Historically, in children with intestinal failure associated liver disease (IFALD), the presence of splenomegaly and moderate bridging fibrosis would be considered as evidence of advanced liver disease and portal hypertension and be recommended for liver-inclusive intestinal transplant graft. In our experience, the assessment of portal hypertension based on conventional investigations, which are well established in other chronic liver diseases, could be misleading in some children with IFALD, and further investigations could help in assessing the severity of liver disease. Hepatic venous wedge pressure gradient (HVWPG) is used in chronic liver diseases for objectively assessing the severity of portal hypertension. We postulated that HVWPG may be useful to assess the severity of portal hypertension in children with IFALD and, therefore, help in the decision-making process for the need for a liver-inclusive intestinal graft.

Retrospective analysis of children with IFALD who had HVWPG measured between 2005 and 2020. Demographic details, laboratory parameters, liver biopsy, HVWPG and clinical outcomes were reviewed. Children were grouped into two categories based on HVWPG gradient: HVWPG ≥ 10 mmHg (significant portal hypertension) and HVWPG < 10 mmHg.

Between 2005 and 2020, 23 children (median age: 33 months, interquartile range: 11-54) had 27 HVWPG measurements (4 children had repeat measurements). No procedural complications were documented. 16/23 children had HVWPG < 10 mmHg, 7/23 children had HVWPG ≥ 10 mmHg. Of the 16 children with HVWPG < 10 mmHg, 10 children were referred to the local team for intestinal rehabilitation, while 6 children were recommended for transplantation (4 for isolated intestinal transplant and 2 for liver-inclusive intestinal transplant) as they fulfilled other indications for intestinal transplantation (impaired venous access, etc.). Of the seven children who had significant portal hypertension (HVWPG ≥ 10 mmHg), six were recommended for liver-inclusive intestinal transplant. There was a cohort of four children with at least bridging fibrosis and HVWPG < 10 mmHg who had repeat measurements due to failed intestinal rehabilitation strategies to wean from parenteral nutrition and worsening clinical signs (increasing splenomegaly, etc.). Two children were recommended for liver-inclusive intestinal transplant in view of increase in HVWPG to ≥10 mmHg.

HVWPG measurements can guide in the decision-making process in children with IFALD, especially those with bridging fibrosis without significant clinical evidence of portal hypertension for deciding on the need for liver-inclusive intestinal transplantation.

Curcumin (CUR), a bioactive compound found in turmeric, has garnered attention for its potential anti-inflammatory properties and impact on liver health. Numerous studies suggest that CUR may be crucial in mitigating liver inflammation. The compound's anti-inflammatory effects are believed to be attributed to its ability to modulate various molecular pathways involved in the inflammatory response. Research indicates that CUR may suppress the activation of inflammatory cells and the production of pro-inflammatory cytokines in the liver. Additionally, it has been observed to inhibit the activity of transcription factors that play a key role in inflammation. By targeting these molecular mechanisms, CUR may help alleviate the inflammatory burden on the liver. Moreover, CUR's antioxidant properties are thought to contribute to its protective effects on the liver. Oxidative stress is closely linked to inflammation, and CUR's ability to neutralize free radicals may further support its anti-inflammatory action. While the evidence is promising, it is essential to note that more research is needed to fully understand the precise mechanisms through which CUR influences liver inflammation. Nevertheless, these findings suggest that CUR could be a potential therapeutic agent in managing liver inflammatory conditions. In this review, we explore the potential impact of CUR on inflammation, highlighting the key mechanisms involved, as reported in the literature.

