CLN - The Sample
A recent study demonstrates a new method for condensing Sigma metrics from hundreds of analyzers into a single metric of assay quality (J Appl Lab Med 2024; doi: 10.1093/jalm/jfad125).
The method produces a broad snapshot that may serve as a baseline for understanding assay performance in the presence of variability in instruments, materials handling, environmental conditions, and reagent lots in labs running Vitros analyzers.
Commercial lab companies use Sigma metrics to highlight the quality of their assays and incorporate observed accuracy, precision, and total allowed error. The higher a process Sigma level, the better its performance. But studies assessing Sigma metrics are limited by a dearth of well-controlled systems. The metric typically runs on a scale of 0−6 but is sometimes higher.
In response, researchers developed an algorithm to extract quality control data and derive the Sigma metric for 115 analytes from sites connected to the Quidel/Ortho E-Connectivity database. The researchers then used results of this process to derive the Sigma metric for each assay.
Of the 115 assays, 68.7%, or 79 assays, achieved a metric of 6 Sigma or better, and 85.2%, or 98 assays, achieved Sigma 5 or better. Troponin, creatinine, high-sensitivity C-reactive protein, procalcitonin, and potassium were among tests key in managing critically ill patients that achieved Sigma metrics of 5 or better. Another important assay, pro B-natriuretic peptide, achieved a Sigma metric of 4.1.
Scores of assay metrics included in the comprehensive metabolic panel were glucose, 5.8; calcium, above 6; sodium, 3.8; potassium above 6; carbon dioxide, 5.2; chloride, 4.4; urea nitrogen, 6; albumin, 4.6; total protein, 5.5, alkaline phosphatase, above 6; alanine aminotransferase, above 6; aspartate aminotransferase, above 6; and bilirubin, above 6.
Because study analyzers are running in working laboratories from around the world, the study can serve as a baseline for understanding the assay performance achieved in the presence of lab-to-lab, instrument-to-instrument, material handling, environmental conditions, and reagent lot variability. The significant number of assays demonstrating high Sigma levels did so despite this variation, the researchers wrote.
Elevated levels of carcinoembryonicantigen (CEA), carbohydrateantigen19-9 (CA19-9), and cancer antigen 125 (CA125) are associated with overall survival in appendiceal adenocarcinoma, according to a recent paper (JAMA Network Open 2024; doi:10.1001/jamanetworkopen.2024.0260).
The three serum tumor biomarkers have been useful for managing gastrointestinal and gynecological cancers. However, information regarding their utility in appendiceal adenocarcinoma is limited.
In response, the researchers conducted a retrospective cohort study on 1,338 patients with a median age of 56.5 years at diagnosis at a single tertiary comprehensive care facility. Just over 80% of patients had metastatic disease. CEA was elevated in 56% of patients, while CA19-9 and CA125 were elevated in 34% and 27% of patients, respectively. Individually, elevation of CEA, CA19-9, or CA125 was associated with worse 5-year survival. Elevated versus normal survival was 81% versus 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9−5.6), 84% versus 92% for CA19-9 (HR, 2.2; 95% CI, 1.4−3.4), and 69% versus 93% for CA125 (HR, 4.6; 95% CI, 2.7−7.8).
Although metastatic tumors had higher levels of all tumor markers, when the researchers restricted their survival analysis to 1,080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were still associated with worse survival (HR for CEA, 3.4; 95% CI, 2.5−4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2−2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4−6.4; P < .001). Tumor grade was not associated with CEA or CA19-9 level, while CA125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 versus 15.0).
Study limitations include its retrospective design, the low number of patients (30% of the cohort) undergoing next-generation sequencing, selective tumor marker test ordering by different physicians, and lack of consideration for patients’ chemotherapy and cytoreductive surgery history.
Despite these limitations, the study highlights the importance of including all three biomarkers in initial workups of patients with the disease, the researchers noted.
A large study identified new genetic factors associated with type 2 diabetes (T2D) and pointed to the value of integrating multi-ancestry genome-wide association study (GWAS) data with single-cell epigenomics to untangle variation in factors that drive the development and progression of the disease (Nature, 2024; doi: 10.1038/s41586-024-07019-6).
T2D is a heterogeneous disease that develops through diverse disease processes and molecular mechanisms that are often specific to cell type.
To characterize the genetic contribution to these processes across ancestry groups, the researchers aggregated GWAS data from 2,535,601 individuals. Of these, 39.7% did not have European ancestry and represented 428,452 T2D cases.
The researchers identified 1,289 independent association signals at genome-wide significance that map to 611 loci. Of these, 145 loci had been previously unreported. The researchers also defined eight nonoverlapping clusters of T2D signals characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells, and enteroendocrine cells.
After building cluster-specific partitioned polygenic scores in an additional 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, the researchers tested their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease, and end-stage diabetic nephropathy across ancestry groups, all of which highlight the importance of obesity-related processes in the development of vascular outcomes.
These findings may help diabetes care throughout the world, the researchers concluded.