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. 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.

A Comparison of Cancer Detection Rates Between Template Systematic Biopsies Obtained Using Magnetic Resonance Imaging-Ultrasound Fusion Machine and Freehand Transrectal Ultrasound-Guided Systematic Biopsies.

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 (ARTEMIS™, 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.

Racial disparity in the utilization of multiparametric MRI-ultrasound fusion biopsy for the detection of prostate cancer.

BACKGROUND: Black men have significantly higher incidence and are up to three times more likely to die of prostate cancer (PCa) than White men. Multiparametric magnetic resonance imaging-ultrasound fusion biopsy (FBx) has emerged as a promising modality for the detection of PCa. The goal of our study is to identify differences in utilization of FBx between Black and White men presenting with suspicion of PCa. METHODS: We performed a retrospective review of Black and White men who presented with suspicion of PCa and required biopsy from January 2014 to December 2018. Multivariate logistic regression analysis was done to study the influence of race on the utilization of FBx. RESULTS: Six hundred nineteen (Black: 182, White: 437) men were included in the study. Forty-one out of 182 (22.5%) Black men underwent FBx compared with 225/437 (51.5%) of White men (P < 0.001). After adjusting for age, race, prostate-specific antigen level, digital rectal exam, family history of PCa and health insurance provider, Black race was found to be a significant negative predictor of obtaining FBx (OR:0.32, 95% CI: 0.21-0.51, P < 0.001). Black race stayed an independent negative predictor (OR: 0.36, 95% CI: 0.20-0.64, P < 0.001) in the cohort of patients who were biopsy naïve; however, although reduced, there was no significant difference in the cohort with a prior negative biopsy (OR: 0.51, 95% CI: 0.19-1.36, P = 0.179). CONCLUSIONS: Although FBx is a superior modality for early detection of PCa, we found that Black men were less likely to undergo FBx when presenting with PCa suspicion. Further investigation is needed to evaluate if this difference is patient preference or if there are underlying socioeconomic, cultural or provider biases influencing this disparity.