RARE DISEASE
Chronic intestinal failure
Chronic intestinal failure
Chronic intestinal failure
Synonyms: CIF
Synonyms: CIF
Synonyms: CIF
Drug discovery
1
drug
With orphan designation
Overview
Chronic intestinal failure (CIF) is characterized by irreversible gut dysfunction, necessitating long-term parenteral or enteral nutrition to sustain life. It primarily results from short bowel syndrome, dysmotility disorders, or mucosal diseases. Management requires a multidisciplinary approach focusing on intestinal rehabilitation, pharmacotherapy, and surgical interventions to optimize absorption, reduce complications, and improve quality of life (QoL) [1][6][17].
Burden
High healthcare utilization: Median annual hospitalizations of 1.9–2.0 episodes, with extended stays (29–34 days) [17].
Mortality: Historically linked to sepsis or intestinal failure-associated liver disease (IFALD), with 5-year survival rates of 71% on parenteral nutrition [6][4].
Economic/QoL impact: Annual costs exceed $150,000 per patient; QoL scores are significantly lower than the general population [6][17][19].
Therapies
Multidisciplinary care: Home IV support (HIVS), antimotility agents (e.g., loperamide), antisecretory drugs (e.g., PPIs), and GLP-2 analogs (e.g., teduglutide) to enhance absorption [1][2][17].
Surgical interventions: Bowel-lengthening procedures (e.g., STEP), ostomy revisions, and intestinal transplantation for refractory cases [1][8][18].
Complication management: Catheter-related bloodstream infection protocols, liver disease monitoring, and electrolyte replacement [6][17][19].
Categories: rare gastroenterological diseases, rare transplant-related disorders
Research Papers
630 drug discovery papers about Chronic intestinal failure, with 1 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
630 drug discovery papers about Chronic intestinal failure, with 1 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-08 | Integrated Stress Response and Necroptosis Drive Epithelial Dysfunction in Crohn's Disease: Repurposing Cancer Drugs for Permeability Barrier Healing.
Intestinal permeability dysfunction is a central pathogenic driver of Crohn's disease (CD), fueling microbial translocation, chronic inflammation, and progressive tissue injury. While current therapies suppress inflammation, none directly restore epithelial barrier function. Importantly, in patients with CD, epithelial barrier healing rather than mucosal healing is associated with long-term remission and a reduced risk of disease complications. Yet permeability barrier healing remains an unaddressed therapeutic target in CD. Here, we investigated whether pharmacologic inhibition of the integrated stress response (ISR) and RIPK3-mediated necroptosis, 2 convergent pathways of epithelial injury, can promote epithelial viability, regeneration, and barrier integrity in CD. We employed villin-1/gelsolin double knockout mice with epithelial-intrinsic ISR activation, Tnf ΔARE/+ mice with chronic inflammation, and CD patient-derived enteroids (PDEs). Animals and PDE were treated with integrated stress response inhibitor, RIPK3 inhibitor necrostatin-1, or US Food and Drug Administration-approved cancer drugs pazopanib and ponatinib, repurposed as potent RIPK3 inhibitors. Epithelial survival, regenerative growth (enteroid formation, budding), and barrier function (transepithelial electrical resistance) were assessed. Chronic ISR activation and necroptosis were prominent in both murine models and CD PDEs, causing epithelial death, Paneth cell expansion, impaired enteroid survival, and regenerative failure. Pharmacologic inhibition with integrated stress response inhibitor, necrostatin-1, pazopanib, or ponatinib restored villus architecture, reduced inflammation, enhanced epithelial survival and regeneration, and significantly improved transepithelial electrical resistance. ISR activation and RIPK3-mediated necroptosis converge to drive epithelial injury and barrier dysfunction in CD. Repurposing pazopanib and ponatinib offers a potentially translatable approach to restore barrier integrity in CD.
2026-04-11 | Successful initiation of fully parenteral antiretroviral therapy in a treatment-naïve person with HIV-1 infection and intestinal failure.
In patients with severe surgical and gastrointestinal complications, standard oral combination antiretroviral therapy (ARV) may be temporarily impossible. Long-acting cabotegravir/rilpivirine (CAB/RPV LA) is approved for virologically suppressed individuals pretreated with oral therapy, but data on its use in treatment-naïve, critically ill patients with absent enteral absorption are extremely limited. We report a 26-year-old male admitted with fulminant hypertriglyceridaemic necrotizing pancreatitis complicated by abdominal compartment syndrome, multiple laparotomies, open abdomen with enteric fistulae, short bowel syndrome type I, chronic intestinal failure requiring parenteral nutrition, portal vein thrombosis, and prolonged intensive care. HIV-1 infection was diagnosed early (HIV RNA 5,000 copies/mL; CD4+ 780 cells/µL). Within three months, HIV RNA rose to 320,000 copies/mL and CD4+ declined to 570 cells/µL. Given absent gastrointestinal passage, standard ARV was initially deferred, but rapid virological rebound necessitated urgent treatment. An off-label fully parenteral regimen was initiated: intravenous zidovudine (AZT) with intramuscular CAB/RPV LA. Therapy was well tolerated alongside surgery, parenteral nutrition, antimicrobials, and anticoagulation. HIV RNA decreased to <20 copies/mL within 65 days and remained suppressed, with CD4+ recovery. Intravenous AZT was discontinued after 35 days, and CAB/RPV LA continued as maintenance during recovery and home parenteral nutrition. Fully parenteral ARV, including CAB/RPV LA, may provide a safe and effective bridge to durable viral suppression in patients with absolute contraindications to oral therapy, warranting further evaluation.
2026-03-03 | Building lifelines: A narrative review and pragmatic implementation framework for developing centralised adult chronic intestinal failure services.
Home parenteral nutrition (HPN) is life-sustaining for patients with chronic intestinal failure (IF), yet access remains inconsistent worldwide. HPN has evolved into a complex, multidisciplinary service that requires coordinated planning, durable investment, and strong governance to deliver safe, equitable care from hospital to home. This narrative review integrates clinical, organisational, and policy evidence and translates it into a pragmatic implementation roadmap for adult chronic IF health systems at different stages of maturity. We synthesise the volume-outcome signal linking higher-centre caseloads and structured nutrition support teams (NSTs) with lower mortality and complications; consolidate contemporary quality standards (minimum volumes, team composition, governance); and appraise health-economic analyses pertinent to HPN. International exemplars translating guidance into implementable actions enable the development of a four-domain framework to develop cohesive and practical chronic IF services globally: (1) identify and connect the network - map expertise, align professional societies and patient organisations, and establish referral communications; (2) develop the structure - formal centre designation, referral criteria, core infrastructural elements; (3) operationalise care - standardised shared-care/remote-discharge protocols, defined escalation to accredited centres with requisite governance and NST expertise and telehealth-enabled regional support (4) measure and improve - registry participation, routine audit, patient-reported outcomes, and transparent feedback loops. Cross-cutting enablers include robust governance, diagnosis-adjusted reimbursement aligned to NST resourcing, and policy mechanisms (designation, commissioning, funding) that secure access and consistent performance across geographies. Applied iteratively, this framework supports phased, resource-conscious scale-up of safe, high-quality, and equitable chronic IF/HPN services, aiming to reduce complications and mortality while strengthening patient experience, system resilience, and accountability.
2026-02-24 | Hydrogen sulfide rescues IFNγ/TNFα-induced intestinal epithelial barrier dysfunction by enhancing oxidative phosphorylation.