Malabsorption is a complex and multifaceted condition characterised by the defective passage of nutrients into the blood and lymphatic streams. Several congenital or acquired disorders may cause either selective or global malabsorption in both children and adults, such as cystic fibrosis, exocrine pancreatic insufficiency (EPI), coeliac disease (CD) and other enteropathies, lactase deficiency, small intestinal bacterial overgrowth (SIBO), autoimmune atrophic gastritis, Crohn's disease, and gastric or small bowel resections. Early recognition of malabsorption is key for tailoring a proper diagnostic work-up for identifying the cause of malabsorption. Patient's medical and pharmacological history are essential for identifying risk factors. Several examinations like endoscopy with small intestinal biopsies, non-invasive functional tests, and radiologic imaging are useful in diagnosing malabsorption. Due to its high prevalence, CD should always be looked for in case of malabsorption with no other obvious explanations and in high-risk individuals. Nutritional support is key in management of patients with malabsorption; different options are available, including oral supplements, enteral or parenteral nutrition. In patients with short bowel syndrome, teduglutide proved effective in reducing the need for parenteral nutrition, thus improving the quality of life of these patients. Primary care physicians have a central role in early detection of malabsorption and should be involved into multidisciplinary teams for improving the overall management of these patients. In this European consensus, involving 10 scientific societies and several experts, we have dissected all the issues around malabsorption, including the definitions and diagnostic testing (Part 1), high-risk categories and special populations, nutritional assessment and management, and primary care perspective (Part 2).

Congenital tufting enteropathy (CTE) is a rare autosomal recessive inherited disorder caused by mutations in the epithelial cell adhesion molecule (EpCAM) gene, characterized by severe diarrhea and growth failure. Between December 2017 and December 2023, eight patients diagnosed with CTE at our hospital were retrospectively analyzed for their clinical and genetic features, alongside a comprehensive literature review. All patients presented with severe malnutrition and growth failure upon admission. Parenteral nutrition (PN) with high caloric intake was required for all patients to achieve growth catch-up. A total of 142 patients with EpCAM mutations were reviewed, including 137 previously reported cases and five newly identified patients described in this study. Among the 114 CTE patients with detailed treatment information, 108 patients received PN therapy, with six patients successfully weaned off PN. Additionally, 19 patients underwent intestinal transplantation (IT). Outcome analysis revealed that 30 patients (27.3%) died, including five post-IT deaths. A total of 68 EpCAM mutations were identified, with most located in exon 3. The most frequently reported variant was c.499dup C. In this study, four novel mutations were detected in our patients. This study provides a comprehensive overview of the clinical and genetic characteristics of CTE, enhancing the understanding of its phenotype and genotype, particularly in Asian patients.

Adult intestinal retransplant has increased substantially during the past decade, outpacing the rate of primary transplants to become the fourth most common reason for intestinal transplant. Although intestinal retransplant is a viable option for patients with failed transplants, long-term survival is often lower. We compared intestinal retransplant to primary intestinal transplant for rates of graft failure, acute rejection, and mortality.

We collected data from the United Network for Organ Sharing database for intestinal retransplant and first-time intestinal transplant for the period from 2010 to 2024. We compared recipient and deceased donor characteristics of primary intestinal transplant alone and intestinal retransplant via Pearson chi-square tests. We contrasted graft failure, mortality, and acute rejection by using log-rank tests, multivariate Cox analysis, and logistic regression analysis.

We selected 741 patients; 60 (8.1%) were intestinal retransplant recipients. On log-rank tests, intestinal retransplant showed 20% higher rate of graft failure and mortality after 5 years (P < .001). Regression analysis showed that retransplant was associated with 61% higher rate of graft failure (hazard ratio = 1.615, P = .002), 107% higher rate of acute rejection (odds ratio = 2.072, P = .049), and an 82% increase in mortality (hazard ratio = 1.823, P < .001). No associations between sex, race and ethnicity, or induction or maintenance regimens and graft failure or mortality for intestinal retransplant were shown.

Adult intestinal retransplant was associated with higher rates of graft failure related to rejection and infection, and retransplant status was associated with higher rates of graft failure and mortality. No associations between different regimens of induction or maintenance and graft failure or mortality were shown. Race/ethnicity and sex did not affect graft failure or mortality. Further research of intestinal retransplant will improve knowledge of risk factors associated with negative outcomes.

