Administration of 4% tetrasodium EDTA lock solution and central venous catheter complications in high-risk pediatric patients with intestinal failure: A retrospective cohort study.

BACKGROUND: Selection of central venous catheter (CVC) lock solution impacts catheter mechanical complications and central line-associated bloodstream infections (CLABSIs) in pediatric patients with intestinal failure. Disadvantages of the current clinical standards, heparin and ethanol lock therapy (ELT), led to the discovery of new lock solutions. High-risk pediatric patients with intestinal failure who lost access to ELT during a recent shortage were offered enrollment in a compassionate use trial with 4% tetrasodium EDTA (T-EDTA), a lock solution with antimicrobial, antibiofilm, and antithrombotic properties. METHODS: We performed a descriptive cohort study including 14 high-risk pediatric patients with intestinal failure receiving 4% T-EDTA as a daily catheter lock solution. CVC complications were documented (repairs, occlusions, replacements, and CLABSIs). Complication rates on 4% T-EDTA were compared with baseline rates, during which patients were receiving either heparin or ELT (designated as heparin/ELT). RESULTS: Patients initiated 4% T-EDTA at the time they were enrolled in the compassionate use protocol. Use of 4% T-EDTA resulted in a 50% reduction in CVC complications, compared with baseline rates on heparin/ELT (incidence rate ratio: 0.50; 95% CI, 0.25-1.004; P = 0.051). CONCLUSION: In a compassionate use protocol for high-risk pediatric patients with intestinal failure, the use of 4% T-EDTA reduced composite catheter complications, including those leading to emergency department visits, hospital admissions, additional procedures, and mortality. This outcome suggests 4% T-EDTA has benefits over currently available lock solutions.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Glycemic and sleep effects of daytime compared with those of overnight infusions of home parenteral nutrition in adults with short bowel syndrome: A quasi-experimental pilot trial.

BACKGROUND: Patients with short bowel syndrome (SBS) dependent on home parenteral nutrition (HPN) commonly cycle infusions overnight, likely contributing to circadian misalignment and sleep disruption. METHODS: The objective of this quasi-experimental, single-arm, controlled, pilot trial was to examine the feasibility, safety, and efficacy of daytime infusions of HPN in adults with SBS without diabetes. Enrolled patients were fitted with a continuous glucose monitor and wrist actigraph and were instructed to cycle their infusions overnight for 1 wk, followed by daytime for another week. The 24-h average blood glucose, the time spent >140 mg/dL or <70 mg/dL, and sleep fragmentation were derived for each week and compared using Wilcoxon signed-rank test. Patient-reported quality-of-life outcomes were also compared between the weeks. RESULTS: Twenty patients (mean age, 51.7 y; 75% female; mean body mass index, 21.5 kg/m2) completed the trial. Overnight infusions started at 21:00 and daytime infusions at 09:00. No serious adverse events were noted. There were no differences in 24-h glycemia (daytime-median: 93.00 mg/dL; 95% CI: 87.7-99.9 mg/dL, compared with overnight-median: 91.1 mg/dL; 95% CI: 89.6-99.0 mg/dL; P = 0.922). During the day hours (09:00-21:00), the mean glucose concentrations were 13.5 (5.7-22.0) mg/dL higher, and the time spent <70 mg/dL was 15.0 (-170.0, 22.5) min lower with daytime than with overnight HPN. Conversely, during the night hours (21:00-09:00), the glucose concentrations were 16.6 (-23.1, -2.2) mg/dL lower with daytime than with overnight HPN. There were no differences in actigraphy-derived measures of sleep and activity rhythms; however, sleep timing was later, and light at night exposure was lower with daytime than with overnight HPN. Patients reported less sleep disruptions due to urination and fewer episodes of uncontrollable diarrhea or ostomy output with daytime HPN. CONCLUSIONS: Daytime HPN was feasible and safe in adults with SBS and, compared with overnight HPN, improved subjective sleep without increasing 24-h glucose concentrations. This trial was registered at clinicaltrials.gov as NCT04743960 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04743960).

Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide.

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.

Air Displacement Plethysmography is an Accurate and Feasible Noninvasive Measure of Fat-Free Mass in Children With Intestinal Failure.

BACKGROUND: The nutritional status of children with intestinal failure (IF) can be difficult to determine using body weight and currently available anthropometric techniques. Air displacement plethysmography (ADP) is a noninvasive measure of whole-body composition that measures body mass and volume, with a calculation of percent body fat (%BF) and fat-free mass (FFM) that may be useful during the provision of specialized nutrition. OBJECTIVES: To evaluate the validity and feasibility of measuring body composition in children with IF using ADP compared with deuterium dilution (DD), as well as secondarily with other measures of body composition, namely bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and four-site skinfold anthropometry. METHODS: We conducted a prospective cohort study of 18 children recruited through the Center for Advanced Intestinal Rehabilitation at Boston Children's Hospital. Patients 2-17 years of age with IF dependent on parenteral nutrition (PN) for more than 90 days were included. Spearman rank correlation and Bland-Altman limits of agreement (LOA) analysis were used to compare ADP to 4 alternative measures of body composition. RESULTS: Eighteen children with IF, median age 7.1 [interquartile range (IQR) 5.4-9.3] years, 9 female (50%), and median residual bowel length 31 (IQR 22-85) cm were enrolled. Median PN energy intake was 46 (IQR 39-49) kcal/kg/day. Incomplete bladder emptying lead to invalid measures of DD in 4 subjects. Spearman correlation coefficients for %BF were low to moderate between ADP and DD ( r = 0.29), DXA ( r = 0.62), BIA ( r = 0.50), and skinfold ( r = 0.40). Correlations for FFM were high between ADP and these other measures (range 0.95-0.98). Comparing ADP with DD and skinfold measures, Bland-Altman analysis showed small mean bias (-1.9 and +1.5 kg) and acceptable 95% LOA ranges (10.7 and 22.9 kg), respectively, with larger bias (-10.7 and -7.7 kg) and LOA ranges (38.7 and 45.2 kg) compared to DXA and BIA. %BF by ADP and skinfold thickness were moderately correlated ( r = 0.43) with low bias (-0.2%) but very wide LOA (25.7%). CONCLUSIONS: Body composition via ADP is feasible and valid in children with IF as a measure of FFM but appears less suitable for the measurement of %BF. The technique holds promise as a noninvasive measure of body composition to assess the efficacy of nutritional, medical, and surgical interventions.

Nutritional and medical approaches to intestinal failure.

PURPOSE OF REVIEW: Advances in the field of intestinal failure continue to reduce mortality rates of this complex syndrome. Over the last 20 months (January 2021- October 2022), several important papers were published that relate to the nutritional and medical management of intestinal failure and rehabilitation. RECENT FINDINGS: New reports on the epidemiology of intestinal failure have shown that short bowel syndrome (SBS) remains the most common cause of intestinal failure worldwide in both adults and children. Advances in the provision of parenteral nutrition (PN), the advent of Glucagon-like peptide-2 (GLP-2) analogs, and the development of interdisciplinary centers have allowed for safer and longer courses of parenteral support. Unfortunately, rates of enteral anatomy continue to lag behind these advancements, requiring greater focus on quality of life, neurodevelopmental outcomes, and management of sequalae of long-term PN such as Intestinal Failure Associated Liver Disease (IFALD), small bowel bacterial overgrowth (SBBO), and Metabolic Bone Disease (MBD). SUMMARY: There have been significant advances in the nutritional and medical approaches in intestinal failure, including advances in PN, use of GLP-2 analogs, and key developments in the medical management of this condition. As children with intestinal failure increasingly survive to adulthood, new challenges exist with respect to the management of a changing population of patients with SBS. Interdisciplinary centers remain standard of care for this complex patient population.

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

High Rate of Venous Thromboembolism in Severe Pediatric Intestinal Failure.

