Sarcopenia prevalence in pediatric intestinal transplant recipients: Implications on post-transplant outcomes.

BACKGROUND: Sarcopenia has been associated with poor surgical outcomes but has not been studied in pediatric intestinal transplantation. We aimed to determine sarcopenia prevalence in intestinal transplant recipients and the association of sarcopenia with outcomes. METHODS: We performed a cross-sectional retrospective chart review of intestinal transplant recipients from 2000-present. We estimated total psoas muscle area (tPMA) at L3-L4 and L4-L5 from computed tomography scans prior to or in the immediate peri-operative period. Sarcopenia was defined by tPMA below the 5th percentile for age and sex. We built a Cox-proportional hazards model to determine the association between sarcopenia and patient and graft survival. RESULTS: Of the 56 intestinal transplant recipients included, 36 (64%) were sarcopenic. Graft survival was 79% at one year and 59% at five years. Overall patient survival was 86% at one year and 76% at five years. Peri-transplant sarcopenia was associated with improved graft survival (Hazard ratio 0.42, 95% confidence interval: 0.20-0.88) but not overall survival (Hazard ratio 0.47, 95% confidence interval: 0.19-1.20). CONCLUSIONS: In this first report of sarcopenia in pediatric intestinal transplant, we found a high sarcopenia prevalence without an association with worse outcomes. The potential improved graft survival in sarcopenic patients along with underlying mechanisms warrant further exploration.

Long-term outcomes of intestinal transplantation from donors aged under 1 year.

BACKGROUND: The aim of the study was to analyze the long-term outcomes of transplants utilizing ITx donors <1 year and to compare these results with older donors. METHODS: Between January 2007 and December 2019, the primary ITx donors in the Children's Hospital of Pittsburgh of UPMC were retrospectively reviewed. Short- and long-term outcomes of recipients receiving a deceased donor organ from donors <1 year were compared with those found in all other recipients. RESULTS: During the study period, there were 89 primary ITx donors, using 30 donors (33.7%) aged <1 year. The mean age of their recipients was 1.6 ± 0.7 (0.7-3.2) years. The 30 graft types were isolated intestine (n = 3, 10.0%), liver bowel (n = 20, 66.7%), and multivisceral (n = 7, 23.3%). Technical complications occurred in 12 (40.0%) recipients. Candidates transplanted with intestine allografts from donors <1 year of age had shorter wait times (p < .001), more liver-inclusive grafts (p < .001), and less donor-specific antibodies (DSA) (p = .014). During follow-up, the recipients had less graft loss (p = .018), and more remained alive with graft in place (p = .011). Among children transplanted with such donors, 3-year and graft survival rates were 86.7% and 82.9% compared to 62.8% and 49.9% in the cohort of donors >1 year (p = .032 and .011). CONCLUSIONS: Donor age <1 year was associated with improved graft survival. Optimal utilization of this population for toddler candidates would increase intestine availability, reduce time to transplantation, and potentially improve long-term outcome.

Caregiver Decision-making in Pediatric Intestinal Failure: A Qualitative Study Focused on Iron Deficiency Anemia.

BACKGROUND: Caregivers of children with intestinal failure (IF) face difficult decisions without a clear best alternative. Providers assist in decision-making but often lack knowledge of caregiver perspectives. Using decision-making around anemia treatment as a focal point, we explored how caregivers of children with IF prefer to make decisions. Our goal was to offer insight to guide providers as they assist in decision-making. METHODS: We conducted 12 half-hour semistructured interviews with parents of children with IF. Interview questions addressed general decision-making and specifics of iron supplementation, including key factors and stakeholders in decision-making. Interviews were transcribed verbatim. Two investigators coded the transcripts and inductively derived themes. RESULTS: Four themes were identified regarding decision-making. They involved the search for reliable, accurate, and positive information; the role of caretakers on the medical team; the relationships between caretakers and the medical team; and effective communication. Themes around anemia treatment included: identification of anemia by bloodwork; proactive supplementation; individualized regimens; prioritizing safety and convenience. CONCLUSIONS: Understanding caregiver perspectives regarding anemia treatment in pediatric IF identifies opportunities for systematic quality improvement.

