Journal of Applied Laboratory Medicine最新文献

Background: Acute graft-versus-host disease (aGVHD) is a common complication of allogenic hematopoietic cell transplantation (HCT). The aGVHD presymptomatic algorithm is comprised of 2 serum biomarkers, suppression of tumorigenicity 2 and regenerating islet-derived 3-alpha. This test was developed to predict severe aGVHD and 6-month nonrelapse mortality (NRM) in allogeneic HCT recipients.

Methods: The medical records of 223 patients tested with the aGVHD presymptomatic algorithm between January 2020 and June 2024 were retrospectively reviewed. Sensitivity and specificity for the prediction of severe aGVHD (grade III or IV) and 6-month NRM were determined. Logistic regression modeling was used to assess the odds ratios of risk factors for severe aGVHD and 6-month NRM. The likelihood ratio test was used to evaluate whether the addition of the aGVHD presymptomatic algorithm improved model fit.

Results: Severe aGVHD occurred in 8.5% of patients, and 6-month NRM was 7.2%. The aGVHD presymptomatic algorithm demonstrated a sensitivity of 21.1% (95% CI, 8.0%-43.9%) and specificity of 83.3% (95% CI, 77.6%-87.9%) for severe aGVHD and a sensitivity of 43.8% (95% CI, 23.1%-66.8%) and specificity of 85.0% (95% CI, 79.5%-89.3%) for 6-month NRM. The addition of results from the aGVHD presymptomatic algorithm to conventional risk factors did not improve prediction of aGVHD but improved prediction of 6-month NRM.

Conclusions: The aGVHD presymptomatic algorithm was suboptimal for routine clinical use. Further development of predictive aGVHD biomarkers may be required to aid in the management of allogeneic HCT recipients.

Background: Health literacy and numeracy are broad terms that relate to a patient's understanding of their health information. While there is a substantial amount of research on this topic in a general sense as well as in relation to how deficiencies in these skills impact patients' understanding of laboratory results, little is known regarding the extent to which underlying factors, which are impacted by health literacy/numeracy, affect how patients interpret their results. This literature review attempts to shed light on the current literature on this more focused and narrow issue, including recommendations to address these barriers.

Content: To perform this review, the key terms "health literacy AND numeracy," "health literacy AND laboratory results," and "patient understanding of laboratory test results" were searched in the PubMed Central, Health Source: Nursing/Academic Edition, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. After reviewing articles for inclusion and exclusion criteria, a total of 16 articles were included. Major themes from the articles utilized were (a) the impact of the laboratory, (b) factors that affect health literacy and numeracy of laboratory data, and (c) recommendations to improve patient understanding and comprehension of their test results.

Summary: Many factors affect patients' comprehension of laboratory data, such as access to this information, data presentation, and holistic influences. Recommendations for improving patient health numeracy of laboratory information are to improve how data is presented to patients and to increase access to supplemental resources via patient portals.

Background: Rapid, accurate diagnosis in acute and emergent care remains a major challenge, with delays directly impacting patient outcomes. Extracellular vesicles (EVs), nanoscale membranous particles secreted by all cell types and found in virtually all biological fluids, have the potential to transform acute diagnostics as minimally invasive biomarkers. As key intercellular messengers and carriers of biological cargo, EVs reflect the physiological and pathological states of their parent cells. While EV research has largely focused on chronic diseases such as cancer and neurodegeneration, their role in acute pathologies remains under-investigated.

Content: This review describes the current landscape of EVs in laboratory medicine, with a focus on their potential for acute and emergent conditions, including sepsis, stroke, traumatic brain injury, and myocardial infarction. We examine advances in EV isolation and characterization techniques and discuss the unique challenges of implementing these approaches in a clinical setting. In particular, we highlight emerging technologies that aim to address existing barriers, including lack of standardization, long processing times, and limited clinical scalability.

