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Intestinal failure‐associated liver disease (IFALD) is a serious complication of long‐term parenteral nutrition in patients with short bowel syndrome (SBS), and is the main cause of death in SBS patients. Prevention of IFALD is one of the major challenges in the treatment of SBS. Impairment of intestinal barrier function is a key factor in triggering IFALD, therefore promoting intestinal repair is particularly important. Intestinal repair mainly relies on the function of intestinal stem cells (ISC), which require robust mitochondrial fatty acid oxidation (FAO) for self‐renewal. Herein, we report that aberrant LGR5+ ISC function in IFALD may be attributed to impaired farnesoid X receptor (FXR) signaling, a transcriptional factor activated by steroids and bile acids. In both surgical biopsies and patient‐derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T‐βMCA in PDOs (an antagonist for FXR) dose‐dependently reduced the population of LGR5+ cells and the proliferation rate of enterocytes, concomitant with decreased key genes involved in FAO including CPT1a. Interestingly, however, treatment with Tropifexor in PDOs (an agonist for FXR) only enhanced FAO capacity, without improvement in ISC function and enterocyte proliferation. In conclusion, these findings suggested that impaired FXR may accelerate the depletion of LGR5 + ISC population through disrupted FAO processes, which may serve as a new potential target of preventive interventions against IFALD for SBS patients. [ABSTRACT FROM AUTHOR]

Background: Patients receiving home parenteral nutrition (HPN) are known to experience psychological distress and have profoundly disrupted sleep. The aim of this analysis was to examine the relationship between sleep patterns with depressive symptoms and HPN characteristics. Methods: The study was a secondary analysis of cross‐sectional data examining sleep patterns using subjective and objective measures. Sleep was assessed by surveys and 7‐day actigraphy. The Patient Health Questionnaire‐8 was used to evaluate depressive symptoms. Participants provided information on HPN. Spearman correlations were calculated between sleep measures with depressive symptoms and HPN characteristics. Correlations were further examined in multivariable linear regression models. Results: Thirty‐two adults (age = 53 years; 75% female; 94% White) were included. Lower sleep quality (r = 0.54–0.60; P < 0.001) and later sleep timing (r = −0.35; P = 0.049) were correlated with higher depressive symptoms. Sleep patterns were also correlated with several HPN characteristics (r = −0.47 to 0.51). In linear regression models, rate of infusion was associated with sleep duration (β = −0.004 [0.002] h; P = 0.046) in which each 100 mL/h was associated with 24‐min shorter duration. Higher total energy was associated with lower sleep quality (β = 0.0004 [0.0002] log‐unit; P = 0.042), and higher volume was associated with longer sleep onset latency (β = 0.0006 [0.0003] log‐min; P = 0.049). Conclusions: We provide evidence supporting the link between poor and later sleep with higher depressive symptoms and identify potentially modifiable infusion characteristics (notably, slower rate of infusion and lower total energy and volume) that, on further verification, may support sleep among those receiving HPN. [ABSTRACT FROM AUTHOR]

The role of long‐term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long‐term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro‐intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut–brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro‐gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify – and hopefully reduce the potential for harm associated with – the use of long‐term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life‐threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time‐limited period to achieve nutritional safety, while the wider multi‐disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To investigate the clinical characteristics and course of parenteral nutrition‐associated cholestasis (PNAC) in very low birth weight (VLBW) infants.The charts of VLBW infants were retrospectively reviewed. The clinical characteristics of infants with and without PNAC were compared, trends in liver enzymes were investigated, and the characteristics of infants with PNAC were analysed based on age of onset.PNAC was observed in 53 (13.2%) of 403 infants who survived and completed follow‐up and was associated with significantly lower gestational age, birth weight, and adverse neonatal outcomes. PNAC started at a median 32 (interquartile range 23–47) days, PN was applied for 53 (34.5–64.5) days, the maximum direct bilirubin (DB) was observed at 63 (50–76) postnatal days, and PNAC resolved at 94 (79–122) postnatal days postnatal age. PNAC lasted 61 (38–89.5) days. AST and ALT normalised at 111 (100.3–142.0) and 109.5 (97–161.3) postnatal days. Infants with early‐onset PNAC had significantly longer PN duration, higher maximum DB, and higher maximum AST than those with late‐onset PNAC.Elevated DB, AST, and ALT persist for a long period after discontinuing PN. We suggest a cautious approach that involves waiting and reducing the frequency of additional repetitive examinations. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Patients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta‐analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO.MEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model.Final dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6–69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0–11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid‐suppressing agents (72.0%, 95% CI 57.5–83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7–70.2).This systematic review and meta‐analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid‐suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case–control studies and clinical heterogeneity seen in the studies. [ABSTRACT FROM AUTHOR]

Background: Malrotation and volvulus classically present with bilious vomiting. It is more common earlier in life, but there are other causes of bile‐stained vomiting. This leads some clinicians to 'watch and wait'. In the presence of a volvulus, this is potentially a fatal decision. It is not clear from the literature if there is a safe time window in which children can be observed in the hope of avoiding transfers or radiological investigations. Aim: To determine whether time to identification and management of midgut volvulus correlated with morbidity and mortality; and whether there were patterns to transition of care. Methods: Multicentre, retrospective review of all children with malrotation ± volvulus at two tertiary children's hospitals in Brisbane from 2000 to 2012. Data collected included age at presentation, timing between symptom onset and presentation, radiological findings, and definitive surgical management. Outcomes included patient length of stay (LOS), total parenteral nutrition (TPN) duration, re‐operations and death. Results: There were 96 cases of malrotation identified, with 23 excluded (elective operation, insufficient data). Neonates made up 66% of included cases. Only 14% of cases were over 12 months old. Bilious vomiting or bile‐stained aspirates were the presenting symptoms in 71% (52). Overall mortality was 5.56%. Time from symptom onset to presentation or management was not significantly associated with morbidity or mortality. More than half (53%, 39/73) of patients received total parenteral nutrition; 20/39 for more than 10 days. Neonates and infants had a significantly higher rate of TPN compared with older children (P < 0.001). Those requiring TPN post‐operatively had a significantly higher mortality compared with those who did not (P = 0.02). Time from symptom onset to presentation or definitive management was not significantly associated with LOS, TPN duration, or need for re‐operation. Conclusion: Malrotation remains a time‐critical diagnosis to secure and treat. Even a short duration of symptoms can be associated with high morbidity or mortality. There is no place for 'watch and wait' for such patients, and malrotation/volvulus should be emergently actively excluded with contrast studies. [ABSTRACT FROM AUTHOR]

Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS‐IF). Glucagon‐like peptide‐2 analogs, such as apraglutide, have been developed as a treatment option for SBS‐IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase 1, open‐label, multicenter, nonrandomized, parallel‐group study, a single dose of apraglutide 5 mg was administered subcutaneously to individuals with severely impaired renal function (<30 mL/min/1.73 m2) and healthy volunteers with normal renal function (≥90 mL/min/1.73 m2). Primary pharmacokinetic endpoints were maximum observed concentration (Cmax) and exposure to apraglutide (area under the curve [AUC] from time 0 to infinity [AUCinf], and AUC from time 0 to the last quantifiable concentration [AUClast]). Each group comprised 8 individuals. Results show that patients with severe renal impairment do not have increased apraglutide exposure. Apraglutide achieved a lower Cmax and AUCinf in individuals with severe renal impairment versus those with normal renal function (Cmax = 36.9 vs 59.5 ng/L; AUCinf = 3100 vs 4470 h · ng/mL, respectively). The respective geometric mean ratios were 0.620 and 0.693 for Cmax and AUCinf, and the upper bound of their 90% confidence intervals were <2, indicating patients with severe renal impairment were not overexposed to apraglutide versus those with normal renal function. Adverse events were mild or moderate in severity. Apraglutide does not require dose reduction for any degree of renal impairment and could be used in a broader patient population of renally impaired patients without dose adjustment. [ABSTRACT FROM AUTHOR]

The article discusses the findings of the 7th National Audit Project (NAP7) on peri-operative pediatric cardiac arrests in the UK. It reveals that while the incidence of cardiac arrest in children undergoing anesthesia is lower than previously thought, the immediate mortality rate is 17%, with higher rates in neonates and infants. The study emphasizes the importance of preparation, universal training, appropriate risk assessment, clear communication, and standardized equipment to improve outcomes in pediatric cardiac emergencies. It also calls for increased awareness and attention to the risks and challenges associated with pediatric anesthesia and resuscitation. [Extracted from the article]

Background: Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta‐analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model. Methods: This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta‐analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random‐effects model. Subgroup analyses accounted for AP severity and nutrition support initiation. Results: A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n = 1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR = 0.34; 95%CI: 0.16–0.73) and nasojejunal (NJ) feeding (RR = 0.46; 95%CI: 0.25–0.84) in comparison to nil per os. Similarly, NG (RR = 0.45; 95%CI: 0.24–0.83) and NJ (RR = 0.60; 95%CI: 0.40–0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48 h, particularly in severe cases. Conclusion: For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24 h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays an integral role in locomotion, but also as part of the integrative physiological system. Recent progress has identified crosstalk between skeletal muscle and various physiological systems, including the immune system. Both the musculoskeletal and immune systems are impacted by aging. Increased age is associated with decreased muscle mass and function, while the immune system undergoes "inflammaging" and immunosenescence. Exercise is identified as a preventative medicine that can mitigate loss of function for both systems. This review summarizes: (1) the inflammatory pathways active in skeletal muscle; and (2) the inflammatory and skeletal muscle response to unaccustomed exercise in younger and older adults. Compared to younger adults, it appears older individuals have a muted pro‐inflammatory response and elevated anti‐inflammatory response to exercise. This important difference could contribute to decreased regeneration and recovery following unaccustomed exercise in older adults, as well as in chronic disease. The current research provides specific information on the role inflammation plays in altering skeletal muscle form and function, and adaptation to exercise; however, the pursuit of more knowledge in this area will delineate specific interventions that may enhance skeletal muscle recovery and promote resiliency in this tissue particularly with aging. [ABSTRACT FROM AUTHOR]

Background: Nutritional status in pediatric patients undergoing heart transplantation (HT) is frequently a focus of clinical management and requires high resource utilization. Pre‐operative nutrition status has been shown to affect post‐operative mortality but no studies have been performed to assess how nutritional status may change and the risk of developing nutritional comorbidities long‐term in the post‐transplant period. Methods: A single‐center retrospective chart review of patients ≥2 years of age who underwent heart transplantation between 1/1/2005 and 4/30/2020 was performed. Patient data were collected at listing, time of transplant, 1‐year, and 3‐year follow‐up post‐transplant. Nutrition status was classified based on body mass index (BMI) percentile in the primary analysis. Alternative nutritional indices, namely the nutrition risk index (NRI), prognostic nutrition index (PNI), and BMI z‐score, were utilized in secondary analyses. Results: Of the 63 patients included, the proportion of patients with overweight/obese status increased from 21% at listing to 41% at 3‐year follow‐up. No underweight patients at listing became overweight/obese at follow‐up. Of patients who were overweight/obese at listing, 88% maintained that status at 3‐year follow‐up. Overweight/obese status at listing, 1‐year, and 3‐year post‐transplantation were significantly associated with developing metabolic syndrome. In comparison to the alternative nutritional indices, BMI percentile best predicted post‐transplant metabolic syndrome. Conclusions: The results suggest that pediatric patients who undergo heart transplantation are at risk of developing overweight/obesity and related nutritional sequelae (ie, metabolic syndrome). Improved surveillance and interventions targeted toward overweight/obese HT patients should be investigated to reduce the burden of associated comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: 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. Objectives: To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care. Methods: The review is based on the authors' experience supported by an in‐depth review of the published literature. Results: 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. Discussion: 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. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) results in several complications and mortality in intensive care unit (ICU) patients. Limited studies have investigated the effect of enteral nutrition (EN) on the survival of COVID‐19 patients in the ICU. The aim of this study was to investigate the association of EN with biochemical and pathological indices associated with mortality in ICU patients with COVID‐19. Methods: This case–control study was conducted on 240 patients with COVID‐19 hospitalized in the ICU including 120 eventual nonsurvived as the cases and 120 survived patients as the controls. All of the patients received EN as a high protein high volume or standard formula. Data on general information, anthropometric measurements, and the results of lab tests were collected. Results: The recovered patients received significantly more high protein (60.8% vs. 39.6%, p =.004) and high volume (61.6% vs. 42.3%, p =.005) formula compared to the nonsurvived group. Mortality was inversely associated with high volume (odds ratio [OR]: 0.45 confidence interval [CI]95%, p =.008) and high protein (OR: 0.42 CI95%, p =.003) formula. The results remained significant after adjusting for age and sex. Further adjustment for underlying diseases, smoking, body mass index, and the acute physiology and chronic health evaluation II (APACHE II) score did not change the results. Conclusion: The findings of the study showed that there was a significant inverse association between mortality and high volume and high protein formula in patients with COVID‐19. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