To explore the meaning of adaptation after visceral transplantation in terms of patient experiences, symptoms, self-efficacy, transplant-specific and mental well-being.

A convergent parallel mixed-methods study, consisting of interviews and generic as well as transplant-specific questionnaires. Results were integrated using meta-inference.

The study comprises a population of 17 visceral transplant recipients in Scandinavia, 12 women and 5 men with a mean age of 40.6 years (range 19-63 years) and an average follow-up of 9.4 years (range 0-25 years). Data were collected between May 2023 and January 2024 through open-ended in-depth interviews with 12 participants and analysed in accordance with phenomenological hermeneutics. Questionnaires from all 17 participants were analysed to measure transplant-specific well-being, symptoms, self-efficacy as well as anxiety and depressive symptoms.

Being a visceral transplant recipient is a dynamic and life-long adaptation process that comprises two distinct yet interconnected trajectories: coherence and endurance. Coherence involves the person's ability to make sense of their situation and find meaning despite the challenges and adversity of the chronic condition. In contrast, endurance involves a person's capacity to withstand hardship and endure unpleasant or difficult experiences. Both trajectories interact dynamically, influencing and reinforcing each other. Resilience based on coherence enabled acceptance and adjustment. Conversely, uncertainty, resignation and feeling unsupported resulted in a lack of acceptance, manifested as resistance. The challenge involved in adaptation was demonstrated by 47% showing borderline elevated or elevated levels of anxiety and 18% reporting symptoms of depression. Self-efficacy varied considerably.

The meaning of adaptation after visceral transplantation in terms of experiences, symptoms, transplant-specific and mental well-being is balancing between coherence and endurance facilitated by acceptance and hampered by resistance. The uncertainty inherent in being a visceral transplant recipient may lead to heightened self-rated anxiety symptoms and diminished self-efficacy.

What problem did the study adress? This study adresses the challenges involved in being a visceral transplant recipient and adapting to life after a visceral transplantation. What were the main findings?

COREQ checklist (consolidated criteria for reporting qualitative research).

No Patient or Public Contribution was organised.

We aimed to evaluate health-related quality of life (HRQoL) in intestinal failure (IF) patients after different modes of intestinal rehabilitation.

HRQoL was assessed using the generic 36-item Short Form Survey (SF-36, ver. 2) and visual analogue scale (VAS) in 6 different areas: diet, sleep, gastrointestinal (GI) symptoms, diarrhea, musculoskeletal pain, and other symptoms.

Twenty-two patients completed the questionnaires, of which 7 had received intestinal transplant (ITx), 9 were continuing home total parenteral nutrition (HPN), and 6 had tapered off total parenteral nutrition (TPN). SF-36 physical component summary scores were highest in the ITx group (median, 65.6; interquartile range [IQR], 31.6-80.3) compared to the HPN (median, 48.4; IQR, 44.7-66.3) or tapered group (median, 54.2; IQR, 45.2-61.6). Mental component summary scores were lowest in the ITx group (median, 48.8; IQR, 37.1-63.6), compared to the TPN (median, 60.2; IQR, 41.6-78.5) or tapered group (median, 51.0; IQR, 48.8-56.0). Differences were not significant in all items of the SF-36. VAS scores showed that patients in the ITx group showed the best results in diet (0.9), gastrointestinal (GI) symptoms (1.4), and musculoskeletal pain (2.4). There was a significant difference in sleep (P = 0.036), with the ITx (1.43) and HPN groups (1.33) showing better outcomes compared with the tapered group (4.67). Patients in the tapered group showed the least favorable results in all performance areas, except GI symptoms.

SF-36 did not show a significant difference between the ITx, HPN, and tapered groups, but VAS showed a significant difference in sleep between groups. Further studies, including serial data, will allow a better understanding of the effects of different modes of intestinal rehabilitation.