The intestinal epithelial barrier is essential for protection against pathogens and toxins while allowing nutrient and water absorption. Barrier dysfunction is increasingly recognized as a key pathophysiological mechanism in diseases affecting the gastrointestinal (GI) tract and distant organs. Hydrogen sulfide has emerged as an important regulator of intestinal homeostasis. This study investigates the effects of the H₂S-releasing compound 4-hydroxithiobenzamide (TBZ) on epithelial barrier integrity. Although TBZ did not prevent interferon-γ and tumor necrosis factor-α (IFN/TNF)-induced epithelial cell death, it reversed cytokine-induced increases in transepithelial permeability. Notably, TBZ alone increased paracellular permeability but normalized it under inflammatory conditions, indicating a context-dependent effect. H₂S-producing enzymes localized apically in IECs, suggesting subcellular regulation. Transcriptomic analysis identified oxidative phosphorylation as a pathway mediating TBZ’s effects. Functional studies confirmed that TBZ enhances oxidative phosphorylation, while inhibition of complex IV abolished barrier protection. In conclusion, our data indicate that hydrogen sulfide counteracts IFN/TNF-induced epithelial barrier dysfunction through transcriptional and functional enhancement of oxidative phosphorylation.
2025-12-26 | Effect of vitamin D supplementation on skeletal muscle function and quality of life in patients with chronic intestinal failure: a randomized controlled trial : Clean version.
BACKGROUND: Vitamin D deficiency is common in patients with chronic intestinal failure (CIF); however, the effectiveness of high-dose vitamin D supplementation remains unclear. This study aimed to investigate the effects of high-dose vitamin D supplementation on skeletal muscle mass, function, and quality of life (QoL) in patients with CIF. METHODS: This was a single-center, prospective, randomized, double-blind, placebo-controlled trial conducted at a tertiary hospital in China. Participants included individuals aged 18–70 years with chronic intestinal failure and vitamin D deficiency (serum 25(OH)D < 30 ng/ml). Eighty-four adult patients were randomly assigned (1:1) to either the vitamin D group (intramuscular injection of 600,000 units of vitamin D2 every two weeks for 10 weeks) or the control group (matched placebo). The primary outcomes were appendicular skeletal muscle mass index (assessed by bioelectrical impedance), handgrip strength, 6-meter walking speed, and quality of life (SF-36 scales) from the date of randomization to the end of the 12-week follow-up period. The analysis was performed on an intention-to-treat principle. RESULTS: Eighty-four patients were randomized to the control group (n = 42; mean age, 52.8 ± 15.6 years) or the vitamin D group (n = 42; mean age, 52.9 ± 16.2 years). At the 12-week follow-up, serum 25-hydroxyvitamin D levels were significantly higher in the vitamin D group than in the control group (96.7 ± 5.8 vs. 23.8 ± 4.1 ng/mL; p < 0.001). Compared with the control group, the vitamin D group showed clinically meaningful improvements in the appendicular skeletal muscle mass index, handgrip strength, 6-meter walking speed, and the SF-36 physical component summary score (all p < 0.05 after Bonferroni correction). No other clinically significant differences were observed between the groups in the remaining secondary clinical and safety endpoints. CONCLUSION: High-dose intramuscular vitamin D2 supplementation for 10 weeks was significantly associated with improved skeletal muscle mass, function, and QoL in patients with CIF. THIS TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT06283615. Registered 11 March 2024, https://clinicaltrials.gov/study/NCT06283615 .
cell therapies
2026-09-03 | Expanding Indications of Nonvascularized Rectus Fascia as a Cross-Disciplinary Allograft: A Prospective Single-Center Study.
To report the expanding application of nonvascularized rectus fascia allotransplantation (NVRF-alloTx) in solid organ transplant (SOT) and non-SOT patients and evaluate its effectiveness, integration, and immunologic response in complex abdominal and thoracic reconstruction. Synthetic and biological meshes are limited by infection risk, long-term failure, donor-site morbidity, and high cost. NVRF-alloTx, first applied in intestinal/multivisceral-Tx with a 5.9% herniation rate, offers a simple and promising alternative for challenging defects. This prospective single-center study included all consecutive patients undergoing NVRF-alloTx (2020-2025). Patients were divided into 2 groups: (1) reconstruction in SOT patients (simultaneous or elective closure post-SOT) and (2) reconstruction in non-SOT patients, without immunosuppression. NVRF-allografts were procured from deceased donors, preserved at 2°C, and implanted without HLA-matching. Primary endpoints were successful closure, graft failure, and functional outcome. Clinical and radiologic follow-up was performed, with HLA donor-specific antibody (HLA-DSA) testing and histology whenever available. Forty-seven NVRF-Tx procedures were performed in 41 patients using grafts from 48 deceased donors: group 1 (n=17) and group 2 (n=24). In 2 patients (4.9%), the graft did not integrate due to pancreatic leakage and vasopressor therapy. Others resulted in successful functional outcomes. Histology (n=5) showed graft integration through host fibrotic remodeling with neovascularization evident from 1 month after implantation. (De novo) HLA-DSA developed more frequently in non-SOT NVRF recipients than in SOT NVRF recipients. NVRF-alloTx is a versatile and effective reconstructive option for complex defects in SOT and non-SOT patients, providing an alternative to conventional meshes in challenging clinical scenarios.
2026-06-08 | Living Donor Intestinal Transplant: Indication, Techniques, Surgical Complications, and Outcomes in Recipients and Donors: A Systematic Review.
Living donor intestinal transplantation (LDITx) is an alternative option to cadaveric transplants as a last resort in treating intestinal failure. There are limited data on LDITx outcomes. This systematic review evaluates LDITx in terms of indications, contraindications, surgical complications, and patient outcomes. A comprehensive search was conducted across PubMed, Cochrane Library, Virtual Health Library, and Web of Science databases following the PRISMA guidelines. After filtration, data were systematically extracted from all relevant observational studies, case series, and case reports. Quality assessments were performed using the CARE guideline for case reports and case series, while STROBE was used for observational studies. Fifty-four studies were included, comprising 11 observational studies, 9 case series, and 34 case reports. The main indications of LDITx were the availability of a compatible donor and the urgency of the recipient's clinical condition. The standard surgical technique involves segmental ileal resection and transplantation. Postoperative complications included infections, ischemic events, and vascular complications. Recipients had either manageable complications or no complications. About 21.2% of the population experienced at least one episode of rejection, with an overall mortality rate of 23%. Many cases reported successful TPN weaning and good outcomes for the recipients and donors. In patients with chronic IF complicated by severe TPN-related morbidity or underlying pathologies causing SBS, LDITx represents an effective treatment option and an alternative to the more conventional cadaveric intestinal transplantation, bypassing problematic time sensitivity and donor availability.