OBJECTIVE: To quantify the rate of venous thromboembolism (VTE) in patients with pediatric intestinal failure and identify associated risk factors. STUDY DESIGN: We performed a retrospective cohort study in pediatric patients (<21 years old) with severe pediatric intestinal failure (≥90 consecutive days of parenteral nutrition) secondary to short bowel syndrome who were treated from 2014 to 2021 at an interdisciplinary intestinal rehabilitation program. The primary outcome was the incidence of VTE. Multivariable regression was performed to identify independent clinical predictors of VTE. RESULTS: A total of 263 patients (59.7% male) met the criteria for inclusion. The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days. On univariate analysis, the number of catheter days, number of catheters, and history of central line-associated blood stream infection were associated with VTE. On multivariable logistic regression, a higher number of catheters was an independent risk factor for VTE (aOR, 1.17; 95% CI, 1.06-1.29). Additionally, earlier gestational age was a risk factor for VTE such that every week decrease in gestational age conferred a 9% increased risk of VTE (aOR, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: In this retrospective study, 28.1% of patients with severe pediatric intestinal failure developed VTE; the number of catheters and early gestational age were noted to be independent risk factors for VTE. This high incidence of VTE highlights the need to investigate VTE in pediatric intestinal failure prospectively, including the potential benefit of prophylactic anticoagulation.

Antibiotic Therapy for Culture-Proven Bacterial Overgrowth in Children With Intestinal Failure Results in Improved Symptoms and Growth.

OBJECTIVES: To evaluate symptoms, enteral tolerance, growth, and antibiotic regimens in pediatric intestinal failure (IF) patients after treated with antibiotic therapy for small bowel bacterial overgrowth (SBBO). METHODS: Single-center retrospective review of children 0-18 years with IF with endoscopic cultures demonstrating >10 5 CFU/mL from 2010 to 2017. Symptoms, enteral tolerance, growth, and antibiotic regimens were evaluated at the time of endoscopy and 6 months later. RESULTS: Of 505 patients followed in our intestinal rehabilitation program, 104 underwent upper gastrointestinal endoscopy and 78 had positive duodenal cultures. Clinical data pre- and post-endoscopy were available for 56 patients. Compared to baseline, in the 6 months following targeted antibiotic treatment, children showed significant improvement in emesis or feeding intolerance (58.9% vs 23.2%, P < 0.001), abdominal pain (16.1% vs 7.1%, P = 0.02), high stool output (42.9% vs 19.6%, P = 0.002), and gross GI bleeding (19.6% vs 3.6%, P = 0.003). Mean BMI-for-age z scores increased significantly (-0.03 ± 0.94 vs 0.27 ± 0.82, P = 0.03); however, height-for-age z scores, weight-for-age z scores, and percent of calories from enteral intake were not significantly different after therapy. Antibiotic regimens remained highly variable. CONCLUSIONS: Children with IF and culture-positive SBBO showed significant improvement in symptoms and BMI-for-age z scores after duodenal culture with subsequent targeted antibiotic therapy. Longer follow-up may be needed to detect improvements in linear growth and percent of calories from enteral feeds. Antibiotic regimens remain highly variable. Long-term consequences of chronic antimicrobial therapy, including antimicrobial resistance, remain unknown. Prospective studies focused on standardizing duodenal sampling technique, correlating culture and pathology data, and evaluating antibiotic resistance patterns are needed.

Noninvasive assessment of liver fibrosis in pediatric intestinal failure patients using liver stiffness measurement by Vibration-Controlled Transient Elastography.

