Aetiology Of Intestinal Failure Research Articles

Age-related trajectory of bone density in children with intestinal failure: A longitudinal retrospective cohort study.

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. 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. 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. 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.

Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?

The incidence and significance of pneumatosis intestinalis (PI) in children with a diagnosis of intestinal failure is not well understood. The aim of this study was to identify clinical and anatomical factors associated with the imaging findings of PI in patients with intestinal failure. We performed a retrospective review of all children with a diagnosis of intestinal failure at Children's Hospital Colorado between January 2019 and April 2022. Patients were stratified and compared based on the incidence of PI on abdominal imaging. Differences were compared using 2-sample Wilcoxon tests, chi-square, or Fisher exact tests. There were 111 patients identified with a diagnosis of intestinal failure and 30.6% (34) developed at least 1 instance of PI. There were no differences in etiology of intestinal failure or anatomy between those who developed PI and those who did not. Patients who developed PI, were less likely to be on total parental nutrition (60.6% vs 98.6%, P < 0.001) and more likely to be receiving any form of enteral feeds (87.9% vs 66.2%, P = 0.035) or tube feeds (75.8% vs 44.2%, P = 0.0045). Of the children with PI, 30.3% (10) were undergoing an enteral feed advancement at time of PI development. Three patients with PI underwent laparotomy for PI treatment, 2 of which were negative laparotomies. The development of PI in children with intestinal failure is likely a benign finding. It is associated with enteral feeding and may be due to increased intestinal stress.

Factors Associated With Chronic Intestinal Inflammation Resembling Inflammatory Bowel Disease in Pediatric Intestinal Failure: A Matched Case-Control Study.

There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure. This was a single-center retrospective case-control study of children <18 years old with intestinal failure. Cases were defined by abnormal amounts of chronic intestinal inflammation on biopsies. Children with diversion colitis, eosinophilic colitis, or isolated anastomotic ulceration were excluded. Cases were matched 1:2 to intestinal failure controls based on sex, etiology of intestinal failure, and duration of intestinal failure. Multivariable conditional logistic regression was used to compare clinical factors between cases and controls, accounting for clustering within matched sets. A subgroup analysis was performed assessing factors associated with escalation of anti-inflammatory therapy. Thirty cases were identified and matched to 60 controls. On univariate analysis, longer parenteral nutrition (PN) duration (1677 vs 834 days, P = 0.03), current PN use (33.3% vs 20.0%, P = 0.037), and culture-proven bacterial overgrowth (53.3% vs 31.7%, P = 0.05) were associated with chronic intestinal inflammation. On multivariable analysis, no variable reached statistical significance. On subgroup analysis, duration of intestinal failure, location of inflammation, and worst degree of inflammation on histology were associated with escalation of therapy. PN dependence and intestinal dysbiosis are associated with chronic intestinal inflammation in children with intestinal failure. Severity of inflammation is associated with escalation of therapy. Further analysis is needed to assess these associations and the efficacy of treatments in this population.

Analysis of transition from intravenous iron sucrose to ferric carboxymaltose infusions in pediatric patients with intestinal failure.

Iron supplementation is required for pediatric patients with intestinal failure (IF). There is a paucity of literature on optimal iron formulation and outcomes in this patient population that requires ongoing supplementation. The aim of this study was to assess outcomes in pediatric patients with IF receiving iron sucrose (IS) vs ferric carboxymaltose (FCM) iron infusions. This was a single-center observational cohort study of pediatric patients with IF requiring ongoing intravenous iron supplementation. Patients were transitioned from IS to FCM as iron therapy. Longitudinal linear mixed-effects models and generalized estimating equations were used to compare outcomes, including hematologic, iron, and growth parameters for 12-month treatment duration on each iron formulation. Adverse effects were descriptively summarized. Twenty-three patients were included. Sixteen received IS and later switched to FCM, five received IS only, and two received FCM only. Most patients' etiology of IF was short bowel syndrome (FCM: 81%, IS: 83%). No differences were seen over time for iron, hematologic, and growth metrics between IS and FCM. The median number of infusions over 12 months for those taking IS was 15 (interquartile range [IQR] = 13-26) and 2 for FCM (IQR = 1-2). Asymptomatic hypophosphatemia was noted in both groups. Similar central line-associated bloodstream infection rates were noted. IS and FCM infusions both maintained hematologic and iron parameters with no significant difference noted between the two types of iron, though the number of FCM infusions was significantly less. No significant adverse effects were noted.