2026-01-21 | DOP127 Crohn’s disease and intestinal/multivisceral transplant: Who needs it and what are the outcomes? Experience from a High-Volume Centre
Abstract Background Intestinal/multivisceral transplant (IT/MVT) remains the least frequent solid organ transplant, generally indicated in patients with severe complications of intestinal failure (IF) (1). Crohn’s disease (CD) may lead to IF through multiple mechanisms (2) yet published evidence on transplant outcomes in this setting is scarce. The primary aim of this study was to describe the outcomes of CD patients who underwent IT/MVT in our centre. Methods We retrospectively reviewed CD patients undergoing IT/MVT between 2008 and 2024 at Cambridge. Baseline CD characteristics, surgical history, indication for transplant (Table 1), and transplant characteristics and outcomes (Table 2) were collected. Survival was analysed using Kaplan–Meier and stratified by grafts including or not including liver (Figure 1). Results A total of 24 patients receiving 25 transplants (including 1 retransplant) were included. Fifty-four percent were male, most diagnosed at A2 age (58%), with ileocolonic disease (92%) and proximal involvement in 54%. 83% had stricturing or penetrating behaviour, with a median CD duration of 28.5 years. Prior therapy included immunomodulators (75%) and biologics (71%). Patients had a median of 5 previous surgeries and residual small bowel length of 70 cm; despite this, 58% had active CD at the time of transplant. Short bowel syndrome was the leading cause of IF (83%), and the main indication for transplant was IF-associated liver disease (48%). Median age at transplant was 50 years, with a median follow-up of 35 months; 56% received grafts excluding liver. Although 40% experienced rejection episodes, at last follow-up 88% had complete intestinal function without artificial nutritional support. Three patients developed CD recurrence, which did not result in graft loss. Overall survival is shown in Table 2; in patients with grafts excluding liver, survival was 100%, 90.9% and 90.9% at 1, 3 and 5 years, respectively. Conclusion Our experience shows that in patients with severe, long-standing CD leading to IF and life-threatening complications, IT/MVT is a valuable therapeutic option with excellent outcomes. We recommend early referral of similar cases to specialised centres with expertise in IF and IT/MVT. References: 1. Pironi L, Arends J, Bozzetti F, et al. ESPEN guideline on chronic intestinal failure in adults. Clin Nutr. 2021;40(9):5196-5220. 2. Limketkai BN, Parian AM, Shah ND, Colombel JF. Short Bowel Syndrome and Intestinal Failure in Crohn’s Disease. Inflamm Bowel Dis. 2016;22(5):1209-18. Conflict of interest: López Romero-Salazar, Francisco: Author reports educational/travel grants and/or speaker fees from AbbVie, Dr Falk, J&J, Lilly, Pfizer and Takeda. Butler, Andrew: No conflict of interest Amin, Irum: No conflict of interest Massey, Dunecan: No conflict of interest Neil, Russell: No conflict of interest Woodward, Jeremy: No conflict of interest Rutter, Charlotte: No conflict of interest
2025-12-31 | Rationale and design of the AlloFIST trial: a phase I/IIa study to evaluate dose escalation of allogeneic adipose-derived stroma/stem cells for the treatment of Crohn's fistula.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%-39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%-70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD. This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5×107 and 10×107 cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%. The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 - Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels. NCT06636032.The results will be disseminated through conventional scientific channels.
2025-03-24 | [How close is fecal microbiota transplantation to moving to precision medicine?].
Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.
proteins
2026-08-27 | Dietary and Parenteral Nutritional Management of Short Bowel Syndrome with Intestinal Failure in Adults
Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure in adults, arising when the residual small bowel can no longer absorb the macronutrients, water and electrolytes needed to sustain health without intravenous supplementation. Its management is, at its core, a nutritional problem. This review synthesises current evidence and guideline recommendations on the two pillars of that management: dietary (oral/enteral) therapy and parenteral nutritional support. We frame both around the two variables that dominate clinical behaviour, namely residual intestinal anatomy and the phase of intestinal adaptation, and translate them into anatomy-tailored dietary strategies, rational fluid and electrolyte replacement, micronutrient surveillance, and the composition, delivery and complications of (home) parenteral nutrition. We also position the pharmacological adjuncts, culminating in glucagon-like peptide-2 (GLP-2) analogues, within a stepwise strategy to reduce parenteral-support dependence. The goal throughout is a practical, physiology-anchored approach that maximises enteral autonomy and quality of life while preventing the metabolic, hepatic and catheter-related complications of long-term intravenous feeding.
2026-07-02 | Development of Teduglutide purity certified reference material (GBW09342) through amino acid-based isotope dilution mass spectrometry and sulfur-based isotope dilution inductively coupled plasma mass spectrometry.
As a severe intestinal disorder, short bowel syndrome (SBS) has become the leading cause of chronic intestinal failure worldwide. Teduglutide, a 33-amino-acid glucagon-like peptide-2 (GLP-2) analog, offers a novel therapeutic option for individuals suffering from SBS. In this study, Teduglutide purity certified reference material (CRM) with certified value and expanded uncertainty of (85.0% ± 2.7%) was developed with Teduglutide produced through recombinant gene expression technique. After a comprehensive purity verification and structure confirmation, two independent isotope dilution mass spectrometry (IDMS) strategies based on amino acid (AA) and sulfur measurements were employed for CRM certification, with the later strategy being used for the first time to certify a solid purity CRM. The Teduglutide purity CRM showed good homogeneity, it also exhibited satisfying stability for at least 14 days at 4 °C, 24 h for 25 °C and 12 months at -20 °C. The development of Teduglutide purity CRM (GBW09342) enables the establishment of accurate and reliable analytical methods for purity assessment, which is essential for ensuring the quality, consistency, and clinical safety of corresponding pharmaceutical products. It also provides a reliable reference for the quality control of other peptide-related drugs.
2026-06-16 | Current state of medical rehabilitation for adult short bowel syndrome patients with intestinal failure.
Short bowel syndrome intestinal failure (SBS-IF) occupies a unique position at the interface between chronic organ failure management and intestinal transplantation (iTx). Historically, patients with SBF-IF progressed inevitably toward lifelong home parenteral support (HPS) dependence and, in a small and highly selected subset with impending HPS failure, ultimately to iTx. Recent advances in pro-adaptive pharmacological strategies, focusing on glucagon-like peptide (GLP)-2 and GLP-1-based approaches as adjuncts to conventional antimotility and antisecretory therapies, are reviewed, with implications for decision-making across the SBS-IF disease trajectory presented. SBS-IF is now recognized as a dynamic and modifiable form of organ failure. Targeted pro-adaptive interventions reduce HPS dependence and improve patient-centered outcomes. Conventional antimotility and antisecretory therapies remain foundational, whereas GLP-2 analogues are the first pathophysiology-targeted, pro-adaptive therapies in SBS-IF, while GLP-1 receptor agonists have emerged as promising adjuncts in selected patients, particularly those with high-output phenotypes. Multidisciplinary intestinal failure rehabilitation and gut-directed pharmacotherapy have altered the natural history of SBS-IF. Medical rehabilitation has shifted iTx from a default end-stage therapy to a targeted rescue option reserved for irreversible HPS failure, to be considered after optimized rehabilitation but before the transplant window is lost.
2026-06-03 | Cost-effectiveness of Taurolidine as secondary prevention of recurrent catheter-related bloodstream infections in patients with chronic intestinal failure: Findings from a randomized controlled trial.
Catheter-related bloodstream infections (CRBSIs) are a major complication in patients with chronic intestinal failure (CIF) dependent on home parenteral support (HPS), contributing substantially to morbidity, mortality, and costs. Taurolidine-containing catheter lock solutions reduce CRBSIs, but data on cost-effectiveness remain limited. This cost-effectiveness analysis used data from a double-blind, randomized controlled trial (2019-2022; ClinicalTrials.gov: NCT06660641) comparing 1.35% taurolidine with 0.9% saline as catheter lock solutions for secondary prevention of recurrent CRBSIs in 61 adults with CIF and a history of CRBSI. Economic analyses adopted a healthcare-provider perspective and included direct medical costs related to treatment and CRBSI management. Clinical outcomes were evaluated using recurrent-event methods, and costs were estimated using Diagnosis-Related Group (DRG) tariffs and a micro-costing approach (MCAP). Incremental cost-effectiveness ratios (ICERs) were calculated. Taurolidine significantly reduced recurrent CRBSIs (ratio: 0.23; 95% CI: 0.09-0.60; p = 0.0028) and associated CVC removals (ratio: 0.09; 95% CI: 0.02-0.41; p = 0.0019). The number needed to treat was 2.4 patients per year. Patients in the taurolidine group had fewer admission days (mean 3.3 vs 16.0; p = 0.015). Despite higher acquisition costs, taurolidine reduced the total hospital expenditures by 39% (DRG) to 64% (MCAP). Mean savings per patient at 24 months were €6395 (DRG; p = 0.016) and €15,434 (MCAP; p = 0.014). Taurolidine also reduced the probability of extreme high-cost CRBSI episodes. Incremental cost-effectiveness ratios (ICERs) indicated dominance, with 94.5-99.6% of bootstrap replications showing taurolidine to be more effective and less costly. In patients with CIF and prior CRBSI, 1.35% taurolidine is a clinically superior and cost-saving secondary prevention strategy that reduces recurrent CRBSIs, CVC removals, and hospital resource use. These findings support routine use in secondary prevention and highlight the need to evaluate taurolidine for primary prevention, where early risk stratification remains challenging.
