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. A derivation cohort using 4 of 12 IAMs which were available in all participants (percent perforin‐positive and percent granzyme‐positive CD8 cells, absolute number of CD8 cells, soluble interleukin‐2 receptor level) were sufficient to define high (n = 10), medium (n = 15), and low IAM (n = 22) cohorts. High IAM was more frequent among those with indeterminate etiology than those with defined diagnoses (80% versus 20%, P < 0.001). High IAM was associated with higher peak serum total bilirubin levels than low IAM (median peak 21.7 versus 4.8 mg/dL, P < 0.001) and peak coma grades. The 21‐day outcomes differed between groups, with liver transplantation more frequent in high IAM participants (62.5%) than those with medium (28.2%) or low IAM (4.8%) (P = 0.002); no deaths were reported. In an independent validation cohort (n = 71) enrolled in a prior study, segregation of IAM groups by etiology, initial biochemistries, and short‐term outcomes was similar, although not statistically significant. High serum aminotransferases, total bilirubin levels, and leukopenia at study entry predicted a high immune activation profile. Conclusion Four circulating T‐lymphocyte activation markers identify a subgroup of PALF participants with evidence of immune activation associated with a distinct clinical phenotype and liver transplantation; these biomarkers may identify PALF participants eligible for future clinical trials of early targeted immunosuppression.

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Introduction: There are reports that the 12-core template systematic biopsies (SBx) obtained by using software registration machines (e.g., Artemis) have higher cancer detection rates (CDRs) of prostate cancer (PCa) than the standard, freehand 12-core transrectal ultrasound (TRUS)-guided biopsies. The goal of our study is to compare the clinically significant (CS) CDRs of SBx in two independent cohorts who underwent freehand TRUS-SBx alone (Cohort A) or machine-guided SBx as part of a combined MRI-ultrasound (MRI-US) fusion biopsy (FBx) (Cohort B). Materials and Methods: A retrospective review of all patients undergoing prostate biopsies over a 4-year period at the University of Cincinnati Medical Center was performed. CS cancer was defined as having a Gleason score ‡7. MRI-US FBx were obtained by using an Artemis software registration device (ARTEMISÔ, Eigen, Inc., Grass Valley, CA). Statistical significance was considered at p < 0.05. Results: Nine hundred and thirty men underwent SBx (Cohort A: 474, Cohort B: 456). There were no statistical differences between cohort A and B in CS CDRs in the overall population (39.3% vs 33.8%; p = 0.093), biopsy naive patients (40.4% vs 39.8%; p = 0.951), or patients with a prior negative biopsy (22.7% vs 25.0%; p = 0.910). Multivariate logistic regression controlling for age, race, prostate-specific antigen level, prostate volume, abnormal digital rectal exam, and family history of PCa demonstrated comparable CS CDRs, which was maintained when further stratified by prior biopsy history (all patients: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.71-1.38, p = 0.958; biopsy naive: OR 0.79, 95% CI 0.51-1.22, p = 0.291; prior negative biopsy: OR 0.64, 95% CI 0.21-1.75, p = 0.403). Conclusions: Our study did not find a significant difference in the CS CDRs of machine-guided SBx compared with the freehand TRUS-SBx. Unless the SBx is done at the time of FBx, the use of these machines for obtaining SBx only is unlikely to result in any increase of CS CDRs.