Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.

Objective: Extremely premature infants are treated with acetaminophen (APAP) for pain and patent ductus arteriosus. High doses of APAP in adults are toxic, and a recent study found an association between APAP metabolite levels in mothers' breast milk and both bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in their premature infants. In this study, we determined levels of APAP metabolites in urine of infants at high risk for BPD and ROP.

Hepatitis B Virus Treatment in Children: Common Challenges and Management Options in a Case-Based Format.

The management of hepatitis B virus (HBV) in pediatrics presents many challenges, given the potential sequelae of untreated infection including hepatic fibrosis, cirrhosis, and malignancy, and a lack of clear guidance on the timing of treatment initiation. The goal of this review is to feature common clinical scenarios that occur in the evaluation and treatment of HBV infection in children. Each vignette presents an opportunity to discuss guidelines and evidence-based practices as well as review landmark studies and evolving practices.

Identification of pediatric activated T-cell hepatitis using clinical immune studies.

Background And Aims: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group.

Methods: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022.

"Where Did This Come From?": Antibiotic Prophylaxis in Biliary Atresia After Kasai Procedure.

For patients with Biliary atresia, antibiotic prophylaxis after Kasai portoenterostomy is a common practice. Societal guidelines often cite one reference as supportive evidence for this practice. In this paper, we go back to review the quality of this evidence and suggest more research is required to demonstrate the efficacy of antibiotic prophylaxis in this population.

Immunosuppression minimization is safe and associated with good long-term success in pediatric recipients of liver transplant.

Immunosuppression reduction after liver transplant is an important strategy to mitigate long-term medication side effects. We describe our center's experience with immunosuppression minimization to once-daily calcineurin inhibitor dosing. Success was defined as continuing daily calcineurin inhibitor monotherapy with normal transaminases and no rejection.

The Urinary Metabolomic Fingerprint in Extremely Preterm Infants on Total Parenteral Nutrition vs. Enteral Feeds.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential for sustaining premature infants until they transition to enteral feeds, but there is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born <29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status.

Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.

A distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We aimed to evaluate the peripheral blood T-cell phenotype in PALF patients with activated T-cell hepatitis compared to indeterminate cause.

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure.

There has been a recent surge in cases of pediatric acute hepatitis and pediatric acute liver failure (PALF) of unknown cause. Several reports have described clusters of these children who were positive for adenovirus (AdV) DNA, primarily in peripheral blood but some in liver tissue. We tested archived liver tissue specimens from a historical cohort of 44 children with PALF who were enrolled in a multicenter biorepository between 2007 and 2014 for AdV 40/41 using quantitative polymerase chain reaction.

The hydrocortisone-responsive urinary metabolome of premature infants.

Background: Extremely premature infants are at risk for circulatory collapse or respiratory failure that are often treated with hydrocortisone (HC); however, there is no information on the metabolic consequences of this therapy.

Methods: Longitudinal urine samples from infants <28 weeks gestation in the Trial of Late Surfactant were analyzed by untargeted UHPLC:MS/MS. Fourteen infants who received a tapering course of HC beginning at 3 mg/kg/day for ≥9 days were compared to 14 matched control infants.

Fluid balance in pediatric postoperative liver transplant recipients.

Background: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients.

Methods: We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital.

RNA-Sequencing Analysis Identifies Etiology Specific Transcriptional Signatures in Neonatal Acute Liver Failure.

Objective: To assess hepatic transcriptional signatures in infants with gestational alloimmune liver disease (GALD) compared with other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF.

Study Design: Neonates with ALF (international normalized ratio ≥2 within 30 days of life) and deceased neonates without liver disease (<30 days of age) with available liver tissue between 2010 and 2021 were identified at Ann & Robert H. Lurie Children's Hospital of Chicago.

Heart rate variability is associated with encephalopathy and outcomes in pediatric acute liver failure.

