Clinical chemistry and laboratory medicine最新文献

Objectives: Lipoprotein(a) is an atherogenic particle causative of atherosclerotic cardiovascular disease. Novel treatments have been developed that lower lipoprotein(a) to unprecedented levels with cardiovascular outcomes trials ongoing. Many guidelines recommend testing once in the lifetime of everyone, but testing rates remain low. In this study we compare a lipoprotein(a) point of care testing device to laboratory analysers and assess its performance.

Methods: Lipoprotein(a) concentrations on residual patient samples measured on the Randox and Roche assays were compared to a novel point of care device, iProtin. Furthermore, assessment of iProtin performance characteristics were performed, including intra- and inter-assay coefficient of variation and dilutional studies.

Results: Lipoprotein(a) concentrations measured on the Randox and Roche assays showed strong correlation with iProtin. Regression analysis using Passing-Bablock showed the best fits for iProtin based on 58 serum samples were: 1.15 × Randox + 7.28 nmol/L and 1.02 × Roche + 17.54 nmol/L. The R² values for Randox/iProtin and Roche/iProtin were 0.906 and 0.912 respectively. Correlation between Roche and Randox showed Roche=1.15 × Randox - 13.33 nmol/L with an R² value of 0.973. Inter-assay coefficient of variation of the iProtin device showed a day-to-day imprecision over 5 days of 15.5 % (low concentration quality control) and 6.2 % (high concentration quality control). Within day imprecision was 13.2 % (lower concentration patient sample) and 14.3 % (higher concentration patient sample).

Conclusions: Point of care testing could be a complimentary option to laboratory testing of lipoprotein(a), especially in remote areas. It may help (re-)stratify cardiovascular risk and help tailor treatment decisions.

Objectives: Our aim is to determine whether drone transport introduces relevant variability in analytical results and to assess its suitability for integration into routine hospital laboratory operations.

Methods: A two-phase study was conducted. The stability phase involved three sets of samples from 31 healthy volunteers transported by drone, by road, and processed without transport. The pilot phase included paired samples from 104 primary care patients transported by drone and by road. A broad panel of 53 biochemical, hematological and urinary analytes was assessed. Analytical performance was evaluated using mean bias, comparison with reference change values (RCVs) and hemolysis grading.

Results: Most analytes showed minimal differences between transport methods. In the stability study, glucose and MCH in road-transported samples, and lactate dehydrogenase (LDH) and mean corpuscular hemoglobin (MCH) in drone-transported samples, exceeded their respective RCVs, with LDH likely affected by mild hemolysis. In the pilot study, statistically significant differences were observed between transport methods for potassium, exhibiting a bias of -1.7 % (-2.6 to -0.8 %). Hemolysis was slightly more frequent in drone samples during the stability study but comparable in the pilot study.

Conclusions: Drone transport preserved the analytical integrity of a comprehensive test panel and has the potential to reduce logistical constraints. These findings support its implementation as a reliable and sustainable alternative to conventional transport in clinical laboratory settings.

Objectives: Dried blood spot (DBS) sampling enables convenient at-home blood collection, suitable for patients needing regular check-ups, such as those receiving testosterone replacement therapy (TRT). This study assessed the feasibility and reliability of DBS sampling for monitoring testosterone concentrations in patients undergoing TRT, aiming to provide a convenient at-home alternative to venipuncture.

Methods: Twenty healthy volunteers (12F/8M) and 56 male patients (n=59 samples) receiving TRT were included. Blood was collected parallel by venipuncture (reference) and patient-performed finger prick (DBS) following instruction materials and additional verbal guidance from the andrology consultant. Feasibility and patients' experience were evaluated through questionnaires. Testosterone concentrations in both serum and DBS were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: In healthy volunteers, serum and DBS testosterone concentrations were highly correlated (y=-0.021 + 0.66x; r=0.99). For patients receiving intramuscular testosterone undecanoate, this correlation was strong (y=1.3 + 0.54x; r=0.87). However, DBS samples from patients using testosterone gel showed extremely elevated testosterone levels compared to serum, likely due to local contamination. Most healthy volunteers and in general all patients preferred at-home DBS-sampling over venipuncture at the hospital when regular check-ups are necessary, citing convenience and reduced travel time.