Short bowel syndrome (SBS) is a devastating malabsorptive condition and the most common cause of chronic intestinal failure (CIF). During the intestinal rehabilitation process, patients may need parenteral support for months or years, parenteral nutrition (PN), or hydration/electrolyte supplementation, as a bridge for the desired enteral autonomy.

Several classification criteria have been highlighted to reflect different perspectives in CIF. The management of CIF-SBS in adults is a multidisciplinary process that aims to reduce gastrointestinal secretions, slow transit, correct/prevent malnutrition, dehydration, and specific nutrient deficiencies, and prevent refeeding syndrome. The nutritional support team should have the expertise to take care of these complex patients: fluid support; oral, enteral, and PN; disease/PN-related complications; pharmacologic treatment; and surgical prevention/treatment.

CIF-SBS is a complex disease with undesired consequences, if not adequately identified and managed. A comprehensive approach performed by a multidisciplinary team is essential to reduce PN dependence, promote enteral independence, and improve quality of life.

Short bowel syndrome is considered a low prevalence disease. The scant information available about intestinal failure in Latin America was the driving force to expand this registry.

A prospective, multicenter observational registry was created for patients with chronic intestinal failure short bowel at specialized centers in Latin America. Demographics, clinical characteristics, nutrition assessment, parenteral nutrition management, intestinal rehabilitation, related complications, clinical outcome, and survival were analyzed.

From May 2020 to July 2023, 167 patients (115 adults, 52 children) from 20 centers were enrolled. For the adults, the mean age was 37.2 ± 18 years, 48% were female, and the mean follow-up was 22.6 ± 18.3 months. The main etiology was surgical resections (postsurgical complications: 37%; ischemia: 25%); the mean intestinal length was 73 ± 55 cm. The complications were as follows: infections: 0.4/1000 catheter-days; thrombosis: 0.24/1000 catheter-days; liver disease: 2.6%. The outcomes were as follows: 28% were rehabilitated, 15% died, 9.6% were lost to follow-up, 0.9% underwent transplant, and 45.6% continued follow-up. For the children, the mean age 48 ± 52 months, 48% were female, 52% were premature. The mean follow-up was 17.2 ± 5.6 months; the mean remaining intestinal length was 38 ± 45 cm. The leading etiologies were atresia (25%), NEC (23%), and gastroschisis (21%). The complication were as follows: infections: 2/1000 catheter-days; thrombosis: 2.22/1000 catheter-day; 25% developed liver disease. The outcomes were as follows: 7.7% died, 3.8% were rehabilitated, and 88.5% continued follow-up.

The RESTORE amendment served as a registry and educational tool for the participating teams. The aspiration is to objectively show current aspects of intestinal failure in the region and carry them to international standards. Including all Latin American countries and etiologies of chronic intestinal failure besides short gut would serve to complete this registry.

Intestinal allografts, with many resident immune cells and as a destination for circulating lymphocytes of the recipient, appear to be the most challenging solid organ transplants. The high incidence of acute rejection and frequent reports of fatal graft-versus-host disease (GvHD) after intestinal transplantation call for more research to describe the molecular mechanisms involved in the immunopathogenesis of post-transplant complications to define new therapeutic targets. In addition, according to the rapid development of immunosuppressive agents, it is time to consider novel therapeutic approaches in managing treatment-refractory patients with rejection or severe GvHD. Herein, the main immunological challenges before and after intestinal transplant including, brain-dead donor inflammation, acute rejection, antibody-mediated, and chronic rejections, as well as GvHD have been described. Besides, the new immune-based therapies used in experimental and clinical settings to improve tolerance toward intestinal allograft, and cases of operational tolerance have been reviewed.

Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms.

A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7).

Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%.

Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

Pediatric chronic intestinal failure (PIF) is a rare and heterogeneous condition characterized by the inability of the patient's intestine to adequately absorb the required fluids and/or nutrients for growth and homeostasis. As a result, patients will become dependent on home parenteral nutrition (HPN). A MEDLINE search was performed in May 2024 with keywords "intestinal failure", "parenteral nutrition" and "pediatric". Different underlying conditions which may result in PIF include short bowel syndrome, intestinal neuromuscular motility disorders and congenital enteropathies. Most common complications associated with HPN are catheter-related bloodstream infections, catheter-related thrombosis, intestinal failure-associated liver disease, small intestinal bacterial overgrowth, metabolic bone disease and renal impairment. Treatment for children with PIF has markedly improved with a great reduction in morbidity and mortality. Centralization of care in specialist centers and international collaboration between centers is paramount to further improve care for this vulnerable patient group. A recently promising medical therapy has become available for children with short bowel syndrome which includes glucagon-like peptide 2, a naturally occurring hormone which is known to delay gastric emptying and induce epithelial proliferation. Despite advances in curative and supportive treatment, further research is necessary to improve nutritional, pharmacological and surgical care and prevention of complications associated with parenteral nutrition use.

To report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails.

We retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022.

ITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years; 27% had died and the graft was removed in 8%, mostly early after ITx.

ITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx.

To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center.

Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression.

Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005).

Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

Children with chronic intestinal failure (IF) require a long-term central venous catheter (CVC) for provision of parenteral nutrition. Vascular, mechanical and infectious complications such as central line-associated bloodstream infections (CLABSI) may lead to progressive loss of venous access sites. Handling and management of CVCs therefore play an important role. Our vascular rehabilitation concept (VRC) is a core component of our intestinal rehabilitation program (IRP) and consists of an education program, optimization of skin care, catheter fixation and lock solution, and the use of hybrid technique for catheter placement. Aim of this study is to analyse the effectiveness of our VRC on CLABSI rates and need for CVC replacements.

Retrospective analysis of all children treated in our IRP that were followed up between 2018 and 2023.

A total of 117 children with chronic IF could be included for analysis of 248864 catheter days (CD). 91 patients were referred from other hospitals (127117 CD before and 89359 CD after entry into our IRP). Children receiving primary care at our IRP (32388 CD) showed a significantly lower CLABSI and line replacement rate than patients referred from external centers (p < 0.001). After entering our IRP, CLABSI rates and need for CVC replacements per 1000 CD decreased significantly in referred patients: 1.19 to 0.26 and 1.77 to 0.59, respectively (p < 0.001).

Management of paediatric chronic IF patients by an IRP with a vascular rehabilitation concept significantly lowers the rate of CLABSI episodes and the need for catheter replacements.

It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions.

Using polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients.

We confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection (recipient age range at the time of transplant: 1-9 years, median: 2 years) revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in deceased adult donors. In available pan-scope biopsies from pediatric recipients, we observed higher percentages of naïve recipient B cells in colon allograft compared to small bowel allograft and increased BCR overlap between native colon vs colon allograft compared to that between native colon vs ileum allograft in most cases, suggesting differential clonal distribution in large intestine vs small intestine.

Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of stabilization of the mucosal B cell repertoire in pediatric ITx patients.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Outcomes for patients with chronic intestinal failure have improved with organization of experts into multidisciplinary teams delivering care in intestinal rehabilitation programs. There have been improvements in understanding of intestinal failure complications as well as development of newer therapies that have amplified the improvements in survival. In spite of this encouraging trend, patients who fail PN are often referred too late for intestinal transplantation. The author proposes a more rational framework that might allow earlier identification of intestinal failure patients at risk for PN-failure, who could appropriately be considered earlier for intestinal transplantation with improvements in overall outcomes.

The traditional procedure for multivisceral transplant (MVT) is to transplant the stomach, pancreas, intestine, and liver en bloc. During surgery, the native spleen is routinely removed from the recipient, and it usually creates more space in the abdomen to insert the allogeneic graft. Thus, recipients often become asplenic after MVT. Considering all of the risks and benefits, we advocate that temporary transplant of the donor spleen could be the best option for MVT recipients; it could potentially reduce the rate of intestinal allograft rejection without increasing the risk for graft-versus-host disease.

