Protective effects of magnolol, an active compound of Houpu Sanwu Tang, on intestinal barrier function in sepsis: Mechanisms of PPARG activation and inhibition of JAK-STAT and NF-κB signaling.

Major burn injury triggers systemic inflammation and metabolic responses beyond the skin. Early intestinal barrier failure can amplify post-burn inflammation and organ dysfunction, yet the dynamic epithelial lesions that generate focal leakage in vivo remain unclear. We characterized villus-tip epithelial shedding, epithelial gap formation, and tracer leak sites early after burn using intravital multiphoton fluorescence microscopy. Male C57BL/6 mice were assigned to Control or Burn groups (30-35% total body surface area full-thickness burn; n=6/group). Intestinal permeability was assessed at 2, 4, and 6 hours post-injury using luminal fluorescein isothiocyanate-dextran (4 kilodaltons) with portal venous sampling. Distal-ileum intravital imaging was performed 330-420 minutes post-injury (1-minute intervals). Ten villi per mouse were quantified for shedding duration and prevalence, condensation-first versus extrusion-first sequence, epithelial gap density, goblet-cell proportion, and focal luminal tracer leak sites. Major burn shortened shedding duration and increased shedding prevalence during the 90-minute observation (p<0.05), with a shift toward a condensation-first pattern and fewer extrusion-first events (p<0.05). Burn increased epithelial gap density and goblet-cell proportion (p<0.05). Portal serum fluorescein isothiocyanate-dextran concentrations were elevated at 6 hours (p<0.05), and imaging localized tracer penetration to discrete post-shedding epithelial defects, consistent with incomplete sealing. Major burn rapidly disrupts intestinal barrier integrity through accelerated stress-associated shedding, increased gap formation, and focal leak sites. These time-resolved structural lesions provide an in vivo substrate for early hyperpermeability and suggest a time-critical window for gut-directed interventions to mitigate downstream post-burn complications.

We evaluated the efficacy and safety of teduglutide in a real-world cohort in which national reimbursement policies required treatment interruptions. The primary outcomes were reduction in parenteral support (PS) and treatment-related adverse effects, and the secondary outcome was the impact of the mandated withdrawal periods. In this retrospective registry-based nationwide study, we identified all pediatric short bowel-associated intestinal failure (IF) patients treated with teduglutide and reviewed clinical records to evaluate PS reduction and adverse effects during treatment and withdrawal. Twenty pediatric IF patients had teduglutide initiated (age range: 1.4-17 years) between 2016 and 2022. Patients had a median 16% small bowel remaining, and 16 (79%) had the ileocecal valve removed. Children who continued teduglutide over 6 months (n = 19) had a median of 31 (range: 13-56) months of follow-up on medication. Their median reductions in daily PS energy and fluid volume requirement were 42% and 28 mL/kg/day, respectively. Weekly infusion-free nights increased from 0.5 to 4. Seventeen (89%) patients reached >20% energy reduction. Six patients (32%) successfully weaned off PS. Four patients (20%) experienced intestinal bleeding while on teduglutide. Stomal prolapses occurred in all patients with end-jejunostomies. Periodic withdrawal (n = 37) led to adverse effects on 84% of occasions (n = 32), including two unplanned hospitalizations and 14 (38%) outpatient visits, dehydration in 19 (51%), and diarrhea in 28 (76%) occasions. Teduglutide resulted in clinically significant PS reduction and increased infusion-free nights. The periodic withdrawal of teduglutide was harmful and should not be routinely employed. ClinicalTrials.gov identifier: HUS/265/2023.

Multi-omics analysis of pediatric short bowel syndrome induced intestinal failure and associated liver disease: Association with gut microbial deviations.

Intestinal failure outcomes in children with small-intestinal Hirschsprung disease: A matched study.