O-42: Pediatric Composite Liver-intestine Transplantation with Native Splenopancreatic Preservation: Immunologic Complications and Long-term Outcomes

Introduction: Combined liver-intestine transplantation is the only proven treatment for the moribund child with intestinal failure and decompensated liver disease. Native splenopancreatic preservation may provide immunologic benefits that results in improved long-term outcomes. Methods: All pediatric patients who underwent combined liver-intestine transplantation with native splenopancreatic preservation at our institution from November 2003 until June 2019 were included in this study. Freedom from rejection and survival were estimated using the Kaplan-Meier method. Risk factors for graft loss and death were identified using Cox proportional hazard regression analysis. Results: Pediatric recipients included 68 infants with a median follow up of 9.8 years. Recipient median age was 1.3 years old with a median weight of 9.3kg and were more commonly male. Short gut syndrome was the most etiology of intestinal failure. Donors were generally younger (median age 0.4 years old) and smaller (median weight 6.9kg) than recipients. The most common cause of donor death was intracranial hemorrhage. Early rejection (<1 year) occurred in 10 (15%) and late rejection (>1 year) in 9 (13%) recipients. De novo donor specific antibody developed in 17 (25%) recipients. PTLD occurred in 4 (5.9%) and GVHD in 4 (5.9%) recipients. The 10-year survival with a functioning graft was 80.4% in this group. Multivariate Cox regression analysis identified inpatient status at time of transplant, donor-recipient weight ratio >0.9, and development of GVHD as statistically significant risk factors for graft loss and death after transplant. Conclusions: In this large pediatric cohort of combined liver-intestine transplant recipients with native splenopancreatic preservation there was a relatively low rate of immunologic complications and excellent long-term outcomes.

Etiology and Management of Pediatric Intestinal Failure: Focus on the Non-Digestive Causes.

Background: Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF results from intrinsic diseases of the gastrointestinal tract (digestive IF) (DIF); few cases arise from digestive vascular components, gut annexed (liver and pancreas) and extra-digestive organs or from systemic diseases (non-digestive IF) (NDIF). The present review revised etiology and treatments of DIF and NDIF, with special focus on the pathophysiological mechanisms, whereby NDIF develops. Methods: We performed a comprehensive search of published literature from January 2010 to the present by selecting the following search strings: “intestinal failure” OR “home parenteral nutrition” OR “short bowel syndrome” OR “chronic pseudo-obstruction” OR “chronic intestinal pseudo-obstruction” OR “autoimmune enteropathy” OR “long-term parenteral nutrition”. Results: We collected overall 1656 patients with well-documented etiology of IF: 1419 with DIF (86%) and 237 with NDIF (14%), 55% males and 45% females. Among DIF cases, 66% had SBS and among NDIF cases 90% had malabsorption/maldigestion. Conclusions: The improved availability of diagnostic and therapeutic tools has increased prevalence and life expectancy of rare and severe diseases responsible for IF. The present review greatly expands the spectrum of knowledge on the pathophysiological mechanisms through which the diseases not strictly affecting the intestine can cause IF. In view of the rarity of the majority of pediatric IF diseases, the development of IF Registries is strongly required; in fact, through information flow within the network, the Registries could improve IF knowledge and management.

How good is quality-of-life for children receiving home parenteral nutrition? – A pilot study

