Clinical Biochemistry[JOURNAL]
Sun
200 papers
Analytical outlier rates for Roche fifth generation cardiac troponin T stat using biotin sensitive and insensitive reagent lots.
Karon BS, Wockenfus AM, Kelly BR … +3 more , Spears GM, Jaffe AS, Donato LJ
Clin Biochem · 2026 Jul · PMID 42401420 · Publisher ↗
INTRODUCTION: We compared analytical outlier rates for cardiac troponin T (cTnT) between biotin sensitive and insensitive testing reagents, and between testing platforms Roche Cobas e411 and e601. METHODS: Plasma samples...
INTRODUCTION: We compared analytical outlier rates for cardiac troponin T (cTnT) between biotin sensitive and insensitive testing reagents, and between testing platforms Roche Cobas e411 and e601. METHODS: Plasma samples from hospitalized patients were tested on a Roche Cobas e411 analyzer using lots of Roche Elecsys Troponin T Gen 5 Stat reagent labelled free of biotin interference at ≤20 ng/mL (biotin sensitive reagent, n = 1997); compared to samples tested on a Roche Cobas e601 analyzer using the same reagent labelled free from biotin interference at ≤1200 ng/mL (biotin insensitive, n = 2555). Samples with measurable cTnT (≥6 ng/L) were aliquoted, re-centrifuged and retested on the same analyzer. Analytical outliers were defined as repeat value that differed from the initial value by a critical difference (CD): where CD = z x 2 x SD, with a z-value of 3.719. RESULTS: The total number of outliers that were observed for the biotin-sensitive reagent on the e411 was 68/1997 (3.4%), compared to 208/2555 (8.1%) on the biotin-insensitive reagent measured on the e601 (p < 0.0001). Outliers were observed in 45 (2.6%) of samples with initial values <100 ng/L using the biotin-sensitive reagent compared to 138 (6.4%) of samples using biotin insensitive (p < 0.0001). Among these samples, outliers with repeat values differing by ≥10 ng/L occurred for 0.8% and 1.3% of samples tested with the biotin sensitive and insensitive reagent, respectively. CONCLUSIONS: cTnT analytical outliers occurred more than twice as often using biotin-insensitive reagent on the Cobas e601 analyzer compared to biotin-sensitive reagent on the Cobas e411.
Evaluation of hemoglobin interference thresholds for chemical urinalysis panels.
Robinson JL, Bharti V
Clin Biochem · 2026 Jul · PMID 42386023 · Publisher ↗
INTRODUCTION: Chemical urinalysis provides rapid analysis of multiple tests simultaneously including glucose, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, pH, specific gravity, protein and hemoglobin. W...
INTRODUCTION: Chemical urinalysis provides rapid analysis of multiple tests simultaneously including glucose, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, pH, specific gravity, protein and hemoglobin. While highly coloured urines may impact readability of urine dipsticks there is no specific data on the effects of visible blood for dipstick analysis. We aimed to evaluate the effect of urinary hemoglobin on 10SG multistix and establish a process for handling visibly bloody urines received in our laboratories. METHODS: In vitro bloody urine pools were made using residual RBCs or leukoreduced RBCs and tested for interference patterns among tests included on the 10SG multistix. We further examined the effect of centrifugation and lysis on bloody urine samples both in vitro and among visibly bloody patient urine specimens. RESULTS: The presence of blood in urine samples caused profound interference for leukocyte esterase, nitrite, protein, glucose, ketones, and urobilinogen. Urine protein was most sensitive to hemoglobin interference at >0.2 g Hgb/L; and clinically significant interference was observed at >1 g Hgb/L with 10SG dipsticks. Bloody patient urines demonstrated similar interference patterns observed in vitro, although some clinical samples were positive for bilirubin. This phenomenon was replicated in vitro after RBC lysis. Centrifugation was not a viable strategy to eliminate interference due to blood. CONCLUSION: Visibly bloody urines are wholly unreliable for chemical urinalysis with 10SG multistix when hemoglobin is >1 g/L. An optimal process was established to withhold results of visibly bloody urines when dipstick hemoglobin is 3+ and protein is >1+ using 10SG multistix.
Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.
Izquierdo-Martínez A, Rubio-Prieto JL, Rodriguez-Rodriguez A … +2 more , Martínez-Martos Z, Delgado-Pecellín C
Clin Biochem · 2026 Jul · PMID 42386022 · Publisher ↗
INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failu...
INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.
Agreement between POC glucose meters and blood gas analyzers varies across ICU patient populations.
Huang Y, Brulé S
Clin Biochem · 2026 Jun · PMID 42379483 · Publisher ↗
BACKGROUND: Point-of-care (POC) glucose meters are widely used in intensive care units (ICUs) for rapid glucose monitoring. However, their accuracy may be affected by pathological and physiological factors in different c...
BACKGROUND: Point-of-care (POC) glucose meters are widely used in intensive care units (ICUs) for rapid glucose monitoring. However, their accuracy may be affected by pathological and physiological factors in different critically ill patients. METHODS: Dataset 1 consisted of a three-year quality assurance (QA) practice (2022-2024) using non-ICU samples. Dataset 2 included paired glucose results from patients in general ICU, cardiac ICU, and neonatal ICU collected over six months (July to December 2024), with measurements obtained within a 20-min interval. Agreement of results between glucose meters and blood gas analyzers (BGAs) was assessed using Deming regression, ISO 15197:2013 criteria, and the Diabetes Technology Society (DTS) Error Grid. RESULTS: In the QA dataset (n = 1476), glucose meter results showed excellent correlation with BGAs (r = 0.9930), with 92.6% (<5.0 mmol/L) and 88.2% (≥5.0 mmol/L) of results meeting ISO criteria. In ICU patients (n = 985), correlation was significantly lower (r = 0.8509), with slightly reduced agreement at higher glucose concentrations (82.5%). Performance varied across ICU populations, with the lowest correlation observed in the general ICU (r = 0.8068). Agreement at critically high glucose levels was markedly reduced in clinical settings compared with QA data (43.2% vs. 74.2%). DTS Error Grid analysis showed that 1.23% of the differences between glucose meters and BGAs fell within moderate- or high-risk zones. CONCLUSIONS: The analytical accuracy of POC glucose meters is significantly reduced in ICU settings and varies among patient populations. Meter performance evaluation should be conducted under real clinical conditions, with particular attention to extreme glucose levels. The performance data should be shared with ICU physicians to support appropriate interpretation of glucose results.
From variability to value: Advancing vancomycin therapeutic drug monitoring toward decision-grade practice through commutability-informed external quality assessment and uncertainty-aware reporting.
Charan LS, Kaur R, G MK … +1 more , Vijayasimha M
Clin Biochem · 2026 Jun · PMID 42379482 · Publisher ↗
BACKGROUND: Persistent inter-laboratory variability in vancomycin therapeutic drug monitoring (TDM) continues to challenge the reliability of exposure-guided dosing despite advances in analytical methods and external qua...
BACKGROUND: Persistent inter-laboratory variability in vancomycin therapeutic drug monitoring (TDM) continues to challenge the reliability of exposure-guided dosing despite advances in analytical methods and external quality assessment (EQA). CONTENT: Building on recent longitudinal evidence demonstrating sustained variability across analytical platforms, this correspondence proposes a practical framework for translating EQA findings into decision-grade laboratory practice. The framework emphasizes three complementary components: (1) transparent reporting of commutability characteristics and limitations of EQA materials, (2) uncertainty-aware interpretation of results in relation to clinically relevant decision thresholds, and (3) standardized reporting of traceability and analytical descriptors to improve interoperability and cross-site comparability. Together, these measures extend EQA beyond retrospective performance assessment toward supporting clinically meaningful interpretation of laboratory results. SUMMARY: Integrating commutability-informed EQA with uncertainty-aware reporting and harmonized reporting standards can strengthen the clinical utility of vancomycin TDM. This decision-oriented approach has the potential to enhance reproducibility, improve confidence in exposure-guided dosing, facilitate harmonization across laboratories, and reinforce antimicrobial stewardship through more reliable therapeutic decision-making.