<h2>Abstract</h2><h3>Background</h3> A new role within an intestinal failure unit was devised, which involved training a dietitian to undertake the role of an Advanced Practitioner working within the medical team. In the United Kingdom, dietitians can only undertake supplementary prescribing qualifications, and this study evaluates the safety and effectiveness of this type of prescribing practice in an intestinal failure Advanced Practitioner role. <h3>Materials and methods</h3> All adult inpatients with types 2 and 3 intestinal failure were included. An appropriate clinical management plan was agreed by the multidisciplinary team and a medical and surgical consultant reviewed the prescriptions made, including the clinical indication and rationale. Descriptive statistical analysis was used and data presented as means (+/- standard deviation) for continuous variables and percentages for categorical variables. <h3>Results</h3> A total of 1030 prescription episodes were made by the supplementary prescriber in the 6-month study period. Of these episodes, 96.2 % (<i>n</i> = 991) related to parenteral or intravenous fluid prescriptions; 13.6 % (<i>n</i> = 135) of which related to a combination of parenteral support and intravenous fluid prescriptions and 0.2 % (<i>n</i> = 2) of these episodes were for resuscitation purposes. No prescription amendments were required following a weekly review by the medical or surgical consultant. <h3>Conclusion</h3> This study demonstrates that a dietetic-based Advanced Practitioner in a busy intestinal failure unit effectively and safely incorporated supplementary prescribing into their role. Supplementary prescribing was used to initiate a range of prescriptions, as part of a clinical management plan, and all were deemed to be the optimal prescription choice for the indication identified.

Studies investigating growth impairment (GI) in children with intestinal failure (IF) have seldom reported its associated factors. We hypothesized that a deficient nutritional intake would affect GI in children with IF. Nineteen patients (2-16 years old) who underwent home-based parenteral nutrition (PN) management at our institution, were divided into patients with or without GI (GI+/GI-). GI was defined as a height-for-age z-score (HAZ) ≤ -2. We performed between-group comparisons of HAZ in the intestinal rehabilitation program (IRP)/nutrition support team (NST) introduction time, PN dependency, residual small intestine length (RSIL), nutritional intake (calorie, protein, lipids, and carbohydrates), caloric intake ratio, and nutrient intake as a percentage of the recommended intake. Six patients were in the GI+ group. PN dependency was significantly higher in the GI+ group (GI+, 109.8 %; GI < median, 61.7 %, P = 0.036). RSIL did not differ significantly between the groups (50 cm vs. 45 cm, P = 0.879). In the GI+ group, the caloric percentage of lipids was significantly lower (11.9 % vs. 17.5 %, P = 0.002), but that for carbohydrates was significantly higher (76.8 % vs. 66.8 %, P = 0.002), while lipid sufficiency was significantly lower (37.5 % vs. 89.6 %, respectively; P < 0.001). Protein intake in the GI+ group was significantly lower; however, the corresponding sufficiency was > 100 % in both groups (136.5 % vs. 209.2 %, P = 0.005). For children with IF, a low intake ratio of proteins and lipids relative to energy requirement and required nutrient levels may inhibit adequate growth.

Microbiota-oriented strategies to mitigate parenteral nutrition–related complications in intestinal failure: A narrative review

Background &amp; Aims: Resting energy expenditure (REE) is a critical parameter for assessing energy requirements in patients with chronic intestinal failure (CIF). This study aimed to investigate the influence of intestinal functionality, defined by the need for parenteral nutrition (PN), on REE and to evaluate the accuracy of Harris-Benedict equation (HB-equation) used to estimate REE (eREE) in individuals with CIF. Methods: A cross-sectional study was conducted among patients diagnosed with CIF. Data collected was demographic information, body composition measured by bioelectric impedance analysis, measured REE (mREE) by indirect calorimetry and data from the patients’ medical records like pathophysiological mechanisms, underlying diseases, receiving PN or not, information related to nutritional risk and blood samples (CRP and albumin). Furthermore, eREE was calculated by the HB-equation. Results: Overall, 201 patients were included (mean age: 61.8±14.8 years, sex: 65.0% female). There was a significant difference between patients with short bowel syndrome, other underlying pathophysiological mechanisms and other diseases P<0.001. No significant difference was observed in overall mREE between patients receiving PN and those not receiving PN. However, significant differences were observed for REE/kg body weight, REE/kg muscle mass, and REE/kg fat free mass between patients receiving PN and those not receiving PN. REE was lower, when estimated compared to measured (P=0.003), and the group with SBS, cancer and those not receiving PN, had lower REE when estimated compared to measured (P<0.05). Conclusion: Intestinal functionality had no influence on REE, however REE/kg mass was higher in the PN-group for body weight, muscle mass and fat free mass. When comparing the HB-equation with IC, eREE was overall lower compared to mREE. This study emphasizes the need for more accurate equations to estimate REE in CIF patients, highlighting that IC is essential for precise measurement at present time.