Summary: By summarizing existing knowledge and identifying critical research gaps, this review intends to refocus attention toward EV applications for acute care. As EV-based diagnostics continue to advance, their successful integration into clinical work flows has the potential to significantly transform healthcare delivery, enabling real-time, personalized diagnostics and improving health outcomes across a wide range of settings.

Background: Bicarbonate concentration is widely used to assess acid-base disorders in patients, and the concentration can be directly measured or calculated. When discrepant results between measured bicarbonate (mHCO3-) and calculated bicarbonate (cHCO3-) are observed, it can lead to confusion among clinicians and potential for misdiagnosis. Here we assessed the agreement between cHCO3- from the Radiometer blood gas analyzer and mHCO3- from 3 different chemistry instruments.

Methods: Three institutions that measure bicarbonate using chemistry analyzers from 3 different manufacturers and derive bicarbonate on Radiometer blood gas analyzers participated in this study. De-identified patient data include plasma mHCO3- and blood gas cHCO3- results (arterial and venous) collected within +/- 20 min. Correlations and biases were determined.

Results: Deming regression analysis showed good correlations between cHCO3- and mHCO3-. Bland-Altman analysis revealed the greatest bias between Radiometer and Abbott Architect (-2.63 mmol/L), followed by Siemens Advia (0.49 mmol/L) and Beckman AU680 (-0.45 mmol/L).

Conclusions: This is the first study to compare cHCO3- from the Radiometer blood gas analyzer against mHCO3- results from multiple chemistry analyzers. Our results suggest that the Radiometer blood gas analyzer, Siemens Advia, and Beckman AU680 agree well with each other. However, bicarbonate results may be negatively biased when measured on the Abbott Architect compared with the other methods.

Background: Determination of steroid hormones by mass spectrometry (MS) offers several advantages over immunoassays. Modern MS instruments have high selectivity and sensitivity and permit measurements of several compounds at picomolar concentrations in one sample volume, which is advantageous when conducting biobank studies.

Methods: We developed a LC-MS/MS method for the determination of 17β-estradiol, 17α-ethinylestradiol, estrone, estrone 3-sulfate, estriol, progesterone, testosterone, dehydroepiandrosterone sulfate, aldosterone, cortisone, and cortisol in 300 μL human serum. Samples were subjected to robotized protein precipitation with acetonitrile and liquid-liquid extraction with ethyl acetate/heptane, and the aqueous and organic phases were used to determine conjugated and unconjugated steroids, respectively. The steroids were separated from isobars and compounds with similar mass (M + 2) on a C18 reversed phase column. Ammonium hydroxide was infused post-column to enhance ionization, and ions were measured in multiple reaction monitoring negative and positive mode.

Results: The lower limits of quantification for 17β-estradiol and estrone were 3.6 (0.98 pg/mL) and 2.1 pmol/L (0.57 pg/mL), respectively. For medium concentrations of steroid hormones, total CVs were in the range 2.3% to 10.5%, and accuracies were 97% to 109%. The method was validated in terms of linearity (r2 ≥ 0.9779) and assay recovery (83%-114%), and certified control sera were analyzed. Steroid profiles were obtained in 921 women with a mean age of 56 years (range 44-66 years) from the European Community Respiratory Health Survey.

Conclusions: We developed a selective and sensitive LC-MS/MS method for 11 steroids in human serum. It is suitable for biobank studies.

Background: JAK2, CALR, and MPL mutations are defining features of myeloproliferative neoplasms (MPNs). Molecular testing for variants in these genes is standard of care in the diagnosis of MPNs. A high reimbursement denial rate led to review of ordering practices and test utilization to identify potential areas for optimization, education, or triage to improve laboratory stewardship.

Methods: MPN panel orders placed between January 1, 2023 and December 31, 2023 were analyzed by ordering provider, complete blood count (CBC) values, demographics, test results, and International Classification of Diseases, 10th revision (ICD10) code. Laboratory staff manually review orders prior to testing. Clinical appropriateness was defined as unexplained cytosis or atypical thrombosis.