Children on home parenteral nutrition and their parents not only engage with complex nutritional issues but also have to manage difficult social and financial problems with social and clinical support that may not always meet their needs. Baxter's HPN-QOL questionnaire, assesses the QOL of adult patients treated with HPN, and has been developed rigorously using standard guidelines, measuring various dimensions of QOL. Our aim was to use this tool to explore how HPN influences the QOL of paediatric patients. The HPN-QOL questionnaire was modified to suit a paediatric HPN population. Data on demographics, aetiology of intestinal failure and duration of HPN were collected from a departmental database. Quality-of-Life grading of functional and symptom scales, HPN specific items and overall QOL Numerical Rating Scales were determined. Fourteen out of 17 families returned the completed questionnaires. QOL was significantly impaired by increased dependency regarding items of daily living such as eating, dressing, washing, and mobility, but was not affected in the domains of school attendance, general fatigue, pain and body image. There were no significant differences in QOL when patients with and without enterostomy were compared. Patients felt well supported by the hospital nutrition team in managing logistics related to HPN. QOL in HPN patients was not significantly affected by the medical aspects of care. This descriptive study highlights the need for further integration of medical and social care in order to support families of children receiving HPN as QOL was impaired in relation to activities of daily living and social functioning.

Visceral transplantation in patients with intestinal-failure associated liver disease: Evolving indications, graft selection, and outcomes.

Intestinal failure (IF)-associated liver disease (IFALD) is widely recognized as a lethal complication of long-term parenteral nutrition. The pathophysiology of IFALD is poorly understood but appears to be multifactorial and related to the inflammatory state in the patient with IF. Visceral transplant for IFALD includes variants of intestine, liver, or combined liver-intestine allografts. Graft selection for an individual patient depends on the etiology of IF, abdominal and vascular anatomy, severity of IFALD, and potential for intestinal rehabilitation. The past decade has witnessed dramatic improvement in the management of IFALD, principally due to improved lipid emulsion formulations and the multidisciplinary care of the patient with IF. As the recognition and treatment of IFALD continue to improve, the requirement of liver-inclusive visceral grafts appears to be decreasing, representing a paradigm shift in the care of the patient with IF. This review highlights the current indications, graft selection, and outcomes of visceral transplantation for IFALD.

Correlation of Sonographic Findings and Liver Biochemistry Tests in Pediatric Patients with Intestinal Failure

Introduction: Intestinal failure-associated liver disease (IFALD) develops in children dependent upon long-term parenteral nutrition (PN). Laboratory and radiographic abnormalities are characteristic of the disorder. Sonographic findings (SF) include steatosis, edema, and biliary stones/sludge. Steatosis seems more prevalent in adults, while cholestasis is more prominent in children. IFALD can progress to fibrosis, cirrhosis, and end-stage liver disease. Abdominal ultrasound is a cost-effective and non-invasive modality that can be useful in examining the liver of patients with intestinal failure (IF). The aim of this study is to review liver SF and their correlation with liver biochemistry tests (LT) in pediatric patients with IF. Methods: We retrospectively reviewed the charts of 163 pediatric IF patients followed at our Center between 1998-2016. We specifically reviewed demographics, etiology of IF, SF and liver biochemistry tests. Results: Sixty eligible patients were included in this analysis (median age: 2.3 years, range: 1 month-18 years, 52% male). IF was caused by necrotizing enterocolitis (42%), gastrointestinal dysmotility (23%), intestinal atresia (13%), gastroschisis (8%) and volvulus (8%). Forty-six of 60 patients had elevated LT. Thirty-nine patients (85%) were cholestatic, and 35 patients (76%) had abnormal SF: splenomegaly (57%), hepatomegaly (54%), increased liver echogenicity (37%), gallbladder sludge (23%), cholelithiasis (17%), and heterogeneous liver (17%). Seven of 14 (50%) patients with normal LT had abnormal SF: splenomegaly (57%), cholelithiasis (43%), increased liver echogenicity (14%), and gallbladder sludge (14%). Conclusion: Abnormal SF were present in most pediatric IF patients with elevated LT and in half of the patients with normal LT. Increased liver echogenicity, suggestive of hepatic steatosis or edema, was more prevalent in children with IF than expected. Based on our single-center experience, we recommend the routine use of sonographic screening in pediatric patients with IF, regardless of LT, to achieve early detection and treatment of IFALD.

