Advance Care Planning for Children With Rare Diseases: A Pilot RCT.

BACKGROUND AND OBJECTIVE: Pediatric rare diseases are often life-limiting conditions and/or require constant caregiving. Investigators assessed the initial efficacy of the FAmily CEntered (FACE) pediatric advance care planning (pACP), FACE-Rare, intervention on families' quality of life. METHODS: A pilot-phase, single-blinded, intent-to-treat, randomized controlled clinical trial enrolled families from 1 pediatric quaternary hospital between 2021 and 2023. Intervention families received 3 weekly 60-minute (FACE-Rare pACP) sessions: (1) Carer Support Needs Assessment Tool or Action Plan, (2) Carer Support Needs Assessment Tol Action Plan Review, and (3) Pediatric Next Steps: Respecting Choices pACP. Controls received treatment as usual (TAU). Outcome measures were Beck Anxiety Inventory, Family Appraisal of Caregiving, Functional Assessment of Chronic Illness Therapy (FACIT)-Spirituality, and health care utilization. Generalized mixed effect models with γ response assessed the intervention effect at 3-month follow-up. RESULTS: Children (n = 21) were aged 1 to 10 years, 48% male, 24% Black; and 100% technology dependent. Primary family caregivers (n = 21) were aged 30 to 43 years, 19% male, 19% Black; and 27% household income below the Federal poverty level. Dyads underwent 1:1 randomization: 9 to FACE-Rare and 12 to TAU. TAU caregivers reported statistically lower meaning and peace than FACE-Rare caregivers (0.9, P = .03, confidence interval [CI]: 0.75-0.99). Black caregivers reported significantly less caregiver distress (0.7, P = .04, CI: 0.47-0.98) than non-Black caregivers. Poor families reported more anxiety (3.5, P = .002, CI: 1.62-7.94), more caregiver strain (1.2, P = .006, CI: 1.07-1.42); and less family well-being (0.8, P = .02, CI: 0.64-0.95). CONCLUSIONS: FACE®-Rare was feasible, acceptable, safe, and demonstrated initial efficacy, providing greater feelings of meaning and peace to caregivers. Poverty impacted well-being. A multisite trial is needed to determine generalizability.

Prevalence of eosinophilic gastrointestinal diseases in children with short bowel syndrome: A single center study.

Patients with short bowel syndrome (SBS) have multiple risk factors for eosinophilic gastrointestinal diseases (EGIDs) including increased risk for intestinal dysbiosis and food allergy compared to their counterparts with normal anatomy. However, there is limited data on the prevalence of EGIDs in children with SBS. We aimed to define the prevalence of EGIDs in an SBS cohort and its association with different risk factors via a retrospective chart review of patients with SBS at Children's National Hospital. The prevalence of eosinophilic esophagitis in our SBS cohort was 10%, eosinophilic gastritis was 4.9%, and eosinophilic enteritis was 4.9%. SBS patients with history of allergy or atopy were more likely to have esophageal and intestinal eosinophilia on biopsy than patients without allergy. The prevalence of EGIDs in our SBS cohort is significantly higher than in the general population and may be associated with allergic polarization.

Twelve-year outcomes of intestinal failure-associated liver disease in children with short-bowel syndrome: 97% transplant-free survival and 81% enteral autonomy.

Our aim was to analyze the outcomes in children with short-bowel syndrome (SBS), parenteral nutrition dependence (PND), and intestinal failure-associated liver disease (IFALD) treated in our Intestinal Rehabilitation Program (IRP) during 2007-2018. We retrospectively reviewed charts of 135 patients with SBS-PND at the time of enrollment in IRP; of these, 89 (66%) had IFALD, defined as conjugated bilirubin (CB) of ≥2 mg/dl at enrollment and/or abnormal liver biopsy showing stage 2-4 fibrosis. Outcomes included resolution of CB, enteral autonomy, laboratory parameters (platelets, aspartate aminotransferase to platelet ratio index), growth trends, transplant rates, and mortality. Of the 89 patients, 74 had elevated CB at enrollment; the other 15 had normalized CB but had fibrosis on liver biopsy. Thirty-eight patients had liver biopsies: 36 (95%) had fibrosis, including 21/36 with bridging fibrosis/cirrhosis. The median proportion of residual small bowel was 23% (interquartile range, 13%-38%) of the expected length for age and median, daily energy requirement by PN was 100%. Two received a transplant, three died (one posttransplant), and the remaining 85 survived; 69 (81%) achieved enteral autonomy. Seventy-three (99%) of the 74 patients with hyperbilirubinemia normalized their CB with medical treatment. In a subset of eight of 89 patients with initial platelet count of <100,000/µl(median 50,500/µl) and median CB of 21 mg/dl, seven achieved CB normalization and had improved platelet count. Overall survival was 97% (censored 96.3%). We demonstrate high transplant-free survival and enteral autonomy rates among children with SBS-IFALD relying on low-dose soybean lipid emulsion.

Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.

Proprotein convertase 1/3 (PC1/3), encoded by the PCSK1 gene, is expressed in neuronal and (entero)endocrine cell types, where it cleaves and hence activates a number of protein precursors that play a key role in energy homeostasis. Loss-of-function mutations in PCSK1 cause a recessive complex endocrinopathy characterized by malabsorptive diarrhea and early-onset obesity. Despite the fact that neonatal malabsorptive diarrhea is observed in all patients, it has remained understudied. The aim of this study was to investigate the enteroendocrine pathologies in a male patient with congenital PCSK1 deficiency carrying the novel homozygous c.1034A>C (p.E345A) mutation. This patient developed malabsorptive diarrhea and metabolic acidosis within the first week of life, but rapid weight gain was observed after total parenteral nutrition, and he displayed high proinsulin levels and low adrenocorticotropin. In vitro analysis showed that the p.E345A mutation in PC1/3 resulted in a (near) normal autocatalytic proPC1/3 processing and only partially impaired PC1/3 secretion, but the processing of a substrate in trans was completely blocked. Immunohistochemical staining did not reveal changes in the proGIP/GIP and proglucagon/GLP-1 ratio in colonic tissue. Hence, we report a novel PCSK1 deficient patient who, despite neonatal malabsorptive diarrhea, showed a normal morphology in the small intestine.

The bacterial communities of the small intestine and stool in children with short bowel syndrome.

Short bowel syndrome (SBS) presents an increasing problem in pediatrics. SBS often results from surgical resection of necrotic bowel following necrotizing enterocolitis or treatment of anatomic gastrointestinal defects. SBS is associated with significant morbidity and mortality, and creates substantial burdens for patients, families, and the health system. Recent reports have demonstrated that the fecal microbiome of children with SBS is significantly different from healthy control and severe intestinal microbial imbalances is associated with poor growth. We hypothesized that children with SBS and adverse clinical features such as PN dependent, shorter bowel length and lack of ileocecal valve would demonstrate more gut dysbiosis compare with the SBS non-PN dependent. An improved understanding of SBS pathogenesis would enhance management and potentially suggest new interventions. We studied microbial communities of SBS and control non-SBS patients from the jejunum, obtained endoscopically or by ostomy aspiration, and stool. We enrolled SBS patients who did and did not require parenteral nutrition (PN), as a surrogate marker for the seriousness of their disease. We studied the microbiota using high-throughput DNA sequencing of 16S rRNA genes and statistical analyses. We found that microbial diversity was significantly greater in jejunal aspirate than in stool samples in SBS patients, unlike non-SBS patients; that SBS patients receiving enteral feeds had greater diversity, and that SBS patients on PN and enteral feeds had lower differences in diversity in jejunal vs. stool samples. We found a trend toward increased diversity in patients with an intact ileocecal valve, and found that certain taxa were more abundant in the certain sample types, and in SBS patients vs. non-SBS patients. SBS patients have lower microbial diversity, especially patients with more severe disease, patients requiring PN, and those lacking an ileocecal valve. SBS patients, particularly those with more complex characteristics, exhibit differences in their intestinal microbiota. Particular individual taxa were over- and under-represented in patients with more unfavorable disease. While diminished diversity and alterations in microbiota composition are likely consequences of SBS, future efforts aimed at increasing microbial diversity and interventions targeting specific microbiota characteristics might constitute a testable approach to ameliorate some clinical SBS clinical consequences.

Autologous intestinal reconstruction: a single institution study of the serial transverse enteroplasty (STEP) and the longitudinal intestinal lengthening and tailoring (LILT).

