Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones.

Interpreting positive celiac serology in children with new-onset type 1 diabetes.

Objectives: The association of celiac disease (CD) in type 1 diabetes mellitus (T1DM) is well-established, yet variation exists in screening practices. This study measures the accuracy of early screening with tissue transglutaminase Immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) in newly diagnosed T1DM.

Methods: This is a retrospective study of children with T1DM between 2013 and 2019 with early CD screening and follow-up.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Validation of Diagnosis Codes for Low Birth Weight and Small-for-Gestational Age in the Medicaid Analytic Extract Database.

Background: The accuracy of low birth weight (LBW) and small for gestational age (SGA) in administrative healthcare records is crucial for perinatal studies but has few validity studies.

Methods: Using 1999-2010 MAX linked to birth certificates (BC), we identified mother-infant dyads (≥30 days enrollment after delivery, with valid gestational age (GA) and birth weight (BW)). LBW and SGA were identified based on ICD-9-CM codes.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Light-dark shift promotes colon carcinogenesis through accelerated colon aging.

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC.

Cutoff points for handgrip strength in patients with liver cirrhosis: a multicenter study.

Objectives: This study aimed to define handgrip strength (HGS) cutoff points to predict 1-year mortality in adult patients with liver cirrhosis.

Methods: This is an analysis of cohort databases from four reference centers in Brazil. Inpatients or outpatients with cirrhosis and aged ≥18 years were included.

Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study.

Background Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed.

Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.

Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2).

Outcomes for infants with BRUE diagnosed with oropharyngeal dysphagia or gastroesophageal reflux disease: a multicenter study from the Pediatric Health Information System Database.

We aimed to determine the prevalence of gastroesophageal reflux disease (GERD) and oropharyngeal dysphagia as explanatory diagnoses, risk factors for acid suppression treatment, and risk factors for repeat hospital visit in infants hospitalized after brief resolved unexplained event (BRUE) using a multicenter pediatric database. We performed a multicenter retrospective database study of infants admitted with BRUE in the Pediatric Health Information System between 2016 and 2021. Data included diagnostic testing, explanatory diagnoses, treatment with acid suppression, and related repeat hospital visits within 6 months.

Identifying risk factors for vomiting during diarrhea: A secondary analysis of a randomized trial of zinc supplementation.

Objectives: Supplemental zinc during acute diarrhea reduces illness duration but also increases vomiting. In a recent trial, we found that children receiving lower daily doses of zinc (5 mg or 10 mg vs. 20 mg) had lower rates of vomiting with comparable stool output and duration of diarrhea.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Validity of the Diabetic Wound Assessment Learning Tool.

Purpose: The development of the Diabetic Wound Assessment Learning Tool (DiWALT) has previously been described. However, an examination of its application to a larger, more heterogeneous group of participants is lacking. In order to allow for a more robust assessment of the psychometric properties of the DiWALT, we applied it to a broader group of participants.

Secondary bile acid derivatives are contributors to the fecal bile acid pool and associated with bile acid modulating nutrients.

Objective: Accumulation of hydrophobic bile acids is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic bile acids. The impact of diet on secondary bile acid (BA) derivative production has not been determined.

Venous Thromboembolism Occurrence and Association with Gastrointestinal Disorders in Children with Cystic Fibrosis: An Analysis from the TriNetX Research Network Global Multicenter Real-World Dataset.

The purpose of this study is to (1) estimate and compare the prevalence of venous thromboembolism (VTE) in children (age 0 to ≤21) with versus without cystic fibrosis (CF); (2) investigate putative associations between specific gastrointestinal (GI) manifestations and the development of VTE among children with CF. This was a multicenter case-control analysis among patients aged 0 to ≤ 21 years between 2010 and 2020, using the TriNetX Research Network. Data queries included ICD-9/10 (International Classification of Diseases-9th/10th Revision) diagnosis codes.

Childhood-onset inflammatory bowel disease and chronic non-bacterial osteomyelitis: A Swedish nationwide cohort study 2002-2022.

Background And Aims: Nationwide, population-based studies of chronic non-bacterial osteomyelitis (CNO) in patients with childhood-onset inflammatory bowel disease (IBD) are lacking.

Methods: We used nationwide registers to identify all children in Sweden diagnosed with IBD during 2002-2022 and the occurrence of CNO in this IBD cohort and general population non-IBD comparators. To estimate the temporal associations between IBD and CNO we used Cox regression.

Celiac Disease in Children and YouTube: Do the Videos Contain Accurate Information?

Objective: Celiac disease (CD) is a gluten-associated enteropathy whose incidence has been increasing in recent years. Parents whose children are diagnosed with CD search for information about the disease via the internet. YouTube is one of the most frequently used platforms to access information due to the number of users and ease of access.

Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network.

Background And Aims: Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN).

Methods: DILIN cases with MP as a suspected drug were reviewed.

Impact of diagnostic testing on outcomes of children with rumination syndrome.

Objectives: Rumination syndrome (RS) is diagnosed based on clinical criteria with or without diagnostic testing showing characteristic findings on antroduodenal manometry (ADM), high-resolution esophageal manometry (HREM), and multichannel intraluminal impedance-pH testing (MII-pH). The objective of this study was to evaluate the correlation between diagnostic testing and clinical outcomes.

Methods: We conducted a retrospective review of children with RS evaluated at our institution.

The change of alanine aminotransferase distributions among US youths, NHANES 1988-2020.

Objectives: The trend of alanine aminotransferase (ALT), a biomarker of metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease), remains poorly described for the pediatric population because no widely accepted cutoffs are available to categorize ALT value. We described the nuanced changes in the distribution of ALT continuous values.

Study Design: We analyzed the data from 15,702 adolescents aged 12-19 who participated in the National Health and Nutrition Examination Surveys between 1988 and 2020.