Response to the letter to the editor: From variability to value: Advancing vancomycin therapeutic drug monitoring toward decision-grade practice through commutability-informed external quality assessment and uncertainty-aware reporting.
Larsson A
Clin Biochem · 2026 Jun · PMID 42364759 · Publisher ↗
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What are the correlates of laboratory productivity in clinical laboratories in the Asia Pacific region?
Badrick T, Jeanette WJT, Rebecca ZH … +1 more , Wong W
Clin Biochem · 2026 Jun · PMID 42349537 · Publisher ↗
BACKGROUND: Benchmarking is a valuable quality improvement activity for any organisation. Peer comparisons for non-analytical processes are difficult in laboratory medicine because of a lack of structured opportunities....
BACKGROUND: Benchmarking is a valuable quality improvement activity for any organisation. Peer comparisons for non-analytical processes are difficult in laboratory medicine because of a lack of structured opportunities. Lab Insights is a Roche program that provides benchmarking across management, operations, and productivity. This paper examines the relationship among physical laboratory automation, IT capabilities, and productivity. METHODS: The anonymous electronic Survey was conducted from 2022 to 2024 in the Asia-Pacific region, including 5089 professionals from across 22 countries. The Survey has been run triennially since 2010, allowing some comparison between years. For statistical modelling, multiple linear regression using ordinary least squares was employed to assess the strength and significance of operational factors, with staff productivity (samples per full-time equivalent (FTE)) as the dependent variable. RESULTS: The surveys from 2019 and 2022 were compared to evaluate engagement, which was found to be high. The automation components most closely associated with productivity increases are sample aliquoting, add-on/rerun, sample quality check/serum indices, and sample delivery automation, in that order. Negative factors impacting productivity include limited space availability, the lack of an aliquoter for all samples, and the need to manually email critical results. CONCLUSIONS: This analysis showed that some IT functionalities are associated with improved productivity, namely turnaround time monitoring for urgent/routine assays, sample rejection rates, automatic reporting of critical results, test billing software, productivity and data export functions. Perhaps a productivity/KPI (key performance indicator) dashboard is also perceived by the survey respondents as significant for improving workflow management and, hence, productivity.
From analytical metrics to clinical impact: Rethinking sigma metrics in the era of EFLM-based specifications.
Baharuddin B, Prawitasari DS, Handayani L
Clin Biochem · 2026 Jun · PMID 42342192 · Publisher ↗
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Utility of biomarkers of ethanol metabolism in differentiating auto-brewery syndrome from alcohol use.
Damianos JA
Clin Biochem · 2026 Jun · PMID 42320708 · Publisher ↗
Auto-brewery syndrome (ABS) is a rare disorder featuring episodes of intoxication caused by intestinal fermentation of dietary carbohydrates into ethanol. This article presents the case of a patient referred for evaluati...
Auto-brewery syndrome (ABS) is a rare disorder featuring episodes of intoxication caused by intestinal fermentation of dietary carbohydrates into ethanol. This article presents the case of a patient referred for evaluation of ABS. He underwent a comprehensive workup which did not support the diagnosis of ABS. Ethanol biomarkers followed throughout his course aided in refuting the diagnosis.
Molecular and biochemical correlates of urinary composition in kidney stone pathogenesis.
Malti, Manna R, Bhargava A
Clin Biochem · 2026 Jun · PMID 42320707 · Publisher ↗
Kidney stone disease is one of the most common urological problems worldwide, with a high rate of recurrence. Even though surgical and medical treatments are available, many patients develop stones again due to underlyin...
Kidney stone disease is one of the most common urological problems worldwide, with a high rate of recurrence. Even though surgical and medical treatments are available, many patients develop stones again due to underlying metabolic and biochemical abnormalities. Among the various factors involved, urinary composition plays a major role in the initiation and progression of stone formation. Changes in urinary levels of calcium, oxalate, phosphate, uric acid, and cystine increase the risk of supersaturation, which leads to crystal nucleation and growth. At the same time, reduced levels of natural inhibitors such as citrate and magnesium further promote crystal aggregation. Urinary pH also significantly influences the type of stone formed by affecting the solubility of different constituents. In addition, renal microstructural factors, including Randall's plaque formation and tubular epithelial injury, contribute to crystal retention and stone development. Understanding the correlation between urine chemistry and stone formation is essential for proper risk assessment and prevention. This review discusses the biochemical mechanisms linking urinary composition with kidney stone formation and highlights its clinical importance in improving patient management and recurrence prevention.