Conclusions: At-home DBS sampling is a feasible and reliable method for monitoring testosterone in patients treated with intramuscular testosterone undecanoate, improving patient comfort and convenience. However, DBS sampling at-home is currently unsuitable for patients using testosterone gel, likely due to contamination issues. Comprehensive patient education on collection of DBS samples is crucial to ensure high-quality DBS and accurate testosterone quantification.

Objectives: Complement inhibitor pegcetacoplan binds to C3 and its activation product C3b. Pegcetacoplan has been approved for the treatment of paroxysmal nocturnal hemoglobinuria. Because pegcetacoplan exerts broad inhibition of the complement cascade its efficacy is also investigated in numerous other diseases caused by complement dysregulation, such as C3 glomerulopathy. Pegcetacoplan causes a number of counterintuitive changes in laboratory results.

Methods: In-depth complement analysis in two patients with PNH and three patients with C3 glomerulopathy, all treated with pegcetacoplan.

Results: C3 levels increase up to 300 % above reference levels. In vitro testing showed that this is not a turbidimetric artifact in the C3 immunoassay due to pegcetacoplan-C3 complex formation but appears to be caused by increased half-life of C3 bound to pegcetacoplan. Unbiased mass spectrometric plasma proteome analysis confirmed the dramatic pegcetacoplan-induced increase in circulating C3. Surprisingly, also a three-fold increase of properdin was observed during pegcetacoplan treatment. Serum protein electrophoresis showed an additional band in all patients after pegcetacoplan exposure. This C3-band does not migrate at its expected position because of changes in the mass and charge of C3 bound to pegcetacoplan and should therefore not be misinterpreted as an M-protein. Both in vitro experiments and real clinical practice laboratory results demonstrated that pegcetacoplan completely blocked the alternative complement pathway while the classical pathway is affected but remains largely intact.

Conclusions: Because of the increasing use of pegcetacoplan in routine clinical practice, it is important that both clinicians and laboratory specialists are aware of these unexpected therapy-induced laboratory findings.

Objectives: Serum protein electrophoresis is one of the keystone investigations for screening for monoclonal proteins and assessing the serum protein profile. The newly released Helena V8ultra capillary electrophoresis system has been evaluated.

Methods: In total, 164 serum samples were assessed on the Helena V8 UltraCE system and compared with the Sebia Capillarys™ instrument. Abnormalities suggestive of monoclonal proteins were confirmed by immunosubtraction. Imprecision studies intervals were determined. Special attention was paid to complement C3 polymorphism.

Results: The imprecision of the Helena V8ultra was inferior or equal from 0.73 % (albumin) to 4.32 % (alpha₂ globulin). The mean bias of Helena V8ultraCE vs. Sebia Capillarys was about -0.225 % for albumin; -0.791 % for alpha₁ globulins; 1.353 % for alpha₂ globulins; -2.317 % for beta globulins; 0.066 % for gamma globulins. Among the 6 samples with monoclonal proteins confirmed by immunofixation, all were seen on both methods, with only 1 discordant result. The theoretical plate number (albumin fraction) was 2,371 ± 718 (Helena V8UltraCE) vs. 445 ± 115 (Sebia Capillarys 2). The high resolution also allows to distinguish Complement C3 phenotypes. CV values for the various fractions were low, ranging from 0.47 % (albumin) to 0.89 % (gamma globulins). IgG, IgA and IgM M-proteins could be detected in the electropherogram with an excellent sensitivity (<0.1 g/L).

Conclusions: Our evaluation confirms the good analytical performance of the Helena V8 analyzer as a suitable alternative to the Sebia Capillarys instrument. The high resolution allows detailed analysis of individual protein fractions which is an excellent basis for studying microheterogeneity.

Objectives: The performance of a novel urine particle analyzer, fluidlab 2 (Anvajo GmbH, Dresden, Germany), was evaluated against phase-contrast visual microscopy according to the most recent EFLM European Urinalysis Guideline.

