related one, as well as points concerning the use of lipid emulsions for pediatric patients with short-bowel syndrome.

Les liquides d'épanchements peuvent renfermer quelques surprises. Nous documentons le cas d'un patient de quatorze mois, hospitalisé en cardiologie, présentant un syndrome de grêle court et recevant une nutrition parentérale au long cours par cathéter Broviac®. Le patient présentait de multiples occlusions veineuses consécutives aux changements itératifs du dispositif. En parallèle d'une plastie de la veine cave supérieure, un Broviac® a été posé en intra-atrial droit devant l'absence d'autres abords veineux périphériques. Ce dispositif comporte un orifice de sortie sous-cutané pour apporter une solution de nutrition hyperosmolaire de type émulsion lipidique. Le liquide recueilli dans les drains péricardiques en post-opératoire est lactescent, particulièrement à partir du septième jour. Le lipidogramme du liquide d'épanchement péricardique semble conclure à la présence de chylomicrons - un chylopéricarde. Cependant, le dosage de certains analytes penche en faveur d'un perfusopéricarde, probablement pseudochyleux, lié au cisaillement du Broviac® dont l'extrémité a migré de l'oreillette droite au péricarde. Le patient, sous régime sans graisses, sans nutrition parentérale, sera réopéré pour drainer l'épanchement et repositionner le cathéter, avec succès. À la lumière de données originales quant à l'interférence des émulsions lipidiques sur le lipidogramme, nous tâcherons de déterminer si l'apparente présence de chylomicrons sur le gel serait le témoin d'une réelle lésion du lymphatique, ou plutôt le fruit d'une contamination par l'émulsion, si ce n'est par le sang. Des considérations au sujet des épanchements péricardiques, dont les chylopéricarde et nutripéricarde, ainsi que sur les émulsions lipidiques pédiatriques dans le contexte du grêle court émailleront ce travail.

Mitchell-Riley Syndrome: Improving Clinical Outcomes and Searching for Functional Impact of RFX-6 Mutations.

Aims/Hypothesis: Caused by biallelic mutations of the gene encoding the transcription factor RFX6, the rare Mitchell-Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Moreover, it demonstrates how the mutations impair the RFX6 function. Methods: Clinical records were analyzed and described in detail. The functional impact of two RFX6R181W and RFX6V506G variants was assessed by measuring their ability to transactivate insulin transcription and genes that encode the L-type calcium channels required for normal pancreatic beta-cell function. Results: All four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life and were treated with intravenous insulin therapy before switching to subcutaneous insulin pump therapy. All patients faced recurrent hypoglycemic episodes, exacerbated when parenteral nutrition (PN) was disconnected. A sensor-augmented insulin pump therapy with a predictive low-glucose suspension system was installed with good results. One patient had a homozygous c.1517T>G (p.Val506Gly) mutation, two patients had a homozygous p.Arg181Trp mutation, and one patient presented with new compound heterozygosity. The RFX6V506G and RFX6R181W mutations failed to transactivate the expression of insulin and genes that encode L-type calcium channel subunits required for normal pancreatic beta-cell function. Conclusions/Interpretation: Multidisciplinary and intensive disease management improved the clinical outcomes in four patients with MRS, including adjustment of parenteral/oral nutrition progression and advanced diabetes technologies. A better understanding of RFX6 function, in both intestine and pancreas cells, may break ground in new therapies, particularly regarding the use of drugs that modulate the enteroendocrine system.

Cannabinoids Improve Gastrointestinal Symptoms in a Parenteral Nutrition-Dependent Patient With Chronic Intestinal Pseudo-Obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is a rare and challenging cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life. Cannabinoids have been successfully used in some conditions. However, their use in CIPO has never been reported in the literature. We report a case of successful use of medicinal cannabinoids in a patient with CIPO, resulting in a significant reduction of abdominal pain, vomiting, and subocclusive episodes and increased appetite and weight, without major adverse events. Although further observations are required to consolidate these findings, this case may be helpful for other patients suffering from the same condition.