Background: Central line–associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%‐tetrasodium ethylenediaminetetraacetic acid (T‐EDTA) locking solution. Methods: We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14‐day exclusive PN (TPN) trials or in 7‐day short bowel syndrome (SBS) trials, before and after initiation of T‐EDTA. Lines were locked with a 1‐ml solution for 2 h daily (T‐EDTATPN, n = 17; T‐EDTASBS, n = 48) and compared with our prior standard of care using 1.5‐ml heparin flushes twice daily (CONTPN, n = 34; CONSBS, n = 48). Line patency and signs of sepsis were checked twice daily. Jugular catheters were replaced for occlusions whenever possible. Humane end points were used for sepsis not responding to antibiotic treatment or unresolved catheter occlusions. Results: Compared with CON, sepsis was reduced using T‐EDTA, significantly for TPN (P = 0.006) and with a trend for SBS piglets (P = 0.059). Line occlusions necessitating line changes were reduced 15% in TPN studies (P = 0.16), and no line occlusions occurred for T‐EDTA SBS piglets. Conclusion: In our neonatal piglet research, use of T‐EDTA locking solution decreased sepsis and, although not statistically significant, reduced occlusions requiring line replacements. Given the expense of animal research, adding a locking solution must be cost‐effective, and we were able to show that T‐EDTA significantly reduced total research costs and improved animal welfare. [ABSTRACT FROM AUTHOR]

Aims: The New Zealand National Intestinal Failure and Rehabilitation Service (NZ‐NIFRS) was established in October 2015 to gather longitudinal data on the aetiology, clinical course and outcomes of children with intestinal failure (IF). One main objective is to achieve health equity for patients with IF in NZ. Methods: Clinical outcomes (enteral autonomy, parenteral nutrition (PN) dependence, death or intestinal transplantation) for IF patients diagnosed from October 2015 to 2018 were analysed; comparisons were made by ethnicity and socio‐economic status (SES) using published 'prioritised‐ethnicity' health data and the NZ index of deprivation, respectively. The Cox proportional‐hazards model was used to assess time to enteral autonomy. Results: Of the 208 patients (55.77% male, 43.75% preterm), 170 (81.73%) achieved enteral autonomy and 14 (6.73%) remained PN dependent. Pacific and Māori children accounted for 12.98% and 27.88% of the patient cohort, respectively, compared to 9.46% and 25.65% of the NZ paediatric population. More significantly, IF patients with a high NZ socio‐economic deprivation score were overrepresented, with 35.92% in the highest deprivation quintile and 10.19% in the least deprived quintile, compared to 23.53% and 20.31%, respectively, of the NZ paediatric population. There were no significant differences in primary clinical outcomes for any patients based on ethnicity or SES. Conclusion: While disparities in ethnicity and social deprivation do exist in the incidence of IF in NZ children, clinical outcomes are similar for children regardless of ethnicity or SES. NZ‐NIFRS has achieved one of its core objectives: to achieve health equity for all patients with IF nationwide. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota‐derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota‐derived MLT, while administration with MLT could mitigate OP‐related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short‐chain fatty acids and decreased trimethylamine N‐oxide‐related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro‐inflammatory cytokines, and restore gut‐barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the "gut‐bone" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to describe children developing late gastrointestinal (GI) complications after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), focusing on Kampo medicine. Methods: At the Nagoya University Hospital Department of Pediatrics, 179 consecutive patients underwent allo‐HSCT over five years, of whom 167 achieved engraftment and survived at least 100 days post transplant and therefore were included in the study. Results: Thirteen patients (7.8%) developed late GI symptoms. Among these, three had upper GI symptoms, three had lower GI symptoms, while seven had upper/lower GI symptoms. Total parenteral nutrition was administered in 10 (77%) patients for a median of 81 days (range: 20–303). Four (31%) had histologically proven graft‐versus‐host‐disease (GVHD), two (15%) had adverse drug reactions, and one (8%) had a viral infection. All three patients with lower GI symptoms responded to Kampo formulas' warming interior [TM1]. Two patients with upper GI symptoms had epigastric rigidity and responded to Aurantii Fructus Immaturus‐based formulas. One patient developed severe cachexia, which was successfully reversed with Kampo medicines. There were no adverse effects due to Kampo medicines. Conclusions: Late GI complications may be a burden on children after allo‐HSCT. Kampo medicines may provide a safe and promising therapy to resolve GI symptoms not otherwise specified. [ABSTRACT FROM AUTHOR]

Background: Pantoea agglomerans is an environmental pathogen known to cause infection in immunocompromised individuals, particularly after thorn injuries. However, previous data showed few cases of human disease caused by contaminated medical products such as parenteral nutrition, anesthetic agents, blood, and peritoneal dialysis solutions. Infection in hemodialysis patients is rare. In this study, we presented a detailed account of several hemodialysis patients infected with this contagious pathogen and compared them with noninfected dialysis patients. Methods: We retrospectively reviewed the hospital records of 105 hemodialysis patients. Seventeen of 105 patients were diagnosed with P. agglomerans infection. We carefully analyzed their entire in‐hospital course. Results: Among infected patients, 52.9% were male with a median age of 49 (IQR: 32–66) years. Compared to the noninfected patients, age below 50 years, prior kidney transplantation, prior immunosuppression and antibiotics use, and dialysis via a tunneled vascular catheter were the significant epidemiological features. Despite negative microbiological investigations, we suspect the possible infectious spread via infected central venous catheter was the likely infectious source. Most importantly, all patients responded well to intravenous antibiotics. Only two patients required the removal of the tunneled catheter. Their mortality rate was 0%. Conclusion: P. agglomerans infection, although considered rare, is becoming increasingly prevalent among dialysis patients. Its occurrence must be appraised as an infectious outbreak rather than mere contamination. Prompt treatment, source identification, and early implementation of preventive strategies should always be the goal to curtail this infection at an early stage. [ABSTRACT FROM AUTHOR]

Aim: The gastrointestinal bile acid (BA)/microbiota axis has emerged as a potential mediator of health and disease, particularly in relation to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer. Whilst it presents an exciting new avenue for therapies, it has not yet been characterized in surgical resection of the ileum, where BA reabsorption occurs. The identification of BA/microbiota signatures may provide future therapies with perioperative personalized medicine. In this work we conduct a systematic review with the aim of investigating the microbiome and BA changes that are associated with resection of the ileum. Method: The databases included were MEDLINE, EMBASE, Web of Science and Cochrane libraries. The outcomes of interest were faecal microbiome and BA signatures after ileal resection. Results: Of the initial 3106 articles, three studies met the inclusion/exclusion criteria for data extraction. A total of 257 patients (46% surgery, 54% nonsurgery controls) were included in the three studies. Two studies included patients with short bowel syndrome and the other included patients with IBD. Large‐scale microbiota changes were reported. In general, alpha diversity had decreased amongst patients with ileal surgery. Phylum‐level changes included decreased Bacteroidetes and increased Proteobacteria and Fusobacteria in patients with an intestinal resection. Surgery was associated with increased total faecal BAs, cholic acid and chenodeoxycholic acid. There were decreases in deoxycholic acid and glycine and taurine conjugated bile salts. Integrated BA and microbiota data identified correlations with several bacterial families and BA. Conclusion: The BA/microbiota axis is still a novel area with minimal observational data in surgery. Further mechanistic research is necessary to further explore this and identify its role in improving perioperative outcomes. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), mainly comprising ulcerative colitis and Crohn's disease, is a group of gradually progressive diseases bringing significant mental anguish and imposes serious economic burdens. Interplay of genetic, environmental, and immunological factors have been implicated in its pathogenesis. Nutrients, as crucial environmental determinants, mainly encompassing carbohydrates, fats, proteins, and micronutrients, are closely related to the pathogenesis and development of IBD. Nutrition is essential for maintaining the dynamic balance of intestinal eco‐environments to ensure intestinal barrier and immune homeostasis, while this balance can be disrupted easily by maladjusted nutrition. Research has firmly established that nutrition has the potential to shape the composition and function of gut microbiota to affect the disease course. Unhealthy diet and eating disorders lead to gut microbiota dysbiosis and further destroy the function of intestinal barrier such as the disruption of membrane integrity and increased permeability, thereby triggering intestinal inflammation. Notably, appropriate nutritional interventions, such as the Mediterranean diet, can positively modulate intestinal microecology, which may provide a promising strategy for future IBD prevention. In this review, we provide insights into the interplay between nutrition and gut microbiota and its effects on IBD and present some previously overlooked lines of evidence regarding the role of derived metabolites in IBD processes, such as trimethylamine N‐oxide and imidazole propionate. Furthermore, we provide some insights into reducing the risk of onset and exacerbation of IBD by modifying nutrition and discuss several outstanding challenges and opportunities for future study. [ABSTRACT FROM AUTHOR]

