Acute mesenteric ischaemia is one of the most common reasons for chronic intestinal failure, requiring intravenous supplementation to maintain health for prolonged periods when short bowel develops. Both acute mesenteric ischaemia and intestinal failure occur infrequently, have some issues with application of current definitions and are seldom studied in prospective way. The current review summarizes the available evidence on definitions, epidemiology and outcome of intestinal failure after acute mesenteric ischaemia and explores intestinal failure as a long-term outcome of acute mesenteric ischaemia.

Background Patients with type 2 intestinal failure (T2IF) due to double enterostomy or enterocutaneous fistula (DES/ECF) require parenteral nutrition (PN), carrying risks of catheter sepsis, venous thrombosis, and liver disease. Chyme reinfusion therapy (CRT) may reduce PN dependence but has not been evaluated in a randomised controlled trial (RCT). This study assessed whether device-assisted CRT using The Insides System reduces PN requirements. Methods: This multicentre, open-label RCT enrolled PN-dependent adults with T2IF due to DES/ECF across 12 centres in the UK and USA. Patients with insufficient distal limb length, proximal bowel obstruction, active sepsis, or severe hepatorenal failure were excluded. Participants were block randomised 2:1 to device-assisted CRT plus standard care (active) or standard care (control). The primary endpoint was 50% or greater reduction in PN caloric intake at 30 days, using an intention-to-treat analysis, for a comparison between randomised groups using a two tailed p-value of 0.025 to allow for a single interim analysis. Secondary outcomes were rate of PN cessation at 30 and 60 days, quality of life, and adverse events. Results: The population comprised 39 (26 active, 13 control) participants. At Day 30, 8/26 (31%) active participants achieved the primary endpoint versus no controls (p=0.035). By Day 60, 10/23 (43%) active participants had completely ceased PN versus no controls (p=0.008), with median intestinal losses reduced by 1,344 mL/day at Day 30 (p=0.005) and 1,450 mL/day at Day 60 (p=0.026 between group). Device-related adverse events were predominantly mild; one death unrelated to the device occurred. Conclusion: CRT with the Insides System demonstrated substantial therapeutic advantages in patients with T2IF from DES/ECF, with 31% of participants reducing PN calories by 50% at 30 days and >40% of participants achieving complete PN cessation by 60 days, and an acceptable safety profile. Trial registration: ClinicalTrials.gov [NCT04577456][1] Funding: This trial was sponsored by The Insides Company Ltd. ### Competing Interest Statement This trial was sponsored by The Insides Company Ltd. The sponsor contracted all trial operations to independent parties. Databean Inc. and GLCC Ltd served as the independent contract research organisations, with independent clinical monitoring, an independent Data Safety Monitoring Board, and independent principal investigators and clinical sites. The trial was conducted in compliance with FDA 21 CFR and ISO 14155. The sponsor had no role in participant recruitment, clinical data collection, or endpoint adjudication. The sponsor provided input in the preparation of the manuscript. ### Clinical Trial ClinicalTrials.gov ([NCT04577456][1]) ### Funding Statement This trial was sponsored by The Insides Company Ltd. The sponsor contracted all trial operations to independent parties. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted in full compliance with the ethical principles set forth in the Declaration of Helsinki (World Medical Association, Fortaleza 2013) and the requirements of Good Clinical Practice (GCP) as defined by the International Council for Harmonisation (ICH E6, R2), in accordance with applicable regulatory requirements. The rights, safety, and well-being of participants were the primary considerations and prevailed over the interests of science and society. Informed consent was obtained from all participants or their legally authorized representatives prior to enrolment, and the study protocol, along with any amendments, received approval from an independent ethics committee/institutional review board. The sponsor, investigators, and study staff fulfilled their responsibilities to ensure the reliability and integrity of the study data. The study protocol and associated documents and amendments were reviewed and approved in the USA by Advarra IRB (ref Pro00051593). In the UK the Health Research Authority for the UK and Wales (HRA and HRAW) reviewed and approved the study through the Integrated Research Application System (ref IRAS 279869). This included an ethical review by the independent Surrey Research Ethics Committee. The above mentioned IRBs rules over the trial, and full ethical approval was given for this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04577456&atom=%2Fmedrxiv%2Fearly%2F2026%2F05%2F04%2F2026.04.26.26351226.atom

The rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful generation and thorough characterisation of transplantable-sized porcine large intestinal scaffolds via perfusion decellularisation. This method effectively preserved extracellular matrix (ECM) structural and biochemical integrity while minimising immunogenicity through cellular component removal. Crucially, native vasculature remained intact, confirmed by histology, DNA quantification, and high-resolution CT angiography. Despite efficient decellularisation, challenges including residual nucleic acids, ECM heterogeneity, and partial microvascular occlusion were noted, echoing ongoing limitations in engineered, perfusable, full-thickness scaffolds. In vivo implantation demonstrated favourable biocompatibility and host integration; however, thrombosis occurred due to the lack of pre-seeded cells, emphasising the necessity of recellularisation for functional perfusion prior to implantation. This study addresses significant field limitations, presenting the first reproducible approach for structurally intact, perfusable, full-thickness large intestinal scaffolds of transplantable dimensions. Our innovations offer a strong foundation for future integration of patient-derived cells, stem cells, and organoids, progressing toward clinically viable, scalable, tissue-engineered large intestine constructs, from xenogeneic sources, relevant for regenerative medicine, disease modelling, and pharmacological screening.

BACKGROUND:Jejunal access is indicated in patients with impaired oral intake or gastroparesis who require enteral nutrition or medication delivery. There are various approaches to establishing jejunal access; including radiological, endoscopic and surgical methods. This study aims to evaluate the complication and re-intervention rates between endoscopic and surgical placement of jejunal tubes (JT). METHOD:We retrospectively collected data on patients undergoing surgical or endoscopic placement of JT at a single centre over a ten-year period (2011-2021). We analysed the following information: age, gender, underlying pathology necessitating the JT placement, significant co-morbidities as well as the following outcome data: rates of tube occlusion, dislodgement and need for re-admission and re-intervention. RESULTS:There were 165 patients included in the cohort. Of these, 96/165 underwent endoscopic placement either using Direct Percutaneous Endoscopic Jejunostomy (DPEJ) (14/96) or through Percutaneous Endoscopic Gastrostomy with Jejunal Extension (PEG-J) (82/96), and the remaining 69/165 underwent surgical placement either via a surgical flange (SF) tube (45/69) or the surgical Witzel (SW) technique (18/69). Idiopathic gastroparesis as an indication for JT placement (including Ehlers-Danlos Syndrome patients) affected 63.8 % of the surgical and 42.7 % of the endoscopic cohorts. At mean follow up of almost 17 months, the overall need for re-intervention, JT dislodgment and JT occlusion were 32.4 %, 8.8 % and 14.7 % in the surgical cohort, versus 62.8 %, 25.5 % and 27.7 % in the endoscopic cohort (p values of 0.0002, 0.0075 and 0.057, respectively). Individual re-intervention rates were 38.9 % for SW, 31.1 % for SF, 61 % for PEG-J and 64.3 % for DPEJ. CONCLUSION:Surgical siting of JT demonstrates significantly reduced dislodgement rates, and requirement for re-intervention in the long-term as compared to endoscopic JT placement.

Intestinal failure (IF) is a chronic condition that impairs the intestine's ability to digest and absorb nutrients. Home parenteral nutrition (HPN) is the primary treatment for IF, but intestinal transplant (ITx) is recommended in specific high-risk scenarios1. ITx can enhance quality of life and reduce healthcare costs compared to HPN2. In the UK, there are 10 major IF surgeries per million annually, with projections of 800 procedures per million in the next decade3 Graft-loss-due-to-rejection occurs in 15-33% of cases, contributing to 16% of post-surgery IF-related deaths4. To minimise graft rejection, we aim to facilitate non-immunoreactive intestinal graft engineering for transplant by establishing a decellularization protocol of clinically relevant (>50cm) porcine small intestine fragments. To date, attempts of intestinal decellularisation have been limited to small fragments5 due to the size and complexity of the tissue. This study introduces a dual submersion and perfusion protocol relying on chemical, physical and enzymatical decellularization strategies that results in removal of 97.05% total nuclear material. There was no significant difference between the DNA and GAG quantified in proximal, central and distal sections relative to perfusion site, which validates the protocol system design. Results demonstrate the potential for larger, functional grafts for transplantation and improved management of long-term IF. References 1. Klek, S. et al. Clinical Nutrition 35, 1209–1218 (2016). 2. Canovai, E. et al. Transplantation 105, 897–904 (2021). 3. NHS Service Specification. 170077S-230701S (2023). 4. Venick, R. Intestinal Transplant Registry Report (2023). 5. Meran, L et al., Nat Protoc 18, 108–135 (2023).

