Teduglutide (TED), a glucagon-like peptide 2 analogue licensed for children with short bowel syndrome (SBS), is increasingly used in the attempt to augment intestinal absorption and lower parenteral nutrition (PN) needs. Data from real-life studies on TED efficacy and predictors of response in children with SBS are limited. This study aimed to define pre-treatment and on-treatment predictors of response, in terms of PN reduction and weaning, in TED treated children with SBS. In this multicenter cohort study, we collected retrospective and prospective data of children with SBS undergoing TED treatment in 7 countries in Europe (Italy, Spain, Croatia, Germany, France, Israel, Portugal). All children with SBS starting TED treatment and not included in clinical trials were eligible. Information on patients’ post-surgical anatomy, amount of PN calories and volume required at baseline and at 3, 6 and 12 months after TED start, along with biochemical markers of PN tolerance and complications, were recorded. The main outcome was predicting factors of 1 year response to TED treatment defined as a reduction of ≥20% of PN needs. Between 01.06.2021 and 31.05.2023, we collected information on 104 children (64 males, 61.5%; 40 females, 38.5%) the median age at enrolment was 6.7 years old (IQR: 3.6–10.4); at 12 months’ follow up after TED start 68 children achieved response (cumulative incidence: 70%, 95% CI 61%–79%), whereas complete PN weaning was achieved in 21 children (cumulative incidence: 22%, 95% CI 15%–31%). Multivariable logistic regression analysis showed that predictors of response were longer residual small bowel length (p = 0.027), higher weight Z-score at baseline (p = 0.0061) and normal liver enzymes (p = 0.010). Pre-treatment PN calories <35 kcal/kg/day (p = 0.044) and citrulline ≥14 μmol/L (p = 0.047) predicted complete PN weaning, as well as haemoglobin and citrulline rise in the first 6 months of treatment (p = 0.014 and p = 0.044 respectively). In children with SBS, longer residual small bowel, better nutritional status and absence of liver disease were associated with response to teduglutide. Complete PN weaning was predicted by lower calories needs and higher citrulline at baseline. An increase of haemoglobin and citrulline in the first 6 months of treatment were further predictors of complete PN weaning. Even if limited by the real-life design of the study, these findings may guide a tailored indication for the use of teduglutide in children with short bowel syndrome. The European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Networking grant.

Children with chronic intestinal failure (IF) require a long-term central venous catheter (CVC) for provision of parenteral nutrition. Vascular, mechanical and infectious complications such as central line-associated bloodstream infections (CLABSI) may lead to progressive loss of venous access sites. Handling and management of CVCs therefore play an important role. Our vascular rehabilitation concept (VRC) is a core component of our intestinal rehabilitation program (IRP) and consists of an education program, optimization of skin care, catheter fixation and lock solution, and the use of hybrid technique for catheter placement. Aim of this study is to analyse the effectiveness of our VRC on CLABSI rates and need for CVC replacements. Retrospective analysis of all children treated in our IRP that were followed up between 2018 and 2023. A total of 117 children with chronic IF could be included for analysis of 248864 catheter days (CD). 91 patients were referred from other hospitals (127117 CD before and 89359 CD after entry into our IRP). Children receiving primary care at our IRP (32388 CD) showed a significantly lower CLABSI and line replacement rate than patients referred from external centers (p < 0.001). After entering our IRP, CLABSI rates and need for CVC replacements per 1000 CD decreased significantly in referred patients: 1.19 to 0.26 and 1.77 to 0.59, respectively (p < 0.001). Management of paediatric chronic IF patients by an IRP with a vascular rehabilitation concept significantly lowers the rate of CLABSI episodes and the need for catheter replacements.