Background and Aim: Resection for Crohn's disease (CD) related strictures is definitive but carries risk of morbidity, recurrence, and short bowel syndrome. On the contrary, the durability of endotherapy (ET) for CD‐related strictures is questionable. Prospective comparative studies are limited. We aimed to prospectively compare the outcomes of ET in CD strictures with a case‐matched surgical therapy (ST) cohort. Methods: Patients undergoing ET or resection for primary CD strictures (symptomatic, non‐traversable, < 5 cm length, n ≤ 3) between January 2021 and March 2022 in a high‐volume tertiary center were compared with regard to recurrent symptoms, escalation of therapy, re‐intervention, and re‐operation based on propensity matched analysis. Results: Fifty‐nine patients [49% ET, 57.6% male, median (years): 34 (15–74)] had ≥ 12 months of follow up. Before propensity matching, cumulative re‐intervention rate was significantly higher with ET [34.5% (10/29) vs 3.3% (1/30) ST, P = 0.002]. Recurrent symptoms (34.5% vs 26.7%, P = 0.42), escalation of medical therapy (27.5% vs 23.3%, P = 0.64), and re‐operation (7.4% vs 3.1%, P = 0.55) were comparable. In propensity matched analysis adjusted for demographics, disease, and stricture characteristics [n = 42, 21 each, 62% male, median (years): 32 (15–60)], cumulative probability of re‐intervention rates was higher in ET (28.6% vs 4.8%, P = 0.042). The cumulative probability of recurrent symptoms (ET: 33.3% vs surgery 33.3%, P = 0.93), therapy escalation (ET: 23.8% vs surgery 28.6%, P = 0.75), and re‐operation (ET: 9.5% vs surgery 4.8%, P = 0.57) was similar. Conclusions: ET for CD strictures require higher re‐interventions compared with resection although re‐operation could be avoided in the majority with comparable symptom free survival at 1 year. [ABSTRACT FROM AUTHOR]

Background: The study purpose was to add to limited literature assessing anti‐HLA donor‐specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. Methods: This single‐center retrospective review included intestinal/MV recipients transplanted 1/1/15–9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post‐transplant. The primary outcome was biopsy‐proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. Results: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post‐transplant DSA. Fifteen patients in the DSA(+) group had T‐cell‐mediated BPAR versus five in the DSA(−) group (63% vs 45%, p =.47). Days to BPAR were 25 [IQR 19–165] (DSA(+) group) versus 232 [IQR 25.5–632.5] (DSA(−) group) (p =.066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow‐up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA‐ DQ (35%). Time to first DSA and to clearance did not differ between class I and II. Conclusion: Findings confirm previous data that suggest post‐transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein‐Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre‐emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre‐emptive interventions in patients who are EBV seronegative pre‐transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre‐transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre‐emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority. [ABSTRACT FROM AUTHOR]

Background: Achievement of enteral autonomy (EA) is the ultimate treatment goal in pediatric intestinal failure (IF). We aimed to assess predictors of EA in pediatric short bowel syndrome (SBS) and explore the impact of residual small bowel (SB) and large bowel (LB) length on EA. Methods: A retrospective cohort study was performed on infants aged <12 months (n = 367, six centers) with SBS referred between 2010 and 2015. The cohort was stratified based on the achievement of EA. Statistical testing was completed using t‐test, chi‐square, Cox proportional hazards regression model, and Kaplan‐Meier analysis. Results: EA was achieved in 229 patients. In the multivariable analysis, the percentage of residual LB (hazard ratio [HR] = 1.02; 95% CI = 1.01–1.02) and SB (HR = 1.01; 95% CI = 1.01–1.02) length, presence of the ileocecal valve (HR = 2.02; 95% CI=1.41–2.88), and not coming from a high‐volume transplantation center (HR = 2.42; 95% CI = 1.68–3.49) were positively associated with EA, whereas a negative association was seen with the presence of stoma at the time when shortest remnant was documented (HR = 0.72; 95% CI = 0.52–1.00). EA achievement was significantly different between the anatomical subgroups (log‐rank test P < 0.001) with an EA rate of 80.4% in infants with ≥50% SB and LB (median time 209 days); 62.5% with ≥50% SB and <50% LB (397 days); 58.3% with <50% SB and ≥50% LB (1192 days), and 25.9% with <50% SB and LB. Necrotizing enterocolitis (NEC) was not associated with a better achievement of EA (NEC vs other etiologies: log‐rank test P = 0.33). Conclusions: Overall, 62% of infants with IF secondary to SBS achieved EA over a mean time of follow‐up of 2.3 years. A colon length of >50% can compensate for the loss of small bowel (<50%) and account for similar EA rates as those in children with residual SB > 50%. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) following extensive intestinal resection is often characterized by impaired absorption of orally administered drugs, including tyrosine kinase inhibitors (TKI). We report the case of a patient with EGFR‐mutated non‐small cell lung carcinoma treated with 80 mg/day of the TKI osimertinib who achieved partial response of the tumour, but was subsequently subjected to a double‐barrelled jejunostomy due to ileus. Due to the development of SBS after the bypass surgery, plasma concentrations of osimertinib were monitored using mass spectrometry. The therapeutic drug monitoring confirmed a malabsorption of osimertinib in the patient (108 ng/mL, which is below the 5th percentile of the expected plasma concentration) and was useful to guide adjustments of TKI dosing in order to achieve adequate blood levels (161 ng/mL after increase of the dose to 120 mg/day) in order to maintain tumour control. [ABSTRACT FROM AUTHOR]