Results: Orders for 257 unique patients were included for analysis. Most orders were placed by hematology/oncology providers (79.0%). Of orders, 72.8% had a cytosis-related ICD10 code, and 11.7% a thrombosis-related ICD10 code. MPN panel results were negative in 76.3% of patients and positive (pathogenic mutations in JAK2/CALR/MPL) in 13.2%. A χ2 test did not show a statistically significant association between ICD10 category and positive results. Of patients with positive results, 79.4% had thrombocytosis on CBC, but 70.6% had normal or low hemoglobin.

Conclusions: Orders for our institution's MPN panel are generally appropriate and placed correctly. Our findings do not support additional interventions or clinical decision support, utilizing features such as the patient's CBC values or ICD10 codes, as likely to be of significant benefit. The limited reimbursement remains challenging, but we will continue to engage stakeholders to advocate for continued access.

Background: Tacrolimus therapeutic drug monitoring is a routine and critical assay for managing transplant patients. Tacrolimus can be measured from whole blood samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay (IA). LC-MS/MS provides accurate parent drug quantification with minimal metabolite interference but requires expensive analyzers, highly trained staff, and is often a very manual process. Immunoassays offer faster, simpler workflows, but historically have been prone to significant cross-reaction with the drug's metabolites or other therapeutic drugs, leading to a falsely elevated result. Newer immunoassays show promising improvements in specificity.

Methods: Using 73 residual patient samples, we compared our in-house LC-MS/MS tacrolimus assay to the Roche Elecsys® tacrolimus electrochemiluminescence immunoassay on the cobas® e801 analyzer. Comparative analysis was done with Deming regression and Bland-Altman comparison. Linearity, within-individual imprecision, and total imprecision post immunoassay implementation were also evaluated, along with changes and improvements to workflow and turnaround times (TAT).

Results: The Roche Elecsys tacrolimus assay correlated well with our LC-MS/MS method (Deming regression equation: y = 1.004x + 0.4848). The bias was 0.52 ng/mL (an average of 8.1%) as determined by Bland-Altman comparison. When switching to the immunoassay we observed a 42%-51% improvement in TAT across the median, 75th percentile, and 90th percentile.

Conclusions: We observed excellent correlation between the Roche Elecsys tacrolimus assay on an e801 analyzer vs our in-house LC-MS/MS assay, with good precision and linearity across reportable ranges. Changing from mass spectrometry to tacrolimus immunoassay substantially improved our TAT and workflow.

Background: The rise of synthetic cathinones (SC), and in particular 3,4-MDPHP (3,4-methylenedioxy-α-pyrrolidinohexanophenone), is a concerning health threat. This paper represents the most extensive case series on 3,4-MDPHP suspected intoxications to date, offering a detailed analysis of its impact.

Methods: This study presents the analytical findings for 108 hospitalized patients who tested positive for 3,4-MDPHP, out of a total of 465 subjects admitted for suspected new psychoactive substances (NPS) intoxication. Analyses were performed by GC-MS and LC-MS/MS. The potential cross-reactivity of 3,4-MDPHP with the Syva EMIT II Plus urine ecstasy immunoassay is also investigated.

Results: 3,4-MDPHP was detected in 56% of NPS positive cases. A wide range of 3,4-MDPHP concentrations was observed in both blood (1-257 ng/mL) and urine (2-32 250 ng/mL). 3,4-MDPHP was the sole detected substance in 73.1% of cases, while 26.9% involved co-consumption with other drugs of abuse, primarily cocaine. Investigations about 3,4-MDPHP cross-reactivity with Syva EMIT II Plus urine ecstasy demonstrated that unmodified 3,4-MDPHP does not trigger a positive result, but its metabolites seem to be involved in a positive cross-reaction.

Conclusion: This study confirms the high prevalence (108/465) of 3,4-MDPHP in NPS related intoxication cases in our cohort. It is essential for clinical laboratories and emergency departments to be aware of the potential cross-reactivity in ecstasy immunoassay, as this may lead to significant diagnostic errors and misinterpretation of results.