PURPOSE: To review the effectiveness of the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) operations in a cohort of patients with short bowel syndrome (SBS). METHODS: We conducted a retrospective analysis of children with SBS treated at our institution from 2004 until 2014. Children aged 0 days to 18 years with SBS who underwent autologous intestinal reconstruction were included in the study. RESULTS: Twenty-two SBS patients underwent 31 different lengthening procedures (LP). Seventeen patients underwent their primary lengthening procedures at our institution: 9 (53%) patients underwent a LILT, 7 (41%) underwent a STEP and 1 (6%) had a simultaneous LILT and STEP procedure. 12/22 patients had a second STEP, two had a third STEP and one patient had an intestinal transplantation after the LP. Median intestinal length at the time of surgery was 25 cm (range 12-90 cm). There was no difference in gain of intestinal length after LILT vs. STEP (p = 0.74). Length of stay and initiation of feeds were similar. Serum albumin increased after autologous bowel lengthening (p < 0.001). 50% were weaned off parenteral nutrition (PN) (5/9 of the LILT, 1/7 of the STEP, 1/1 of the combined LILT/STEP). There were no surgical complications or deaths. CONCLUSION: In patients with SBS, LILT and STEP procedures are effective for autologous intestinal reconstruction and enable intestinal rehabilitation.

Ostomy in continuity: A novel approach for the management of children with complex short bowel syndrome.

INTRODUCTION: Despite medical and surgical management, a subset of children with short bowel syndrome (SBS) who have discrepancy between proximal small bowel and distal colon have persistent feeding intolerance. We propose the use of an Ostomy in Continuity (OIC) (Bishop-Koop or Santulli) as a salvage procedure to decompress the proximal bowel while still maintaining maximal intestinal length, in these patients. METHODS: A retrospective chart review of 104 SBS patients identified sixteen patients who underwent an OIC. Measures of reliance on parenteral nutrition (PN), growth, intestinal failure associated liver disease, the rate of central venous catheter infections and enterocolitis were collected. These parameters were compared before and after the placement of OIC in the same patients at a median follow-up period of 24months (range 3-52months). Outcome measures include intestinal autonomy and survival without intestinal and liver transplant. RESULTS: All 16 patients showed significant improvement in their enteral tolerance after OIC. The mean PN caloric requirement decreased from 95% to 21% (p=0.0001). The median weight Z score improved from -1.18 to 0.20 (p=0.0006) and the median height Z score improved from -2.74 to -1 (p=0.0001). The mean conjugated bilirubin decreased from 10.3mg/dl to 0.3mg/dl (p=0.0001) in nine patients with hyperbilirubinemia. There was no decrease in central venous catheter infections (CVCI) but there was a decrease in the rate of enterocolitis. None of the patients required intestinal or liver transplant. There was one minor skin excoriation complication in one patient with a Bishop-Koop stoma. CONCLUSIONS: The application of an ostomy in continuity within a comprehensive intestinal rehabilitation program is a novel approach in the treatment of refractory short bowel syndrome that improves intestinal autonomy and decreases the rate of enterocolitis. TYPE OF STUDY: Case Series. LEVEL OF EVIDENCE: IV (Cohort Study).

Central Line-Associated Mucor velutinosus Bloodstream Infection in an Immunocompetent Pediatric Patient.

We report here the isolation of Mucor velutinosus from multiple blood cultures performed on samples from Broviac catheters and culture of a Broviac insertion-site wound sample from a 6-year-old boy with a history of intestinal failure secondary to chronic intestinal pseudo-obstruction, parenteral nutrition, and jejunostomy tube dependence. Examination of a slide from the culture revealed the presence of wide nonseptate hyphae with sporangiophores, columella, and chlamydospores. The fungal isolate was sent to the National Institutes of Health for further evaluation and was identified as Mucor velutinosus by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and genomic sequencing. The patient was treated successfully with intravenous amphotericin B and prompt removal of his central line. To the best of our knowledge, this is the first case of M velutinosus bloodstream infection in a child without cancer.

Long-term outcomes for infants with intestinal atresia studied at Children's National Medical Center.