Management of Central Venous Access in Children With Intestinal Failure: A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group.

ABSTRACT: Intestinal failure requires the placement and maintenance of a long-term central venous catheter for the provision of fluids and/or nutrients. Complications associated with this access contribute to significant morbidity and mortality, while the loss of access is an increasingly common reason for intestinal transplant referral. As more emphasis has been placed on the prevention of central line-associated bloodstream infections and new technologies have developed, care for central lines has improved; however, because care has evolved independently in local centers, care of central venous access varies significantly in this vulnerable population. The present position paper from the Intestinal Failure Special Interest Group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) reviews current evidence and provides recommendations for central line management in children with intestinal failure.

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: A Case Series With Long-term Follow-up and Prolonged Survival.

OBJECTIVES: Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients. METHODS: We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years. RESULTS: We identified 25 patients with MMIHS (68% girls, 13 transplanted). One transplanted and 1 nontransplanted patient were lost to follow-up. We estimated 100, 100, and 86% for 5-, 10-, and 20-year survival, respectively, with only 1 death. Of the 22 patients alive at the time of study (11 transplanted, 11 nontransplanted), median age was 9.2 years (range 2.7-22.9 years). Longest posttransplant follow-up was 16 years. Seventeen patients had available prenatal imaging reports; all showed distended bladder. Eight had genetic testing (5, ACTG2; 2, MYH11; 1, MYL9). Almost all patients had normal growth with median weight z-score -0.77 (interquartile range -1.39 to 0.26), height z score -1.2 (-2.04 to -0.48) and body mass index z-score 0.23 (-0.37 to 0.93) with no statistical difference between transplanted and nontransplanted patients. All nontransplanted patients were on parenteral nutrition with minimal/no feeds, and all except 1 of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin, and creatinine fell within the reference ranges. CONCLUSIONS: This is the largest single-center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper: Plant-based Milks.

Parents and caretakers are increasingly feeding infants and young children plant-based "milk" (PBM) alternatives to cow milk (CM). The US Food and Drug Administration currently defines "milk" and related milk products by the product source and the inherent nutrients provided by bovine milk. Substitution of a milk that does not provide a similar nutritional profile to CM can be deleterious to a child's nutritional status, growth, and development. Milk's contribution to the protein intake of young children is especially important. For almond or rice milk, an 8 oz serving provides only about 2% or 8%, respectively, of the protein equivalent found in a serving of CM. Adverse effects from the misuse of certain plant-based beverages have been well-documented and include failure to gain weight, decreased stature, kwashiorkor, electrolyte disorders, kidney stones, and severe nutrient deficiencies including iron deficiency anemia, rickets, and scurvy. Such adverse nutritional outcomes are largely preventable. It is the position of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Nutrition Committee, on behalf of the society, that only appropriate commercial infant formulas be used as alternatives to human milk in the first year of life. In young children beyond the first year of life requiring a dairy-free diet, commercial formula may be a preferable alternative to cow's milk, when such formula constitutes a substantial source of otherwise absent or reduced nutrients (eg, protein, calcium, vitamin D) in the child's restricted diet. Consumer education is required to clarify that PBMs do not represent an equivalent source of such nutrients. In this position paper, we provide specific recommendations for clinical care, labelling, and needed research relative to PBMs.

Prophylactic rtPA in the Prevention of Line-associated Thrombosis and Infection in Short Bowel Syndrome.

