Search Results (15)

Background/Objectives: Short bowel syndrome (SBS) is the leading cause of pediatric intestinal failure. Plasma citrulline is considered a marker indicating an enterocyte volume and may help evaluate the response to teduglutide; however, this interpretation may vary depending on the remnant bowel anatomy. Methods: We conducted a retrospective case series of four pediatric patients with SBS (aged < 15 years) who received teduglutide for 12 months at our hospital between 2018 and 2023. Changes in plasma citrulline levels and parenteral nutrition requirements were assessed in addition to bowel anatomy classification. Results: This study included two males and two females. All patients showed an increase in plasma citrulline levels and a reduction in the requirement for parenteral nutrition (PN) after 12 months of teduglutide treatment. In SBS type 2 (jejunocolic anastomosis), citrulline levels increased by 114% and 52%, with PN reduction rates of 100% and 30%, respectively. In SBS type 3 (jejunoileal anastomosis), citrulline levels increased by 13.6% and 34%, with PN reductions of 33% and 73%, respectively. Conclusions: Teduglutide treatment increased plasma citrulline levels and reduced PN levels in all cases. However, the magnitude of the citrulline change varied across bowel anatomy types, suggesting that the anatomical difference in the remnant bowel may influence the biomarker response. Further detailed pediatric cases are required to clarify the role of citrulline in evaluating GLP-2 analogue treatment outcomes. Full article

Short bowel syndrome (SBS) is a malabsorptive condition resulting from reduced functional small intestinal length. SBS is closely related to intestinal failure (IF), defined as the reduction of functional intestinal mass below that which can sustain life, resulting in parenteral nutrition (PN) support for 60 days or greater within a consecutive 74-day period. IF frequently results from intestinal resection necessitated by such diseases as necrotizing enterocolitis in children and Crohn’s disease in adults. Clinical manifestations of IF may include diarrhea, growth failure, bacterial overgrowth, and vitamin deficiencies. Nutritional rehabilitation is the cornerstone of IF management. Surgical interventions are aimed at preserving intestinal length and restoring continuity. Medical management involves individualized enteral and parenteral nutrition therapy, GLP-2 agonists (e.g., teduglutide) that promote mucosal growth, and drugs for symptom management such as antidiarrheals. Experimental therapies such as the use of devices to induce intestinal growth through distraction enterogenesis are under development for the treatment of IF. An interdisciplinary approach involving surgeons, gastroenterologists, dietitians, nurses, and social workers is crucial in the management of these complex patients. Ultimately, a combination of nutritional, medical, and surgical management may be necessary to improve clinical outcomes in patients with IF. Full article

Glucagon-like peptide-2 (GLP-2) is a gut hormone that plays a pivotal role in regulating intestinal epithelial cell growth and function, making it a promising therapeutic agent for intestinal damage and bone-related diseases. Nonetheless, the therapeutic potential of GLP-2 is substantially diminished due to its inactivation by dipeptidyl peptidase 4 (DPP-4). In recent years, advancements have been made in developing dipeptidyl peptidase 4 (DPP-4) resistant GLP-2 analogues with an extended half-life. The murine model with extensive experimental bowel resection maintained on parenteral nutrition has been used for assessing the physiology and pharmacology of GLP-2, and for the preclinical validation of GLP-2 analogues. However, it possesses certain limitations, such as complex procedure, considerable variability, and time-consuming nature. Consequently, there is a pressing need for the development of a cell-based bioassay to assess GLP-2 analogues. Here, we successfully developed a mechanism-of-action (MOA)-reflective cell-based reporter gene assay (RGA), utilizing a stable HEK293 cell line expressing the GLP-2 receptor and a luciferase reporter gene. This innovative approach allows for precise quantification of the potency of GLP-2 analogues. The RGA demonstrated good accuracy, linearity, precision, and specificity, with potential applications in stability testing, drug screening, and therapeutic monitoring of GLP-2 analogues. Moreover, RNA sequencing reveals the multi-target regulatory effect of GLP-2 analogues. The establishment of this RGA provides a valuable tool for evaluating the potency of GLP-2 analogues and the screening of potential therapeutic drugs targeting to GLP-2 receptor. Full article