2026-05-14 | Chronic intestinal failure: Medical treatment, home parenteral nutrition, training and monitoring.
Chronic intestinal failure (CIF) requires parenteral nutrition (PN) as its main treatment to sustain health. Short Bowel Syndrom (SBS) is its main cause. Medical management includes dietary approaches, anti-secretory and anti-motility drugs. Recently, GLP-2 analogs like teduglutide for selected patients have helped treated patient to reduce PN. A multidisciplinary nutritional support team (NSTs) is essential for HPN training, covering catheter care, complication prevention, and lifestyle adaptation to promote patients' autonomy. Monitoring protocols recommend 3 months-interval visits for stable patients, to assess clinical status, anthropometrics and biochemistry. Vitamins, trace elements, and HPN complications should be monitored annually or as needed.
antibodies
2026-09-19 | Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn's disease.
Type I interferons (IFN-Is) are central regulators of intestinal epithelial homeostasis, yet their role in driving epithelial dysfunction and therapeutic non-response in Crohn's disease (CD) remains poorly defined. Here, we investigated epithelial tumor necrosis factor (TNF)-IFN-I crosstalk as a previously unrecognized contributor to anti-TNF non-response in CD. We analyzed human intestinal biopsies, single-cell RNA sequencing data from CD donors, and used murine TNFR1-deficient and patient-derived organoids exposed to inflammatory cytokines and clinically relevant treatments. Colonic epithelia from anti-TNF non-responders (NR-CD) showed enrichment of IFN-I genes associated with epithelial stress, impaired regeneration, and inflammatory cytokine production. Using patient-derived and murine TNFR1-deficient organoids, we demonstrated that TNF signaling sustains epithelial IFN-I responses linked to immune regulation and antiviral pathways, establishing a mechanistic connection between chronic TNF signaling and epithelial barrier failure. Low-dose butyrate (0.1 mM) suppressed cytokine-induced IFN-I genes and enhanced epithelial turnover in non-IBD and responder CD (R-CD) organoids but did not rescue the apoptosis and defective repair characteristic of NR-CD organoids. Notably, anti-IFN-I antibody treatment selectively attenuated IFN-I signaling and restored epithelial integrity in NR-CD organoids, identifying epithelial IFN-I blockade as a novel therapeutic rescue strategy for anti-TNF refractory disease. TNF-IFN-I crosstalk drives epithelial dysfunction in CD. Elevated epithelial IFN-I genes distinguish anti-TNF non-responders and underlie differential therapeutic responses. Together, this work supports integration of epithelial IFN-I gene expression and patient-derived ex vivo functional testing into treatment decisions for CD patients.
2026-04-21 | Interleukin-23 Inhibitors in Inflammatory Bowel Disease.
Selective inhibition of interleukin-23 (IL-23) has emerged as a highly effective therapeutic strategy in inflammatory bowel disease, targeting a central pathway of chronic intestinal inflammation while preserving host defense mechanisms. Across phase II and phase III randomized controlled trials, risankizumab, mirikizumab, and guselkumab consistently demonstrated robust efficacy in both ulcerative colitis and Crohn's disease, achieving clinical remission rates approaching 40-50% in ulcerative colitis and exceeding 50% in Crohn's disease during maintenance, with parallel improvements in endoscopic and histological outcomes. Notably, mirikizumab and guselkumab showed particularly high rates of endoscopic and histological remission in ulcerative colitis, whereas guselkumab achieved some of the highest induction remission rates in Crohn's disease. These benefits were durable over time, with long-term extension studies confirming sustained remission beyond two years in a substantial proportion of patients. Across trials, IL-23 inhibitors displayed a favorable safety profile, with low rates of serious adverse events, infections, and major cardiovascular events, supporting their use in long-term disease management. Real-world evidence further reinforces these findings, demonstrating consistent effectiveness in heavily pretreated and complex patient populations, including those with prior biologic failure, comorbidities, or difficult-to-treat disease phenotypes. In particular, risankizumab has shown strong performance in multi-refractory Crohn's disease cohorts, while emerging data for mirikizumab confirm its effectiveness in real-life ulcerative colitis settings. Beyond clinical outcomes, differences in molecular structure, pharmacokinetics, and Fc-mediated interactions may contribute to subtle distinctions among agents, potentially influencing therapeutic positioning. Ongoing development of oral compounds and combination strategies targeting complementary inflammatory pathways is expected to further expand the role of IL-23 inhibition. Overall, interleukin-23 inhibitors represent a cornerstone of modern inflammatory bowel disease therapy, combining high efficacy, durable responses, and an excellent safety profile, with growing evidence supporting their use across a broad spectrum of patients.
2025-12-03 | Cytomegalovirus and Crohn's disease as competing causes of small bowel inflammation after double-lung transplantation.
Cytomegalovirus (CMV) infection remains a significant cause of morbidity following solid organ transplantation, most frequently affecting the gastrointestinal tract. In transplant recipients presenting with diarrhea, alternative etiologies such as inflammatory bowel disease (IBD) should be considered. The emergence of antiviral resistance poses a therapeutic challenge, and molecular testing for resistance-associated mutations is essential in cases of treatment failure. A lung transplant recipient developed chronic diarrhea leading to functional intestinal failure. CMV infection was identified in intestinal biopsies and initially managed with two courses of valganciclovir. Due to persistent symptoms, genotypic analysis was performed, revealing UL97 mutations conferring ganciclovir resistance. Sequential therapy with foscarnet, maribavir, and letermovir achieved virological clearance, but diarrhea persisted. Small bowel enteroscopy with biopsies showed ongoing mucosal inflammation and minimal residual CMV activity. These findings were consistent with ganciclovir-resistant CMV enteritis coexisting with de novo Crohn's disease. The patient was commenced on standard biological therapy for Crohn's disease, resulting in marked clinical improvement and recovery. This case illustrates the diagnostic challenge of distinguishing CMV enteritis from de novo Crohn's disease and determining the primary driver of the clinical presentation.
2025-11-03 | Intestinal reengineering: Scientific advances in intestinal transplantation.
Intestinal transplantation (ITx) has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies. Despite its growing clinical acceptance, ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation. This review comprehensively summarizes the historical evolution, clinical indications, and advancements in surgical techniques, with emphasis on innovations in vascular anastomosis, multivisceral transplantation, and ex vivo preservation. Special attention is given to the unique immunological challenges of ITx, including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions, and the distinct roles of key immune cells. Pediatric and adult recipients exhibit divergent etiologies, immune responses, and complication profiles, necessitating individualized approaches. Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes, chronic rejection, graft dysfunction, and immunosuppressive toxicity remain significant barriers. Looking ahead, future directions should prioritize precision immunomodulation, microbiome-targeted therapies, and integrated platforms for gene editing, 3D bioprinting, and immune monitoring. Through multidisciplinary collaboration and translational research, ITx is poised to evolve from a high-risk salvage therapy into a personalized, sustainable solution that enhances long-term survival and patient quality of life.
2025-10-02 | [Pharmacist-Led Shared Decision-Making in a Pediatric Patient with Crohn's Disease and Growth Failure: A Case Report].