PURPOSE: The purpose of this study was to evaluate the diagnostic utility of noninvasive Vibration-Controlled Transient Elastography (VCTE) for assessing liver fibrosis in pediatric intestinal failure (PIF) patients. METHODS: Data from children with severe intestinal failure (≥90 days parenteral nutrition dependence) who underwent liver stiffness measurement (LSM), as measured by VCTE, at our institution between December 2015 and March 2018 were reviewed. LSM was compared to METAVIR fibrosis score (F0-F4) on liver biopsy performed within 1 year of VCTE. RESULTS: Seventy children underwent 75 LSM. Sixty-three patients (38% female) had at least one valid LSM, and 63% had a history of cholestasis (direct bilirubin ≥2 mg/dL). Median (IQR) age at first valid LSM was 4.5 years (2.6, 8.7). Sixteen patients had a liver biopsy. LSM differentiated between METAVIR F0-F1 (n = 6) and F2-F4 (n = 10) with an area under the receiver operating characteristic (AUROC) curve of 0.883 (95% CI: 0.686-0.999). The optimal cut-point derived to predict F2-F4 was an LSM ≥6 kPa (sensitivity 80%, specificity 100%). CONCLUSION: LSM as determined by VCTE can distinguish mild (F0-F1) from moderate/severe (F2-F4) liver fibrosis in PIF. VCTE could allow for serial noninvasive monitoring of liver injury, potentially facilitating timely modifications to hepatoprotective management. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: II.

Long-term outcomes of ultrashort bowel syndrome due to malrotation with midgut volvulus managed at an interdisciplinary pediatric intestinal rehabilitation center.

PURPOSE: The purpose of this study was to describe long-term outcomes of pediatric-onset ultrashort bowel syndrome owing to midgut volvulus managed at an interdisciplinary intestinal rehabilitation center. METHODS: Patients with a history of malrotation and pediatric-onset midgut volvulus causing extensive bowel loss (<20% residual small bowel length expected for postconception age) and treated between 2010 and 2017 were reviewed. Data are expressed as median (IQR). RESULTS: Twenty-three patients had midgut volvulus at age 1 (0-21) day leading to 9 (8-12) percent predicted residual bowel length. Eight (35%) had gastroschisis. Follow-up was 8.5 (6.6-12.2) years from volvulus. Five (22%) patients underwent intestinal/multivisceral transplantation, and all achieved enteral autonomy. Eighteen (78%) patients remained transplant-free, 7 of whom achieved enteral autonomy after 718 (682-1030) days of parenteral nutrition. Transplant-free enteral autonomy was achieved by 0/6 patients with gastroschisis, compared to 7/12 without gastroschisis (p = 0.04). For the overall group, 18 (78%) patients had small bowel bacterial overgrowth, and 7 manifested symptomatic D-lactic acidosis. We observed 2 mortalities, one awaiting transplant and one 4 years following transplantation. CONCLUSION: Midgut volvulus owing to malrotation with extensive bowel loss is associated with favorable long-term survival. Transplant-free enteral autonomy may be feasible, particularly in the absence of gastroschisis. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: IIb, retrospective cohort study.

Essential Fatty Acid Status in Surgical Infants Receiving Parenteral Nutrition With a Composite Lipid Emulsion: A Case Series.

Infants requiring prolonged parenteral nutrition (PN) may receive intravenous (IV) lipid in the form of soybean oil, fish oil, or a composite lipid emulsion (CLE) (i.e., SMOFlipid®). Soybean oil lipid-dose restriction is a popular method of treating and reducing the risk of intestinal failure-associated liver disease (IFALD) that may influence dosing strategies of other IV fat emulsions. Here we present 4 infants receiving PN with SMOFlipid® as their IV lipid source and examine trends in essential fatty-acid status, triglycerides, and dosing strategy. The infants on restricted doses of CLE developed biochemical essential fatty-acid deficiency (EFAD) that resolved with a dosage increase or by transition to a pure fish-oil lipid emulsion. Three of the 4 infants originally prescribed CLE were diagnosed with IFALD and started a pure fish-oil lipid emulsion after treatable causes of cholestasis were excluded. One of the 4 infants presented with hypertriglyceridemia that resolved upon transition to pure fish-oil lipid emulsion. Misapplication of lipid restriction protocols to CLE regimens render infants at risk for EFAD. CLE should be dosed within recommended ranges to prevent EFAD. Restricted protocols warrant close monitoring of essential fatty-acid status in infants receiving prolonged PN, particularly in those with minimal or no enteral intake. Hypertriglyceridemia and cholestasis are known adverse effects of CLE and require monitoring.