Background/Objectives: Home parenteral support (HPS) is the core of chronic intestinal failure (IF) treatment. For legal reasons, HPS in Portugal lags behind other European countries, and only a few patients were taken care of at home by nurses. Now, the legislation has changed, allowing patient self-care. The authors report their pioneer experience as the largest Portuguese IF center, evaluating the underlying conditions leading to IF, HPS nutritional impact, HPS-related complications and survival. Methods: This is a retrospective study including IF patients who underwent HPS in a Portuguese IF center. The data included demographics, underlying conditions, IF types, HPS duration, BMI at the beginning and end of HPS/follow-up, complications, microbiological agents of infectious complications and current status (deceased or alive with/without HPS). Survival was calculated until death or September 2024. Results: A total of 23 patients (52.2% female, mean age 57.3 years), all with type III IF, were included. Short bowel syndrome (SBS) was the most common cause of IF (69.6%). Of the included patients, 78.3% received home parenteral nutrition; the others received home parenteral hydration. The mean BMI increased significantly, from 19.1 kg/m² to 22.5 kg/m² (p < 0.001). Two patients received Teduglutide. The most common complication was catheter-related bloodstream infection (2.5/1000 catheter days). The complications did not increase with patient self-care. At the end of follow-up, 21.7% of patients remained on HPS, 34.8% were alive without HPS, and 43.5% died. The average survival was 43.4 months. One death (4.35%) was attributable to HPS-related complications. Conclusions: The conditions underlying IF varied, with SBS being the most frequent condition. HPS improved the BMI, allowing considerable survival. Despite the complications and one attributable death, HPS was safe, even when relying on patient self-care. Full article

Background: This study aimed to gain real-world insights from healthcare professionals (HCPs) regarding the management of adult patients with short bowel syndrome and intestinal failure (SBS-IF) who received teduglutide and achieved parenteral support (PS) independence or PS volume stability for ≥12 months. Methods: This cross-sectional survey was conducted in five European countries and Canada via a self-reported questionnaire (November 2022–March 2023) among HCPs who manage patients with SBS-IF and who had prescribed teduglutide to ≥5 patients with SBS-IF receiving PS. Results: Of the 70 HCPs who completed the survey, almost all reported managing patients with SBS-IF who achieved PS independence or PS volume stability (99%, 69/70 and 97%, 68/70, respectively) and maintained the standard teduglutide dose, without changes. A total of 52 HCPs managed patients who achieved PS independence and discontinued teduglutide. Of these HCPs, 73% (38/52) anticipated that these patients would remain PS-independent, not requiring PS reintroduction. Of the remainder, 79% (11/14) estimated that ≤40% of these patients would require PS reintroduction. While many HCPs (81%, 42/52) would reintroduce teduglutide in patients who discontinued its use after achieving PS independence, none would do so for patients who discontinued teduglutide after achieving PS volume stability if a patient’s condition worsened. Conclusions: This survey found that patients with SBS-IF can achieve PS independence or PS volume stability with teduglutide treatment. However, some HCPs (27%, 14/52) believe that a proportion of patients discontinuing teduglutide after achieving PS independence will require PS reintroduction. This survey suggests that teduglutide treatment should continue uninterrupted, unless clinically indicated, but this requires confirmation in future studies. Full article

Background/Objectives: Limited data exist on the epidemiology and clinical management of short bowel syndrome (SBS) and chronic intestinal failure (CIF) in Crohn’s disease (CD). This study aimed to evaluate these aspects in Italy. Methods: Members of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) were invited to complete a cross-sectional web survey. A subgroup analysis examined the influence of different clinical settings on SBS and CIF management in CD. Results: A total of 47/128 (36.7%) IG-IBD centers participated. Among them, 31.9% were teduglutide (TED) prescribers, and 48.9% were academic centers. The median estimated prevalence of CIF among small bowel CD patients was 1%, and it was significantly higher in academic centers (2.0% [IQR 1–5%] vs. 0.13% [IQR 0–1%], p = 0.02). Seventy-eight percent of centers managed fewer than 10 SBS and CD patients. Routine small bowel measurement and nutritional assessment were performed in only 15% and 42.6% of centers, respectively. TED was prescribed by 12 centers to 35 patients, with a treatment success rate exceeding 50% in 81.8% of centers. Conclusions: The estimated prevalence of CIF in CD patients with small bowel involvement in Italy is 1%. The diagnosis and management practices for SBS and CIF are suboptimal, and TED use is limited. Full article