Methods: The fluidlab 2 device combines digital holographic microscopy with neural network-based object detection for particle classification. Its compact benchtop design is suitable for bedside use, reducing turnaround times. The analytical performance (imprecision, linearity, LoQ) was evaluated according to the 2023 EFLM Urinalysis Guideline. Method comparison involved the analysis of 450 urine samples, assessing RBC, WBC, and SEC counts against visual microscopy using Passing-Bablok regression and Spearman's correlation. Bland-Altman plots were used to evaluate the agreement with clinical performance standards, while weighted Cohen's kappa was used to measure diagnostic agreement on an ordinal scale.

Results: By applying Dahlberg's procedure, a desirable relative coefficient of variation R(CV) ≤2.0 was obtained for RBC and WBC. Linearity of up to 7 × 10⁶/L and 6 × 10⁶/L was achieved. The estimated LoQ at CV=30 % reached 20 × 10⁶/L for RBC and 5 × 10⁶/L for WBC. Spearman's correlation coefficient against visual microscopy was 0.86, 0.92 and 0.94 for RBC, WBC and SEC, respectively. Agreement with visual microscopy (Cohen's weighted kappa) was 0.92 for RBC, 0.93 for WBC, 0.96 for SEC, 0.86 for casts, 0.82 for non-SEC, 0.33 for crystals and 0.51 for bacterial counts.

Conclusions: Fluidlab 2 provides desirable imprecision for RBC and WBC, and meets the criteria for linearity and LoQ. Cohen's weighted kappa coefficients show an optimal comparison to visual microscopy for RBC, WBC and SEC and a minimum comparison for casts and non-SEC. This evaluation demonstrated promising results for the use of the fluidlab 2 analyzer in a clinical setting to detect kidney-related diseases based on urine particle analysis.

Agentic artificial intelligence (AI) systems are distinguished by their ability to invoke multiple tools, compose command chains, and combine chain-of-thought reasoning with deep research to execute complex tasks and take actions. This represents a major evolution beyond machine learning and large language models (LLM), toward systems capable of planning, executing, and coordinating complex workflows. In contrast to traditional LLMs, which primarily focus on generating and classifying information, agentic AI introduces elements of autonomy, reasoning, and orchestration, while digital twins extend this concept to dynamic virtual representations of patients and laboratory processes, capable of continuous learning, simulation and adaptation. This transition has profound implications for laboratory medicine, a field characterized by high data complexity, multi-omics integration, and stringent operational demands. At the same time, laboratories face growing expectations regarding efficiency, resource stewardship, and value-based healthcare delivery. This article explores both the opportunities and limitations of agentic AI in laboratory medicine, highlighting its potential to move beyond static automation toward autonomous, outcome-driven innovation. It also examines the ethical, interpretability, and governance considerations that must accompany its implementation.

Objectives: The Kappa Index has proven its diagnostic value for multiple sclerosis (MS), while its prognostic potential remains to be fully explored. The objective of this study is thus to investigate the value of the Kappa Index at disease onset in predicting disease activity and high-efficacy therapy (HET) initiation.

Methods: We enrolled MS patients with available Kappa Index values at disease onset and a follow-up of at least two years. Primary outcome was the time to loss of NEDA3 (no evidence of disease activity-3) defined as the absence of relapses, MRI activity, and disability progression. Secondary outcome was the time to HET initiation.

Results: Of 120 enrolled patients (36 M, 84 F, mean age: 35 ± 11 years), NEDA3 loss occurred in 89 (74 %) by the end of the follow-up period. A total of 98 (82 %) initiated a moderate efficacy therapy (MET); of these, 34 (28 %) transitioned to a HET during follow-up. Kappa Index values above the maximally selected log-rank statistic-derived cut-off of 38 were independent risk factors for NEDA3 loss (HR 1.75, 95 % CI: 1.09-2.80, p=0.021) and HET initiation (3.25, 95 % CI: 1.54-6.87, p=0.002) and also independently predicted HET following MET failure (2.54, 95 % CI: 1.17-5.51, p=0.018).

