Journal of Applied Laboratory Medicine最新文献

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants demonstrate predilection for different regions of the respiratory tract. While saliva-based reverse transcription-polymerase chain reaction (RT-PCR) testing is a convenient, cost-effective alternative to nasopharyngeal swabs (NPS), few studies to date have investigated whether saliva sensitivity differs across variants of concern.

Methods: SARS-CoV-2 RT-PCR was performed on paired NPS and saliva specimens collected from individuals with acute coronavirus disease 2019 (COVID-19) symptoms or exposure to a COVID-19 household contact. Viral genome sequencing of NPS specimens and Los Angeles County surveillance data were used to determine the variant of infection. Saliva sensitivity was calculated using NPS-positive RT-PCR as the reference standard. Factors contributing to the likelihood of saliva SARS-CoV-2 RT-PCR positivity were evaluated with univariate and multivariable analyses.

Results: Between June 2020 and December 2022, 548 saliva samples paired with SARS-CoV-2 positive NPS samples were tested by RT-PCR. Overall, saliva sensitivity for SARS-CoV-2 detection was 61.7% (95% CI, 57.6%-65.7%). Sensitivity was highest with Delta infection (79.6%) compared to pre-Delta (58.5%) and Omicron (61.5%) (P = 0.003 and 0.01, respectively). Saliva sensitivity was higher in symptomatic individuals across all variants compared to asymptomatic cases [pre-Delta 80.6% vs 48.3% (P < 0.001), Delta 100% vs 72.5% (P = 0.03), Omicron 78.7% vs 51.2% (P < 0.001)]. Infection with Delta, symptoms, and high NPS viral load were independently associated with 2.99-, 3.45-, and 4.0-fold higher odds of SARS-CoV-2 detection by saliva-based RT-PCR (P = 0.004, <0.001, and <0.001), respectively.

Conclusions: As new variants emerge, evaluating saliva-based testing approaches may be crucial to ensure effective virus detection.

Background: Benzodiazepines are commonly prescribed medications frequently linked to instances of abuse and overdose. Historically, FDA-cleared benzodiazepine urine immunoassays cross-react poorly with glucuronidated benzodiazepine metabolites, leading to false negatives. Clinical laboratories have addressed this deficiency by creating laboratory-developed tests (LDTs) that incorporate a beta-glucuronidase hydrolysis step to increase the clinical sensitivity of these assays.

Methods: Performance characteristics of 2 FDA-cleared benzodiazepine urine immunoassays (Benzodiazepines Plus, no glucuronidase and Benzodiazepines II, with glucuronidase; Roche Diagnostics) and a previously described benzodiazepine immunoassay LDT (with glucuronidase) were evaluated using 258 clinical urine specimens. The positive immunoassay cutoff was set at 200 ng/mL of nordiazepam and results were compared to an LC-MS/MS benzodiazepine LDT. Clinical sensitivity, specificity, precision, and immunoassay cross-reactivity were determined for all 3 immunoassays.

Results: The Benzodiazepines II and LDT immunoassays exhibited greater clinical sensitivity (100% and 95.2%) compared to the Benzodiazepines Plus assay (66.7%). Clinical specificity of 100% was observed for all 3 assays. Immunoassay response of the Benzodiazepines II assay was greater across the range of concentrations tested (100-1000 ng/mL) relative to the other immunoassays and was the most sensitive immunoassay for the detection of lorazepam glucuronide.

Conclusions: The Benzodiazepines II immunoassay demonstrated the greatest clinical and analytical sensitivity compared to the Benzodiazepines Plus and LDT immunoassays. The incorporation of beta-glucuronidase was crucial, as the Benzodiazepines II and LDT immunoassays demonstrated superior clinical sensitivity when compared to the Benzodiazepines Plus immunoassay that does not incorporate a beta-glucuronidase hydrolysis step.

Background: Since 2019, modified 2-tiered testing (MTTT) algorithms have been available for the diagnosis of Lyme disease. MTTTs replaced the standard algorithms that utilized enzyme immunoassays and immunoblots with sequential enzyme immunoassays that detect different antigens.

Methods: We compared the performance of serological assays from ZEUS Scientific Inc. and DiaSorin Inc. that are used for the diagnosis of Lyme disease. Serological results were compared with clinical information gathered by chart review.

Results: Percent positive agreement (PPA) and percent negative agreement (PNA) for total immunoglobulin G (IgG)/immunoglogulin M (IgM) (n = 120) were 64% (95% confidence interval 54% to 73%) and 100% (87% to 100%), respectively. PPA and PNA for IgG (n = 93) were 91% (80% to 97%) and 66% (52% to 78%), respectively. PPA and PNA for IgM (n = 93) were 75% (62% to 85%) and 95% (82% to 99%), respectively. Fewer positive total IgG/IgM results confirmed positive for either IgG or IgM for ZEUS compared to DiaSorin. Overall MTTT algorithm interpretation was concordant in 58% (55/95) of samples, and concordance improved when the results were limited to IgM in patients with symptom duration <30 days. Treatment with antibiotics was most strongly associated with IgM positivity.

Conclusions: This analysis highlights differences in the performance characteristics between commercially available diagnostic assays for Lyme disease. Our data suggest that the DiaSorin assays would result in fewer positive total IgG/IgM tests, decreasing the required number of confirmatory IgG and IgM tests. This would potentially lead to fewer patients treated with antibiotics.

