Clinical chemistry and laboratory medicine最新文献

Objectives: Quantitation of plasma amino acids (AA) is critical for the diagnosis and monitoring of inherited disorders of AA metabolism. AA analysis using ion-exchange chromatography (IEC) with post-column ninhydrin derivatization is time consuming, with run times of ∼2 h, limiting sample throughput. Liquid chromatography mass-spectrometry can potentially address some of the current challenges.

Methods: Performance of components of the Waters Kairos Amino Acid Kit using liquid chromatography single quadrupole mass-spectrometry (LC-MS) following derivatization of samples with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQ•Tag™ Ultra Derivatization Reagent) was evaluated. Results were compared with the Biochrom-IEC method using patient specimens (n=115), ClinChek^® control and external quality assessment (EQA) material.

Results: The kit reagents and our developed method had a 19-min analysis time, demonstrated acceptable inter-assay imprecision (CV<10 %) and bias vs. IEC-method (overall mean bias <2 %). Excellent correlation (concordance correlation coefficient (CCC) >0.99) with IEC was demonstrated for 10/23 analytes, good correlation (CCC >0.95) for 10/23, with the remaining three amino acids (aspartate, histidine and tryptophan) demonstrating moderate concordance (CCC ≥0.90 but <0.95). 1/23 AAs had a mean bias >10 % using EQA material. The method demonstrated a lower limit of quantitation of ≤2.5 μmol/L for all AA, making this assay suitable for CSF analysis. Calibration stability bias was <5 % over 12-weeks. Derivatized AAs were stable for ≤17 days. The analytical column supplied demonstrated good retention time stability (<0.4 %) and was capable of >2000 injections.

Conclusions: The tested methodology demonstrated good analytical performance and correlation with IEC. This approach confers practical advantages over IEC, including analytical selectivity and workflow time efficiency.

Under the Age-Friendly Health System initiative, "What Matters" is defined as knowing the older adult's specific health outcome goals and care preferences. This involves multiple settings of care (e.g., hospital, skilled nursing facility, outpatient visits) and can include end-of-life care. However, the establishment of testing frequency criterion and the development of wide-scale diagnostic algorithms are often left undefined in older adults with poor prognosis and/or shortened life expectancy. Thus, multidisciplinary development of Geriatric 5M-informed optimization plans at the institution level and quality improvement strategies within the laboratory community may further the successful implementation of age-friendly efforts. While patients, end-users, and systems can attribute to implementation barriers, the development of an evidence-base wherein laboratory expertise is directly associated with patient outcomes is vital. Thus, a concentrated, cooperative age-friendly approach centered on What Matters may present a sustainable strategy for early transformation. Future research centered on piloted interventions on the laboratory's role in older adult care and end of life diagnostic management is needed.

Since several years, sports authorities, including national anti-doping organisations and the World Anti-Doping Agency (WADA) have published that the consumption of food supplements can be at risk for athletes due to potential contamination by prohibited substances. Despite these warnings, supplements are largely used by elite athletes and doping violations involving supplements are weekly reported in the media. Anabolic steroids, selective androgen receptor modulators (SARMs), metabolic modulators, stimulants and diuretics are among the most frequently detected substances in contaminated supplements. The author was involved in 2 cases where trimetazidine was identified as the source of the doping violation but the sport authorities sentenced both athletes. Case 1: trimetazidine in urine at 0.1 ng/mL; trimetazidine negative in 3 × 2 cm hair segments (LOQ at 1 ng/g [pg/mg]); trimetazidine at 4 ng/tablet in the supplement. Case 2: trimetazidine in urine at 0.1 and 1.6 ng/mL on 2 occasions; trimetazidine negative in 6 × 1 cm hair segments (LOQ at 1 ng/g [pg/mg]); trimetazidine at 7.2 μg/tablet in the supplement. Despite all pharmacological parameters were consistent with minute amounts of trimetazidine intake during a scenario of proven contamination, the presence of trimetazidine in the urine samples was recognized as an anti-doping rule violation and the athletes were sanctioned with a period of ineligibility of 6 months. From a forensic perspective, contamination is not doping. To avoid these conflicting issues with contaminations, the debate should move to the interest of using hair test results and the need of implementing a threshold for reporting the presence of a drug in urine at very low concentration.

Objectives: The diagnostic accuracy of presepsin (P-SEP) in the newborn is still under evaluation.