Inflammatory bowel disease (IBD) is an illness of unknown etiology, leading to chronic intestinal inflammation. It is characterized by repeated periods of remission and relapse. In the current treatment of IBD, multiple therapeutic drugs are listed in the Japanese treatment guidelines. Therefore, selecting a drug that matches the patient's condition and lifestyle is important, and the treatment decisions should be made using shared decision-making (SDM). For children, there is no specific age at which decision-making becomes possible. Therefore, medical professionals must make appropriate assessments regarding their decision-making ability. Although SDM has been shown to be useful in adults, there are no reports of SDM use in children. In this case report, a pharmacist performed multiple SDM for a 15-year-old patient with Crohn's disease. The SDM process reflected the child's changing values, leading to the introduction and continuation of biologic agents, and addressing growth disorders after the disease activity was controlled. To our knowledge, this is the first reported case in which a pharmacist performed SDM based on the condition of a pediatric patient with IBD, effectively implemented treat-to-target strategies, and improved the growth disorder. This case demonstrates the importance of properly controlling disease activity in pediatric patients with IBD and highlights the important role of pharmacists in adjusting drug therapy to suit a child's condition.
small molecules
2026-06-08 | Integrated Stress Response and Necroptosis Drive Epithelial Dysfunction in Crohn's Disease: Repurposing Cancer Drugs for Permeability Barrier Healing.
Intestinal permeability dysfunction is a central pathogenic driver of Crohn's disease (CD), fueling microbial translocation, chronic inflammation, and progressive tissue injury. While current therapies suppress inflammation, none directly restore epithelial barrier function. Importantly, in patients with CD, epithelial barrier healing rather than mucosal healing is associated with long-term remission and a reduced risk of disease complications. Yet permeability barrier healing remains an unaddressed therapeutic target in CD. Here, we investigated whether pharmacologic inhibition of the integrated stress response (ISR) and RIPK3-mediated necroptosis, 2 convergent pathways of epithelial injury, can promote epithelial viability, regeneration, and barrier integrity in CD. We employed villin-1/gelsolin double knockout mice with epithelial-intrinsic ISR activation, Tnf ΔARE/+ mice with chronic inflammation, and CD patient-derived enteroids (PDEs). Animals and PDE were treated with integrated stress response inhibitor, RIPK3 inhibitor necrostatin-1, or US Food and Drug Administration-approved cancer drugs pazopanib and ponatinib, repurposed as potent RIPK3 inhibitors. Epithelial survival, regenerative growth (enteroid formation, budding), and barrier function (transepithelial electrical resistance) were assessed. Chronic ISR activation and necroptosis were prominent in both murine models and CD PDEs, causing epithelial death, Paneth cell expansion, impaired enteroid survival, and regenerative failure. Pharmacologic inhibition with integrated stress response inhibitor, necrostatin-1, pazopanib, or ponatinib restored villus architecture, reduced inflammation, enhanced epithelial survival and regeneration, and significantly improved transepithelial electrical resistance. ISR activation and RIPK3-mediated necroptosis converge to drive epithelial injury and barrier dysfunction in CD. Repurposing pazopanib and ponatinib offers a potentially translatable approach to restore barrier integrity in CD.
2026-04-11 | Successful initiation of fully parenteral antiretroviral therapy in a treatment-naïve person with HIV-1 infection and intestinal failure.
In patients with severe surgical and gastrointestinal complications, standard oral combination antiretroviral therapy (ARV) may be temporarily impossible. Long-acting cabotegravir/rilpivirine (CAB/RPV LA) is approved for virologically suppressed individuals pretreated with oral therapy, but data on its use in treatment-naïve, critically ill patients with absent enteral absorption are extremely limited. We report a 26-year-old male admitted with fulminant hypertriglyceridaemic necrotizing pancreatitis complicated by abdominal compartment syndrome, multiple laparotomies, open abdomen with enteric fistulae, short bowel syndrome type I, chronic intestinal failure requiring parenteral nutrition, portal vein thrombosis, and prolonged intensive care. HIV-1 infection was diagnosed early (HIV RNA 5,000 copies/mL; CD4+ 780 cells/µL). Within three months, HIV RNA rose to 320,000 copies/mL and CD4+ declined to 570 cells/µL. Given absent gastrointestinal passage, standard ARV was initially deferred, but rapid virological rebound necessitated urgent treatment. An off-label fully parenteral regimen was initiated: intravenous zidovudine (AZT) with intramuscular CAB/RPV LA. Therapy was well tolerated alongside surgery, parenteral nutrition, antimicrobials, and anticoagulation. HIV RNA decreased to <20 copies/mL within 65 days and remained suppressed, with CD4+ recovery. Intravenous AZT was discontinued after 35 days, and CAB/RPV LA continued as maintenance during recovery and home parenteral nutrition. Fully parenteral ARV, including CAB/RPV LA, may provide a safe and effective bridge to durable viral suppression in patients with absolute contraindications to oral therapy, warranting further evaluation.
2026-03-03 | Building lifelines: A narrative review and pragmatic implementation framework for developing centralised adult chronic intestinal failure services.
Home parenteral nutrition (HPN) is life-sustaining for patients with chronic intestinal failure (IF), yet access remains inconsistent worldwide. HPN has evolved into a complex, multidisciplinary service that requires coordinated planning, durable investment, and strong governance to deliver safe, equitable care from hospital to home. This narrative review integrates clinical, organisational, and policy evidence and translates it into a pragmatic implementation roadmap for adult chronic IF health systems at different stages of maturity. We synthesise the volume-outcome signal linking higher-centre caseloads and structured nutrition support teams (NSTs) with lower mortality and complications; consolidate contemporary quality standards (minimum volumes, team composition, governance); and appraise health-economic analyses pertinent to HPN. International exemplars translating guidance into implementable actions enable the development of a four-domain framework to develop cohesive and practical chronic IF services globally: (1) identify and connect the network - map expertise, align professional societies and patient organisations, and establish referral communications; (2) develop the structure - formal centre designation, referral criteria, core infrastructural elements; (3) operationalise care - standardised shared-care/remote-discharge protocols, defined escalation to accredited centres with requisite governance and NST expertise and telehealth-enabled regional support (4) measure and improve - registry participation, routine audit, patient-reported outcomes, and transparent feedback loops. Cross-cutting enablers include robust governance, diagnosis-adjusted reimbursement aligned to NST resourcing, and policy mechanisms (designation, commissioning, funding) that secure access and consistent performance across geographies. Applied iteratively, this framework supports phased, resource-conscious scale-up of safe, high-quality, and equitable chronic IF/HPN services, aiming to reduce complications and mortality while strengthening patient experience, system resilience, and accountability.
2026-02-24 | Hydrogen sulfide rescues IFNγ/TNFα-induced intestinal epithelial barrier dysfunction by enhancing oxidative phosphorylation.
The intestinal epithelial barrier is essential for protection against pathogens and toxins while allowing nutrient and water absorption. Barrier dysfunction is increasingly recognized as a key pathophysiological mechanism in diseases affecting the gastrointestinal (GI) tract and distant organs. Hydrogen sulfide has emerged as an important regulator of intestinal homeostasis. This study investigates the effects of the H₂S-releasing compound 4-hydroxithiobenzamide (TBZ) on epithelial barrier integrity. Although TBZ did not prevent interferon-γ and tumor necrosis factor-α (IFN/TNF)-induced epithelial cell death, it reversed cytokine-induced increases in transepithelial permeability. Notably, TBZ alone increased paracellular permeability but normalized it under inflammatory conditions, indicating a context-dependent effect. H₂S-producing enzymes localized apically in IECs, suggesting subcellular regulation. Transcriptomic analysis identified oxidative phosphorylation as a pathway mediating TBZ’s effects. Functional studies confirmed that TBZ enhances oxidative phosphorylation, while inhibition of complex IV abolished barrier protection. In conclusion, our data indicate that hydrogen sulfide counteracts IFN/TNF-induced epithelial barrier dysfunction through transcriptional and functional enhancement of oxidative phosphorylation.
2025-12-26 | Effect of vitamin D supplementation on skeletal muscle function and quality of life in patients with chronic intestinal failure: a randomized controlled trial : Clean version.
