Associated Regional and University Pathologists, Inc. (ARUP Laboratories) is a Salt Lake City, Utah-based nonprofit laboratory at University of Utah's Department of Pathology. It is located in the University of Utah Research Park and provides national research lab services. ARUP has 4,000 employees and 65 laboratories.
OBJECTIVES:Laboratory genetic counselors (GCs) in cytogenetics oversee a laboratory stewardship (LS) program to review the appropriateness of incoming test orders, which saves both time and healthcare resources. This is especially important for familial cytogenetic testing performed after proband genomic testing, since appropriate testing methodology may vary between families and among family members. We describe three inappropriate orders for familial cytogenetic testing performed after proband genomic testing that were identified and corrected because of the LS process at ARUP Laboratories. Review of familial testing using an LS program avoids false-negative results in at-risk relatives and shortens the time to provide accurate results, enabling relatives to make informed clinical management decisions. This series highlights the importance of seeking genetic advice prior to submitting familial testing samples and including the proband's test results to help the laboratory confirm the appropriateness of test orders. Structural variants (SVs) are identified by proband chromosome analysis, genomic microarray (GMA), and genome sequencing. Healthcare providers without specialized genetics expertise may not realize that SVs can be cryptic by karyotype or undetectable by GMA (when balanced), and that standard FISH probes may fail to detect SVs due to FISH probe localization not spanning the abnormality, even when the FISH probe is designed to target the patient's condition. This series illustrates the benefits of a routine laboratory LS program for familial cytogenetic testing, particularly when cryptic SVs are involved.
INTRODUCTION:Morphologic evaluation of the peripheral blood smear is critical for diagnosis and ruling out certain hematologic disorders. While air-drying is standard, some laboratories may use heat blocks to expedite drying. Excessive heat may induce morphologic artifacts, but there is a lack of systematic literature on this practice. METHODS:Thirteen residual clinical samples representing normal and pathologic conditions were prepared in triplicate and dried under three conditions: ambient air, 37°C, and 45°C heat blocks. Smears were stained and evaluated by two trained pathology residents using a 100-cell WBC differential, semiquantitative grading of RBC forms (0-3+), and subjective smear quality scoring (0-5). Discrepancies were reconciled after unblinding. RESULTS:Average smear quality was 3.5 (SD 1.1) with no significant difference across drying conditions (p > 0.05). WBC differential counts were unaffected by heat treatment. All diagnostically relevant morphologic findings (e.g., blasts, hypersegmented neutrophils, hereditary RBC forms) were identified in all conditions. However, smears dried at 45°C exhibited spurious morphologic changes, including increased schistocytes (5 cases), spherocytes (5 cases), and elliptocytes (3 cases). CONCLUSIONS:Heat block drying at 37°C yields morphology that approximates air drying but would require internal validation prior to implementation. In contrast, drying at 45°C possibly introduces clinically significant artifacts, risking false-positive interpretations especially for hemolysis. Laboratories should avoid drying at high heat, internally validate any heat block use, and pursue standardized smear preparation protocols to minimize preanalytical variability.
BACKGROUND Pediatric cardiac surgery is associated with systemic inflammation and endothelial dysfunction. Activation of the inflammatory cascade during cardiopulmonary bypass (CPB) causes capillary leak and can lead to effusions. Postoperative chylothorax is a challenging complication of pediatric cardiac surgery and is associated with significant morbidity and mortality. This study aimed to find correlations between biomarkers associated with endothelial dysfunction or systemic inflammation and chylothorax. METHODS 120 pediatric patients undergoing CPB were enrolled between June 2022 and June 2024. Plasma samples were collected at 5 timepoints: prior to the operation, and then 1, 12, 24, and 72 hours after initiation of CPB. Samples were analyzed for neutrophil extracellular traps (NETs), E-selectin, Angiopoietin-2, and a panel of cytokines. Clinical data was collected. RESULTS Of 120 enrolled participants, 9 (7.5%) developed chylothorax. Chylothorax participants were predominantly composed of neonates (78%) and had higher surgical complexity (78%). NETs were higher in participants with chylothorax at 24 and 72 hours after CPB initiation. Angiopoietin-2 showed a trend toward higher levels at 24 and 72 hours, and interleukin-8 was higher at every timepoint sampled after CPB initiation. CONCLUSIONS NETs and proinflammatory cytokines were higher for up to 72 hours postoperatively in participants who developed chylothorax. Inflammatory cytokines had elevated levels beginning at earlier timepoints, followed later by elevated NET levels and a trend towards increased markers of endothelial dysfunction. These findings suggest potential future therapeutic targets for inflammation-mediated chylothorax.