Conclusions: Elevated Kappa Index values at diagnosis predict disease activity, MET failure and HET initiation and may be a valuable adjunctive tool in identifying patients in need of prompt HET initiation.

Objectives: Compare Elecsys (Roche) and Simoa (Quanterix) immunoassays for serum glial fibrillary acidic protein (GFAP) using our reference database and Z scores, and evaluate their prognostic value for progression independent of relapse activity (PIRA) in multiple sclerosis (MS).

Methods: Platform correlation was assessed in 612 samples from healthy controls (n=188; median [interquartile range, IQR] age 45.1 [36.4-61.7] years) and people with MS (n=424; 45.3 [35.2-53.9] years). Elecsys values were converted to Z scores via Passing-Bablok-derived regression and validated in fingolimod (n=414), and B-cell depleting therapy (BCDT; n=353) cohorts. Z scores and hazard ratios (HRs) for time-to-PIRA were compared using Cox regression.

Results: GFAP_Simoa and GFAP_Elecsys measurements were correlated (r=0.94), with Elecsys values ∼54 % lower (GFAP_Elecsys, ng/L=2.847 [95 % confidence interval, CI: 1.335 - 4.98] + 0.457 [0.434 - 0.478] * GFAP_Simoa, ng/L). In univariable Cox models, GFAP_Simoa and GFAP_Elecsys Z scores were associated with time-to-PIRA in both validation cohorts. In multivariable Cox models, higher GFAP_Simoa Z scores were associated with shorter time-to-PIRA in fingolimod cohort (HR: 1.27 [95 % CI 1.08 - 1.50], p=0.0031) and trended toward significance in BCDT (1.18 [0.99 - 1.41, p=0.0693). In contrast, GFAP_Elecsys Z scores were associated with time-to-PIRA in both cohorts (fingolimod: 1.27 [1.09 - 1.48], p=0.0023; BCDT: (1.19 [1.00 - 1.40], p=0.0487).

Conclusions: Serum GFAP measured by Elecsys shows a comparable association with time-to-PIRA as Simoa, and GFAP_Simoa Z scores can be successfully bridged to GFAP_Elecsys Z scores, supporting Elecsys`s potential for clinical implementation.

Objectives: Despite standardization efforts, significant inter-assay variability persists among prostate-specific antigen (PSA) tests, impacting prostate cancer (PCa) diagnosis and monitoring. We aimed to evaluate the analytical and clinical performance of the newly developed Atellica IM high-sensitivity PSA (hsPSA Atellica) assay compared with established PSA assays.

Methods: A total of 236 serum samples from healthy individuals and patients with or without PCa were analyzed using the hsPSA Atellica assay and four FDA-approved PSA assays: Hybritech Access, Architect, Atellica, and Cobas. Analytical performance included limit of detection (LOD), limit of quantification (LOQ), linearity, inter-assay precision, and hook effect. Method comparison was performed using Passing-Bablok regression, Bland-Altman analysis, and kappa index concordance.

Results: The hsPSA Atellica assay demonstrated a LOD of 0.01 μg/L and LOQ of 0.028 μg/L (CV: 3.2 %, accuracy: 115 %). Precision was maintained across concentrations, with CVs of 4.2 %, 3.8 %, and 2.4 % at low, medium, and high levels of PSA. Strong agreement was observed with the compared tests, particularly with Cobas and Hybritech PSA assays. Diagnostic sensitivity and specificity at the 4 μg/L clinical decision threshold were 98 % and 35 %, respectively. In 87 samples between 3 and 10 μg/L, concordance between hsPSA Atellica and Hybritech reached 96.6 % (κ=0.82). The assay remained accurate up to PSA concentrations of 13,311 μg/L, showing minimal hook effect.

Conclusions: The hsPSA Atellica assay shows excellent analytical sensitivity and strong agreement with established assays. To our knowledge, this is the first published evaluation of this assay, supporting its clinical utility in both PCa diagnosis and follow-up.