BACKGROUND: Vitamin D deficiency is common in patients with chronic intestinal failure (CIF); however, the effectiveness of high-dose vitamin D supplementation remains unclear. This study aimed to investigate the effects of high-dose vitamin D supplementation on skeletal muscle mass, function, and quality of life (QoL) in patients with CIF. METHODS: This was a single-center, prospective, randomized, double-blind, placebo-controlled trial conducted at a tertiary hospital in China. Participants included individuals aged 18–70 years with chronic intestinal failure and vitamin D deficiency (serum 25(OH)D < 30 ng/ml). Eighty-four adult patients were randomly assigned (1:1) to either the vitamin D group (intramuscular injection of 600,000 units of vitamin D2 every two weeks for 10 weeks) or the control group (matched placebo). The primary outcomes were appendicular skeletal muscle mass index (assessed by bioelectrical impedance), handgrip strength, 6-meter walking speed, and quality of life (SF-36 scales) from the date of randomization to the end of the 12-week follow-up period. The analysis was performed on an intention-to-treat principle. RESULTS: Eighty-four patients were randomized to the control group (n = 42; mean age, 52.8 ± 15.6 years) or the vitamin D group (n = 42; mean age, 52.9 ± 16.2 years). At the 12-week follow-up, serum 25-hydroxyvitamin D levels were significantly higher in the vitamin D group than in the control group (96.7 ± 5.8 vs. 23.8 ± 4.1 ng/mL; p < 0.001). Compared with the control group, the vitamin D group showed clinically meaningful improvements in the appendicular skeletal muscle mass index, handgrip strength, 6-meter walking speed, and the SF-36 physical component summary score (all p < 0.05 after Bonferroni correction). No other clinically significant differences were observed between the groups in the remaining secondary clinical and safety endpoints. CONCLUSION: High-dose intramuscular vitamin D2 supplementation for 10 weeks was significantly associated with improved skeletal muscle mass, function, and QoL in patients with CIF. THIS TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT06283615. Registered 11 March 2024, https://clinicaltrials.gov/study/NCT06283615 .
cell therapies
2026-09-03 | Expanding Indications of Nonvascularized Rectus Fascia as a Cross-Disciplinary Allograft: A Prospective Single-Center Study.
To report the expanding application of nonvascularized rectus fascia allotransplantation (NVRF-alloTx) in solid organ transplant (SOT) and non-SOT patients and evaluate its effectiveness, integration, and immunologic response in complex abdominal and thoracic reconstruction. Synthetic and biological meshes are limited by infection risk, long-term failure, donor-site morbidity, and high cost. NVRF-alloTx, first applied in intestinal/multivisceral-Tx with a 5.9% herniation rate, offers a simple and promising alternative for challenging defects. This prospective single-center study included all consecutive patients undergoing NVRF-alloTx (2020-2025). Patients were divided into 2 groups: (1) reconstruction in SOT patients (simultaneous or elective closure post-SOT) and (2) reconstruction in non-SOT patients, without immunosuppression. NVRF-allografts were procured from deceased donors, preserved at 2°C, and implanted without HLA-matching. Primary endpoints were successful closure, graft failure, and functional outcome. Clinical and radiologic follow-up was performed, with HLA donor-specific antibody (HLA-DSA) testing and histology whenever available. Forty-seven NVRF-Tx procedures were performed in 41 patients using grafts from 48 deceased donors: group 1 (n=17) and group 2 (n=24). In 2 patients (4.9%), the graft did not integrate due to pancreatic leakage and vasopressor therapy. Others resulted in successful functional outcomes. Histology (n=5) showed graft integration through host fibrotic remodeling with neovascularization evident from 1 month after implantation. (De novo) HLA-DSA developed more frequently in non-SOT NVRF recipients than in SOT NVRF recipients. NVRF-alloTx is a versatile and effective reconstructive option for complex defects in SOT and non-SOT patients, providing an alternative to conventional meshes in challenging clinical scenarios.
2026-06-08 | Living Donor Intestinal Transplant: Indication, Techniques, Surgical Complications, and Outcomes in Recipients and Donors: A Systematic Review.
Living donor intestinal transplantation (LDITx) is an alternative option to cadaveric transplants as a last resort in treating intestinal failure. There are limited data on LDITx outcomes. This systematic review evaluates LDITx in terms of indications, contraindications, surgical complications, and patient outcomes. A comprehensive search was conducted across PubMed, Cochrane Library, Virtual Health Library, and Web of Science databases following the PRISMA guidelines. After filtration, data were systematically extracted from all relevant observational studies, case series, and case reports. Quality assessments were performed using the CARE guideline for case reports and case series, while STROBE was used for observational studies. Fifty-four studies were included, comprising 11 observational studies, 9 case series, and 34 case reports. The main indications of LDITx were the availability of a compatible donor and the urgency of the recipient's clinical condition. The standard surgical technique involves segmental ileal resection and transplantation. Postoperative complications included infections, ischemic events, and vascular complications. Recipients had either manageable complications or no complications. About 21.2% of the population experienced at least one episode of rejection, with an overall mortality rate of 23%. Many cases reported successful TPN weaning and good outcomes for the recipients and donors. In patients with chronic IF complicated by severe TPN-related morbidity or underlying pathologies causing SBS, LDITx represents an effective treatment option and an alternative to the more conventional cadaveric intestinal transplantation, bypassing problematic time sensitivity and donor availability.
2026-01-21 | DOP127 Crohn’s disease and intestinal/multivisceral transplant: Who needs it and what are the outcomes? Experience from a High-Volume Centre
Abstract Background Intestinal/multivisceral transplant (IT/MVT) remains the least frequent solid organ transplant, generally indicated in patients with severe complications of intestinal failure (IF) (1). Crohn’s disease (CD) may lead to IF through multiple mechanisms (2) yet published evidence on transplant outcomes in this setting is scarce. The primary aim of this study was to describe the outcomes of CD patients who underwent IT/MVT in our centre. Methods We retrospectively reviewed CD patients undergoing IT/MVT between 2008 and 2024 at Cambridge. Baseline CD characteristics, surgical history, indication for transplant (Table 1), and transplant characteristics and outcomes (Table 2) were collected. Survival was analysed using Kaplan–Meier and stratified by grafts including or not including liver (Figure 1). Results A total of 24 patients receiving 25 transplants (including 1 retransplant) were included. Fifty-four percent were male, most diagnosed at A2 age (58%), with ileocolonic disease (92%) and proximal involvement in 54%. 83% had stricturing or penetrating behaviour, with a median CD duration of 28.5 years. Prior therapy included immunomodulators (75%) and biologics (71%). Patients had a median of 5 previous surgeries and residual small bowel length of 70 cm; despite this, 58% had active CD at the time of transplant. Short bowel syndrome was the leading cause of IF (83%), and the main indication for transplant was IF-associated liver disease (48%). Median age at transplant was 50 years, with a median follow-up of 35 months; 56% received grafts excluding liver. Although 40% experienced rejection episodes, at last follow-up 88% had complete intestinal function without artificial nutritional support. Three patients developed CD recurrence, which did not result in graft loss. Overall survival is shown in Table 2; in patients with grafts excluding liver, survival was 100%, 90.9% and 90.9% at 1, 3 and 5 years, respectively. Conclusion Our experience shows that in patients with severe, long-standing CD leading to IF and life-threatening complications, IT/MVT is a valuable therapeutic option with excellent outcomes. We recommend early referral of similar cases to specialised centres with expertise in IF and IT/MVT. References: 1. Pironi L, Arends J, Bozzetti F, et al. ESPEN guideline on chronic intestinal failure in adults. Clin Nutr. 2021;40(9):5196-5220. 2. Limketkai BN, Parian AM, Shah ND, Colombel JF. Short Bowel Syndrome and Intestinal Failure in Crohn’s Disease. Inflamm Bowel Dis. 2016;22(5):1209-18. Conflict of interest: López Romero-Salazar, Francisco: Author reports educational/travel grants and/or speaker fees from AbbVie, Dr Falk, J&J, Lilly, Pfizer and Takeda. Butler, Andrew: No conflict of interest Amin, Irum: No conflict of interest Massey, Dunecan: No conflict of interest Neil, Russell: No conflict of interest Woodward, Jeremy: No conflict of interest Rutter, Charlotte: No conflict of interest
2025-12-31 | Rationale and design of the AlloFIST trial: a phase I/IIa study to evaluate dose escalation of allogeneic adipose-derived stroma/stem cells for the treatment of Crohn's fistula.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%-39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%-70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD. This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5×107 and 10×107 cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%. The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 - Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels. NCT06636032.The results will be disseminated through conventional scientific channels.