The understanding of the mechanisms for the development of ascites has evolved over the years, involving the liver, peritoneum, heart, and kidneys as key responsible for its formation. In this article, we review the pathophysiology of ascites formation, introducing the role of the intestine as a major responsible for ascites production through "a game changer" case.

Intestinal failure, defined as the loss of gastrointestinal function to the point where nutrition cannot be maintained by enteral intake alone, presents numerous challenges in children, not least the timing of consideration of intestine transplantation.

To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care.

The review is based on the authors' experience supported by an in-depth review of the published literature.

The history of parenteral nutrition, including out-patient (home) administration, and intestine transplantation are reviewed along with the complications of intestinal failure that may become indications for consideration of intestine transplantation. Current management strategies for children with intestinal failure are discussed along with changes in need for intestine transplantation, recognizing the difficulty in generalizing recommendations due to the high level of heterogeneity of intestinal pathology and residual bowel anatomy and function.

Advances in the medical and surgical care of children with intestinal failure have resulted in improved transplant-free survival and a significant fall in demand for transplantation. Despite these improvements a number of children continue to fail rehabilitative care and require intestine transplantation as life-saving therapy or when the burden on ongoing parenteral nutrition becomes too great to bear.

Short bowel syndrome (SBS) hospitalizations are often complicated with sepsis. There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.

To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.

The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014. The study cohort was further divided based on the presence or absence of sepsis. Trends were identified, and hospitalization characteristics and clinical outcomes were compared. Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.

Of 247097 SBS hospitalizations, 21.7% were complicated by sepsis. Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8% in 2005 to 23.5% in 2014 (P trend < 0.0001). Compared to non-septic SBS hospitalizations, septic SBS hospitalizations had a higher proportion of males (32.8% vs 29.3%, P < 0.0001), patients in the 35-49 (45.9% vs 42.5%, P < 0.0001) and 50-64 (32.1% vs 31.1%, P < 0.0001) age groups, and ethnic minorities, i.e., Blacks (12.4% vs 11.3%, P < 0.0001) and Hispanics (6.7% vs 5.5%, P < 0.0001). Furthermore, septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation (0.33% vs 0.22%, P < 0.0001), inpatient mortality (8.5% vs 1.4%, P < 0.0001), and mean length of stay (16.1 d vs 7.7 d, P < 0.0001) compared to the non-sepsis cohort. A younger age, female gender, White race, and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.

Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and β-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.

This timely review delves into the evolution of multivisceral transplantation (MVT) over the past six decades underscoring how advancements in surgical techniques and immunosuppression have driven transformation, to provide insight into the historical development of MVT, shedding light on its journey from experimentation to a valuable clinical approach.

The review presents contemporary enhancements in surgical methods within the context of intestinal transplantation. The versatility of MVT is emphasized, accommodating diverse organ combinations and techniques. Both isolated intestinal transplantation (IIT) and MVT have seen expanded indications, driven by improved parenteral nutrition, transplantation outcomes, and surgical innovations. Surgical techniques are tailored based on graft type, with various approaches for isolated transplantation. Preservation strategies and ostomy techniques are also covered, along with graft assessment advancements involving donor-specific antibodies.

This review's findings underscore the remarkable evolution of MVT from experimental origins to a comprehensive clinical practice. The progress in surgical techniques and immunosuppression has broadened the spectrum of patients who can benefit from intestinal transplant, including both IIT and MVT. The expansion of indications offers hope to patients with complex gastrointestinal disorders. The detection of donor-specific antibodies in graft assessment advances diagnostic accuracy, ultimately improving patient outcomes.