OBJECTIVES: Intestinal atresia is a common cause of intestinal obstruction in neonates. The predominant cause of late complications in these children is prolonged dependence on parenteral nutrition (PN). Our aims were to analyze the outcomes for patients with intestinal atresia at our institution, and to see how these changed with the implementation of an intestinal rehabilitation program (IRP). METHODS: This is a retrospective cohort study. The patient population is all children with intestinal atresias (118 patients) treated at our institution from July 2000 to June 2010, 20 of whom became PN dependent. RESULTS: Survival to hospital discharge was 95% for all patients, and 100% for those who had isolated atresia. Twenty of 118 patients (17%) were PN dependent beyond initial hospital discharge. At discharge, their median intestinal length was 22.5 cm, and they required PN for a mean of 88.5% of energy needs. Of these 20 patients, 2 died, 2 received transplants, and 2 transferred away for transplantation. The remaining 14 joined the IRP. Their mean energy requirement from PN is presently 10%, down from 87% at IRP enrollment, and 10 patients fully weaned off PN. Eleven of the 14 children had hyperbilirubinemia, with mean direct bilirubin of 7.5 mg/dL. All resolved their cholestasis during an average of 12 weeks. CONCLUSIONS: These results compare favorably with those reported in earlier periods. With programs such as the IRP, patients with short bowel secondary to intestinal atresia can show improvement in liver function and nutritional parameters, and discontinue PN, avoiding the need for transplantation.

Role of an intestinal rehabilitation program in the treatment of advanced intestinal failure.

OBJECTIVE: To analyze outcomes in children with intestinal failure treated by our Intestinal Rehabilitation Program (IRP) in a 4-year period. PATIENTS AND METHODS: A total of 51 parenteral nutrition (PN)-dependent patients (20 male) were enrolled in the IRP. Median age was 1.7 years, with the primary diagnoses being gastroschisis, necrotizing enterocolitis, volvulus, and congenital atresia. Median small bowel intestinal length was 35 cm, with the majority of patients having only jejunum as remaining bowel anatomy. Thirty-six of the 51 patients had liver disease characterized by cirrhosis, advance bridging fibrosis, and portal and periportal fibrosis. Height, weight z score, platelet count, albumin, and bilirubin levels were measured at the beginning and end of the study. RESULTS: Of the 51 patients, 29 had 46 different surgical intestinal repairs. Twenty-nine of the 36 patients with hyperbilirubinemia had normalized serum bilirubin with treatment. Ten patients required transplantation. Five patients died of sepsis, influenza, or complications after intestinal transplantation. Of the remaining 37 patients in the IRP, 31 were weaned from parenteral nutrition (5 with cirrhosis); 6 patients are in the process of weaning. Survival rate of the patients in the IRP was 90%. Growth has continued along the same curve, and some patients have exhibited significant catch-up. CONCLUSIONS: With an aggressive medical/surgical approach, even patients with intestinal failure and advanced liver disease can avoid transplantation. Patients in the IRP showed improved liver function and nutritional parameters with the ability to discontinue PN while maintaining growth. Early referral of these patients to specialized centers before the development of advanced liver disease is recommended.

Isolated liver transplantation in infants with end-stage liver disease due to short bowel syndrome.

Infants with short bowel syndrome (SBS) and associated liver failure are often referred for combined liver/intestinal transplantation. We speculated that in some young children, nutritional autonomy would be possible with restoration of normal liver function. Features we believed to predict nutritional autonomy include history of at least 50% enteral tolerance, age less than 2 yr, and no underlying intestinal disease. This report documents our experience with liver transplantation alone in children with liver failure associated with SBS. Twenty-three children with SBS and end-stage liver disease, considered to have good prognostic features for eventual full enteral adaptation, underwent isolated liver transplantation. Median age was 11 months (range, 6.5 to 48 months). Median pretransplant weight was 7.4 kg (range, 5.2 to 15 kg). All had growth retardation and advanced liver disease. Bowel length ranged from 25 to 100 cm. Twenty-three children underwent 28 isolated liver transplants. There were 14 whole livers and 14 partial grafts (five living donors). Seventeen patients are alive at a median follow-up of 57 months (range, 6 to 121 months). Actuarial patient and graft survival rates at 1 yr are 82% and 75% and at 5 yr are 72% and 60%, respectively. Four deaths resulted from sepsis, all within 4 months of transplantation, and 1 death resulted from progressive liver failure. Two allografts developed chronic rejection; both children were successfully retransplanted with isolated livers. Of 17 surviving patients, three require supplemental intravenous support; the remaining 14 have achieved enteral autonomy, at a median of 3 months (range, 1 to 72 months) after transplantation. Linear growth is maintained and, in many, catch-up growth is evident. Median change in z score for height is 0.57 (range, -4.47 to 2.68), and median change in z score for weight is 0.42 (range, -1.65 to 3.05). In conclusion, Isolated liver transplantation in children with liver failure as a result of SBS, who have favorable prognostic features for full enteral adaptation, is feasible with satisfactory long-term survival.