PO-0116 Results Of A Single Centre Register For Paediatric Intestinal Failure

Aim Intestinal failure (IF) is a rare condition requiring long term parenteral nutrition (PN). The complex management of IF needs a multidisciplinary approach by expert team of paediatricians, surgeons, gastroenterologists, nurses and dieticians. The risks of medical, surgical and nutritional complications must be prevented or managed appropriately. The primary aims of the register were to list the patients, the aetiology of IF, the therapeutic approach of the disease and the follow-up. Methods We collected retrospectively the data of 21 patients followed in our centre for IF between 1999 and 2013. Results Twenty-one patients were included, their age ranged between 2 mo and 15 yrs (mean 7.4 yrs). The causes of IF were short bowel syndrome (16), malabsorption (1) and intestinal motility disorders (4). Sex ratio was 0.29 (F/M). All children required home PN. The duration of PN was (43.1 ± 46.9 mo). 10/21 (47.6%) patients could be totally weaned from PN after 25.4 ± 33.5 months, 5/21 (24%-after 109 ± 74.9 months) were off PN after longitudinal intestinal lengthening tapering (4LILT) or 1 after combined serial tapering enteroplasty (STEP) and (LILT). PN partially weaned in the 6/21 (23.8%) remaining patients. Conclusions Results of this single centre experience demonstrate that with a proactive multidisciplinary IF management, including surgical rehabilitation procedures, the majority of patients have obtained partial or full enteral autonomy. Extension of this register to other centre in Belgium or Europe would be interesting and probably enhance the quality of patient follow-up.

PTH-122 Home Parenteral Nutrition In Palliative Care: A Retrospective Study To Identify Potential Prognostic Indicators

IntroductionThe use of home parenteral nutrition (HPN) in the palliative setting is less common in the UK than in Europe and the USA. It remains controversial with little evidence base...

G196(P) Residual Small Bowel Length Predicts Raised D-Lactate When Screening For Bacterial Overgrowth in Children with Intestinal Failure

AimsSmall bowel bacterial overgrowth (SBBO) may cause non specific symptoms in children with intestinal failure (parenteral nutrition (PN) >28days). Rapid detection of raised serum D-lactate (DL) may be a clinically...

OC-037 Vitamin D deficiency is common in intestinal failure patients

IntroductionVitamin D is essential due to its role in bone health and its immunomodulatory propeties.1 Patients with intestinal failure (IF) are at risk of Vitamin D deficiency due to inadequate...

PTH-063 Nutritional requirements and prevalence of cholestasis in patients with a short bowel due to infarction

Introduction Patients with a short bowel and a retained colon due to ischaemia are now the most common indication for home parenteral nutrition in the UK.1 To date most studies have compared short bowel length and intravenous nutrition (IVN) requirements in patients with mixed aetiology of intestinal failure.2 IVN patients with Methods Retrospective data were collected using St Mark9s Intestinal Failure database. Biochemical parameters obtained from computer lab system. Chronic cholestasis was considered to be two of bilirubin, alkaline phosphatise or γ-glutamyl transferase >1.5 times the upper limit of normal for >6 months.3 Results Since 2003 a total of 88 patients (male 47%) have been referred to St Marks Intestinal Failure Unit with SB infarction. 12-month follow-up data were available for 57 patients diagnosed with arterial SB infarction (46% male, mean age at diagnosis 56.3 years) and four patients with venous SB infarction (male 25%, mean age at diagnosis 35.5 years). Following continuity surgery 92% of patients with SB length 12 months after initial diagnosis. In comparison only 28% with SB length >50 cm were receiving IVN. Comparing patients that were receiving and not receiving IVN there was a significant difference in residual SB length (p= 50 cm. Following continuity surgery 31% with residual SB 50 cm. All five patients (4 patients 12 months following diagnosis had chronic cholestasis. Conclusion Residual SB length corresponds to IVN requirements. Less than

Outcomes of intestinal failure—a comparison between children with short bowel and dysmotile intestine