High-value laboratory testing in erectile dysfunction, reduced sexual desire, and suspected hypogonadism: analytical pitfalls and selective biomarker use.
Broul M, Kelbich P, Jizerová A … +3 more , Partlová D, Hujová A, Liegertová M
Clin Biochem · 2026 Jun · PMID 42303206 · Publisher ↗
In men presenting with erectile dysfunction, reduced sexual desire, or suspected hypogonadism, laboratory work-up frequently oscillates between indiscriminate hormone panels and underuse of high-yield metabolic testing....
In men presenting with erectile dysfunction, reduced sexual desire, or suspected hypogonadism, laboratory work-up frequently oscillates between indiscriminate hormone panels and underuse of high-yield metabolic testing. From a clinical biochemistry perspective, the key question is not how many biomarkers can be ordered, but which tests are analytically fit for purpose and likely to change management. This evidence-informed narrative review examines biomarkers commonly used in erectile dysfunction and androgen-deficiency phenotypes, with emphasis on glycemic biomarkers, lipids, testosterone, sex hormone-binding globulin (SHBG), calculated free testosterone, prolactin, thyroid function tests, and selectively indicated estradiol. The review focuses on preanalytical control, assay limitations, interpretative pitfalls, and laboratory stewardship. In most men with erectile dysfunction, the highest-value initial laboratory panel consists of fasting glucose and/or hemoglobin A1c (HbA1c), a lipid profile, and early-morning fasting testosterone, provided recent results are unavailable. Low or borderline testosterone should be confirmed on a second independent early-morning fasting sample before biochemical classification, with attention to assay performance and to SHBG with calculated free testosterone when indicated. Prolactin testing is reserved for selected endocrine phenotypes and must account for medication use, macroprolactin, and the hook effect. Thyroid tests and estradiol should be phenotype driven rather than routine. A selective, analytically robust testing strategy can reduce misclassification, support cardiovascular and endocrine phenotyping, and better align biomarker results with clinically actionable decisions.
Establishment of PCOS-specific prolactin reference intervals to optimize laboratory demand management for macroprolactin screening.
María SF, Sofía DE, Paula TQ … +2 more , Pedro AR, Bárbara FC
Clin Biochem · 2026 Jun · PMID 42289212 · Publisher ↗
BACKGROUND AND AIM: Women with polycystic ovary syndrome (PCOS) often have elevated prolactin serum concentrations. This can lead to unnecessary macroprolactin screening and diagnostic confusion. This study aimed to esta...
BACKGROUND AND AIM: Women with polycystic ovary syndrome (PCOS) often have elevated prolactin serum concentrations. This can lead to unnecessary macroprolactin screening and diagnostic confusion. This study aimed to establish disease-specific prolactin reference intervals in women with PCOS to optimize laboratory demand management. METHODS: A retrospective observational study was conducted between June 2022 and January 2024. Cases of confirmed macroprolactinemia were excluded beforehand. The cohort included 130 women of reproductive age (18-42 years) diagnosed with PCOS according to the 2003 Rotterdam criteria. To ensure cohort homogeneity, only patients presenting with the hyperandrogenic phenotype (biochemical hyperandrogenism) were selected. Exclusion criteria included oral contraceptive use, pregnancy, thyroid dysfunction, chronic kidney disease, and prolactin-elevating medications. Patients in the menopausal transition or with premature ovarian insufficiency (FSH > 25.8 mIU/L) were also excluded from the study. The reference intervals for prolactin serum concentrations were calculated by an indirect method based on laboratory results extracted from the Laboratory Information System (Modulab®) and using the non-parametric percentile method (2.5th and 97.5th). RESULTS: The PCOS-specific reference intervals for serum prolactin concentrations were 132.2-804.1 mIU/L. Compared to the upper reference limit of 637 mIU/L for the general population, implementing this PCOS-specific upper reference limit would have reduced the need for reflex macroprolactin testing from 13.1% (17 cases) to 2.3% (3 cases). CONCLUSION: The newly proposed reference intervals for women with the hyperandrogenic PCOS phenotype apply specifically to premenopausal women aged 18 to 42 years who are not experiencing the menopausal transition. Implementing the reference intervals obtained in this study will significantly improve laboratory demand management by reducing unnecessary reflex testing and facilitating the design of more targeted diagnostic strategies.