Virtual Telemedicine Visits in Pediatric Home Parenteral Nutrition Patients: A Quality Improvement Initiative.

BACKGROUND: Despite being less costly than prolonged hospitalization, home parenteral nutrition (HPN) is associated with high rates of post-discharge complications, including frequent readmissions and central line-associated bloodstream infections (CLABSIs). Telemedicine has been associated with improved outcomes and reduced healthcare utilization in other high-risk populations, but no studies to date have supported effectiveness of telemedicine in pediatric HPN. METHODS: We prospectively collected data on pediatric patients managed at a single HPN program who participated in postdischarge telemedicine visits from March 1, 2014 to March 30, 2016. We excluded patients with a history of HPN and strictly palliative care goals. Univariate analysis was performed for primary outcomes: Community-acquired CLABSI and 30-day readmission rate. RESULTS: Twenty-six families participated in the pilot initiative with median (interquartile range) patient age 1.5 (5.7) years old, diagnosis of short bowel syndrome in 16 (62%), and in-state residence in 17 (55%). Ishikawa (fishbone) diagram identified causes of post-discharge HPN complications. Areas of focus during telemedicine visit included central venous catheter care methods, materials, clinical concerns, and equipment. Compared to historical comparison group, the telemedicine group experienced CLABSI rates of 1.0 versus 2.7 per 1,000 line days and readmission rates of 38% versus 17% (p = 0.03, 0.02, respectively). CONCLUSIONS: Telemedicine visits identified opportunities for improvement for families newly discharged on HPN. In a small cohort of patients who experienced telemedicine visits, we found lower CLABSI rates alongside higher readmission rates compared with a historical comparison group. Further studies are needed to optimize telemedicine in delivering care to this high-risk population.

Interleukin 2 Promotes Hepatic Regulatory T Cell Responses and Protects From Biliary Fibrosis in Murine Sclerosing Cholangitis.

In the multidrug resistance protein 2 (Mdr2)-/- mouse model, low phospholipid bile instigates biliary epithelial injury, sterile inflammation, and fibrosis, thereby recapitulating disease mechanisms implicated in biliary atresia (BA) and primary sclerosing cholangitis. We hypothesize that T lymphocytes contribute to the biliary injury and fibrosis in murine sclerosing cholangitis (SC) and that they are susceptible to suppression by regulatory T cells (Tregs). In juvenile Mdr2-/- mice, intrahepatic CD8+ lymphocytes were expanded, and contraction of intrahepatic Tregs coincided with rising serum alanine transferase and alkaline phosphatase (ALP) levels between days 14-30 of life. Antibody-mediated depletion of intrahepatic CD8+ lymphocytes during that time reduced ALP levels and the expression of osteopontin (Opn), a pro-fibrogenic cytokine. Depletion of intrahepatic Tregs with anti-CD25 antibody between days 7-30 increased intrahepatic CD8+ T cells, Opn expression, and fibrosis. Conversely, expansion of intrahepatic Tregs with interleukin 2/anti-interleukin 2 immune complexes (IL-2c) downregulated hepatic expression of Opn and Tnf, reduced frequency of intrahepatic CD8+ lymphocytes, and diminished biliary injury and fibrosis. Treatment with IL-2c upregulated hepatic Treg expression of CD39, an ectonucleotidase capable of hydrolyzing pro-inflammatory adenosine triphosphate. In vitro, Tregs expressing CD39 suppressed the proliferation of hepatic CD8+ lymphocytes from Mdr2-/- mice more efficiently than those lacking CD39. In infants with BA, infiltration of interlobular bile ducts with CD8+ cells was associated with biliary expression of Opn and its transcription was negatively correlated with mRNA expression of Treg-associated genes. Conclusion: Hepatic CD8+ T lymphocytes drive biliary injury and fibrosis in murine SC. Their proliferation is controlled by hepatic Tregs through the purinergic pathway, which is responsive to IL-2c, suggesting that Treg-directed low-dose Il-2 treatment may be considered as therapy for SC.