Introduction: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. Methods: This was a single‐center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1‐year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD‐EPI equation at 0‐, 6‐ and 12‐months post‐transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1‐year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p <.1 in univariate analysis were considered for multivariable modeling. Results: Thirty‐three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1‐year post‐transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (β = –.77, p <.01) and stoma days (β = –.06, p <.01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. Conclusions: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) affects gut microbial homeostasis, and intestinal microecology (IM) may also affect the prognosis of HSCT through multiple mechanisms. In order to further understand the key issues of the correlation between intestinal microecology and HSCT and to learn and absorb new research progress, the Tumor and Microecology Committee of China Anti‐Cancer Association organized relevant experts to discuss together and propose the "Expert Consensus on the Relevance of Intestinal Microecology and Hematopoietic Stem Cell Transplantation" for clinicians' reference in their practical work. It is a reference for clinicians in practice and provides a basis for further in‐depth research in the field of tumor and microecology. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a rare condition that is seldom associated with hematological malignancies. In this case report, we present the unique case of a 7‐year‐old girl diagnosed with juvenile myelomonocytic leukemia (JMML) and intestinal BD. The patient received allogeneic hematopoietic stem cell transplantation (allo‐HSCT), which resulted in complete remission of both JMML and BD. Our findings suggest that allo‐HSCT may be a feasible treatment option for JMML patients with coexisting BD, and holds promise for achieving remission of both illnesses. However, further clinical investigations are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric‐onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. Methods: A multicenter case–control study in which 35 pediatric‐onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self‐reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co‐occurrence networks and for predicting functional abundances based on marker gene sequences. Results: Two microbial co‐occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short‐chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family‐level findings from an independent Canadian‐US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. Interpretation: Our results suggest that short‐chain fatty acid producers may be important contributors to multiple sclerosis onset. [ABSTRACT FROM AUTHOR]

Background: To determine variables associated with outcomes in infants with intestinal failure (IF) and ostomy following reanastomosis (RA). Methods: A single‐center, descriptive cohort study of 120 infants with IF and a stoma from January 2011 to December 2020 with subsequent RA during initial hospitalization. The primary outcome was achievement of enteral autonomy (EA) following RA. Other outcomes were duration of hospital stay, and mortality. Penalized logistic regression and linear regression were used for data analysis. Results: The median gestational age was 26 weeks, and the median birth weight was 890 g. Three infants died. The median duration between ostomy creation and RA was 80 days (interquartile range; 62.5, 100.5). For each additional day of discontinuity, the odds of EA decreased by 2% (odds ratio [OR] = 0.980; 95% confidence interval [CI]: 0.962, 0.999; P = 0.038), and death increased by 4.2% (OR = 1.042; 95% CI: 1.010, 1.075; P = 0.009). For each additional mL/kg/day of enteral feeds at RA, the odds of EA increased by 7.5% (OR = 1.075; 95% CI: 1.027, 1.126, P = 0.002) and duration of hospital stay decreased by 0.35 days (slope coefficient = −0.351; 95% CI: −0.540, −0.163; P < 0.001). Conclusion: Shorter duration of intestinal discontinuity and enteral nutrition before RA could positively influence EA and duration of stay in infants with IF and ostomy following RA. [ABSTRACT FROM AUTHOR]

This article discusses bowel preserving surgery for stricturing jejunoileal Crohn's disease, specifically focusing on the Heineke-Mikulicz strictureplasty technique. The Heineke-Mikulicz technique is a minimally invasive option for Crohn's strictures that involves opening the stricture longitudinally, closing it transversely, and suturing the enterotomy. The article provides a step-by-step video vignette demonstrating the technique. It also discusses the use of adjuncts such as stricture biopsy and marking each strictureplasty with metallic clips. The article emphasizes the importance of documenting the number and location of strictures, as well as the length of small bowel resected and left in situ. The article concludes by mentioning the postoperative recovery process and the lack of funding for the study. [Extracted from the article]

Background: Enteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS‐IF) because of unpredictable absorption. SEFA‐6179 is an enterally administered medium‐chain fatty acid analogue under development for intestinal failure–associated liver disease. We investigate the pharmacokinetics of two SEFA‐6179 formulations in two large‐animal models of SBS‐IF, including a new pseudojejunostomy model. Methods: Twenty Yucatan minipigs were obtained. Half underwent pre‐resection pharmacokinetic study with single‐dose SEFA‐6179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single‐dose pharmacokinetic study was performed. Results: Both SBS‐IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs −0.9 kg, P = 0.03) and liquid diarrhea (Bristol 5 vs Bristol 7, P = 0.0007). Compared with pre‐resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA‐6179 measured by area under the curve (jejunoileal: 37% less, P = 0.049; pseudojejunostomy: 74% less, P = 0.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre‐resection (65% less, P = 0.04), but not lower in the jejunoileal group (P = 0.47). Conclusion: In two SBS‐IF minipig models, SEFA‐6179 had substantially decreased absorption compared with pre‐resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS‐IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS‐IF who have enterostomies. [ABSTRACT FROM AUTHOR]

Introduction: The International Intestinal Failure Registry (IIFR) is an international consortium to study intestinal failure (IF) outcomes in a large contemporary pediatric cohort. We aimed to identify predictors of early (1‐year) enteral autonomy. Methods: We included IIFR pilot phase patients. IF was defined by a parenteral nutrition need for at least 60 days due to a primary gastrointestinal etiology. The primary outcome was time to enteral autonomy achievement. We built a mixed‐effects Weibull accelerated failure time model with random effects by center to analyze variables associated with enteral autonomy achievement with a primary outcome of time ratio (TR). Results: We included 189 patients (82% with short bowel syndrome) representing 11 international centers. Cumulative incidence of early enteral autonomy was 51.6%, and death was 6.5%. In multivariable analysis, ostomy presence (TR, 2.63; 95% CI, 1.41–4.90) was associated with increased time to enteral autonomy achievement, and Asian/Indian (TR, 0.28; 95% CI, 0.10–0.81) and Pacific Islander race (TR, 0.34; 95% CI, 0.13–0.90) were associated with decreased time to enteral autonomy achievement. In a second model in the subset with measured percentage of bowel length remaining, ostomy presence (TR, 4.21; 95% CI, 1.90–9.33) was associated with increased time to enteral autonomy achievement, whereas greater percentage of bowel remaining (TR, 0.96; 95% CI, 0.94–0.98) was associated with decreased time to enteral autonomy achievement. Conclusions: Minimizing bowel resection at initial surgery and establishing bowel continuity by ostomy reversal can effectively decrease the time to early enteral autonomy achievement in children with IF. [ABSTRACT FROM AUTHOR]