Living and deceased donor liver transplantation for unresectable hepatoblastoma at a single center.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The application of living donor liver transplantation (LDLT) in the management of unresectable HB may add new therapeutic opportunities. We evaluated the outcomes of patients who underwent liver transplantation for treatment of unresectable HB in the period between August 1985 and June 2003. Ten children had a diagnosis of unresectable HB. Mean age at transplantation was 5.8 yr. Eight patients were transplanted with deceased donor grafts. Two patients underwent LDLT. Pre-transplant chemotherapy was used in 90% of cases. Post-transplant survival ranges from 3.7 to 18.6 yr. Three patients died of recurrent disease at 4, 14 and 38 months. The two LDLT recipients were able to get pre-transplant chemotherapy with a rapid decision towards transplantation; both are alive and well at 5.5 and 11 yr post-transplant. Our experience supports the role of LDLT and deceased donor liver transplantation in the management of unresectable HB when waiting times can be detrimental to the patient's survival.

A multidisciplinary approach to the treatment of intestinal failure.

Intestinal failure is most commonly treated by the administration of total parenteral nutrition (TPN). In some patients, however, surgical therapy may increase the ability to use the intestine for nutrition and thereby decrease the complications of TPN therapy. A multidisciplinary comprehensive intestinal failure program was initiated at the University of Nebraska Medical Center in October 2000. Here we describe the surgical approaches to patients with short bowel syndrome and the subsequent impact on the need for TPN and on survival. Fifty patients (children=30, adults=20) underwent surgical procedures to restore intestinal continuity (n=5), repair enterocutaneous fistulas (n=5), resect dysmotile or strictured/obstructed bowel segments or mesenteric desmoid tumors (n=7), stricturoplasty (n=2), Bianchi tapering and lengthening (n=20), serial transverse enteroplasty (n=8), and other operations (n=8). Of these 50 patients, three patients did not require TPN after surgical intervention and seven had remnant small bowel anatomy that precluded TPN weaning (e.g., end duodenostomy) and were listed for transplantation or continued on full TPN support. Of the 40 remaining patients, most received the majority of calories from TPN at the time of referral, i.e., mean calories from TPN=90%. Subsequent to the surgical and medical therapy, 26 (65%) have been completely weaned off TPN. In addition, 10 had substantial decreases in their TPN requirements (i.e., from 85% of calories from TPN at onset decreased to a median 35% of required calories at most recent follow-up). Four patients remained on the same amount of TPN support. Four of the seven patients listed for transplantation underwent successful transplantation. Despite the complications of short bowel syndrome, 86% (n=43) of the patients are alive and well at a mean follow-up of 2 years. Patient deaths occurred primarily in those listed or eligible for transplantation and were related to advanced liver disease (n=3), gastrointestinal hemorrhage (n=1), or line sepsis (n=1). Two other patients died, one from influenza A infection and one from unknown cause at home, months after complete discontinuation of TPN. In this series of patients with short bowel syndrome, surgical intervention led to weaning or discontinuation of TPN support in 85% of patients. An organized multidisciplinary approach to the patient with short bowel syndrome is recommended.

Quality of life after pediatric intestinal transplantation: the perception of pediatric recipients and their parents.

The objective was to examine the perception of physical and psychosocial functioning of pediatric intestinal transplant recipients who are beyond the perioperative period and compare these with normal and chronically ill children. Child and parent forms of the Child Health Questionnaire were administered to all 29 pediatric intestinal transplant recipients between the ages of 5 and 18 years who had had a small bowel transplantation 1 year previous and had a functional allograft. Comparison was made with published norms and scores for pediatric patients on hemodialysis. Intestinal transplant recipients (on average 5 years after intestinal transplantation and at a mean age 11 years) reported similar scores in all domains compared with normal children. Parents of intestinal transplant recipients noted decreased function in several domains related to their child's general health, physical functioning, and the impact of the illness on parental time, emotions and family activities. Intestinal transplant recipients beyond the perioperative period perceive their physical and psychosocial functioning as similar to normal school children. Parental proxy assessments differ from the recipients, with the parent's perception of decreased general health and physical functioning for intestinal transplant recipients compared with norms.