BACKGROUND: Central venous access devices (CVADs) are essential for total parenteral nutrition administration in patients with short bowel syndrome (SBS). They are, however, fraught with complications including infection and venous thromboembolism (VTE), which increases associated morbidity and mortality in this population. There is evidence linking the development of CVAD-associated thrombosis and line-related infection. Thus, it has been postulated that prevention of catheter-related clot formation could minimize the risk of infection originating from the catheter. Recombinant tissue plasminogen activator (rtPA, alteplase), lyses clots by binding plasmin-bound fibrin in a clot and cleaving plasminogen to plasmin; moreover, it is widely used to clear occluded CVADs. METHODS: Prophylactic rtPA lock therapy in children with SBS was evaluated as a single site pilot study to minimize line-associated VTE, infection, need for line replacement, and hospitalization at the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center. rtPA lock therapy was administered by parents/caregivers on a weekly basis over a 6-month time period in place of heparin lock therapy. Comparisons were made between line-associated complications in the cohort in the 6 months before study versus during the study period. RESULTS: Six out of 8 subjects completed the study over a 1-year time period. As a group, subjects experienced a significant decrease in the number of line-associated bloodstream infections from a mean of 1.9 infections in the 6 months before the study to a mean of 0.5 infections (P = 0.025). There was no change in the need for line replacement amongst subjects while on study. The primary outcome of VTE was not found in the cohort, and it is unclear whether rtPA lock therapy contributed to the lack of thrombosis development. Given the success of rtPA in this pilot study in reducing bloodstream infections, further investigation or rtPA lock therapy in patients with SBS is warranted.

Bloodstream Infections in Patients With Intestinal Failure Presenting to a Pediatric Emergency Department With Fever and a Central Line.

OBJECTIVE: Previous small studies have found a high occurrence of bloodstream infections (BSIs) in patients with intestinal failure, and these rates are higher than reported rates in other pediatric populations with central lines. The primary study objective was to describe the occurrence of BSIs in patients with intestinal failure who present to the pediatric emergency department (ED) with fever. METHODS: This 5-year retrospective chart review included febrile patients with intestinal failure and central lines who presented to the Children's Hospital of Pittsburgh ED between 2006 and 2011. Each febrile episode was analyzed at the visit level. RESULTS: During the study, 72 patients with 519 febrile episodes were identified. Central blood cultures were obtained in 93% (480/519) of episodes and 69% (330/480) were positive. Of all BSIs, 38% (124/330) were polymicrobial, 32% (105/330) were a single gram-positive organism, 25% (84/330) were a single gram-negative organism, and 5% (17/330) were a single fungal organism. Of the bacterial pathogens, 48% (223/460) were gram-negative. Overall, 60% were enteric organisms. CONCLUSIONS: Pediatric patients with intestinal failure and central lines have a high occurrence of BSIs with 69% of cultures positive in this study of ED febrile episodes. In contrast to reports in other populations with central lines, BSI occurrence in patients with intestinal failure and fever is higher and larger proportions are gram-negative and enteric organisms. For these patients, we recommend central and peripheral blood cultures, empiric broad spectrum antibiotics targeting gram-negative and enteric organisms, and hospital admission.

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

OBJECTIVES: In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. STUDY DESIGN: A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. RESULTS: A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. CONCLUSIONS: A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

Nutrition support considerations in pediatric small bowel transplantation.

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

Pediatric intestine transplant cost: Analysis of the Pediatric Health Information System database.

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.

Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.

OBJECTIVE: To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation era. STUDY DESIGN: The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multicenter cohort of infants with IF. Entry criteria included infants <12 months receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as number (%). RESULTS: 272 infants with a gestational age of 34 weeks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 months (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and proton pump inhibitors (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1000 catheter days. The cumulative incidences for enteral autonomy, death, and intestinal transplantation were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the fifth year after study entry. CONCLUSIONS: Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality, and need for transplantation.

Consumer-centric approach to enhance access to pediatric specialty care.

OBJECTIVES: Health systems must adapt to an increased consumer-centric environment to remain relevant in an ever-growing competitive health care landscape in which convenience is a key driver of patient satisfaction and loyalty. To adapt to this new environment, health systems must redesign processes to transform the delivery of ambulatory care and provide near real-time access to specialty care. STUDY DESIGN: A pediatric academic medical center in western Pennsylvania used a process-improvement approach to enhance timely access to specialty care and deliver a consumer-centric patient experience. METHODS: Critical factors in this process included engagement of key stakeholders, implementation of scheduling best practices, development of a set of scheduling guidelines, increased use of advanced practice providers, and use of data analytics to measure and benchmark performance. RESULTS: The time to schedule a new patient appointment decreased from 42 to 4 days and the patient satisfaction access domain increased by 57 percentile points. CONCLUSIONS: These factors should scale to other institutions, thereby enabling generalizable results.