Modest sensitivity of 24 h urine free cortisol LC-MS/MS to detect Cushing's disease.
Lithgow KC, Mann JA, Starreveld Y … +4 more , Orton D, Venos ES, Leung AA, Kline GA
Clin Biochem · 2026 Jun · PMID 42235845 · Publisher ↗
PURPOSE: Cushing's disease (CD) is a rare disorder of endogenous hypercortisolism arising from a corticotroph adenoma and is associated with significant morbidity and mortality. Measurement of 24-h urine free cortisol (U...
PURPOSE: Cushing's disease (CD) is a rare disorder of endogenous hypercortisolism arising from a corticotroph adenoma and is associated with significant morbidity and mortality. Measurement of 24-h urine free cortisol (UFC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a recommended first-line screening test. We aimed to evaluate the diagnostic sensitivity of newly established, sex-specific UFC LC-MS/MS reference ranges in a surgical cohort of patients with CD. METHODS: We performed retrospective analysis of adults undergoing pituitary surgery for confirmed CD at a tertiary center between June 2021 and July 2025. All patients met clinical, biochemical, and radiological criteria for CD. UFC was quantified using an accredited LC-MS/MS assay, according to recently published, sex-specific, optimized reference intervals. Sensitivity of both urine volume-corrected (VC-UFC; nmol/day) and uncorrected (U-UFC; nmol/L) reference ranges were assessed. RESULTS: Sixteen patients (UFC measurements: 28 measurements from 13 females and 8 measurements from 3 males) met inclusion criteria; 88% had histologic confirmation of corticotroph adenoma. Sensitivity of any single UFC measure for CD was 78% (95% CI 61% to 90%); 75% for males (95% CI 25% to 97%) and 79% for females (95% CI 59% to 92%) for VC-UFC and 56% (95% CI 38% to 72%); 88% for males (95% CI 47% to 100%) and 46% for females (95% CI 28% to 66%) for U-UFC. CONCLUSION: Despite use of LC-MS/MS and rigorously validated reference ranges, UFC demonstrated only modest sensitivity for detecting CD. These findings underscore the limitations of single UFC as a screening test and support the need for multiple collections and complementary biochemical assessments in suspected CD.
Choosing wisely-directed HFE testing improves diagnostic yield and test utilization in hereditary hemochromatosis.
Nfonsam LE, Hohenadel BA, Pai M … +1 more , Waye JS
Clin Biochem · 2026 May · PMID 42217717 · Publisher ↗
BACKGROUND: Appropriate laboratory test utilization is essential for sustainable clinical and laboratory practice. HFE-associated hereditary hemochromatosis is a common cause of iron overload in individuals of Northern E...
BACKGROUND: Appropriate laboratory test utilization is essential for sustainable clinical and laboratory practice. HFE-associated hereditary hemochromatosis is a common cause of iron overload in individuals of Northern European ancestry and is primarily associated with the p.(Cys282Tyr, C282Y) variant and, less frequently, p.(His63Asp, H63D). In 2019, Choosing Wisely Canada (CWC) recommended restricting HFE genotyping to patients with elevated ferritin and transferrin saturation (>45%) or a documented family history. We evaluated the impact of implementing these criteria at the point of order entry, on test utilization and diagnostic yield. METHODS: We retrospectively compared HFE genotyping data from three years before (June 2019-June 2022) and three years after (June 2022-June 2025) CWC implementation in a tertiary-care molecular diagnostics laboratory. RESULTS: Post-implementation, overall testing volume decreased by 40%. Despite reduced volume, detection of clinically significant genotypes increased substantially: C282Y homozygotes increased from 7.6% to 14.8% (+95%), and C282Y/H63D compound heterozygotes increased from 5.8% to 9.1% (+57%). CONCLUSIONS: Implementation of CWC-based pre-analytical criteria significantly improved diagnostic yield while reducing unnecessary testing. These findings support guideline-directed HFE genotyping as an effective laboratory stewardship strategy in clinical biochemistry and genetics.