Background: More than half of children with pediatric acute liver failure (PALF) experience hepatic encephalopathy (HE), which is related to poor outcomes; however, HE is difficult to diagnose in children. The objective of this study was to evaluate if heart rate variability (HRV), a continuous measure of autonomic nervous system function, was related to the presence and severity of HE as well as clinical outcomes in children with PALF.

Methods: We conducted a retrospective observational cohort study of 38 critically ill children with PALF to examine the association between HRV and HE severity and clinical outcome.

An Update on Pediatric Acute Liver Failure: Emerging Understanding of the Impact of Immune Dysregulation and Novel Opportunities for Intervention.

Pediatric acute liver failure (PALF) is a complex, unpredictable, often rapidly progressive, potentially devastating clinical syndrome that occurs in infants, children, and adolescents without pre-existing liver disease. PALF is characterized by acute onset of hepatocellular injury and liver-based coagulopathy, frequently accompanied by hepatic encephalopathy. Etiologies include drug and toxin exposures, metabolic and genetic disorders, infections, and immune-mediated disease.

Characterization and within-site variation of environmental metal concentrations around a contaminated site using a community-engaged approach.

Historic industrial activity led to extensive lead and arsenic contamination within residential areas of East Chicago, Indiana, United States. Although remediation is underway, community concerns about this contamination remain. Therefore, the goal for this analysis was to characterize environmental contamination in soil within and around these areas.

Severe Hepatitis in Pediatric Coronavirus Disease 2019.

Hepatic involvement in coronavirus disease 2019 (COVID-19) is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of four previously healthy children who presented with significant hepatitis as the primary manifestation of COVID-19 infection.

Transcriptional Analysis of Liver Tissue Identifies Distinct Phenotypes of Indeterminate Pediatric Acute Liver Failure.

Many patients with indeterminate pediatric acute liver failure (PALF) have evidence of T-cell driven immune injury; however, the precise inflammatory pathways are not well defined. We have characterized the hepatic cytokine and transcriptional signatures of patients with PALF. A retrospective review was performed on 22 children presenting with indeterminate (IND-PALF; n = 17) or other known diagnoses (DX-PALF; n = 6) with available archived liver tissue.

Blood metabolomics in infants enrolled in a dose escalation pilot trial of budesonide in surfactant.

Background: The pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain.

Methods: In a pilot dose escalation trial, we administered ≤5 daily doses of budesonide in surfactant to 24 intubated premature infants (Steroid And Surfactant in ELGANs (SASSIE)).

What Historians of Medicine Can Learn from Historians of Capitalism.

After briefly surveying the New History of Capitalism and its objectives, this article explores ways that the history of medicine and the history of capitalism can productively interact. The article argues that historians of medicine should adopt a broad definition of "capitalism" to accommodate the distinctive nature of medical and health care markets. Across millennia and diverse cultures, medical markets have demonstrated extensive commodification, with spiritual or religious goods and services composing a significant portion of commercial trade.

A Laterally Vibrating Lithium Niobate MEMS Resonator Array Operating at 500 °C in Air.

This paper reports the high-temperature characteristics of a laterally vibrating piezoelectric lithium niobate (LiNbO; LN) MEMS resonator array up to 500 °C in air. After a high-temperature burn-in treatment, device quality factor () was enhanced to 508 and the resonance shifted to a lower frequency and remained stable up to 500 °C. During subsequent in situ high-temperature testing, the resonant frequencies of two coupled shear horizontal (SH0) modes in the array were 87.

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome.

Background: Infants born at extremely low gestational age are at high risk for bronchopulmonary dysplasia and continuing lung disease. There are no early clinical biomarkers for pulmonary outcome and limited therapeutic interventions.

Objectives: We performed global proteomics of premature infant tracheal aspirate (TA) and plasma to determine the composition and source of lung fluid proteins and to identify potential biomarkers of respiratory outcome.

Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.

Objectives: In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis.

Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure.

Background And Aims: Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome.

Approach And Results: Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8 ) lymphocytes and subjected to unsupervised hierarchical analyses.