2025-03-24 | [How close is fecal microbiota transplantation to moving to precision medicine?].
Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.
proteins
2026-08-27 | Dietary and Parenteral Nutritional Management of Short Bowel Syndrome with Intestinal Failure in Adults
Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure in adults, arising when the residual small bowel can no longer absorb the macronutrients, water and electrolytes needed to sustain health without intravenous supplementation. Its management is, at its core, a nutritional problem. This review synthesises current evidence and guideline recommendations on the two pillars of that management: dietary (oral/enteral) therapy and parenteral nutritional support. We frame both around the two variables that dominate clinical behaviour, namely residual intestinal anatomy and the phase of intestinal adaptation, and translate them into anatomy-tailored dietary strategies, rational fluid and electrolyte replacement, micronutrient surveillance, and the composition, delivery and complications of (home) parenteral nutrition. We also position the pharmacological adjuncts, culminating in glucagon-like peptide-2 (GLP-2) analogues, within a stepwise strategy to reduce parenteral-support dependence. The goal throughout is a practical, physiology-anchored approach that maximises enteral autonomy and quality of life while preventing the metabolic, hepatic and catheter-related complications of long-term intravenous feeding.
2026-07-02 | Development of Teduglutide purity certified reference material (GBW09342) through amino acid-based isotope dilution mass spectrometry and sulfur-based isotope dilution inductively coupled plasma mass spectrometry.
As a severe intestinal disorder, short bowel syndrome (SBS) has become the leading cause of chronic intestinal failure worldwide. Teduglutide, a 33-amino-acid glucagon-like peptide-2 (GLP-2) analog, offers a novel therapeutic option for individuals suffering from SBS. In this study, Teduglutide purity certified reference material (CRM) with certified value and expanded uncertainty of (85.0% ± 2.7%) was developed with Teduglutide produced through recombinant gene expression technique. After a comprehensive purity verification and structure confirmation, two independent isotope dilution mass spectrometry (IDMS) strategies based on amino acid (AA) and sulfur measurements were employed for CRM certification, with the later strategy being used for the first time to certify a solid purity CRM. The Teduglutide purity CRM showed good homogeneity, it also exhibited satisfying stability for at least 14 days at 4 °C, 24 h for 25 °C and 12 months at -20 °C. The development of Teduglutide purity CRM (GBW09342) enables the establishment of accurate and reliable analytical methods for purity assessment, which is essential for ensuring the quality, consistency, and clinical safety of corresponding pharmaceutical products. It also provides a reliable reference for the quality control of other peptide-related drugs.
2026-06-16 | Current state of medical rehabilitation for adult short bowel syndrome patients with intestinal failure.
Short bowel syndrome intestinal failure (SBS-IF) occupies a unique position at the interface between chronic organ failure management and intestinal transplantation (iTx). Historically, patients with SBF-IF progressed inevitably toward lifelong home parenteral support (HPS) dependence and, in a small and highly selected subset with impending HPS failure, ultimately to iTx. Recent advances in pro-adaptive pharmacological strategies, focusing on glucagon-like peptide (GLP)-2 and GLP-1-based approaches as adjuncts to conventional antimotility and antisecretory therapies, are reviewed, with implications for decision-making across the SBS-IF disease trajectory presented. SBS-IF is now recognized as a dynamic and modifiable form of organ failure. Targeted pro-adaptive interventions reduce HPS dependence and improve patient-centered outcomes. Conventional antimotility and antisecretory therapies remain foundational, whereas GLP-2 analogues are the first pathophysiology-targeted, pro-adaptive therapies in SBS-IF, while GLP-1 receptor agonists have emerged as promising adjuncts in selected patients, particularly those with high-output phenotypes. Multidisciplinary intestinal failure rehabilitation and gut-directed pharmacotherapy have altered the natural history of SBS-IF. Medical rehabilitation has shifted iTx from a default end-stage therapy to a targeted rescue option reserved for irreversible HPS failure, to be considered after optimized rehabilitation but before the transplant window is lost.
2026-06-03 | Cost-effectiveness of Taurolidine as secondary prevention of recurrent catheter-related bloodstream infections in patients with chronic intestinal failure: Findings from a randomized controlled trial.
Catheter-related bloodstream infections (CRBSIs) are a major complication in patients with chronic intestinal failure (CIF) dependent on home parenteral support (HPS), contributing substantially to morbidity, mortality, and costs. Taurolidine-containing catheter lock solutions reduce CRBSIs, but data on cost-effectiveness remain limited. This cost-effectiveness analysis used data from a double-blind, randomized controlled trial (2019-2022; ClinicalTrials.gov: NCT06660641) comparing 1.35% taurolidine with 0.9% saline as catheter lock solutions for secondary prevention of recurrent CRBSIs in 61 adults with CIF and a history of CRBSI. Economic analyses adopted a healthcare-provider perspective and included direct medical costs related to treatment and CRBSI management. Clinical outcomes were evaluated using recurrent-event methods, and costs were estimated using Diagnosis-Related Group (DRG) tariffs and a micro-costing approach (MCAP). Incremental cost-effectiveness ratios (ICERs) were calculated. Taurolidine significantly reduced recurrent CRBSIs (ratio: 0.23; 95% CI: 0.09-0.60; p = 0.0028) and associated CVC removals (ratio: 0.09; 95% CI: 0.02-0.41; p = 0.0019). The number needed to treat was 2.4 patients per year. Patients in the taurolidine group had fewer admission days (mean 3.3 vs 16.0; p = 0.015). Despite higher acquisition costs, taurolidine reduced the total hospital expenditures by 39% (DRG) to 64% (MCAP). Mean savings per patient at 24 months were €6395 (DRG; p = 0.016) and €15,434 (MCAP; p = 0.014). Taurolidine also reduced the probability of extreme high-cost CRBSI episodes. Incremental cost-effectiveness ratios (ICERs) indicated dominance, with 94.5-99.6% of bootstrap replications showing taurolidine to be more effective and less costly. In patients with CIF and prior CRBSI, 1.35% taurolidine is a clinically superior and cost-saving secondary prevention strategy that reduces recurrent CRBSIs, CVC removals, and hospital resource use. These findings support routine use in secondary prevention and highlight the need to evaluate taurolidine for primary prevention, where early risk stratification remains challenging.
2026-05-14 | Chronic intestinal failure: Medical treatment, home parenteral nutrition, training and monitoring.
Chronic intestinal failure (CIF) requires parenteral nutrition (PN) as its main treatment to sustain health. Short Bowel Syndrom (SBS) is its main cause. Medical management includes dietary approaches, anti-secretory and anti-motility drugs. Recently, GLP-2 analogs like teduglutide for selected patients have helped treated patient to reduce PN. A multidisciplinary nutritional support team (NSTs) is essential for HPN training, covering catheter care, complication prevention, and lifestyle adaptation to promote patients' autonomy. Monitoring protocols recommend 3 months-interval visits for stable patients, to assess clinical status, anthropometrics and biochemistry. Vitamins, trace elements, and HPN complications should be monitored annually or as needed.
antibodies
2026-09-19 | Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn's disease.