Cryoglobulinemia and Cryofibrinogenemia: Ten years of experience and diagnostic perspectives from a large laboratory-based cohort.
Natali P, Debbia D, Napodano C … +6 more , Basile U, D'Ambrosio F, Basile V, Marino M, Mascia MT, Sandri G
Clin Biochem · 2026 May · PMID 42208754 · Publisher ↗
OBJECTIVES: Cryoproteins include cryoglobulins (CG), detectable in serum and plasma, and cryofibrinogen (CF), detectable only in plasma. Although they share clinical features, CG and CF differ in pathogenesis and diagnos...
OBJECTIVES: Cryoproteins include cryoglobulins (CG), detectable in serum and plasma, and cryofibrinogen (CF), detectable only in plasma. Although they share clinical features, CG and CF differ in pathogenesis and diagnostic management. Cryofibrinogenemia remains poorly characterized and likely underdiagnosed. METHODS: We retrospectively analyzed CG tests performed between 2015 and 2024 and CF tests between 2020 and 2024 at the Laboratory of the Public Health Hospital of Modena, evaluating clinical and epidemiological characteristics. RESULTS: Among 10,874 patients tested for CG, 14% were positive: type III (50%), type II (45%), and type I (5%). Mean age at first detection differed significantly between males (60 years) and females (66 years; p < 0.001). Since 2020, male predominance was observed. Cryocrit levels were higher in HCV-positive patients (p < 0.001), with a marked reduction in HCV-related cases and cryocrit values over time. In patients achieving sustained virological response, cryocrit levels were comparable to HCV-negative patients. No temporal differences of cryocrit were observed in HCV-negative cases. In the 2020-2024 cohort (n = 628), CF was detected in 47%. Among 574 patients tested for both CG and CF, cryoprotein positivity was observed in 54%: isolated CF in 70%, combined CF/CG in 23%, and isolated CG in 7%. In systemic sclerosis patients (n = 239), isolated CF was significantly more frequent (p = 0.022; OR = 1.82). CONCLUSIONS: Parallel CG and CF testing improves diagnostic accuracy in cryoproteinemias. CF determination should be systematically included in diagnostic protocols, as CG testing alone may be insufficient in complex clinical scenarios.
Spuriously elevated estradiol due to immunoassay interference in the workup of a suspected ovarian tumor: Diagnostic pitfalls and laboratory workflow recommendations.
Lupoli GA, Polito C, Jannuzzi G … +5 more , Fiorenza M, Marino A, Di Meglio L, Salvatore D, Terracciano D
Clin Biochem · 2026 May · PMID 42203166 · Publisher ↗
BACKGROUND: Falsely elevated estradiol levels due to analytical interference are rare but clinically relevant diagnostic pitfalls, particularly when results suggest an estrogen-producing tumor. CASE PRESENTATION: We repo...
BACKGROUND: Falsely elevated estradiol levels due to analytical interference are rare but clinically relevant diagnostic pitfalls, particularly when results suggest an estrogen-producing tumor. CASE PRESENTATION: We report the case of a 51-year-old woman with markedly increased estradiol concentrations inconsistent with her clinical presentation and hormonal status. Persistently elevated estradiol values, together with imaging findings and concern for granulosa cell tumor, contributed to the diagnostic workup of a suspected estrogen-producing ovarian tumor. Bilateral salpingo-oophorectomy was performed within a multifactorial preoperative assessment; histopathology showed no evidence of malignancy. LABORATORY INVESTIGATION: Postoperatively, estradiol remained markedly elevated despite gonadotropin values consistent with surgical menopause. Re-measurement on an alternative immunoassay platform revealed low postmenopausal estradiol levels, whereas the original competitive chemiluminescent assay continued to show persistently elevated values. Polyethylene glycol precipitation produced a substantial reduction in estradiol concentration, supporting immunoglobulin-mediated analytical interference, most likely due to heterophile antibodies. DISCUSSION: This case highlights the vulnerability of competitive immunoassays to analytical interference, which may paradoxically generate falsely elevated results through signal suppression. Clinical-biochemical discordance should prompt timely communication between clinicians and laboratory specialists, repeat testing, alternative-platform measurement, and targeted interference studies. CONCLUSION: Recognition of analytical interference is essential to prevent misdiagnosis and avoid unnecessary or potentially harmful interventions. We propose a practical diagnostic workflow to support the identification and management of discordant estradiol results in routine laboratory practice.