Suramin directly targets PI3K to alleviate experimental colitis by restoring intestinal barrier and activating autophagy.

Accumulated Consequences: Severe Intestinal Failure in Familial Mediterranean Fever.

There is a drive in some countries to increase the use of multichamber bags as an alternative to compounded parenteral support for patients with chronic intestinal failure to preserve aseptic pharmacy capacity. If a required regimen is that of a multichamber bag plus one intravenous fluid product, then the potential combinations of available products can exceed 3000. A computer-based selection algorithm known as "PNMatch" was developed, which uses a "k-nearest neighbor" strategy for matching. After completion of the computational design for the algorithm, a staged testing and development process was undertaken, evaluating the algorithm against clinician prescribing. A matching assessment was then undertaken against existing prescriptions. Algorithm functionality was assessed through 20 parenteral nutrition formulation requests, all of which were successfully processed. Prescription selection demonstrated a 90% exact match rate, with one unmatched case and one nonimproved match. The mean time for prescription selection using PNMatch was 116 s. Multichamber bag requests were then evaluated. Most prescriptions matched closely with the existing formulations, achieving a Cohen kappa value of 0.8. Further analysis of 44 formulation requests showed successful product selection for 43 requests. The mean difference in volume was -75.3 ml, and for potassium, it was -4.9 mmol. This is the first demonstration of the successful development and testing of a computer-based selection algorithm for the prescription of a multichamber bag-based regimen for patients with chronic intestinal failure. This has the potential to improve efficiency and reduce variability in parenteral support prescribing.

Pure fish oil-based fat emulsion (FO-ILE) dosed at 1 g/kg/day is FDA approved for the treatment of intestinal failure associated liver disease. However, this limited fat provision can lead to suboptimal weight gain and excessive caloric intake from dextrose, particularly in neonates. There is limited data on the use of FO-ILE at doses higher than 1 g/kg/day. This study describes our experience with pediatric patients receiving 1.5 g/kg/day of FO-ILE. A retrospective chart review was performed on patients receiving parenteral nutrition aged 0-18 years and receiving FO-ILE at a dose of 1.5 g/kg/day for at least 14 days. Clinical outcomes of interest included weight gain, glucose infusion rates (GIRs) and adverse effects including cholestasis, postprocedure hemorrhage, hypertriglyceridemia and essential fatty acid (EFA) deficiency. Nine patients (range 2 months-12.9 years) receiving 1.5 g/kg/day of FO-ILE were included. Seven patients showed improved weight gain. Decrease of GIR was noted in four patients. One patient experienced worsening cholestasis with no clear etiology which prompted the decrease of FO-ILE to 1 g/kg/day with later resolution of cholestasis. Seven patients underwent invasive procedures, with one patient experiencing more than expected bleeding after circumcision not necessitating a decrease in dose. None of the patients developed hypertriglyceridemia. Eight patients had an EFA panel collected, all within normal limits. Our findings suggest that higher doses of FO-ILE may be safe and beneficial in patients with suboptimal weight gain, and elevated GIR. Larger and long-term studies are required to validate these observations.