Cost-effectiveness of ethanol lock prophylaxis to prevent central line-associated bloodstream infections in children with intestinal failure in the United States.

INTRODUCTION: Central line-associated bloodstream infections (CLABSIs) lead to significant morbidity and mortality in children with intestinal failure (IF). Ethanol lock prophylaxis (ELP) greatly reduces CLABSI frequency with minimal side effects. However, in the United States, a recently approved orphan drug designation for dehydrated alcohol has greatly increased 70% ethanol cost from about $10/day to $1000/day. We examined the cost-effectiveness of ELP in relation to these changes. METHODS: We simulated a previously developed IF Markov model over 1 year. Costs were measured in 2020 US dollars and effectiveness in quality-adjusted life-years (QALYs). CLABSI rate with and without ELP was estimated from the largest available comparative observational study. The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Secondary outcomes included CLABSI frequency. Sensitivity analyses on all model parameters were performed. RESULTS: In the base model, children with IF not using ELP accumulated $131,815 in costs and 0.32 QALYs per patient compared with $437,884 and 0.33 QALYs per patient in those using ELP. The ICER was nearly $17 million/QALY gained. ELP resulted in a 40% reduction in CLABSI frequency. ELP became cost-effective at $68/day and cost-saving at $63/day. Sensitivity analysis identified no other plausible parameter variation to reach the benchmark of $100,000/QALY gained. CONCLUSIONS: At the current price, ELP is not cost-effective for CLABSI prevention in children with IF in the United States. This study highlights the critical need for the approval of an affordable lock therapy option to prevent CLABSIs in these children.

Current practices in lipid emulsion utilization in the prevention and treatment of intestinal failure-associated liver disease: A survey of pediatric intestinal rehabilitation and transplant centers.

BACKGROUND: Newer intravenous lipid emulsions (ILEs), such as fish oil-based intravenous lipid emulsions (FO-ILEs) and soybean oil, medium-chain triglycerides, olive oil, and fish oil-based intravenous lipid emulsions (SMOF-ILEs), provide alternatives to soybean oil-based intravenous lipid emulsions (SO-ILEs). We explored current ILE practice patterns among intestinal rehabilitation and transplant centers. METHODS: A survey was developed addressing ILE availability, ILE preference in clinical scenarios, and factors influencing ILE choice. This survey was reviewed locally and by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation Special Interest Group, the Intestinal Rehabilitation and Transplant Association scientific committee, and the American Society of Parenteral and Enteral Nutrition pediatric intestinal failure section research committee. We recruited providers nationally and internationally from centers with and without intestinal transplant programs. RESULTS: We included 34 complete responses, 29 from the United States. Sixteen centers performed intestinal transplants. All centers had access to SMOF-ILEs, 85% had access to FO-ILEs, and 91% had access to SO-ILEs. In new patients, 85% use SMOF-ILEs as the first choice ILE. In those with new intestinal failure-associated liver disease (IFALD), FO-ILE was preferred to SMOF-ILE (56% vs 38%). In those developing IFALD on SMOF-ILE, 65% switched to FO-ILE, whereas 24% remained on SMOF-ILE. CONCLUSIONS: Centers have routine access to alternative ILEs, and these are quickly replacing SO-ILEs in all circumstances. Future work should focus on how this shift in practice affects outcomes to provide decision support in specific clinical scenarios.

NOD2 gene polymorphism rs2066844 associates with need for combined liver-intestine transplantation in children with short-gut syndrome.

