BACKGROUND: Short bowel syndrome (SBS) is a rare but serious form of organ failure, and patients with SBS depend on total parenteral nutrition (PN) to maintain growth and development. The present study aimed to evaluate the experiences and outcomes of children with SBS managed by a multidisciplinary intestinal rehabilitation programme in a tertiary paediatric centre.
METHODS: A retrospective single-centre analysis of all paediatric patients with a clinical diagnosis of SBS between 2001 and 2022 was performed. Clinical outcomes and their predictors were extracted and analysed.
RESULTS: Of the 64 children included in the study, 43 (67%) had extensive necrotising enterocolitis. The median bowel length was 45 cm (interquartile range (IQR) = 18-65) and 18.9% (IQR = 10-28.5) of the expected length based on age. Over a mean follow-up period of 8.9 years, 57 patients (89%) survived, and 50 (78%) weaned off PN. The presence of intestinal failure-associated liver disease (IFALD) (OR = 6.375, p = 0.02) and patients managed before the introduction of fish oil-based PN in 2007 (OR = 5.895, p = 0.001) were significant predictors of mortality. There was an overall improvement in survival over time (p = 0.003). Ultrashort bowel length was not associated with significantly higher mortality (OR = 1.1, p = 0.65) but was a poor prognostic factor for weaning off PN (OR = 3.57, p = 0.004). Among all patients who weaned off PN, two had bowel lengthening procedures and one received a glucagon-like peptide 2 (GLP-2) analogue.
CONCLUSIONS: A multidisciplinary intestinal rehabilitation programme offers a comprehensive approach for patients with SBS and has been shown to be effective with favourable outcomes. Improvements in the choice of PN and the development of new treatment strategies potentially improved the survival and enteral autonomy of SBS patients.
METHODS: III.

BACKGROUND: Cross-sectional plasma citrulline concentration (CIT) is considered a marker of enterocyte mass. The role of CIT in clinical practice in patients with short bowel syndrome (SBS) is not clearly defined.
OBJECTIVE: To assess the accuracy of CIT to discriminate SBS from healthy controls (HC) and SBS with intestinal failure (SBS-IF), requiring intravenous supplementation (IVS), from SBS with intestinal insufficiency (SBS-II).
METHODS: Cross-sectional study on unselected outpatients (31 SBS-II, 113 SBS-IF) and 19 healthy controls (HC). Demographic data, SBS characteristics, nutritional status, oral intake, intestinal fat absorption, renal function and IF severity, categorized by the volume of the required IVS, were collected at time of CIT evaluation (µmol/L). Data as mean±SD.
RESULTS: CIT was 36.6 ± 6.0 in HC, 30.2 ± 14.0 in SBS-II and 18.8 ± 12.3 in SBS-IF (p < 0.001). CIT cutoff was 31 for the diagnosis of SBS (sensitivity 79 %, specificity 89 %), and 14 for the discrimination between SBS-IF and SBS-II (sensitivity 100 %, specificity 51 %). Wide ranges of CIT were observed in all SBS-IF severity categories.
CONCLUSIONS: In unselected SBS patients, CIT was accurate to diagnose SBS, had high sensitivity to diagnose SBS-IF but showed low specificity for SBS-II. In SBS-IF, CIT was not an accurate marker of IF severity.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn\'s disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

BACKGROUND: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure.
METHODS: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences.
RESULTS: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels.
CONCLUSIONS: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Intestinal failure-associated liver disease (IFALD) is a serious complication of long-term parenteral nutrition in patients with short bowel syndrome (SBS), and is the main cause of death in SBS patients. Prevention of IFALD is one of the major challenges in the treatment of SBS. Impairment of intestinal barrier function is a key factor in triggering IFALD, therefore promoting intestinal repair is particularly important. Intestinal repair mainly relies on the function of intestinal stem cells (ISC), which require robust mitochondrial fatty acid oxidation (FAO) for self-renewal. Herein, we report that aberrant LGR5+ ISC function in IFALD may be attributed to impaired farnesoid X receptor (FXR) signaling, a transcriptional factor activated by steroids and bile acids. In both surgical biopsies and patient-derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T-βMCA in PDOs (an antagonist for FXR) dose-dependently reduced the population of LGR5+ cells and the proliferation rate of enterocytes, concomitant with decreased key genes involved in FAO including CPT1a. Interestingly, however, treatment with Tropifexor in PDOs (an agonist for FXR) only enhanced FAO capacity, without improvement in ISC function and enterocyte proliferation. In conclusion, these findings suggested that impaired FXR may accelerate the depletion of LGR5 + ISC population through disrupted FAO processes, which may serve as a new potential target of preventive interventions against IFALD for SBS patients.