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. Full article

(1) Background: We present the first real-world-data study on teduglutide-treated SBS patients in the Slovak Republic and the first study to enable the comparison of the effects of teduglutide treatment between the adult and pediatric populations. (2) Methods: This was a non-interventional retrospective cohort study of adult and pediatric SBS patients treated with teduglutide. Primary and secondary endpoints were the results of teduglutide use at 12 weeks and 6 months after the initiation of treatment, compared to baseline. (3) Results: Teduglutide treatment led to a statistically significant reduction in the volume of intravenous hydration, HPN caloric intake, HPN and intravenous hydration applications per week and to increased urine output in adult patients. The results in the pediatric population were similar, but not statistically significant. A complete weaning off HPN was achieved in 57.14% of all patients (50.00% of children; 62.50% of adults) after a median of 0.99 years of teduglutide treatment (1.07 and 0.98 years for children and adults, respectively). (4) Conclusions: Teduglutide treatment in SBS patients leads to considerable reduction in or even weaning off PN in both pediatric and adult patients. Full article

Introduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Methods: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. Results: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Conclusions: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide. Full article

Teduglutide, a GLP-2 analogue, has been available in France since 2015 to treat short-bowel-syndrome (SBS)-associated chronic intestinal failure (CIF) but it remains very expensive. No real-life data on the number of potential candidates are available. The aim of this real-life study was to assess teduglutide initiation and outcomes in SBS-CIF patients. All SBS-CIF patients cared for in an expert home parenteral support (PS) center between 2015 and 2020 were retrospectively included. Patients were divided into two subpopulations: prevalent patients, already cared for in the center before 2015, and incident patients, whose follow-up started between 2015 and 2020. A total of 331 SBS-CIF patients were included in the study (156 prevalent and 175 incident patients). Teduglutide was initiated in 56 patients (16.9% of the cohort); in 27.9% of prevalent patients and in 8.0% of incident patients, with a mean annual rate of 4.3% and 2.5%, respectively. Teduglutide allowed a reduction in the PS volume by 60% (IQR: 40–100), with a significantly higher reduction in incident versus prevalent patients (p = 0.02). The two- and five-year treatment retention rates were 82% and 64%. Among untreated patients, 50 (18.2%) were considered ineligible for teduglutide for non-medical reasons. More than 25% of prevalent SBS patients were treated with teduglutide compared to 8% of incident patients. The treatment retention rate was >80% at 2 years, which could be explained by a careful selection of patients. Furthermore, this real-life study confirmed the long-term efficacy of teduglutide and showed a better response to teduglutide in incident patients, suggesting a benefit in early treatment. Full article

Background: Quality of life (QoL) data of chronic intestinal failure (cIF) patients treated with the GLP-2 analogue teduglutide are scarce. This study aims to analyze QoL changes over time in teduglutide-treated patients and compare the results to a matched non-treated cIF control group in a real-world setting. Methods: QoL data (SF-36 and SBS-QoL^TM) were obtained from adult cIF patients being treated with teduglutide and compared to previously collected QoL data from a PNLiver trial (DRKS00010993), during which patients had been therapy naive. The dataset was then extended by a pairwise matched control group (non-teduglutide-treated PNLiver trial patients) and follow-up data from this group were collected accordingly. Results: Median teduglutide treatment duration and the follow-up period of controls were both 4.3 years. SBS-QoL^TM subscales and the SBS-QoL^TM sum score showed significant improvements over time in teduglutide-treated patients, as well as for the SF-36 physical and mental component summary scores (all p < 0.02), while non-treated patients showed no significant changes in any of the mentioned scores. Significant differences of QoL changes between treated and non-treated patients were seen for both SF-36 summary scores (p = 0.031 and 0.012). Conclusions: We herein demonstrate for the first time that QoL significantly improved during teduglutide treatment in SBS-cIF patients in a real-world setting compared to individually matched non-treated SBS-cIF patients, indicating relevant clinical benefits. Full article

The differences in outcomes after weaning off intravenous support (IVS) for chronic intestinal failure (IF) are unclear. Adult IF patients who are weaned off IVS at a tertiary care center (June 2019–2022) were included in this study, and nutritional and functional markers were assessed before, during, and after weaning. Short bowel syndrome (SBS) was present in 77/98 of the IF patients, with different outcomes according to the final anatomy. The body weight and the BMI increased during IVS in those with a jejunocolonic (JC) anastomosis (p < 0.001), but weight loss was significant during follow-up (p < 0.001). Malnutrition was present in >60%, with a reduced muscle mass, which was found using bioelectrical impedance analysis (BIA), in >50% of SBS-JC patients. Although reduced hand-grip strength and sarcopenia were less common, the muscle quality, or phase angle (BIA), decreased during follow-up, also correlating with serum albumin and muscle mass (p ≤ 0.01). The muscle quality and albumin were low in the patients restarting IVS, which was only the case with ≤60 cm of small bowel. Closer follow-up and earlier treatment with teduglutide (TED) should be considered in these patients, as none of the TED-treated patients were malnourished or sarcopenic. Studies on the potential benefits of nutritional and physical interventions for low muscle mass and associations with outcomes are needed in chronic IF patients. Full article