OBJECTIVES: The nucleotide-binding oligomerization protein 2 (NOD2) gene single nucleotide polymorphisms (SNPs) associated with Crohn's disease were recently associated with severe rejection after small-bowel transplantation (SBTx). The purpose of this study was to re-test this association and explore whether deficient innate immunity suggested by the NOD2 SNPs predisposes to intestine failure requiring isolated SBTx or combined liver-intestine failure requiring combined liver-SBTx (LSBTx). METHODS: Archived DNA from 85 children with primary isolated SBTx or LSBTx was genotyped with Taqman biallelic discrimination assays. To minimize confounding effects of racial differences in minor allele frequencies (MAFs), allelic associations were tested in 60 Caucasian recipients (discovery cohort). Replication was sought in an independent cohort of 39 Caucasian pediatric and adult SBTx patients. RESULTS: MAF for rs2066845 and rs2066847 was similar to that seen in 538 healthy North American Caucasians. In the discovery cohort, MAF for rs2066844 was significantly higher in LSBTx (13.5 vs. 3.6%, P=0.0007, Fisher's exact test), but not in isolated SBTx recipients (2.2 vs. 3.6%, P=NS), when compared with 538 healthy Caucasians. In addition, among LSBTx recipients who received identical immunosuppression, the minor allele of rs2066844 associated with early rejection in linear regression analysis (P=0.028) (all but one of the risk alleles were found in rejectors), decreased survival (P=0.015, log-rank, Kaplan-Meier analysis), and a 20-fold greater hazard of septic death in proportional hazard analysis (P=0.030). Steroid-resistant (severe) rejection and graft loss were associated with isolated SBTx (P=0.036 and 0.082, respectively), but not with NOD2 SNPs. The association between rs2066844 and combined liver-intestine failure requiring LSBTx was significant in the replication cohort (P=0.014), and achieved greater significance in the combined cohort (P=0.00006). CONCLUSIONS: The NOD2 SNP rs2066844 associates with combined liver and intestinal failure in subjects with short-gut syndrome, who require combined liver-intestine transplantation, and secondarily with early rejection and septic deaths.

sTREM-1 and LBP in central venous catheter-associated bloodstream infections in pediatric intestinal failure.

OBJECTIVE: Central venous catheter-associated bloodstream infections (CVC-BSIs) are a major cause of morbidity and mortality in the pediatric intestinal failure (IF) population. We assessed plasma lipopolysaccharide-binding protein (LBP) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarkers for CVC-BSI. We hypothesized that sTREM-1 and LBP rise with BSI and decline following treatment, and that baseline LBP is higher in the IF population than in controls. PATIENTS AND METHODS: Patients younger than 4 years were recruited from the IF registry at Cincinnati Children's Hospital. LBP and sTREM-1 levels were measured on 22 patients with IF at baseline, 17 patients with IF with BSIs, and 11 healthy controls. RESULTS: Mean sTREM-1 level (pg/mL) and LBP level (µg/mL) rose with CVC-BSI over baseline (115.0 ±â€Š51.2 vs 85.9 ±â€Š27.6, P = 0.011 and 79.8 ±â€Š45.4 vs 20.5 ±â€Š11.3, P < 0.001, respectively) and declined following antibiotic therapy (115.0 ±â€Š51.2 vs 77.9 ±â€Š29.8, P = 0.003 and 79.8 ±â€Š45.4 vs 26.2 ±â€Š10.8, P < 0.001, respectively). Receiver operating characteristic curves showed that neither sTREM-1 nor LBP is sufficient to predict bacteremia versus fever without bacteremia (area under these curves = 0.57 and 0.82, respectively). Baseline LBP was higher in hospitalized patients than in outpatients (27.5 ±â€Š8.7 vs 13.5 ±â€Š9.2, P = 0.002), patients with previous BSIs versus those without (23.5 ±â€Š10.4 vs 10.1 ±â€Š8.3, P = 0.016), and those listed for transplantation versus those not listed (29.6 ±â€Š9.8 vs 16.2 ±â€Š9.5, P = 0.033). CONCLUSIONS: sTREM-1 and LBP rise with CVC-BSI in IF and decline after treatment; however, neither distinguishes infection from nonbacteremic febrile episodes. Baseline LBP may be a marker of disease severity in IF.

Cost-effectiveness of teduglutide in pediatric patients with short bowel syndrome: Markov modeling using traditional cost-effectiveness criteria.