Background We investigated whether mortality, intestinal adaptation, and liver function differ between intestinal failure (IF) patients with either short bowel (SB) or bowel dysmotility (DM). Patients and methods Twenty-six consecutive patients with SB (n = 20) or DM (n = 6) treated between 2000 and 2007 were retrospectively assessed. Intestinal failure was defined as less than 25% of age-adjusted small intestinal length or dependence on parenteral nutrition (PN) more than 6 months. Results Median age-adjusted small intestinal length (17% vs 45%) and gestational age (35 vs 40 weeks) were ( P < .05) shorter, whereas proportion of the remaining colon (86% vs 0%) was ( P < .05) higher in the SB group relative to the DM group. Overall survival was 92%. Median peak serum bilirubin (80 vs 25 μmol/L) and rate of cholestasis (11/20 vs 0/6) were higher ( P < .05) in the SB group. Short bowel rather than DM as an etiology of IF predicted weaning off PN (RR, 39.3; 95% confidence interval [CI], 1.43-526; P < .01) and development of cholestasis (risk ration [RR], 18.3; 95% CI, 0.658-127; P < .05). Three SB children developed liver failure and two died, whereas neither of these occurred in the DM group. Conclusions Children with SB are more likely to wean off PN but more prone to cholestatic liver disease than those with DM as an etiology of IF.

Network Approach to the Child With Primary Intestinal Failure

Intestinal failure (IF) is a rare condition resulting from short gut and other heterogeneous intestinal diseases. Major centers in Italy merged in a national network to build common diagnostic and management approaches and to investigate the natural history of IF. Gastroenterological reference centers with specific expertise in intestinal morphology, diagnosis of autoimmune conditions, intestinal microbiology and parenteral nutrition were identified to act as consultants to the network. These centers of expertise provided specific diagnostic approaches while ensuring high technical standards. The approach allowed each center to learn from a larger cohort of patient samples. A database was set up to investigate etiology, epidemiology and natural history of IF. A common diagnostic algorithm for intractable diarrhea was designed. This process was largely based on electronic communication among centers and specimen shipping. Etiologic diagnosis was obtained in almost all cases of IF secondary to severe protracted diarrhea. The study of the natural history of IF showed a close association between etiology of IF and its outcome. The natural history of IF also provided the starting point for specific therapeutic approaches to its complications such as parenteral nutrition-associated cholestasis and catheter-related sepsis. The network approach to IF provides an effective model to optimize resources and prospectively investigate the natural history of IF, essential steps to design interventions, including intestinal transplantation and improve the outcome of IF.

P0784 INTESTINAL FUNCTION TESTS IN INTESTINAL FAILURE

Introduction: Intestinal failure (IF) is a complex condition requiring parenteral nutrition (PN). The outcome of IF is associated with its primary etiology (1) but individual prognostic factors are not available to predict weaning from PN. We tested the hypothesis that non-invasive intestinal function tests could predict weaning from PN in children with IF. Methods: IF was defined as need for total PN for at least 4 weeks or for supportive PN for at least 3 months. In children with IF we retrospectively evaluated the following non-invasive intestinal function tests: fecal steatocrit, d-xylose oral load, fecal alpha1-antitrypsin. At least 3 determinations for fecal steatocrit and 2 for d-xylose oral load were obtained. Results were analysed in relation with the primary etiology of IF. Statistical analysis was performed with non parametric and logistic regression tests, and X2 test. Results: 10 children with short bowel syndrome (SBS) and 5 with various causes of IF (NSBS) were enrolled. Fecal alpha1-antitrypsin was normal in all cases. Mean values of steatocrit were abnormal in both groups, 17 (range 0–55) and 13 (range 0–53) in children with SBS and non SBS, respectively. Xylose absorption test was significantly different in children with SBS (mean 14, range 3–35.5) versus children with NSBS (mean 26, range 16–44) (p<0.01). When we analysed steatocrit and xylose absorption in children that were eventually weaned from PN, and in those who were not, a difference was detected in SBS and NSBS children. In the latter no statistical correlation was observed between functional tests and gaining of intestinal sufficiency. In children with SBS, at enrolment, xylose absorption was statistically associated with intestinal length and weaning from PN (p<0.05), whereas such correlation was not observed for fecal steatocrit. Among functional tests, fecal steatocrit was normal in all patients weaned from PN and in 1/3 patients who could not be weaned (p=0.08). Xylose test was normal in all but 1 weaned children, and abnormal in all children who did not reach intestinal sufficiency (p<0.05). Conclusion: In children with IF and SBS fecal steatocrit and xylose absorption are markedly abnormal, and the latter correlates with residual intestinal length. Functional tests may help predicting weaning from PN. In NSBS children, only fecal steatocrit is impaired but is not associated with intestinal function.