BACKGROUND AND AIMS:A limited number of randomized controlled trials (RCTs) have examined the use of lipid emulsions (LEs) of different compositions in home parenteral nutrition (HPN), and there are very few data on the long-term use of omega-3 (n-3) polyunsaturated fatty acids (PUFAs). The study's objective was to assess safety and tolerability of an n-3 PUFA-enriched LE in adult patients suffering from chronic intestinal failure (CIF) requiring long-term HPN. METHODS:In this prospective, randomized, controlled, double-blind, multicentre, international clinical trial, which was conducted at eleven sites, adult patients in need of HPN including lipids received either the investigational product, an n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) LE, or the reference product, a standard MCT/LCT LE, for an average duration of eight weeks. The primary outcome was the sum of changes of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives included fatty acid pattern in plasma and red blood cells (RBCs) and triene:tetraene ratio in plasma. RESULTS:74 patients were enrolled up to premature study termination. Liver function parameters showed no clinically relevant differences between study groups and remained within normal ranges. The n-3 PUFAs EPA and DHA increased in plasma and RBCs in the Lipidem group and were higher in the Lipidem group than the reference group at the end of the study resulting in an increased n-3-index in RBCs with Lipidem. Average n-3-index was >8. The plasma triene:tetraene ratio decreased in both groups. CONCLUSION:This study is one of the largest comparing two LEs in the complex setting of HPN treatment of adult patients. Although it has been early terminated its results considerably contribute to the evidence on safety and efficacy of longer-term use of LEs in HPN treatment. The n-3 PUFA-enriched LE Lipidem was safe and well-tolerated, particularly in terms of liver function. Lipidem provided an additional supply of n-3 PUFAs and led to positive changes in fatty acid profiles of plasma and RBCs. The n-3-index was in the desirable range at the end of the study in patients receiving Lipidem. There was no evidence of essential fatty acid deficiency with Lipidem. CLINICALTRIALS: GOV IDENTIFIER:NCT03282955. TRIAL REGISTRATION:EudraCT Number: 2015-000849-23.

Home parenteral support (HPS) is an essential but potentially burdensome treatment that can affect quality of life (QoL). The aims of this longitudinal study were to understand whether any changes in HPS over time were associated with QoL. The Parenteral Nutrition Impact Questionnaire (PNIQ) was used, and data were collected on HPS prescribed at three time points. Data were analysed using multi-level mixed regression models presented as effect size and were adjusted for confounders. Study recruited 572 participants from 15 sites. Of these, 201 and 145 completed surveys at second and third time-points, respectively. PNIQ score was out of 20 with a higher score indicating poorer QoL. Any reduction in HPS infusions per week was associated with an improved PNIQ score of −1.10 (95% CI −2.17, −0.02) unadjusted and −1.34 (95% CI −2.45, −0.24) adjusted. Per day change to the number of infusions per week was associated with a change in the PNIQ score of 0.32 (95% CI −0.15, 0.80) unadjusted and 0.34 (95% CI −0.17, 0.85) adjusted. This is the largest national study to demonstrate improvements in QoL associated with HPS reduction over time using an HPS-specific and patient-centric tool, adding unique data for use of therapies in intestinal failure.