Enteral autonomy is the primary goal of intestinal failure therapy. Intestinal transplantation (ITx) is an option when enteral autonomy cannot be achieved and management complications become life-threatening. The purpose of this review is to summarize existing medical literature related to nutrition requirements, nutrition status, and nutrition support after pediatric ITx. Achieving or maintaining adequate growth after intestinal transplant in children can be challenging because of episodes of rejection that require the use of corticosteroids, occurrences of infection that require a reduction or discontinuation of enteral or parenteral support, and fat malabsorption caused by impaired lymphatic circulation. Nutrient requirements should be assessed and modified regularly based on nutrition status, growth, ventilatory status, wound healing, and the presence of complications. Parenteral nutrition (PN) should be initiated as a continuous infusion early postoperatively. Enteral support should be initiated after evidence of graft bowel function and in the absence of clinical complications. Foods high in simple carbohydrates should be limited, as consumption may result in osmotic diarrhea. Short-term use of a fat-free diet followed by a low-fat diet may reduce the risk of the development of chylous ascites. Micronutrient deficiencies and food allergies are common occurrences after pediatric ITx. Enteral/oral vitamin and mineral supplementation may be required after PN is weaned. Nutrition management of children after ITx can be challenging for all members of the healthcare team. Anthropometric parameters and micronutrient status should be monitored regularly so that interventions to promote growth and prevent or reverse nutrient deficiencies can be implemented promptly.

A growing proportion of children with short bowel syndrome (SBS) remain dependent on long-term parenteral nutrition (PN). Teduglutide offers the potential for more children to decrease PN support and achieve enteral autonomy (EA), but at a significant expense. This study aims to assess the incremental costs of teduglutide plus standard of care compared to standard of care alone in weaning PN support per quality-adjusted life year (QALY) gained in children with SBS.

This is a cost-utility analysis comparing teduglutide with standard of care alone in children with SBS. A microsimulation model of children with SBS on PN aged 1-17 years was constructed over a time horizon of six years, with a cycle length of one month. The study adopted the healthcare system and societal payer perspectives in Ontario, Canada. The health outcome measure was QALYs, with results expressed in terms of incremental costs and QALYs. Scenario analyses were performed to examine the effects of different time horizons, timing of teduglutide initiation, and modeling cost of teduglutide based on pediatric weight-dosing.

Incremental healthcare system costs for teduglutide compared to standard of care were CAD$441,314 (95% CI, 414,006 to 441,314) and incremental QALYs were 1.80 (95% CI, 1.70 to 1.89) resulting in an incremental cost-effectiveness ratio (ICER) of CAD$285,334 (95% CI, 178,209 to 392,459) per QALY gained. Incremental societal costs were CAD$418,504 (95% CI, 409,487 to 427,522) and incremental societal QALYs were 1.91 (95% CI, 1.85 to 1.98) resulting in an ICER of CAD$261,880 (95% CI, 136,887 to 386,874) per QALY gained. Scenario analysis showed that teduglutide was cost-effective when it was started two years after intestinal resection (ICER CAD$48,741, 95% CI, 17,317 to 80,165) and when its monthly cost was adjusted using weight-based dosing, avoiding wastage of the remaining 5 mg dose vial (Teduglutide dominated over SOC as the less costly and most effective strategy).

Although teduglutide was not cost-effective in weaning PN support in children with SBS, starting teduglutide once natural intestinal adaptation is reduced and adjusting its monthly cost to reflect cost by volume as dictated by weight-based dosing rendered the intervention cost-effective relative to standard of care. These results indicate the potential for clinicians to re-assess optimal time for initiation of teduglutide after intestinal resection, drug manufacturers to consider the use of multi-dose or paediatric-dose vials, and the opportunity for decision-makers to re-evaluate teduglutide funding.