G6PD activity in pediatric patients with the G6PD Ilesha variant: A case series G6PD Ilesha variant in Pediatric patients.
Robinson KM, McNulty MD, Crews KR … +7 more , Bragg AW, Ribeiro RC, Bertrand KC, Inaba H, Takemoto CM, Geck RC, Haidar CE
Clin Biochem · 2026 May · PMID 42128218 · Publisher ↗
BACKGROUND: Patients with glucose-6-phosphate deficiency exposed to oxidative triggers may develop hemolytic anemia. The G6PD Ilesha variant (NM_001042351.3: c.466G > A p.Glu156Lys) is a rare variant that is currently ca...
BACKGROUND: Patients with glucose-6-phosphate deficiency exposed to oxidative triggers may develop hemolytic anemia. The G6PD Ilesha variant (NM_001042351.3: c.466G > A p.Glu156Lys) is a rare variant that is currently categorized as a WHO Class U allele: decreased G6PD uncertain clinical significance. However, there is conflicting evidence for the pathogenicity of the G6PD Ilesha variant. CASE REPORT: Here we present a case series of four patients with the Ilesha variant, two hemizygous patients and two heterozygous patients for Ilesha. All four patients had normal G6PD activity. The two heterozygous patients were exposed to rasburicase, a high-risk medication in the setting of G6PD deficiency, and neither had hemolytic anemia. CONCLUSION: The classification of the Ilesha variant may need to be reconsidered.
The contribution of patient travel for phlebotomy to the carbon footprint of clinical laboratories.
Naugler C, Church D
Clin Biochem · 2026 May · PMID 42114799 · Publisher ↗
CONTEXT: Healthcare contributes approximately 5% of global greenhouse gas emissions, yet the carbon footprint of clinical laboratory activity has been studied almost entirely from the perspective of laboratory operations...
CONTEXT: Healthcare contributes approximately 5% of global greenhouse gas emissions, yet the carbon footprint of clinical laboratory activity has been studied almost entirely from the perspective of laboratory operations (instrumentation, consumables, freight, and facility energy use). A critical but unmeasured component is patient travel for phlebotomy, which is required for nearly all outpatient laboratory testing. No prior studies have quantified the carbon impact of this travel at a population level. OBJECTIVE: To estimate the annual greenhouse gas emissions associated with patient travel for community phlebotomy in a large metropolitan health system. DESIGN: This population-based analysis used travel distance to phlebotomy clinic to estimate greenhouse gas emissions for 198,883 phlebotomy visits. RESULTS: The mean round-trip distance for a phlebotomy visit was 24.98 km, corresponding to a maximal estimate of 6.235 kg COe emitted per patient trip. Scaled to the Calgary urban population, patient travel for phlebotomy produced up to 7,440 tonnes COe per year, or 5.45 kg COe per capita annually. These travel-related emissions substantially exceed published estimates of laboratory operational emissions (reagents, consumables, analyzer energy use, staff travel, and waste). CONCLUSIONS: Patient travel is a dominant and previously unrecognized contributor to the carbon footprint of outpatient laboratory testing. These findings indicate that laboratory decarbonization strategies must consider not only laboratory operations but also the emissions associated with patient mobility.
Rapid and highly sensitive detection of MYD88/CXCR4 mutations in Waldenström macroglobulinemia by MAS-qPCR: A pilot study.
