Journal of Applied Laboratory Medicine最新文献

Background: Gastrointestinal pathogen multiplex panels (GPPs) can test a single stool specimen for multiple pathogen targets in less than 5 h with some as little as 1 h. Although GPPs have demonstrated rapid and sensitive detection, their increased cost and unclear reimbursement structures have put into question their value and role in the cost-effective management of patients with gastrointestinal infections. We performed a scoping review to identify and systematically map the existing literature regarding the impact of GPPs on immediate, proximal, and distal clinical and healthcare utilization outcomes across healthcare settings.

Methods: Databases were searched from inception until November 22, 2022. Full research articles in English were eligible for inclusion if they included a multiplexed (≥3 targets) nucleic acid amplification testing method and conventional microbiology comparator method performed on clinical samples.

Results: A total of 6027 potential studies were identified. Following title and abstract screening and full article review, 175 studies were included. The most frequently studied GPPs were laboratory-developed tests (LDTs) (34.9%) and the Biofire® FilmArray® Gastrointestinal Panel (22.3%). The majority of these studies were conducted in the inpatient (37.1%), outpatient (28.0%), and emergency department (ED) (14.0%) settings. The most frequently reported outcomes included diagnostic accuracy (69.7%), organism detection (59%), time to diagnosis (12.6%), and antibiotic changes (8.6%).

Conclusion: We identified a paucity of research reporting on proximal and distal outcomes associated with GPP use. Our review highlights the critical need for well-designed studies focusing on downstream clinical and healthcare utilization outcomes to guide meaningful and cost-effective incorporation of GPPs into diagnostic work flows.

Background: The QuidelOrtho TriageTrue® point-of-care (POC) high-sensitivity troponin I (hs-TnI) assay has been previously validated. We aimed to independently verify the assay's analytical performance and concordance with other assays and to verify secondary POC devices.

Methods: Intra-assay precision: 5 whole blood samples spanning the measuring interval were analyzed up to 20 times in succession. Inter-analyzer and inter-lot precision studies were also carried out and a precision curve generated. Hemolysis was assessed by spiking 8 samples with concentrations from 2 to 320 ng/L with hemolysate.Concordance between >200 TriageTrue samples and one other hs-TnI POC and 4 laboratory analyzers was assessed by Pearson correlation and kappa statistics at the limit of quantitation and upper reference limit.Paired measurements from 9 samples between a primary verified device and 8 secondary devices were compared against prespecified difference limits.

Results: Intra-assay precision CVs were 25% and 12.2% at mean concentrations of 2.4 ng/L and 8.5 ng, respectively, and ranged from 2.8% to 15.9% at higher concentrations >10 ng/L. There was minimal interference by hemolysis up to 10 g/L, which exceeded the manufacturer's claim of 1.96 g/L.Correlation coefficients were 0.89 to 0.99 with other assays with the exception of the Roche hs-TnT assay, where it was 0.79. These were similar to the laboratory assays. Of 116 comparisons with 8 secondary analyzers, all fell within acceptable limits.

Conclusions: The TriageTrue assay performed as reported in the package insert. The assay characteristics offer acceptable performance for use within the intended medical settings.

Background: Polymerized immunoglobulins can be difficult to interpret when observed on serum immunofixation electrophoresis (IFE). The use of reducing agents, such as beta-mercaptoethanol (BME), has been instrumental in resolving cases in which the monoclonal protein is unidentifiable due to polymerization. However, this procedure can be inconvenient to laboratories. We therefore investigated the use of immunotyping (IT) to resolve immunoglobulin aggregates as a potential replacement for BME pretreatment.

Methods: Patient samples with paraprotein polymerization were selected from our routine testing and interpretation workflow in the protein immunology laboratory. Identified specimens were subjected to both repeat IFE testing after BME treatment and IT without BME treatment. Results from both types of repeat testing were compared to each other and to patient history if available. IFE was performed on a Hydrasys 2 (Sebia), and IT was performed on a Capillarys 3 Tera (Sebia).

Results: Five patient samples were identified with an aggregate band visible in all IFE lanes. Results of BME treatment with repeat IFE or IT using the original sample were 100% concordant. One patient was determined to have no monoclonal protein, 3 had immunoglobulin M (IgM) lambda monoclonal proteins, and one had an IgM kappa monoclonal protein.

Conclusions: IT was able to successfully identify paraproteins without the use of BME in samples that were difficult to interpret using IFE due to polymerization. This finding suggests that routine protocols for IT can be used in lieu of a secondary protocol and additional resources for BME treatment prior to IFE analysis.

Background: The diagnosis of laryngopharyngeal reflux disease (LPRD) mostly uses invasive techniques. Our aim was to carry out a performance study of noninvasive saliva biomarkers in LPRD patients and to investigate clinical utility.