Short bowel syndrome (SBS) is a rare condition, the main symptom of which is malabsorption following extensive resection of the small intestine. Treatment for SBS is mainly supportive, consisting of supplementation, prevention and treatment of complications, and promotion of intestinal adaptation. While development of parenteral nutrition and drugs promoting intestinal adaptation has improved clinical outcomes, the prognosis of patients with SBS remains poor. Intestinal transplantation is the only curative therapy but its outcome is unsatisfactory. In the absence of definitive therapy, novel treatment is urgently needed. With the advent of intestinal organoids, research on the intestine has developed remarkably in recent years. Concepts such as the "tissue-engineered small intestine" and "small intestinalized colon," which create a functional small intestine by combining organoids with other technologies, are potentially novel regenerative therapeutic approaches for SBS. Although they are still under development and there are substantial issues to be resolved, the problems that have prevented establishment of the complex function and structure of the small intestine are gradually being overcome. This review discusses the current treatments for SBS, the fundamentals of the intestine and organoids, the current status of these new technologies, and future perspectives.

It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of gut lymphocyte populations. Using polychromatic flow cytometry that includes HLA allele group-specific mAbs distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. We confirm the early presence of naïve donor B cells in the circulation and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa. Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in healthy control adults. Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of establishment of a stable mucosal B cell repertoire.

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.

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.

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.

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).

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.

In 2016, ESPEN published the guideline for Chronic Intestinal Failure (CIF) in adults. An updated version of ESPEN guidelines on CIF due to benign disease in adults was devised in order to incorporate new evidence since the publication of the previous ESPEN guidelines.

The grading system of the Scottish Intercollegiate Guidelines Network (SIGN) was used to grade the literature. Recommendations were graded according to the levels of evidence available as A (strong), B (conditional), 0 (weak) and Good practice points (GPP). The recommendations of the 2016 guideline (graded using the GRADE system) which were still valid, because no studies supporting an update were retrieved, were reworded and re-graded accordingly.

The recommendations of the 2016 guideline were reviewed, particularly focusing on definitions, and new chapters were included to devise recommendations on IF centers, chronic enterocutaneous fistulas, costs of IF, caring for CIF patients during pregnancy, transition of patients from pediatric to adult centers. The new guideline consist of 149 recommendations and 16 statements which were voted for consensus by ESPEN members, online in July 2022 and at conference during the annual Congress in September 2022. The Grade of recommendation is GPP for 96 (64.4%) of the recommendations, 0 for 29 (19.5%), B for 19 (12.7%), and A for only five (3.4%). The grade of consensus is "strong consensus" for 148 (99.3%) and "consensus" for one (0.7%) recommendation. The grade of consensus for the statements is "strong consensus" for 14 (87.5%) and "consensus" for two (12.5%).

It is confirmed that CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for the underlying gastrointestinal disease and to provide HPN support. Most of the recommendations were graded as GPP, but almost all received a strong consensus.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

Whole-intestine engineering can provide a therapeutic alternative to bowel transplantation. Intestinal components including the mucosa, muscular layer, enteric nervous system, and vasculature must be reestablished as a tubular organ to generate an artificial small intestine. This study proposes a novel approach to produce a transplantable, well-organized tubular small intestine using a decellularized scaffold.

Male Lewis rat intestines were used to generate decellularized scaffolds. Patch or tubular grafts were prepared from the decellularized intestine and transplanted into the rat intestine orthotopically. Histological analysis of the decellularized intestine was performed up to 12 wk after transplantation.

Histological examination revealed abundant vascularization into the decellularized patch graft 1 wk after transplantation. Muscular and nervous components, as well as cryptogenesis, were observed in the decellularized patch graft 2 wk after transplantation. Sixteen of the 18 rats survived with normal intake of food and water after the decellularized tubular graft transplantation. Compared with silicone tube grafts, the decellularized tubular grafts significantly promoted the infiltration and growth of intestinal components including the mucosa, muscular layer, and nerve plexus from the recipients. Circular and longitudinal muscle with a well-developed myenteric plexus was regenerated, and intestinal motility was confirmed in the decellularized tubular graft 12 wk after transplantation.

Orthotopic transplantation of decellularized intestine enhanced the reconstruction of the well-organized tubular small intestine with an enteric nervous system in vivo. Our method using a decellularized scaffold represents a promising approach toward whole-intestine engineering and provides a therapeutic alternative for the irreversible intestinal failure.