High Rates of Positive Severe Combined Immunodeficiency Screening Among Newborns with Severe Intestinal Failure.

PURPOSE: Severe combined immunodeficiency (SCID) screening by T-cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA-CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes. METHODS: Records of infants with severe intestinal failure and available newborn screen results treated at a single center 2009-2016 were reviewed retrospectively. Patients with 1 or more positive SCID screens (<252 TREC copies/µL) were compared with those without positive screens. TREC copies/µL were compared with population norms. RESULTS: Of 70 included infants, 34% had newborn screens with TREC <252 copies/µL, compared with 0.3% of the general population; TREC levels for the cohort were lower than the general population (p<0.001). Of those with positive screens, 42% had prior or subsequent negative screening, 8% had no further workup, and 50% had flow cytometry showing: severe T-cell lymphopenia (absolute CD3+ <1500 cells/mcL) in 8, 3 of whom had TTC7A mutation-associated MIA-CID. Four had CD3+ >1500 cells/mcL. MIA-CID patients had the lowest serum citrulline in the cohort; 4 of the 8 patients with CD3+ <1500 cells/mcL on flow cytometry had newborn screening notable for severe hypocitrullinemia (<3 µM). CONCLUSION: Infants with intestinal failure have lower TREC copies/µL than the general population; one-third had levels concerning for SCID, and 11% were diagnosed with severe T-cell lymphopenia. The clinical implications and etiology of this phenomenon remain unknown, but may be related to hypocitrullinemia.

Home Parenteral Nutrition and Intravenous Fluid Errors Discovered Through Novel Clinical Practice of Reconciling Compounding Records: A Case Series.

Home parenteral nutrition (HPN) and home intravenous (IV) hydration are complex, high-risk life-sustaining therapies for children and adults with severe digestive disorders. HPN compounding errors have the potential to cause serious patient harm. Here we present a retrospective case series at an interdisciplinary pediatric HPN program that includes specialized pharmacists reconciling prescriptions against commercial compounding records. Seven HPN or IV hydration patients were affected by significant errors in anion balance, copper, potassium, sodium, and infusion volume. Outpatient pharmacists' or other clinicians' review of compounding records as part of routine quality assurance process is critical for identifying and preventing errors.

Hepatic MDR3 expression impacts lipid homeostasis and susceptibility to inflammatory bile duct obstruction in neonates.

BackgroundHeterozygous mutations in the gene ABCB4, encoding the phospholipid floppase MDR3 (Mdr2 in mice), are associated with various chronic liver diseases. Here we hypothesize that reduced ABCB4 expression predisposes to extrahepatic biliary atresia (EHBA).MethodsLivers from neonatal wild-type (wt) and heterozygous Mdr2-deficient mice were subjected to mass spectrometry-based lipidomics and RNA sequencing studies. Following postnatal infection with rhesus rotavirus (RRV), liver immune responses and EHBA phenotype were assessed. Hepatic microarray data from 40 infants with EHBA were mined for expression levels of ABCB4.ResultsPhosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased, whereas the PC/PE ratio was decreased in neonatal Mdr2+/- mice compared with wt mice. Following RRV challenge, hepatic expression of IFNγ and infiltration with CD8+ and NK+ lymphocytes were increased in Mdr2+/- mice. Plasma total bilirubin levels and prevalence of complete ductal obstruction were higher in these mice. In infants with EHBA, hepatic gene expression of ABCB4 was downregulated in those with an inflammatory compared with a fibrosing molecular phenotype.ConclusionDecreased expression of ABCB4 causes dysregulation in (phospho)lipid homeostasis, and predisposes to aberrant pro-inflammatory lymphocyte responses and an aggravated phenotype of EHBA in neonatal mice. Downregulated ABCB4 is associated with an inflammatory transcriptome signature in infants with EHBA.