Multilevel Analysis of the Neovascularization and Integration Process of a Nonvascularized Rectus Fascia Transplantation.

Background: Failure to close the abdominal wall after intestinal transplantation (ITx) or multivisceral Tx remains a surgical challenge. An attractive method is the use of nonvascularized rectus fascia (NVRF) in which both layers of the donor abdominal rectus fascia are used as an inlay patch without vascular anastomosis. How this graft integrates over time remains unknown. The study aims to provide a multilevel analysis of the neovascularization and integration process of the NVRF. Methods: Three NVRF-Tx were performed after ITx. Clinical, radiological, histological, and immunological data were analyzed to get insights into the neovascularization and integration process of the NVRF. Moreover, cryogenic contrast-enhanced microfocus computed tomography (microCT) analysis was used for detailed reconstruction of the vasculature in and around the NVRF (3-dimensional histology). Results: Two men (31- and 51-y-old) and 1 woman (49-y-old) underwent 2 multivisceral Tx and 1 combined liver-ITx, respectively. A CT scan showed contrast enhancement around the fascia graft at 5 days post-Tx. At 6 weeks, newly formed blood vessels were visualized around the graft with Doppler ultrasound. Biopsies at 2 weeks post-Tx revealed inflammation around the NVRF and early fibrosis. At 6 months, classical 2-dimensional histological analysis of a biopsy confirmed integration of the fascia graft with strong fibrotic reaction without signs of rejection. A cryogenic contrast-enhanced microCT scan of the same biopsy revealed the presence of microvasculature, enveloping and penetrating the donor fascia. Conclusions: We showed clinical, histological, and microCT evidence of the neovascularization and integration process of the NVRF after Tx.

Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers.

INTRODUCTION: Approximately 50% of Crohn's disease (CD) patients develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of CD patients. METHODS: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 CD patients and 10 non-inflammatory bowel disease (IBD) controls. Macroscopically, unaffected, fibrostenotic and inflamed ileum was collected and analysed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed via a Masson's Trichrome staining. Eosinophil and fibroblast co-localization was assessed through immunohistochemistry. RESULTS: The Masson's Trichrome staining confirmed augmented collagen deposition in both the fibrotic as the inflamed region, though with a significant increased collagen deposition in fibrotic compared to inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells and monocytes were identified in fibrotic and inflamed CD ileum compared to unaffected ileum of CD patients as non-IBD controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased Eosinophil Cationic Protein (ECP) protein expression in inflamed deeper layers. Lastly, no differences in eosinophil and fibroblast co-localization was observed between the different regions. CONCLUSION: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of CD patients. Immunologic, proteomic and histological data suggest inflammation and fibrosis are intertwined, with large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.

Celiac disease: Hope for new treatments beyond a gluten-free diet.

BACKGROUND & AIMS: Celiac disease (CD) is a chronic inflammatory disease of the small intestine induced and maintained by gluten ingestion in susceptible individuals. Current treatment consists of strict adherence to a lifelong gluten-free diet (GFD) which is considered safe and effective in the large majority of patients. However, since adherence to a GFD is difficult and has a negative impact on quality of life, an increasing interest in other treatment options has emerged. Moreover, in some individuals a GFD is not sufficiently effective, necessitating alternative treatments. METHODS: By performing a systematic search, we constructed a detailed narrative review. Only treatment options considered relevant and conducted in a phase I, II or III clinical trial were included. RESULTS: Based on the pathophysiology of CD, four major therapeutic approaches can be distinguished: firstly, by focusing on intraluminal gluten detoxification before absorption occurs, secondly, by modulating intestinal permeability and preventing paracellular uptake, thirdly, by enhancing immunological tolerance to gluten and finally, by regulating gluten auto-immunity. CONCLUSIONS: Despite significant efforts, no treatment has yet completed a phase III clinical trial. Future studies will likely focus on the use of supplemental drugs in conjunction to a GFD, with ALV003 and ZED-1227 currently being the most promising therapeutic options.

Breaking the Barrier: The Role of Gut Epithelial Permeability in the Pathogenesis of Hypertension.

PURPOSE OF THE REVIEW: To review what intestinal permeability is and how it is measured, and to summarise the current evidence linking altered intestinal permeability with the development of hypertension. RECENT FINDINGS: Increased gastrointestinal permeability, directly measured in vivo, has been demonstrated in experimental and genetic animal models of hypertension. This is consistent with the passage of microbial substances to the systemic circulation and the activation of inflammatory pathways. Evidence for increased gut permeability in human hypertension has been reliant of a handful of blood biomarkers, with no studies directly measuring gut permeability in hypertensive cohorts. There is emerging literature that some of these putative biomarkers may not accurately reflect permeability of the gastrointestinal tract. Data from animal models of hypertension support they have increased gut permeability; however, there is a dearth of conclusive evidence in humans. Future studies are needed that directly measure intestinal permeability in people with hypertension.