Background: Children with intestinal failure without liver disease may be given soy‐based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium‐chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses. Methods: We compared SLE (n = 15) and MLE (n = 15) at doses of 10–15 g/kg/day in parenteral nutrition (PN). On day 14 we collected serum and tissues. Using gas‐liquid chromatography, percentage fatty acids were measured in serum, brain, and liver phospholipid. Comparisons were made to reference values from litter‐matched controls (n = 8). Results: Comparing median values, linoleic acid (LA) was lower for MLE vs SLE in serum (−27%), liver (−45%), and brain (−33%) (P < 0.001). AA was lower for MLE in serum (−25%), liver (−40%), and brain (−10%). DHA was higher for MLE in serum (+50%), liver (+200%), and brain (+10%). AA levels were lower for MLE vs control piglets in serum (−81%), liver (−63%), and brain (−9%). DHA levels were higher in serum (+41%), liver (+38%), and brain (+19%). Conclusion: This study in piglets has shown that, at unrestricted doses, MLE treatment is associated with low serum and tissue AA compared with SLE and healthy litter‐matched controls. Although not yet proven, low tissue AA levels may have functional consequences, and these data support current practice avoiding MLE dose restriction. [ABSTRACT FROM AUTHOR]

B I Conclusion: i b In adult patients willing to undertake dietary therapy for management of their Crohn's disease, CDED is a well-tolerated approach and is associated with clinical remission at 6 weeks, based on this small cohort of prospective patients. B 36 b B Postpartum dietary therapy for Crohn's disease following Hartmann's procedure: A case report b R Davis SP 1 sp , E Young SP 1 sp , A Day SP 2 sp and D Sathananthan SP 1 sp SP 1 sp I Lyell McEwin Hospital, Adelaide; i SP 2 sp I The Queen Elizabeth Hospital, Adelaide, South Australia, Australia i B I Introduction: i b Medical and surgical management of Crohn's disease (CD) during pregnancy and lactation is complex. Dietary therapy is effective for inducing remission, offering a safe and effective treatment alternative when medical management is contraindicated or when patients opt for non-pharmacological therapies. Dietary therapy can therefore be a suitable option for patients with CD during pregnancy and lactation, with the potential to yield clinical benefit while optimizing nutritional intake and mitigating potential treatment-related side effects. [Extracted from the article]

Background: Acute rejection is the leading cause of mortality and morbidity for children following intestinal transplantation. Rapid detection and prompt treatment are critical; however, the only reliable method of diagnosis and monitoring is endoscopic graft biopsies. The required regular anesthetics are particularly problematic in children, and non‐invasive strategies are needed. Methods: We describe the intestinal ultrasound findings of three children before and after treatment for rejection. Ultrasounds were performed within 24 h of endoscopically obtained biopsies which were used to establish a diagnosis of rejection and to define severity. A single sonographer performed the ultrasounds and was blinded to biopsy results at the time of the scanning. These findings are provided in the context of the ultrasound appearance of seven children who had no features of rejection on surveillance biopsies. Results: Intestinal ultrasound demonstrated increased bowel wall thickness, vascularity, and mesenteric inflammation during moderate to severe rejection episodes. The submucosal layer was particularly thickened, which may represent a finding more specific for rejection. All patients demonstrated improvement in all quantitative ultrasound features correlating with the resolution of acute cellular rejection on histology. Patients with no evidence of rejection on biopsy had a bowel wall thickness range of 0.9–2.8 mm, suggesting a normal upper limit of 3 mm. Conclusion: Moderate and severe acute rejection may be detected and response to treatment can be monitored by intestinal ultrasound and, correlating with clinical improvement, can aid in follow‐up. [ABSTRACT FROM AUTHOR]

Background: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. Cases: The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z‐score: −2.5; height z‐score: −3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7‐year follow‐up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z‐score: −1.0; height z‐score: −1.7). The second patient underwent sequential intestine–liver transplantation at 8 years of age due to end‐stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid–bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2‐year follow‐up examination revealed macrovesicular steatosis (60%) with inflammation. Conclusions: The patients showed different outcomes. Effective therapeutic options to mitigate post‐LT complications in patients with PFIC1 must be considered individually. [ABSTRACT FROM AUTHOR]

Background: Many factors influence the composition of the sinus microflora. The microbial balance is most disturbed by the use of antibacterial agents. Superinfections caused by more than one pathogen may then occur. Despite treatment, including surgery and long‐term antibiotic therapy, many patients with sinusitis do not experience significant relief from their symptoms. It has been hypothesized that an imbalance in the gut microbiota may also be responsible for the chronicity of sinusitis. Our goal was therefore to identify selected gut indicator bacteria that play a role in immunity in patients with chronic sinusitis. In addition, compare the number of selected bacteria in two groups of patients: with chronic sinusitis and with chronic rhinosinusitis (CRS) with concomitant diseases and/or symptoms other than CRS. Results: Significantly decreased numbers of Bifidobacterium spp. and Faecalibacterium prauznitzi bacteria were observed in patients from the G1 group. The majority of patients from this group (12 out of 13) had a significantly decreased number of Bifidobacterium and Akkermansia muciniphila bacteria, which are involved in the nutrition and regeneration of gut epithelium cells and have anti‐inflammatory properties. In group G2 (patients with chronic sinusitis and symptoms of comorbidities) a decreased number of F. prausnitzii, Bifidobacterium spp., A. muciniphila and Lactobacillus spp. bacteria was observed. A small percentage of patients in this group showed overgrowth of yeast‐like fungi. Conclusion: Although the more research is needed, possibly the gut microbiota indicator bacteria number analyses might enable to plan personalized prebiotic and probiotic treatment, which could support intestine microbiota and mucosal immunity patients suffering from chronic sinusitis. [ABSTRACT FROM AUTHOR]