Addressing gaps in pediatric resident education on the management of intestinal failure in the United States: Creation and implementation of a targeted curriculum

To determine the impact of social determinants of health (SDOH) on outcomes in pediatric short bowel syndrome (SBS) patients. A retrospective cohort of SBS children managed by an Intestinal Rehabilitation Program was analyzed. Socio-economic variables including income, race, distance to hospital, parental education and immigrant status were chosen to assess whether they independently predicted the following outcomes: enteral autonomy (EA), central line associated blood stream infection (CLABSI), intestinal failure associated liver disease (IFALD), and mortality. Bowel anatomy, prematurity, and disease type were controlled for. Univariate analysis and Cox proportional hazards model (CPH) were performed, where an alpha-value of <0.05 was significant. A total of 161 patients were analyzed between 2006 and 2019. The median gestational age was 34 (29.0-37.0) weeks and 61.9% were male. EA was achieved in 63.5%, 22.5% developed IFALD, and 10% died. The median CLABSI rate was 4.0 (0.4-11.1) per 1000 catheter days. CPH modeling revealed that the only social factor positively associated with attaining EA was non-white race (p = 0.03). Parental post-secondary education was associated with a lower risk of CLABSI (p = 0.04) while those living larger distances from hospital had an increased risk (p = 0.02). The development of IFALD was also positively associated with greater distance from hospital (p < 0.01). Mortality was positively associated with both having an immigrant background (p = 0.04), non-white race (p = 0.03) and having a parent with post-secondary education (p < 0.01). Although clinical factors such as anatomy and diagnosis predict prognosis in SBS, social determinants also influence outcomes and should be considered in the support of families.

Patients with severe traumatic brain injury have a high incidence of intestinal failure because of systemic stress response and gut-brain axis dysfunction, which is closely related to poor prognosis. Focusing on severe traumatic brain injury complicated with intestinal failure, this article reviews its definition and classification, main risk factors (gastrointestinal dysfunction, intestinal barrier injury, drug effects, etc.), clinical assessment tools, and therapeutic intervention measures centered on enteral nutrition. It emphasizes the important role of individualized plans in improving patients' nutritional status, protecting gut mucosal integrity, and reducing the incidence of complications, so as to provide a reference for clinical standardized diagnosis and treatment.

Severe acute pancreatitis (SAP) often leads to life-threatening multiorgan dysfunction, with intestinal barrier failure being a key driver of systemic inflammation. Although Rhein shows efficacy in SAP, its mechanism for protecting against pancreatitis-associated intestinal injury remains unclear. This study aimed to elucidate the mechanism of Rhein in pancreatitis-associated intestinal injury (PAII), with a focus on intestinal macrophage polarization and peroxisome proliferator-activated receptor γ (PPARγ) signaling. SAP was induced in male C57BL/6J mice by intraperitoneal injections of cerulein and lipopolysaccharide (LPS). Pancreatic and intestinal histopathology were assessed by hematoxylin and eosin staining using both paraffin and frozen sections. The expression of PPARγ, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome components, and macrophage polarization markers was examined by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence. RT-qPCR was also used to quantify the messenger RNA (mRNA) levels of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, mono-cyte chemoattractant protein-1 [MCP-1]) and the anti-inflammatory cytokine IL-10 in colonic tissues. Reactive oxygen species (ROS) levels in colonic tissues were detected by dihydroethidium staining. Serum levels of lipopolysaccharide were measured by enzyme-linked immunosorbent assay (ELISA). For in vitro mechanistic studies, primary bone marrow-derived macrophages isolated from C57BL/6J mice were stimulated with LPS and interferon-γ to induce M1 polarization, with or without Rhein treatment. SAP-induced intestinal injury was characterized by downregulated PPARγ, NLRP3 inflammasome hyperactivation, and dominant M1 macrophage polarization. Rhein restored PPARγ, suppressed NLRP3, and reduced secretion of key M1-sustaining cytokines (IL-6, IL-1β, and TNF-α). This attenuated the proinflammatory milieu, indirectly facilitating an M1-to-M2 phenotypic shift. All benefits were abolished by PPARγ antagonism. Rhein alleviates pancreatitis-associated intestinal injury by activating PPARγ, which suppresses the NLRP3 inflammasome and downstream proinflammatory cytokine cascade, thereby modulating macrophage polarization. The PPARγ-NLRP3 axis is a crucial regulatory pathway and therapeutic target in SAP.