Teduglutide (TED) is widely used in patients with short-bowel-syndrome-associated intestinal failure (SBS-IF) to enhance intestinal adaptation and reduce the need for parenteral support (PS). There are limited data on the effects of discontinuing TED. In this study, we describe the changes in parenteral nutrition (PN) requirements and body mass index (BMI) in a 9-year follow-up of patients receiving home parenteral nutrition after discontinuation of the TED treatment. We performed a retrospective analysis of changes in weekly PN orders and BMI in all patients with PN-dependent SBS from two Polish home parenteral nutrition (HPN) centers who received teduglutide between 2009 and 2013 and still required HPN 9 years after discontinuation of the TED treatment. Data included in the analysis were collected prospectively at mandatory visits to the HPN centers at 12, 24, 60, 84, and 108 months after drug discontinuation and compared with values before and after TED treatment. Weekly PN volume values varied significantly between all of the above time points from baseline to 9 years after TED discontinuation (χ² = 34.860, p < 0.001). After an initial increase within the first year after treatment discontinuation (not statistically significant), the PN volume requirements remained stable for 4 years and increased 5–9 years after treatment discontinuation. The rate of patients requiring an increase in PN volume was 84.62% at 60 and 84 months and 92.30% at 108 months. At 9 years after cessation of the TED treatment, 53.85% of the study group required a 21.21% increase in PN volume compared with values before treatment. The need for PN volume in patients with PN-dependent SBS who discontinued the TED treatment increased within the first year and 4–5 years after treatment cessation, and in some cases might even exceed pretreatment values after 9 years. Full article

Teduglutide has been described as an effective treatment for parenteral support (PS) reduction in patients with short bowel syndrome (SBS). However, a quantitative summary of the available evidence is still lacking. PubMed/Medline, EMBASE, Cochrane library, OVID, and CINAHL databases were systematically searched up to July 2021 for studies reporting the rate of response (defined as a ≥20% reduction in PS) to teduglutide among PS-dependent adult patients. The rate of weaning (defined as the achievement of PS independence) was also evaluated as a secondary end-point. Ten studies were finally considered in the meta-analysis. Pooled data show a response rate of 64% at 6 months, 77% at 1 year and, 82% at ≥2 years; on the other hand, the weaning rate could be estimated as 11% at 6 months, 17% at 1 year, and 21% at ≥2 years. The presence of colon in continuity reduced the response rate (−17%, 95%CI: (−31%, −3%)), but was associated with a higher weaning rate (+16%, 95%CI: (+6%, +25%)). SBS etiology, on the contrary, was not found to be a significant predictor of these outcomes, although a nonsignificant trend towards both higher response rates (+9%, 95%CI: (−8%, +27%)) and higher weaning rates (+7%, 95%CI: (−14%, +28%)) could be observed in patients with Crohn’s disease. This was the first meta-analysis that specifically assessed the efficacy of teduglutide in adult patients with SBS. Our results provide pooled estimates of response and weaning rates over time and identify intestinal anatomy as a significant predictor of these outcomes. Full article

A healthy intestinal barrier prevents uptake of allergens and toxins, whereas intestinal permeability increases following chemotherapy and in many gastrointestinal and systemic diseases and disorders. Currently, there are no approved drugs that target and repair the intestinal epithelial barrier while there is a medical need for such treatment in gastrointestinal and related conditions. The objective of this single-pass intestinal perfusion study in rats was to investigate the preventive cytoprotective effect of three mucosal protective drugs—melatonin, misoprostol, and teduglutide—with different mechanisms of action on an acute jejunal injury induced by exposing the intestine for 15 min to the anionic surfactant, sodium dodecyl sulfate (SDS). The effect was evaluated by monitoring intestinal clearance of ⁵¹Cr-labeled ethylenediaminetetraacetate and intestinal histology before, during, and after luminal exposure to SDS. Our results showed that separate pharmacological pretreatments with luminal misoprostol and melatonin reduced acute SDS-induced intestinal injury by 47% and 58%, respectively, while their use in combination abolished this injury. This data supports further development of drug combinations for oral treatments of conditions and disorders related to a dysregulated or compromised mucosal epithelial barrier. Full article