Background: The quantitation of glycated hemoglobin (Hb A1c) represents an average blood glucose level for a period of 2 to 3 months for diagnosing, monitoring, and managing diabetes mellitus. Unreliable results are reported when hemoglobin (Hb) variants are present in the sample. Patients are advised to use an alternate method due to the presence of the variant Hb and a reflex test to Hb electrophoresis to obtain precise information about the Hb variant. The present study utilizes x axis values from Hb A1c capillary electrophoresis (CE) to identify clinically significant Hb variants Hb E, S, and D.

Methods: Patient samples (n = 60) that showed a variant peak in the Hb A1c test with an x axis value of 190 to 240 were selected for the study. The migration position of the Hb variant (x axis value) and variant percent of the Hb A1c test were compared with the x axis value and variant percent in the Hb electrophoresis test to presumptively identify the variants. The identity of the variants was confirmed using mass spectrometry (MS).

Results: Out of 60 samples, 20 samples were identified as Hb E (x axis 225-227), 20 samples were identified as Hb S (x axis 210-214), and 18 samples were identified as Hb D-Punjab (x axis 200-201). Two variants with an x axis value of 194 were identified as an α variant Hb Q India using MS. There is an overall negative shift of the x axis (-1 to -13 units) and a lower variant percent (-0.2% to -8.7%) in Hb A1c CE when compared with Hb electrophoresis.

Conclusions: The present study highlights the significance of the x axis value and variant percent to identify clinically significant Hb variants in the Hb A1c CE test.

Background: While the real-world impact of estimated glomerular filtration rate (eGFR) equation change on clinical outcome in a longitudinal cohort setting is limited, external valuation of equation performance should be performed in different population cohorts. This study aimed to compare differential impacts of eGFR values, calculated by 5 equations in a Korean patient population, on clinical outcomes.

Methods: This retrospective longitudinal follow-up cohort study analyzed 23 246 participants with standardized creatinine/cystatin C assay-based laboratory results. The primary exposure was baseline eGFR calculated by 5 different equations including the recently developed 2021 race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Clinical outcomes including all-cause mortality, renal replacement therapy, and albuminuria were analyzed to estimate the hazard ratio of the eGFR on clinical outcomes.

Results: Among the 5 equations, CKD-EPI 2021 with creatinine and cystatin C (CKD-EPI 2021-CrCys) showed an earlier increase in hazard ratios for all clinical outcomes, while CKD-EPI 2012 with cystatin C showed a higher hazard ratio for all-cause mortality at low eGFR. Replacing CKD-EPI 2012 with CKD-EPI 2021-CrCys, 5.4% of patients with mortality and 3.3% of patients who received renal replacement therapy were reclassified to a lower risk stage.

Conclusions: The 2021 CKD-EPI equations were acceptable in a Korean population, with better predictive power for clinical outcomes when compared to previous equations. The updated race-free factors for eGFR calculation improved identification of patients at risk for clinical outcomes.

Background: Clinician-ordered peripheral smear review by pathologist (CPSR) is commonly ordered and has been recommended for decades. However, the clinical utility of this labor-intensive test in the reference laboratory has not been examined. The objective of this study is to assess hematologic abnormalities identified in CPSR orders and to correlate them with complete blood count (CBC) and laboratory-derived smear review (LDSR) in the reference laboratory.

Methods: Two hundred consecutive CPSRs with corresponding CBCs from April 2023 were run by Sysmex® XN-11 analyzers, and their peripheral smears were examined by a board-certified hematopathologist. Hematologic abnormalities of CPSRs were assessed, and the correlation between CPSR and CBC/LDSR was reviewed.

Results: Nearly one-third of CPSRs (29%) had normal peripheral smears and CBCs. The majority of CPSRs showed nonspecific quantitative abnormalities. When compared against CPSR results, LDSR criteria identified 100% of hematologic abnormalities appropriately. Samples that were not flagged for review by LDSR rules were also reviewed (n = 174) to rule out clinically meaningful false negatives. One minor discrepancy (0.6% of cases) of small platelet aggregates was observed in a patient with a reported platelet count of 139 K/uL that was missed by the LDSR process.

Conclusions: In the reference laboratory setting, our findings demonstrate that LDSR adequately detects significant hematologic abnormalities and, therefore, CPSR should be discontinued.

Background: The use of laboratory resources has seen a substantial increase in recent years, driven by automation and emerging technologies. However, inappropriate use of laboratory testing, encompassing both overuse and underuse, poses significant challenges.

Content: This review explores the complex interplay between patient safety, economic, and environmental factors-known as the "triple bottom line" or "3Ps" for people, profit, and planet-associated with inappropriate use of laboratory resources. The first part of the review outlines the impact of inappropriate laboratory testing on patient safety and economic outcomes. Then the review examines the available literature on the environmental impact of laboratory activities. Several practical solutions for mitigating the environmental impact of laboratories are discussed. Finally, this review emphasizes how decreasing unnecessary laboratory testing results in cost savings and environmental benefits, as evidenced by interventional studies, without compromising patient safety.

Summary: The implementation of sustainable practices in laboratories can create a virtuous circle in which reduced testing enhances cost-efficiency, reduces the environmental footprint, and ensures patient safety, thereby benefiting the 3Ps. This review highlights the critical need for appropriate laboratory resource utilization in achieving sustainability in healthcare.