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition following admission. Admissions included feeding and medication titration, interdisciplinary care, and home parenteral nutrition team consultation.

BACKGROUND: Short bowel syndrome with chronic intestinal failure (SBS/CIF) is the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance due to a short bowel. Although SBS/CIF is rare, its clinical management is complex, challenging, expensive, and time-consuming.
OBJECTIVE: This study aimed to analyze a single center\'s experience with SBS/CIF in adult patients treated with home parenteral nutrition (HPN).
METHODS: A retrospective single-center analysis of all 13 consecutive adult patients with SBS/CIF was included in an HPN program between January 1994 and August 2023.
RESULTS: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of starting HPN was 44 years. Most were subjected to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients died while on HPN with a median duration of 42 months. The causes of death related to HPN were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive, with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide with good tolerance and need a reduction in HPN support. All eight patients have a satisfactory quality of life (parenteral support needs range between five and two nutrition bags per week).  Conclusion: Home parenteral nutrition remains the gold standard of SBS/CIF treatment, although teduglutide may reduce HPN needs and complications and provide a better quality of life. Despite the small number of patients, the results shown in this study are not inferior to those in large-volume centers. The existence of the commitment and interest of professionals involved in SBS/CIF at Centro Hospitalar Universitário de Santo António, Portugal, was a fundamental key to achieving those results. A multidisciplinary healthcare group for HPN support can be essential to ensuring these patients\' survival and quality of life.

This comprehensive review focuses on advances in surgical techniques and in vivo animal models for treating short bowel syndrome (SBS) with intestinal organoids. Notably, this review discusses a novel method involving the replacement of the epithelium of large intestinal tissue with small intestinal organoids, which improves function and prognosis when grafted back into the small intestine. This study not only underscores the importance of integrating organoid technology and surgical techniques to improve the outcomes of patients with SBS but also acknowledges the challenges that lie ahead, including achieving functional organoids with peristaltic movement and vascularization.

In intestinal resection animal models of short bowel syndrome (SBS), the remaining epithelium mounts a robust adaptive response characterized by early stem cell expansion and increased crypt depth, villus height and nutrient absorption. In humans the adaptive response is critical for resumption of oral nutrition, yet it may be variable, and underlying mechanisms are much less well understood. Current knowledge relating to the role of stem and mesenchymal niche cells in the adaptive response in animal models and in human SBS are addressed in this review.

Malnutrition poses a critical challenge in inflammatory bowel disease, with the potential to detrimentally impact medical treatment, surgical outcomes, and general well-being. Parenteral nutrition is crucial in certain clinical scenarios, such as with patients suffering from short bowel syndrome, intestinal insufficiency, high-yielding gastrointestinal fistula, or complete small bowel obstruction, to effectively manage malnutrition. Nevertheless, research over the years has attempted to define the potential effects of parenteral nutrition on the intestinal barrier and the composition of the gut microbiota. In this narrative review, we have gathered and analyzed findings from both preclinical and clinical studies on this topic. Based on existing evidence, there is a clear correlation between short- and long-term parenteral nutrition and negative effects on the intestinal system. These include mucosal atrophic damage and immunological and neuroendocrine dysregulation, as well as alterations in gut barrier permeability and microbiota composition. However, the mechanistic role of these changes in inflammatory bowel disease remains unclear. Therefore, further research is necessary to effectively address the numerous gaps and unanswered questions pertaining to these issues.