Kunimune Y, Nishioka M, Namba H … +13 more , Todaka K, Fujii T, Kiso N, Nakahara Y, Shinkawa K, Kumano Y, Kodama M, Ebisui T, Nishimoto R, Okayama N, Suehiro Y, Yamasaki T, Yujiri T
Clin Biochem · 2026 May · PMID 42102951 · Publisher ↗
BACKGROUND: Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma characterized by bone marrow infiltration of tumor cells and IgM monoclonal gammopathy. MYD88 mutations are found in more than 90%...
BACKGROUND: Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma characterized by bone marrow infiltration of tumor cells and IgM monoclonal gammopathy. MYD88 mutations are found in more than 90% of WM patients and CXCR4 mutations in approximately 30-40%. For this reason, MYD88 mutation analysis is particularly important for the definitive diagnosis of WM. Furthermore, the CXCR4 S338* mutation is clinically significant for treatment selection in WM patients, as Bruton's tyrosine kinase inhibitors have been reported to be less effective in patients harboring both MYD88 and CXCR4 mutations. However, there are currently no simple methods available for the simultaneous detection of MYD88 and CXCR4 mutations. OBJECTIVE: This study aimed to evaluate the multiplex allele-specific quantitative PCR (MAS-qPCR) assay we developed that is highly sensitive, inexpensive, and capable of simultaneously detecting these two WM-driver mutations using a single-tube reaction on a universal quantitative PCR instrument. METHOD: We established optimal PCR conditions using plasmid DNA containing MYD88 L265P(T > C) and CXCR4 S338*(C > G) or S338*(C > A) mutations. Using the established method, 12 patient specimens were used for comparison with existing methods. RESULTS: The results demonstrated optimal PCR conditions at an annealing temperature of 64°C for 40 cycles. The detection sensitivity of MYD88 L265P(T > C), CXCR4 S338*(C > G), and CXCR4 S338*(C > A) mutations were 0.1% for all variants. The MAS-qPCR method successfully detected mutations in WM patient samples with high accuracy. CONCLUSION: MAS-qPCR may be a highly sensitive and cost-effective screening method for detecting MYD88 L265P and CXCR4 S338* mutations in WM.
Direct serum biomarkers of liver fibrosis in metabolic dysfunction-associated steatotic liver disease: A scoping review.
Pecoraro V, Nascimbeni F, Gabrielli F … +2 more , Fasano T, Trenti T
Clin Biochem · 2026 May · PMID 42097481 · Publisher ↗
No systematic reviews assessing the accuracy of direct serum biomarkers of liver fibrosis have been published, and the evidence about their accuracy in patients with metabolic dysfunction-associated steatotic liver disea...
No systematic reviews assessing the accuracy of direct serum biomarkers of liver fibrosis have been published, and the evidence about their accuracy in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains controversial. To systematically summarize and assess existing evidence on the accuracy of direct serum biomarkers of liver fibrosis in MASLD, a scoping review was conducted according to the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Three databases were systematically searched up to May 2025 for studies reporting the sensitivity, specificity and area under the curve (AUC) for direct serum biomarkers of liver fibrosis (hyaluronic acid [HA], collagen IV [CIV] and CIV7S, procollagen III N-terminal peptide [PIIIP-NP], laminin [LN], cholylglycine [CG]) in biopsy-confirmed MASLD patients. Narrative synthesis of the evidence was conducted. We included 15 studies (12 cohort and 3 cross-sectional studies), involving 1,389 MASLD patients (39.7% with metabolic dysfunction-associated steatohepatitis [MASH]). HA was the most studied biomarker (14 studies), followed by CIV (10), PIIIP-NP (4), CIV7S (5), LN (2) and CG (1). Most studies reported elevated HA, CIV, CIV7S and LN levels in advanced fibrosis (≥F3), with moderate diagnostic accuracy (AUC 0.7-0.97). PIIIP-NP and CG demonstrated inconsistent results. Significant heterogeneity in populations, assays and fibrosis definitions limited cross-study comparability. Direct serum biomarkers seem promising for non-invasive fibrosis assessment in MASLD, but current evidence is limited. Larger, prospective studies integrating HA, CIV and LN into currently available liver disease diagnostic algorithms are required to assess the feasibility of broad clinical implementation for improved value-based healthcare frameworks.
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