Rationale: Peripherally Inserted Central Catheters (PICCs) play a vital role in delivering long-term intravenous therapy to adult patients, but their use carries potential risks such as Central Line-Associated Bloodstream Infection and thrombotic events. Understanding the rationale behind these risks is crucial for optimizing patient care and enhancing safety by identifying contributing factors, including prolonged catheter dwell time, inadequate catheter care, and immunocompromised status, and implementing appropriate prevention strategies to reduce the incidence of thrombosis, CRBSI and improve patient outcomes. Methods: Adult patients with intestinal failure (IF) on home parenteral nutrition treated at St Mark's The National Bowel Hospital and Academic Institute between December 4, 2021, to March 31, 2023, were identified from a prospectively maintained clinical database. Indication for PICC line removal was considered an essential parameter and was carefully recorded to analyze its association with complications. The primary focus of the study was to assess the rates of two specific complications related to PICC line removal: central line-associated bloodstream infections (CLABSI), catheter-related bloodstream infections (CRBSI), and thromboses. These complications were closely monitored and documented during the removal process, allowing for a quantitative analysis of their occurrence. To enhance the clarity and reliability of the data, supplementary sources such as EPRO, ICE, MediViewer, and PACS were reviewed. These electronic databases provided valuable information from patient records, diagnostic results, and medical imaging, enriching the understanding of complications associated with PICC lines. A comprehensive statistical analysis was conducted to explore the relationship between different types of IF, IF etiologies, types of PICCs, the number of days to line infection, and the specific microorganisms cultured. These factors were carefully examined to identify potential associations and patterns contributing to the development of complications. By performing rigorous statistical analyses, we aimed to gain deeper insights into the impact of these variables on the occurrence of CLABSI, CRBSI, and thrombotic events. This approach allowed for a robust examination of the data, enhancing the validity and reliability of the study findings. Results: The study encompassed a cohort of 108 patients, with an equal gender distribution (50% male). The median age of the participants was 57 years (range: 18-85). Among them, 10 patients exhibited IF type 1, 45 patients had IF type 2, and 53 patients presented with IF type 3. Infection as an indication for PICC line removal was observed in 10.19% of cases. The average time to the development of a CVC infection (CRBSI or CLABSI) was 65.82 days. Notably, the highest incidence of CLABSI and CRBSI occurred in patients with IF type 3 (55%), followed by IF type 2 (36%), and IF type 1 (9%). CVC infections occurred most frequently in patients with a mesenteric infarction (27%) and those with surgical complications (27%). The frequency was lower in patients with non-EDS motility disorders (18%), active malignancy (18%) and Crohn's disease/IBD (9%). Different organisms predominated in different groups, as described in Table 1 below.Tabled 1Table 1: Organisms causing a CVC infection in different IF groupsOrganismsNumber of infectionsGroup affectedPICC typeStaph. epidermidis & Staph. haemolyticus2Type 3 IF patients resulting from mesenteric infarction within 8 days of insertionPICC 4FStaph. epidermidis1Type 2 IF patients within 8-28 days of insertionsPICC 4F & 5F1IF type 2 due to surgical complicationsPICC 4F1Type 2 IF due to active malignancyPICC 5F1Type 3 IF due to surgical complications after more than 28 days of insertion.PICC 5FStaph. aureus1Type 2 IF due to surgical complicationsPICC 5F1Type 3 IF due to mesenteric infarctionPICC 4FMixed gram-positive microorganisms1IF type 3 due to non-EDS motility disordersPICC 5FKlebsiella1Type 1 IF due to Crohn's disease/IBDPICC 5FMixed gram-negative microorganisms1Type 2 IF due to active malignancyPICC 5F Open table in a new tab The overall incidence of thrombosis was 4.62% and was associated with the insertion of PICC 5F. The mean age of patients experiencing thrombosis was 41, and it was more frequently observed in the female population (p<0.05). The mean time to the development of a deep vein thrombosis (DVT) was 34 days, with 40% of cases seen in patients with IF type 2 and 3, followed by 20% in IF type 1. Conclusion: In conclusion, our study involved patients with varying types of IF. We observed that IF type 3 had the highest incidence of CLABSI and CRBSI, followed by IF type 2 and IF type 1. Staphylococcus epidermidis and Staphylococcus haemolyticus were the primary microorganisms responsible for infections related to PICCs in IF type 3 patients with mesenteric infarction. Additionally, we found that thrombosis rates were associated with the use of larger-sized PICC 5F, with a higher occurrence in females. These findings underscore the importance of careful monitoring and infection control measures in patients with IF, particularly in those with specific etiologies such as mesenteric infarction and surgical complications. Disclosure of Interest: None declared