Objectives: Paediatric acute liver failure (PALF) is a life‐threatening disease. Management aims to support hepatic regeneration or to bridge to liver transplantation. High‐volume plasmapheresis (HVP) removes protein‐bound substances, alleviates inflammation, and improves survival in adult acute liver failure. However, experience with HVP in PALF is limited. Aim of this study is to report on feasibility, safety, efficacy and outcomes of HVP in PALF.Methods: Retrospective observational study in children with PALF. HVP was performed upon identification of negative prognostic indicators, in toxic aetiology or multiorgan failure (MOF). Exchanged volume with fresh‐frozen plasma corresponded to 1.5–2.0 times the patient's estimated plasma volume. One daily cycle was performed until the patient met criteria for discontinuation, that is, liver regeneration, liver transplantation, or death.Results: Twenty‐two children with PALF (body weight 2.5–106 kg) received 1–7 HVP cycles. No bleeding or procedure‐related mortality occurred. Alkalosis, hypothermia and reduction in platelets were observed. Haemolysis led to HVP termination in one infant. Seven children (32%) survived with their native livers, 13 patients (59%) underwent liver transplantation. Two infants died due to MOF. Overall survival was 86%. International normalization ratio (INR), alanine aminotransaminases (ALT), bilirubin and inotropic support were reduced significantly (p < 0.05) after the first HVP‐cycle (median): INR 2.85 versus 1.5; ALT 1280 versus 434 U/L; bilirubin 12.7 versus 6.7 mg/dL; norepinephrine dosage 0.083 versus 0.009 µg/kg/min. Median soluble‐interleukin‐2‐receptor dropped significantly following HVP (n = 7): 2407 versus 950 U/mL (p < 0.02).Conclusions: HVP in PALF is feasible, safe, improves markers of liver failure and inflammation and is associated with lowering inotropic support. Prospective and controlled studies are required to confirm efficacy of HVP in PALF.

Background: Exocrine pancreatic insufficiency in cystic fibrosis (CF) increases fecal choline losses, but the postnatal course of plasma choline and its metabolites in these patients is unknown. While choline homeostasis is crucial for cellular, bile, and lipoprotein metabolism, via phosphatidylcholine (PC) and via betaine as a methyl donor, choline deficiency is associated with impaired lung and liver function, including hepatic steatosis. Objective: The goal of our study was to evaluate the plasma levels of choline, betaine, trimethylamine oxide (TMAO), PC, and PC subclasses in CF patients from infancy to adulthood and compare those with exocrine pancreatic insufficiency (EPI) to those with pancreatic sufficiency (EPS). Methods: Retrospective analysis of target parameters in plasma samples (July 2015–November 2023) of CF patients (0.64–24.6 years) with tandem mass spectrometry. Results: A total of 477 samples from 162 CF patients were analyzed. In CF patients with EPI (N = 148), plasma choline and betaine concentrations were lower and decreased with age compared to EPS patients showing normal values. TMAO concentrations, indicating intestinal choline degradation by bacterial colonization, were frequently elevated in EPI from infancy onwards, and inversely related to plasma choline and betaine levels. PC-containing linoleic acid levels were lower in EPI, but arachidonic and docosahexaenoic acid content was similar in both patient groups. Conclusion: CF patients with EPI are at risk of choline and betaine deficiency compared to exocrine pancreas-sufficient CF patients. Elevated TMAO concentrations in EPI patients indicate increased bacterial colonization leading to choline degradation before absorption. These findings indicate that laboratory testing of choline, betaine, and TMAO as well as clinical trials on choline supplementation are warranted in CF patients.

Background: Patients with progressive familial intrahepatic cholestasis (PFIC) experience cholestasis-associated symptoms, including severe pruritus. Odevixibat is an ileal bile acid transporter inhibitor indicated for treatment of PFIC in the European Union and for the treatment of pruritus in PFIC in the United States. The aim of the current study was to characterize the real-world effectiveness and safety of odevixibat in patients with PFIC. Methods: This retrospective study included 9 patients with PFIC treated with odevixibat in a single center in Tübingen, Germany. Data were recorded using case report forms. Results: Of the 9 patients (PFIC1, n = 2; PFIC2, n = 7), 5 had improved serum bile acid levels, pruritus, liver function tests, and sleep with odevixibat treatment. Two siblings with periodic relapses of PFIC symptoms also had improved pruritus and sleep within 4 months of treatment. Two siblings with complete loss of bile salt export pump (BSEP) protein did not respond to treatment; both underwent liver transplantation (indications: hepatocellular carcinoma [HCC] manifestation [n = 1] and severe failure to thrive and refractory pruritus [n = 1]). Four patients reported abdominal complaints that were transient or responded to dose reduction; no other safety issues were reported. Conclusions: In this case series, clinical benefits were observed in most patients with PFIC1 and PFIC2 treated with odevixibat. In patients with periodic relapse of PFIC symptoms, ≥3 months of treatment with odevixibat may be required for symptom control. Patients with complete loss of BSEP did not have consistent symptom relief and require careful monitoring. Effectiveness and feasibility results from our cohort demonstrate potential for long-term benefits with odevixibat in real-world treatment of patients with PFIC.