Background: Teduglutide is a synthetic glucagon‐like peptide‐2 analogue approved for the treatment of short bowel syndrome associated with chronic intestinal failure (SBS‐IF) in adult patients. Clinical trials have demonstrated its ability to reduce parenteral support (PS) requirement. This study aimed to describe the effect of 18‐month treatment with teduglutide, evaluating PS and factors associated with PS volume reduction of ≥20% from baseline and weaning. Two‐year clinical outcomes were also assessed. Methods: This descriptive cohort study collected data prospectively from adult patients with SBS‐IF treated with teduglutide and enrolled in a national registry. Data were collected every 6 months and included demographics, clinical, biochemical, PS regimen, and hospitalizations. Results: Thirty‐four patients were included. After 2 years, 74% (n = 25) had a PS volume reduction of ≥20% from baseline, and 26% (n = 9) achieved PS independency. PS volume reduction was significantly associated with longer PS duration, significantly lower basal PS energy intake, and absence of narcotics. PS weaning was significantly associated with fewer infusion days, lower PS volume, longer PS duration, and lower narcotics use at baseline. Alkaline phosphatase was significantly lower in weaned patients after 6 and 18 months of treatment. During the 2‐year study duration, patients who had PS volume reduction of ≥20% had significantly fewer yearly hospitalizations and hospital‐days. Conclusions: Teduglutide reduces PS volume and promotes weaning in adults with SBS‐IF. Lack of narcotics and longer PS duration were associated with PS volume reduction and weaning, and lower baseline PS volume and fewer infusion days were favorable in obtaining enteral autonomy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Amyloidosis is a heterogeneous disease characterized by tissue deposition of abnormally folded fibrillary proteins that can manifest itself by a wide variety of symptoms depending on the affected organs. GI involvement among amyloidosis patients is common. Its clinical manifestation often presents with nonspecific symptoms such as weight loss, diarrhea, and malabsorption. With no specific treatment existing for GI amyloidosis, therapy focuses on impeding amyloid deposition and managing the patients' symptoms with supportive measures. Here, we present an AL‐amyloidosis patient with GI involvement and intestinal failure (IF) who was successfully treated with the glucagon‐like peptide‐2 (GLP‐2) analogue teduglutide. Over the course of treatment with teduglutide, the patient was able to achieve independence from parenteral nutrition and experienced a significant improvement in quality of life (QoL) as stool frequency and consistency improved, urinary output was stabilized and body weight as well as body composition improved over the course of teduglutide therapy. With no longer being exposed to the burden and associated risks of parenteral nutrition, we were able to reduce the potential morbidity and mortality rate as well as to improve the patient's overall QoL. Intestinal tissue biopsy workup revealed a histopathological correlate for the clinical response; Congo‐Red‐positive intestinal depositions almost completely disappeared within 6 months of teduglutide therapy. Implementing intestinotrophic GLP‐2 analogue teduglutide may enrich the spectrum of treatment options for amyloidosis patients with IF who are dependent on parenteral support. [ABSTRACT FROM AUTHOR]

Background: Longitudinal changes in bone health in children with intestinal failure (IF) are unclear. We aimed to better understand the trajectory of bone mineral status over time in children with IF and identify clinical factors that influence the trajectory. Methods: Clinical records of patients attending the Intestinal Rehabilitation Center of Cincinnati Children's Hospital Medical Center between 2012 and 2021 were reviewed. Children diagnosed with IF before age 3 years with at least two lumbar spine dual‐energy x‐ray absorptiometry scans were included. We abstracted information on medical history, parenteral nutrition, bone density, and growth. We calculated bone density z scores with and without adjustment for height z scores. Results: Thirty‐four children with IF met inclusion criteria. Children were shorter than average with a mean height z score of −1.5 ± 1.3. The mean bone density z score was −1.5 ± 1.3 with 25 of the cohort having a z score < −2.0. After height adjustment, the mean bone density z score was −0.42 ± 1.4 with 11% below −2.0. Most dual‐energy x‐ray absorptiometry scans (60%) had a feeding tube artifact. Bone density z scores increased slightly with age and lower parenteral nutrition dependency and were higher in scans without an artifact. Etiologies of IF, line infections, prematurity, and vitamin D status were not associated with height‐adjusted bone density z scores. Conclusion: Children with IF were shorter than expected for age. Deficits in bone mineral status were less common when adjusting for short stature. Etiologies of IF, prematurity, and vitamin D deficiency were not associated with bone density. [ABSTRACT FROM AUTHOR]

As the majority of children with short bowel syndrome (SBS) and intestinal failure (IF) are now surviving into adulthood, there is a paradigm shift from short‐term management to long‐term outcomes and a growing need to focus on healthcare transition (HCT). It is imperative that adolescents and young adults with SBS and IF receive disease education, empowerment, and support as they navigate the transition from pediatric to adult care. Furthermore, both pediatric and adult healthcare providers who manage these patients should be aware of the challenges faced by this population, barriers to their HCT, and strategies to overcome them. This article reviews the literature on HCT in children with chronic illnesses, discusses barriers to HCT in SBS/IF, identifies the important constituents of the transition process in SBS/IF, and provides recommendations for the successful and smooth transition of the pediatric patient to the adult healthcare environment. Structured and multicomponent HCT programs should become the standard of care to ensure uninterrupted high‐quality care across the life span for patients with SBS/IF. [ABSTRACT FROM AUTHOR]

Background and Purpose: Glucagon‐like peptide‐2 (GLP‐2) is secreted postprandially by enteroendocrine L‐cells and stimulates growth of the gut and bone. One GLP‐2 analogue is approved for short bowel syndrome (SBS). To improve therapeutic efficacy, we developed biased GLP‐2 receptor (GLP‐2R) agonists through N‐terminal modifications. Experimental Approach: Variants with Ala and Trp substitutions of the first seven positions of GLP‐2(1‐33) were studied in vitro for affinity, G protein activation (cAMP accumulation), recruitment of β‐arrestin 1 and 2, and internalization of the human and mouse GLP‐2R. The intestinotrophic actions of the most efficacious (cAMP) biased variant were examined in mice. Key Results: Ala substitutions had more profound effects than Trp substitutions. For both, alterations at positions 1, 3 and 6 most severely impaired activity. β‐arrestin recruitment was more affected than cAMP accumulation. Among Ala substitutions, [H1A], [D3A] and [F6A] impaired potency (EC50) for cAMP‐accumulation >20‐fold and efficacy (Emax) to 48%–87%, and were unable to recruit arrestins. The Trp substitutions, [A2W], [D3W] and [G4W] were partial agonists (Emax of 46%–59%) with 1.7–12‐fold decreased potencies in cAMP and diminished β‐arrestin recruitment. The biased variants, [F6A], [F6W] and [S7W] induced less GLP‐2R internalization compared with GLP‐2, which induced internalization in a partly arrestin‐independent manner. In mice, [S7W] enhanced gut trophic actions with increased weight of the small intestine, increased villus height and crypt depth compared with GLP‐2. Conclusion and Implications: G protein‐biased GLP‐2R agonists with diminished receptor desensitization have superior intestinotrophic effects and may represent improved treatment of intestinal insufficiency including SBS. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom nutrition database monitors the changing landscape of adult home parenteral nutrition support (HPS) to inform clinicians and policy makers of the need for this life‐saving treatment. Methods: The UK database is administered by the British Association for Parenteral and Enteral Nutrition. Data for home parenteral nutrition (HPN) has been collected since 2005 and home intravenous fluids (HIVFs) since 2011. During this study the reporting of data to the database by healthcare workers has been voluntary. Data were analyzed using linear regression. Results: A threefold increase of new registrations for patients receiving HPS was noted on this 10‐year period, with a notable increase in the number of patients with advanced malignancy supported with HPS. Crohn's disease and short bowel syndrome were the leading causes for both HPN and HIVF use in the UK. A statistically significant increase in older (P < 0.001) and less independent patients using HPS was noted. Conclusion: The prevalence of HPS is steadily increasing in size with the broadening of its acceptable performance status. The launch of the Intestinal Failure Registry and mandatory registration will increase accuracy in data reporting. [ABSTRACT FROM AUTHOR]