Type I interferons (IFN-Is) are central regulators of intestinal epithelial homeostasis, yet their role in driving epithelial dysfunction and therapeutic non-response in Crohn's disease (CD) remains poorly defined. Here, we investigated epithelial tumor necrosis factor (TNF)-IFN-I crosstalk as a previously unrecognized contributor to anti-TNF non-response in CD. We analyzed human intestinal biopsies, single-cell RNA sequencing data from CD donors, and used murine TNFR1-deficient and patient-derived organoids exposed to inflammatory cytokines and clinically relevant treatments. Colonic epithelia from anti-TNF non-responders (NR-CD) showed enrichment of IFN-I genes associated with epithelial stress, impaired regeneration, and inflammatory cytokine production. Using patient-derived and murine TNFR1-deficient organoids, we demonstrated that TNF signaling sustains epithelial IFN-I responses linked to immune regulation and antiviral pathways, establishing a mechanistic connection between chronic TNF signaling and epithelial barrier failure. Low-dose butyrate (0.1 mM) suppressed cytokine-induced IFN-I genes and enhanced epithelial turnover in non-IBD and responder CD (R-CD) organoids but did not rescue the apoptosis and defective repair characteristic of NR-CD organoids. Notably, anti-IFN-I antibody treatment selectively attenuated IFN-I signaling and restored epithelial integrity in NR-CD organoids, identifying epithelial IFN-I blockade as a novel therapeutic rescue strategy for anti-TNF refractory disease. TNF-IFN-I crosstalk drives epithelial dysfunction in CD. Elevated epithelial IFN-I genes distinguish anti-TNF non-responders and underlie differential therapeutic responses. Together, this work supports integration of epithelial IFN-I gene expression and patient-derived ex vivo functional testing into treatment decisions for CD patients.
2026-04-21 | Interleukin-23 Inhibitors in Inflammatory Bowel Disease.
Selective inhibition of interleukin-23 (IL-23) has emerged as a highly effective therapeutic strategy in inflammatory bowel disease, targeting a central pathway of chronic intestinal inflammation while preserving host defense mechanisms. Across phase II and phase III randomized controlled trials, risankizumab, mirikizumab, and guselkumab consistently demonstrated robust efficacy in both ulcerative colitis and Crohn's disease, achieving clinical remission rates approaching 40-50% in ulcerative colitis and exceeding 50% in Crohn's disease during maintenance, with parallel improvements in endoscopic and histological outcomes. Notably, mirikizumab and guselkumab showed particularly high rates of endoscopic and histological remission in ulcerative colitis, whereas guselkumab achieved some of the highest induction remission rates in Crohn's disease. These benefits were durable over time, with long-term extension studies confirming sustained remission beyond two years in a substantial proportion of patients. Across trials, IL-23 inhibitors displayed a favorable safety profile, with low rates of serious adverse events, infections, and major cardiovascular events, supporting their use in long-term disease management. Real-world evidence further reinforces these findings, demonstrating consistent effectiveness in heavily pretreated and complex patient populations, including those with prior biologic failure, comorbidities, or difficult-to-treat disease phenotypes. In particular, risankizumab has shown strong performance in multi-refractory Crohn's disease cohorts, while emerging data for mirikizumab confirm its effectiveness in real-life ulcerative colitis settings. Beyond clinical outcomes, differences in molecular structure, pharmacokinetics, and Fc-mediated interactions may contribute to subtle distinctions among agents, potentially influencing therapeutic positioning. Ongoing development of oral compounds and combination strategies targeting complementary inflammatory pathways is expected to further expand the role of IL-23 inhibition. Overall, interleukin-23 inhibitors represent a cornerstone of modern inflammatory bowel disease therapy, combining high efficacy, durable responses, and an excellent safety profile, with growing evidence supporting their use across a broad spectrum of patients.
2025-12-03 | Cytomegalovirus and Crohn's disease as competing causes of small bowel inflammation after double-lung transplantation.
Cytomegalovirus (CMV) infection remains a significant cause of morbidity following solid organ transplantation, most frequently affecting the gastrointestinal tract. In transplant recipients presenting with diarrhea, alternative etiologies such as inflammatory bowel disease (IBD) should be considered. The emergence of antiviral resistance poses a therapeutic challenge, and molecular testing for resistance-associated mutations is essential in cases of treatment failure. A lung transplant recipient developed chronic diarrhea leading to functional intestinal failure. CMV infection was identified in intestinal biopsies and initially managed with two courses of valganciclovir. Due to persistent symptoms, genotypic analysis was performed, revealing UL97 mutations conferring ganciclovir resistance. Sequential therapy with foscarnet, maribavir, and letermovir achieved virological clearance, but diarrhea persisted. Small bowel enteroscopy with biopsies showed ongoing mucosal inflammation and minimal residual CMV activity. These findings were consistent with ganciclovir-resistant CMV enteritis coexisting with de novo Crohn's disease. The patient was commenced on standard biological therapy for Crohn's disease, resulting in marked clinical improvement and recovery. This case illustrates the diagnostic challenge of distinguishing CMV enteritis from de novo Crohn's disease and determining the primary driver of the clinical presentation.
2025-11-03 | Intestinal reengineering: Scientific advances in intestinal transplantation.
Intestinal transplantation (ITx) has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies. Despite its growing clinical acceptance, ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation. This review comprehensively summarizes the historical evolution, clinical indications, and advancements in surgical techniques, with emphasis on innovations in vascular anastomosis, multivisceral transplantation, and ex vivo preservation. Special attention is given to the unique immunological challenges of ITx, including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions, and the distinct roles of key immune cells. Pediatric and adult recipients exhibit divergent etiologies, immune responses, and complication profiles, necessitating individualized approaches. Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes, chronic rejection, graft dysfunction, and immunosuppressive toxicity remain significant barriers. Looking ahead, future directions should prioritize precision immunomodulation, microbiome-targeted therapies, and integrated platforms for gene editing, 3D bioprinting, and immune monitoring. Through multidisciplinary collaboration and translational research, ITx is poised to evolve from a high-risk salvage therapy into a personalized, sustainable solution that enhances long-term survival and patient quality of life.
2025-10-02 | [Pharmacist-Led Shared Decision-Making in a Pediatric Patient with Crohn's Disease and Growth Failure: A Case Report].
Inflammatory bowel disease (IBD) is an illness of unknown etiology, leading to chronic intestinal inflammation. It is characterized by repeated periods of remission and relapse. In the current treatment of IBD, multiple therapeutic drugs are listed in the Japanese treatment guidelines. Therefore, selecting a drug that matches the patient's condition and lifestyle is important, and the treatment decisions should be made using shared decision-making (SDM). For children, there is no specific age at which decision-making becomes possible. Therefore, medical professionals must make appropriate assessments regarding their decision-making ability. Although SDM has been shown to be useful in adults, there are no reports of SDM use in children. In this case report, a pharmacist performed multiple SDM for a 15-year-old patient with Crohn's disease. The SDM process reflected the child's changing values, leading to the introduction and continuation of biologic agents, and addressing growth disorders after the disease activity was controlled. To our knowledge, this is the first reported case in which a pharmacist performed SDM based on the condition of a pediatric patient with IBD, effectively implemented treat-to-target strategies, and improved the growth disorder. This case demonstrates the importance of properly controlling disease activity in pediatric patients with IBD and highlights the important role of pharmacists in adjusting drug therapy to suit a child's condition.
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Drug Discovery Landscape
1 orphan drug designation for Chronic intestinal failure.
1 orphan drug designation for Chronic intestinal failure.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Orziloben | small molecules | EMA | Northsea Therapeutics B.V. |
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