Methods: The saliva of 201 patients with an LPRD diagnosis was prospectively collected using a Salivette® device. Findings were compared with 35 healthy controls using nonparametric statistics. Biomarker cut-offs were determined with receiver operating curves (ROCs).

Results: The analytical performance study indicated satisfactory performance against biological acceptability goals for bias, imprecision, and total allowable error. The limit of detection (LOD) was evaluated for all biomarkers in the saliva matrix. Results fell within the analytical measurement range for salivary elastase, trypsin, and pH and close to the LOD for cholesterol. The clinical study reported significantly higher salivary pH and elastase and lower cholesterol in LPRD compared to controls (P < 0.05), while salivary trypsin did not differ significantly. Diagnostic cut-offs determined with ROC were salivary elastase >49 µg/mL, salivary pH >7.6, and salivary cholesterol <2.1 mg/dL (<0.054 mmol/L). The combination of salivary elastase with cholesterol gave a positive predictive value of 93% and a negative predictive value of 100% for the diagnosis of LPRD in this study. Salivary total bilirubin, lipase, and pepsin were mostly undetected.

Conclusions: Noninvasive diagnosis of LPRD is possible, based on a single saliva collection, although our cut-offs should be evaluated in further studies. A reproducible analytical protocol has been obtained. Salivary elastase, cholesterol, and pH show clinical utility for the presence of duodeno-gastric reflux in LPRD patients.

Background: The trace element zinc is essential for multiple biological processes and analyzed in suspected cases of deficiency or toxicity. A systematic approach to abnormal results will aid the diagnosis of a patient with low or high zinc concentration in plasma in a more clinically efficient and cost-effective manner.

Content: True zinc deficiency can be attributed to both acquired and inherited causes; however, falsely low concentrations may be obtained through sample timing, during inflammatory states, and in the presence of certain medications and hypoalbuminemia. High concentrations of zinc may be due to fasting, hemolysis, or environmental contamination of blood test tubes. The clinical status and condition of the patient should be considered to allow a targeted investigation to be carried out.

Summary: Diagnostic flow charts have been created to help aid healthcare professionals to investigate the cause of both low and high zinc concentrations where the cause is not immediately apparent. This article provides a set of algorithms to suggest an investigative strategy in cases of unexpected abnormalities in plasma zinc.

Background: Dipeptidyl peptidase 3 (DPP3) is a peptidase released from dying cells. It cleaves proteins in the renin-angiotensin pathway, which can result in hemodynamic instability. At elevated concentrations DPP3 is associated with worse outcomes, particularly in patients with shock. Herein we describe the assay performance of a DPP3 assay (4TEEN4 Pharmaceuticals GmbH) in human plasma.

Methods: DPP3 concentration was measured using the DPP3 immunoluminometric assay (4TEEN4 Pharmaceuticals GmbH) and the signal was read using a luminometer (Berthold Centro LB963). Analytical performance was established for precision, linearity, accuracy, detection limit, analytical specificity, reference interval, kit lot-to-lot comparison, specimen type, and sample stability.

Results: Limit of detection was verified at 1.6 ng/mL in EDTA plasma with a coefficient of variation (CV) of <10%. Precision studies revealed a CV ≤ 6% at 28.5 ng/mL and 59.4 ng/mL and comparability with a manufacturer performed assay was demonstrated between 7.7 and 195.2 ng/mL. An upper 97.5% limit of 22 ng/mL without age or sex associations was verified in healthy donors. The assay was not susceptible to interference from lipemia or bilirubin. However, measured DPP3 concentrations increased linearly with increasing hemolysis. DPP3 concentrations are stable in EDTA plasma for up to 24 h and at least 11 months when stored ambient or at -80°C, respectively.

Conclusions: DPP3 can be measured precisely in EDTA plasma using the immunoluminometric DPP3 assay. Given the potential clinical use of DPP3 in critical care patients, caution should be taken to avoid inducing pre-analytical hemolysis during sample collection.

Background: Allowable total error (ATE) is a quality concept that defines acceptable analytical performance for a clinical laboratory assay. ATE will vary in terms of the amount of error permissible not only between assays but also based on the test setting and the assay's clinical use. In the clinical laboratory, ATE limits are routinely applied, for example, when evaluating new analytical methodology or equipment for patient testing, troubleshooting unacceptable quality control, or in evaluating instrument comparability.

Content: Currently, there are no universally applicable standards for defining the maximum magnitude of allowable error. However, there are several resources available for users to consider when setting ATE limits. Examples include clinical outcomes studies, biological variation of the measurand, state-of-the-art, professional organizations, and requirements set by regulatory agencies and proficiency testing/external quality assessment scheme organizers. Each of these approaches varies in terms of the resulting magnitude of allowable error for the same assay. This review describes these resources in more detail and discusses the strengths and weaknesses of each approach.

Summary: ATE users should be aware of different resources and their limitations before defining acceptance criteria for an assay in their clinical laboratory.