Short bowel syndrome in children, most commonly following extensive intestinal resection, results in intestinal failure and prolonged dependence on parenteral nutrition. Achieving enteral autonomy—sustained nutritional independence through enteral feeding—is a primary goal to reduce complications, support growth and development, and improve quality of life. Pediatric surgical nurses play a central role in coordinating seamless hospital-to-home transitions through structured family-centered education, nurse-coordinated home monitoring, and collaborative feeding adjustments. This continuity of care article synthesizes evidence-based strategies from multidisciplinary intestinal rehabilitation guidelines and codifies practical nursing practices that support informational, relational, and management continuity. Emphasis is placed on nurse-facilitated home monitoring protocols for intestinal adaptation, incremental feeding advancement, and early complication recognition. Common barriers, including caregiver burden and resource limitations, are addressed, and the potential role of telehealth in sustaining community-based care is explored. This nurse-coordinated model strengthens holistic pediatric surgical nursing practice across hospital, home, and community settings.

The complex care needs of pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF) can negatively impact the health-related quality of life (HRQoL) of patients and their caregivers. We assessed the impact of teduglutide on HRQoL of pediatric patients with SBS-IF. Two long-term extension (LTE) studies (NCT02949362, NCT02954458) assessed HRQoL over 96 weeks using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Family Impact Module. Patients included in this analysis received teduglutide in one of three randomized Phase 3 parent studies and the respective LTE study. We assessed changes in HRQoL over time, as well as the impact of attaining enteral autonomy on HRQoL and predictors of change in HRQoL. In pediatric patients with SBS-IF receiving teduglutide (n = 69), the total mean (standard deviation) patient-reported PedsQL score was 75.0 (16.2). Higher mean number of stools per day at LTE study baseline (p = 0.03) predicted increased patient-reported HRQoL. Longer teduglutide exposure (p = 0.047), increasing length of remnant small intestine (p = 0.034), and older age (p = 0.026) predicted higher caregiver-proxy-reported HRQoL. Mean PedsQL scores remained stable over 96 weeks regardless of patients achieving enteral autonomy. HRQoL of pediatric patients with SBS-IF treated with teduglutide was generally stable over 96 weeks. Predictors of improved HRQoL included higher baseline stool number, longer teduglutide treatment duration, greater length of small intestine, and older age. To better understand these observations, future studies should assess HRQoL before initiation of treatment.

Cell polarity is essential for maintaining intestinal epithelial organization and function. Here we show that combined loss of polarity by epithelial loss of Cdc42 with oncogenic Kras expression in mice causes small intestine failure leading to weight loss, inflammation, epithelial necroptosis, and lethality. These phenotypic defects are characterized by a loss of intestinal stem cells, disrupted epithelial architecture, altered hippo signaling, elevated inflammatory cytokines, and activation of necroptotic cell death, that closely resemble necrotizing enterocolitis (NEC). Single-cell transcriptomic analysis reveals a coordinated dysregulation of polarity machinery, inflammatory pathways, and necroptosis program. Suppression of YAP, IL-1, TNFα signaling or necroptosis rescues the intestinal pathology. Similar NEC-like phenotypes arise when Cdc42 loss and oncogenic Kras activation are initiated from intestinal stem cells. These findings provide mechanism insights involving polarity-YAP-IL1/TNFα signaling induced necroptosis for the synergistic effect of hyperactivation of Kras signaling and loss of polarity in disrupting intestinal epithelia.