Keywords: neonatology; parenteral nutrition; pediatrics; short bowel syndrome EN neonatology parenteral nutrition pediatrics short bowel syndrome 960 962 3 11/08/23 20231101 NES 231101 INTRODUCTION From the time of their initial surgery, children with short bowel syndrome (SBS) begin rehabilitating their remaining bowel in a quest towards reaching enteral autonomy. Patients with an intact colon often tolerate more fiber-containing foods or blended food formulas, which are beneficial because of the additional energy derived from short chain fatty acid (SCFA) fermentation in the colon. Neonatology, parenteral nutrition, pediatrics, short bowel syndrome. [Extracted from the article]

Background: Pediatric intestinal pseudo‐obstruction (PIPO) encompasses a variety of rare, heterogeneous, and disabling disorders that severely affect gastrointestinal motility and are associated with high morbidity and mortality. PIPO management is complex and focuses on maintaining an optimal nutritional status, improving gut function, relieving symptoms, and treating complications. Nutritional issues prevail, and PIPO patients often experience severe undernutrition and faltering growth. Thus, nutritional management plays a pivotal role for achieving the most favorable clinical outcomes. The calorie and nutrient intake of each patient needs to be tailored to age, extent and severity of gut involvement and nutritional needs to support an optimal nutritional status. After defining the extent and severity of gut dysmotility, an experienced team should perform a careful nutritional assessment. An oral diet should always be encouraged and might include bite and dissolve solids, liquid diet or simple oral stimulation. If oral caloric intake is inadequate, liquid gastric feeds should provide the subsequent step. In the presence of severe gastric dysmotility, continuous post‐pyloric feeding represents a viable option. In the most severe cases, parenteral nutrition (PN) is required to meet appropriate nutritional requirements. Purpose: Pediatric data on this topic are scarce and mainly extrapolated from adult studies. In this review, we discuss current evidence and knowledge regarding nutritional options, implications of the use of different feed types, including a blended diet, and the use of PN. Moreover, based on our experience and the evidence from the literature, we propose a flow chart to guide the nutritional management of PIPO patients. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate costs from transplant to discharge in children who had undergone intestine transplant. Methods: We performed a cross‐sectional observational study of pediatric intestine transplant recipients from 2004 through 2020, utilizing the Pediatric Health Information System database. Standardized costs were applied to all charges and converted to 2021 US dollars. We analyzed the association of cost from transplant to discharge with age, sex, race and ethnicity, length of stay, insurance type, transplant year, short bowel syndrome diagnosis, liver‐containing graft, hospitalization status, and immunosuppressive regimen. Predictors with a P value <0.20 in univariable analysis were included in a multivariable model, which was reduced using backwards selection with a P value of 0.05. Results: We identified 376 intestinal transplant recipients across nine centers (median age, 2 years; 44% female). Most patients had short bowel syndrome (294; 78%). The liver was included in 218 transplants (58%). Median posttransplant cost was $263,724 (interquartile range [IQR], $179,564–$384,147), and length of stay was 51.5 days (IQR, 34–77). In the final model, increased cost from transplant to hospital discharge was associated with liver‐containing graft (+$31,805; P = 0.028), T‐cell–depleting antibody use (+$77,004; P < 0.001), and mycophenolate mofetil use (+$50,514; P = 0.012) while controlling for insurance type and length of stay. A 60‐day posttransplant hospital stay would cost an estimated $272,533. Conclusions: Intestine transplant has high immediate cost and long length of stay that varies by center, graft type, and immunosuppression regimen. Future work will examine the cost‐effectiveness of various management strategies before and after transplant. [ABSTRACT FROM AUTHOR]

Background: Autologous gastrointestinal reconstructive surgery (AGIR) has become a key component of intestinal rehabilitation programs. However, the best surgical option for short bowel syndrome (SBS) remains unknown. This paper presents our experience using combined procedures as primary treatment. Methods: We collected data on SBS patients who underwent surgery from 2008 to 2021 in two tertiary European Centres. Combined procedures were defined as more than one technique used on the same patient. Charts were reviewed for demographics, type of procedures, complications, and outcomes. Data are presented as median and IQR. Wilcoxon signed rank was used for all paired analyses. Results: Twenty‐one children (12 females) underwent combined procedures. Preoperative median small bowel length was 20 cm (IQR: 15–35 cm); after lengthening, it was 35.5 cm (IQR: 30.75–50.50 cm) (P < 0.001). Combined procedures were simultaneous in 15 patients and sequential in 6. At a median of 9.2 years (IQR: 7.55–9.78 years) follow‐up, complications were three bowel obstructions after strictures of anastomosis and two wound infections. Two patients achieved enteral autonomy, and others followed a weaning home parenteral nutrition regimen with a median of 4 nights off (IQR: 3–4 nights) starting with a median of 7 nights (IQR: 7–7 nights). Conclusions: Combined AGIR techniques are practical and safe in SBS treatment when tailored to meet patients' needs, combining lengthening, tailoring, and reducing transit time procedures. Therefore, combined AGIR may be considered a resource in intestinal rehabilitation units' armamentarium. [ABSTRACT FROM AUTHOR]

In pediatric patients who undergo heart transplantation, severe immune‐mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune‐mediated bowel disease. This case report discusses a pediatric patient who developed immune‐mediated bowel disease following heart transplantation and was successfully managed with basiliximab. [ABSTRACT FROM AUTHOR]

Background: Improved survival rates for children with intestinal failure (IF) have resulted in an increased population of children receiving long‐term parenteral nutrition (PN). Our objective was to determine burden on caregivers of children with IF receiving long‐term PN. Methods: We performed a cross‐sectional study of caregivers of children with IF receiving long‐term PN in our intestinal rehabilitation program. A healthy comparison group matched on age of the child was enrolled. All participants completed standardized questionnaires, including the Parental Stress Index – Short Form (PSI‐SF), Hospital Anxiety and Depression Scale (HADS), and PedsQL Family Impact Module (PedsQL FIM). Univariate analysis was completed using a Student t test and chi‐square, with an alpha value of <0.05 considered significant. Results: Thirty‐eight caregivers of children with IF and 29 caregivers of healthy children consented, with response rates of 89% and 96.5%, respectively. Our study demonstrated increased stress for caregivers compared with comparison parents (PSI‐SF total score of 83 [SD = 26.8] vs 62.9 [SD = 13.5]; P < 0.01). Caregivers had increased anxiety (HADS anxiety score of 9.3 [SD = 4.8] vs 6.7 [SD = 3.2]; P = 0.02) and higher depression scores (HADS depression score of 6.3 [SD = 4.3] vs 4.1 [SD = 2.6]; P = 0.02) compared with the comparison group. Caregivers of children with IF demonstrated decreased health‐related quality of life (HRQoL) (reduced PedsQL FIM total score of 50.6 [SD = 18.2] vs 84.1 [SD = 20.5]; P < 0.01). Conclusions: Our results demonstrated significant burden of care in caregivers of children with IF receiving long‐term PN, with elevated stress, anxiety, and depression and decreased HRQoL. [ABSTRACT FROM AUTHOR]