BACKGROUND: Teduglutide use in pediatric patients with short bowel syndrome can aid in the achievement of enteral autonomy, but with a price of >$400,000 per y. OBJECTIVE: The current study evaluated the cost-effectiveness of using teduglutide in conjunction with offering intestinal transplantation in US pediatric patients with short bowel syndrome. DESIGN: A Markov model was used to evaluate the costs (in US dollars) and effectiveness [in quality-adjusted life years (QALYs)] of using teduglutide compared with offering intestinal transplantation. Parameters were estimated from published data where available. The primary effect modeled was the probability of weaning from parenteral nutrition while on teduglutide. Sensitivity analyses were performed on all model parameters. RESULTS: Compared with offering only intestinal transplantation, adding teduglutide cost ${\$}$124,353/QALY gained. Reducing the cost of the medication by 16% allowed the cost to reach the typical benchmark of ${\$}$100,000/QALY gained. Probabilistic sensitivity analysis favored transplantation without offering teduglutide in 68% of iterations at a ${\$}$100,000/QALY threshold. Never using teduglutide created an opportunity cost of over ${\$}$100,000 per patient. CONCLUSIONS: At its current price, teduglutide does not provide a cost-effective addition to transplantation in the treatment of pediatric short bowel syndrome. Further work should look to identify cost-reducing strategies, including alternative dosing regimens.

Microsimulation Model to Compare Enteral and Parenteral Iron Supplementation in Children With Intestinal Failure.

BACKGROUND: Children with chronic intestinal failure have a high prevalence of anemia, commonly from iron deficiency, leading to frequent blood transfusions. No current guideline exists for iron supplementation in these children. In this analysis, we evaluate the effectiveness and the cost-effectiveness of using parenteral, enteral, and no iron supplementation to reduce blood transfusions. METHODS: We created a microsimulation model of pediatric intestinal failure over a 1-year time horizon. Model outcomes included cost (US dollars), blood transfusions received, and hemoglobin trend. Strategies tested included no supplementation, daily enteral supplementation, and monthly parenteral supplementation. We estimated parameters for the model using an institutional cohort of 55 patients. Model parameters updated each 1-month cycle using 2 regressions. A multivariate mixed-effects linear regression estimated hemoglobin values at the next month based on data from the prior month. A mixed-effects logistic regression on hemoglobin predicted the probability of receiving a blood transfusion in a given month. RESULTS: Compared with no supplementation, both enteral and parenteral iron supplementation reduced blood transfusions required per patient by 0.3 and 0.5 transfusions per year, respectively. Enteral iron cost $34 per avoided blood transfusion. Parenteral iron cost an additional $6600 per avoided blood transfusion compared with enteral iron. CONCLUSIONS: We found both parenteral and enteral iron to be effective at reducing blood transfusions. The cost of enteral iron makes it the desired choice in patients who can tolerate it. Future work should aim to identify which subpopulations of patients may benefit most from one strategy over the other.

Anatomic and histologic variability of epithelial apoptosis in small bowel transplants.

Surveillance ileoscopies are performed regularly immediately post-transplantation to prevent allograft rejection. We investigated whether variability in apoptosis exists between proximal and distal intestinal limbs of double-barreled ileostomies, and if detection varies according to number of biopsies taken and sections prepared for evaluation. We retrospectively analyzed endoscopy/pathology reports of patients who underwent simultaneous proximal and distal ileoscopies during surveillance. We re-reviewed three sections of selected biopsies for the presence of apoptotic bodies and viral inclusions. Seven patients underwent 26 endoscopies in which both distal and proximal limbs were investigated simultaneously. Apoptosis was identified in each limb simultaneously in 21/26 cases (81%). Of the discrepant results, 3/5 (60%) revealed apoptosis in the proximal limb with normal distal limb and 2/5 (40%) had apoptotic bodies identified in the distal limb and normal proximal biopsies. Re-reviewing discrepant biopsies, two patients had at least one piece of mucosa without apoptosis and apoptotic bodies were seen in only 47% of sections. Histologic variability exists between proximal and distal limbs of double-barreled ileostomies and detection of apoptosis increases with number of pieces obtained and sections examined. Investigating both limbs with adequate sample size and rigorous processing may have clinical implications.