The Leuven Prolonged Acute Stress Test (L-PAST): A novel paradigm to induce a subjective and glucocorticoid stress response for at least ninety minutes.

Laboratory stress tests typically administer stress acutely, ranging from 3 to 15 minutes. However, everyday stressors usually last longer than ten minutes (e.g., examination stressors, work stressors, and social stressors. Moreover, in some studies, it may be relevant to induce stress for a longer period to affect certain psychological or physiological parameters. To this end, we developed a novel stress test that intends to induce psychosocial stress for 90 minutes. The Leuven Prolonged Acute Stress Test (L-PAST) combines physical (hand immersion in cold water), cognitive (mental arithmetic), and psychosocial (social evaluation and feelings of failure) stress elements of two well-known laboratory stress tests, the Maastricht Acute Stress Test (MAST) and the Montreal Imaging Stress Test (MIST). Fifty healthy women were subjected to both the L-PAST and a sham (control) test in a randomized and counterbalanced manner. The stress response was determined by salivary cortisol measurements and assessment of subjective stress ratings at regular time points during the time preceding the stress period (5 min), the stress period (90 min), and the recovery period (35 min). Cognitive reactivity to failure and subjective pain levels were also assessed at various time points. The childhood trauma questionnaire (CTQ) and the perceived stress scale (PSS) were administered prior to the testing phase. As expected, linear mixed models revealed that the stress response was significantly higher during the L-PAST as indicated by a significant time point by condition interaction effect for both the cortisol response (F(10,450)=12.21, p < 0.0001, ηp2=0.11) and the subjective stress response (F(13,637)=13.98, p < 0.0001, ηp2 = 0.12). Moreover, there was a significant time point by condition interaction effect for cognitive reactivity to failure (F(13,637) = 7.97, p < 0.0001, ηp2 = 0.07) and subjective pain (F(13,637) = 38.52, p < 0.0001, ηp2 = 0.27), indicating that the levels were higher during the L-PAST at most stress induction time points. Lastly, higher CTQ scores were associated with higher subjective pain levels during the L-PAST (F(1,44)=6.05, p = 0.02). Collectively, our results confirm the efficacy of the L-PAST in inducing a prolonged subjective as well as cortisol stress response.

Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION: Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. OBJECTIVE: The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. METHODS: Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. RESULTS: 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm). CONCLUSIONS: In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Nutritional management of high-output ileostomies in paediatric patients is vital and more evidence-based guidelines are needed.

AIM: Paediatric patients with high-output ileostomies (HOI) face an elevated risk of complications. This study aimed to comprehensively review the existing literature and offer nutritional management recommendations for paediatric patients with an HOI. METHODS: PubMed and Embase were searched for relevant English or French language papers up to 31 June 2022. The emphasis was placed on studies involving paediatric ileostomy patients, but insights were obtained from adult literature and other intestinal failure pathologies when these were lacking. RESULTS: We identified 16 papers that addressed nutritional issues in paediatric ileostomy patients. Currently, no evidence supports a safe paediatric HOI threshold exceeding 20 mL/kg/day on two consecutive days. Paediatric HOI patients were at risk of dehydration, electrolyte disturbances, micronutrient deficiencies and growth failure. The primary dietary choice for neonates is bolus feeding with breastmilk. In older children, an enteral fluid restriction should be installed favouring isotonic or slightly hypotonic glucose-electrolyte solutions. A diet that is high in calories, complex carbohydrates and proteins, low in insoluble fibre and simple carbohydrates, and moderate in fat is recommended. CONCLUSION: Adequate nutritional management is crucial to prevent complications in children with an HOI. Further research is needed to establish more evidence-based guidelines.

Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.

BACKGROUND AND AIMS: The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS: Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS: In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION: We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.

Understanding the gastrointestinal tract in obesity: From gut motility patterns to enzyme secretion.

BACKGROUND AND PURPOSE: The pathophysiology of obesity has been the product of extensive research, revealing multiple interconnected mechanisms contributing to body weight regulation. The regulation of energy balance involves an intricate network, including the gut-neuroendocrine interplay. As a consequence, research on the gut-brain-microbiota axis in obesity has grown extensively. The physiology of the gastrointestinal tract, far from being underexplored, has significant implications for the development of specific complications in people living with obesity across the fields of gastroenterology, nutrition, and pharmacology. Clinical research indicates higher fasting bile acids serum levels, and blunted postprandial increases in bilious secretions in people living with obesity. Findings are less straightforward for the impact of obesity on gastric emptying with various studies reporting accelerated, normal, or delayed gastric emptying rates. Conversely, the effect of obesity on gastrointestinal pH, gastrointestinal transit, and gastric and pancreatic enzyme secretion is largely unknown. In this review, we explore the current evidence on the gastrointestinal physiology of obesity.

Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study. METHODS: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately. RESULTS: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081). CONCLUSIONS: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS. TRIAL REGISTRATION NUMBER: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

Medication use in a cohort of adults with chronic intestinal failure: A prospective cross-sectional study.

BACKGROUND: Oral drug therapy may be compromised in chronic intestinal failure (IF) because of alterations in absorption and transit. Only scarce literature is available on which medication patients with chronic IF take in daily life. The aim was to describe the medication use in these patients. METHODS: A medication history was obtained from adults with chronic IF treated in our tertiary care IF center. Degree of polypharmacy, drug classes, Biopharmaceutics Classification System classes, route of administration, and formulation of drugs were analyzed. RESULTS: From October 2019 until December 2020, 72 patients (35 patients with short bowel syndrome [SBS] and 37 patients without SBS) were included. Polypharmacy was seen in 85.7% of patients with SBS and 75.7% of patients without SBS. The top three drug classes were proton-pump inhibitors, vitamin D or acetaminophen, and antimotility medication or laxatives/benzodiazepines. Approximately 25% of the drugs were classified as Biopharmaceutics Classification System class I drugs. In patients with SBS (78%) and patients without SBS (74.9%), most medication was taken orally, requiring gastrointestinal absorption of the active substance to be pharmacologically active. Most of these medications (77% in patients with SBS and 80.8% in patients without SBS) were formulated as a capsule or tablet, requiring disintegration and dissolution in the gastrointestinal tract before absorption can take place. CONCLUSION: Polypharmacy was observed in most patients with chronic IF. Most medication was taken orally in formulations requiring disintegration, dissolution, and gastrointestinal absorption, which could be compromised in chronic IF.

10-year follow-up results of the European Achalasia Trial: a multicentre randomised controlled trial comparing pneumatic dilation with laparoscopic Heller myotomy.

OBJECTIVE: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM). DESIGN: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105). Patients completed symptom (Eckardt score) and quality-of-life questionnaires, underwent functional tests and upper endoscopy. Primary outcome was therapeutic success defined as Eckardt score <3 at yearly follow-up. Secondary outcomes were the need for retreatment, lower oesophageal sphincter pressure, oesophageal emptying, gastro-oesophageal reflux and the rate of complications. RESULTS: After 10 years of follow-up, LHM (n=40) and PD (n=36) were equally effective in both the full analysis set (74% vs 74%, p=0.84) and the per protocol set (74% vs 86%, respectively, p=0.07). Subgroup analysis revealed that PD was superior to LHM for type 2 achalasia (p=0.03) while there was a trend, although not significant (p=0.05), that LHM performed better for type 3 achalasia. Barium column height after 5 min at timed barium oesophagram was significantly higher for patients treated with PD compared with LHM, while other parameters, including gastro-oesophageal reflux, were not different. CONCLUSIONS: PD and LHM are equally effective even after 10 years of follow-up with limited risk to develop gastro-oesophageal reflux. Based on these data, we conclude that PD and LHM can both be proposed as initial treatment of achalasia.

INT-767-A Dual Farnesoid-X Receptor (FXR) and Takeda G Protein-Coupled Receptor-5 (TGR5) Agonist Improves Survival in Rats and Attenuates Intestinal Ischemia Reperfusion Injury.

Intestinal ischemia is a potentially catastrophic emergency, with a high rate of morbidity and mortality. Currently, no specific pharmacological treatments are available. Previous work demonstrated that pre-treatment with obeticholic acid (OCA) protected against ischemia reperfusion injury (IRI). Recently, a more potent and water-soluble version has been synthesized: Intercept 767 (INT-767). The aim of this study was to investigate if intravenous treatment with INT-767 can improve outcomes after IRI. In a validated rat model of IRI (60 min ischemia + 60 min reperfusion), three groups were investigated (n = 6/group): (i) sham: surgery without ischemia; (ii) IRI + vehicle; and (iii) IRI + INT-767. The vehicle (0.9% NaCl) or INT-767 (10 mg/kg) were administered intravenously 15 min after start of ischemia. Endpoints were 7-day survival, serum injury markers (L-lactate and I-FABP), histology (Park-Chiu and villus length), permeability (transepithelial electrical resistance and endotoxin translocation), and cytokine expression. Untreated, IRI was uniformly lethal by provoking severe inflammation and structural damage, leading to translocation and sepsis. INT-767 treatment significantly improved survival by reducing inflammation and preserving intestinal structural integrity. This study demonstrates that treatment with INT-767 15 min after onset of intestinal ischemia significantly decreases IRI and improves survival. The ability to administer INT-767 intravenously greatly enhances its clinical potential.

Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidence?

An impaired intestinal barrier function can be detrimental to the host as it may allow the translocation of luminal antigens and toxins into the subepithelial tissue and bloodstream. In turn, this may cause local and systemic immune responses and lead to the development of pathologies. In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans. In the current Review, we discuss the mechanisms that are involved in stress-induced intestinal permeability changes and postulate factors that influence these alterations and that may explain the translational difficulties from in vitro and animal to human studies. As human research differs highly from animal research in the extent to which stress can be applied and intestinal permeability can be measured, it remains difficult to draw conclusions about the presence of a relation between stress and intestinal permeability in (healthy) humans. Future studies should bear in mind these difficulties, and more research into in vivo methods to assess intestinal permeability are warranted.

Intestinal Donation and Utilization: Single-Center Analysis Within Eurotransplant.

Intestinal donor criteria are classically kept strict, thereby limiting donor supply. Indications for intestinal transplantation (ITx) are rare, but improved outcome and new emerging indications lead to increased demand and relaxing donor criteria should be considered. We sought to compare the donor criteria of intestines transplanted at our center with predefined (per protocol) criteria, and to determine how relaxing donor criteria could impact the potential donor pool. Donor criteria used in 22 consecutive ITx at our center between 2000 and 2020 were compared with predefined criteria. Next, multiorgan donors effectively offered by our Donor Network to Eurotransplant between 2014 and 2020 were retrospectively screened, according to predefined and effectively used intestinal donation criteria. Finally, utilization rate of offered intestines was calculated. In our ITx series, the effectively used donor criteria were less strict than those initially predefined. With these relaxed criteria, a favorable 5-year graft/patient survival of 75% and 95%, respectively was reached. Applying these relaxed criteria would lead to a 127% increase in intestinal offers. Paradoxically, 70% of offered intestines were not used. In conclusion, a significant increase in intestinal donation could be obtained by relaxing donor criteria, while still achieving excellent outcome. Offered intestines are underutilized.

Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms.

BACKGROUND & AIMS: Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. METHODS: Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. RESULTS: Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. CONCLUSIONS: Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum.

Intravenous Polyethylene Glycol Alleviates Intestinal Ischemia-Reperfusion Injury in a Rodent Model.

Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.

Outcome After Intestinal Transplantation From Living Versus Deceased Donors: A Propensity-matched Cohort Analysis of the International Intestinal Transplant Registry.

OBJECTIVE: To describe the worldwide experience with living donation (LD) in intestinal transplantation (ITx) and compare short-term and long-term outcomes to a propensity-matched cohort of deceased donors. BACKGROUND: ITx is a rare life-saving procedure for patients with complicated intestinal failure (IF). Living donation (LD)-ITx has been performed with success, but no direct comparison with deceased donation (DD) has been performed. The Intestinal Transplant Registry (ITR) was created in 1985 by the Intestinal Transplant Association to capture the worldwide activity and promote center's collaborations. METHODS: Based on the ITR, 4156 ITx were performed between January 1987 and April 2019, of which 76 (1.8%) were LD, including 5 combined liver-ITx, 7 ITx-colon, and 64 isolated ITx. They were matched with 186 DD-ITx for recipient age/sex, weight, region, IF-cause, retransplant, pretransplant status, ABO compatibility, immunosuppression, and transplant date. Primary endpoints were acute rejection and 1-/5-year patient/graft survival. RESULTS: Most LDs were performed in North America (61%), followed by Asia (29%). The mean recipient age was: 22 years; body mass index: 19kg/m²; and female/male ratio: 1/1.4. Volvulus (N=17) and ischemia (N=17) were the most frequent IF-causes. Fifty-two percent of patients were at home at the time of transplant. One-/5-year patient survival for LD and DD was 74.2/49.8% versus 80.3/48.1%, respectively ( P =0.826). One-/5-year graft survival was 60.3/40.6% versus 69.2/36.1%, respectively ( P =0.956). Acute rejection was diagnosed in 47% of LD versus 51% of DD ( P =0.723). CONCLUSION: Worldwide, LD-ITx has been rarely performed. This retrospective matched ITR analysis revealed no difference in rejection and in patient/graft survival between LD and DD-ITx.