Methods: In a multicenter study, we studied the accuracy of P-SEP as a diagnostic marker of late-onset sepsis (LOS) in critical newborns with underlying disorders, to define the most accurate cut-off to distinguish infected from uninfected patients.

Results: Sixty-nine/351 newborns without infections at admission developed LOS. The median P-SEP value at T0 (admission) was 518.0 ng/L (IQR 313.0-789.0), without significant differences related to underlying diseases (p=0.52). In neonates who developed LOS, P-SEP increased at the onset of infection (T1) (median: 816.0 ng/L) and after 24-48 h (median: 901.0 ng/L) compared with their value at admission (median: 560.0 ng/L) (p<0.01 and p=0.03, respectively). The area under the ROC curve at T1 was 0.71 (95 % CI 0.65-0.78) when all cases of sepsis were included in the analysis and increased to 0.74 (95 % CI 0.66-0.81) considering only confirmed sepsis. Approximately two-thirds of patients were correctly classified, setting the cut-off at 713 ng/L, with a negative predictive value of 89.0 %.

Conclusions: At a cut-off of 713 ng/L, P-SEP has good accuracy in diagnosing LOS in critically ill newborns. In uninfected newborns, the median value of P-SEP is not influenced by any underlying pathology.

Objectives: Diagnosing monoclonal gammopathy in chronic kidney disease (CKD) patients is challenging due to the complex interpretation of serum free light chain (FLC) levels. This study aimed to assess the FLC levels in a large cohort of Chinese CKD patients.

Methods: We enrolled 5,287 patients with all-cause nondialysis CKD from three medical centers between February 2018 and April 2023. Central 95 % reference ranges were established using data from one center and validated in an independent subpopulation from the other two centers. The crude prevalence of light chain monoclonal gammopathy of undetermined significance (LC-MGUS) was assessed against established norms for the entire cohort and subgroups based on estimated glomerular filtration rate (eGFR).

Results: A notable proportion of patients exceeded the standard reference limits for kappa (89.0 %), lambda (72.1 %), and FLC ratio (10.5 %), whereas non-eGFR-based renal reference interval identified only 0.3 % with abnormal FLC ratios. The iStopMM reference ranges showed higher out-of-range rates for absolute FLC levels in patients with preserved kidney function and lower rates in those with impaired kidney function, while the FLC ratio references remained robust across all groups. The crude prevalence of LC-MGUS was 10.4 % using standard ranges, predominantly kappa LC-MGUS (99.8 %). This prevalence decreased to 0.3 % with non-eGFR-based renal reference interval and 0.5 % with the iStopMM ranges. Using the newly established reference ranges, the crude prevalence was found to be 0.9 %.

Conclusions: Our findings suggest that current FLC reference ranges are inadequate for the Chinese population, underscoring the need for eGFR-based reference ranges tailored to this demographic.

Introduction: To analyze the available evidence about the correlation between the presence of detectable amounts of clostebol metabolites in urine and the transdermal or transmucosal contact of clostebol.

Content: A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases. Criteria for including studies were clinical studies reporting: (i) adult subjects; (ii) detection of urine clostebol metabolites derived from transdermal or transmucosal contact of clostebol.

Summary: Seven papers pertinent to our questions were found: 3 case reports, one experimental study and 3 case reports with an experimental section for a total of 32 subjects. The median concentration of urine clostebol's metabolite 4-chloro-androst-4-en-3α-ol-17-one, M1 was 0.5 ng/mL (range 0.086-4.000 ng/mL; 25%-75 % IQ: 0.5-0.9 ng/mL) and 8.1 ng/mL (range 1.0-36.6 ng/mL; 25%-75 % IQ: 2.8-22.0 ng/mL), in subjects with indirect and direct exposure of clostebol, respectively (p=0.005).

Outlook: We found consistent data that the detection of M1 in urine can be reconcilable with a transdermal or transmucosal contact of clostebol. In the cases of indirect exposure, the urine concentrations of M1 seem to be far lower than the concentrations found in case of direct exposure.

Objectives: Cardiac biomarkers are useful for the diagnostic and prognostic assessment of myocardial injury (MI) and heart failure. By measuring specific proteins released into the bloodstream during heart stress or damage, these biomarkers help clinicians detect the presence and extent of heart injury and tailor appropriate treatment plans. This study aims to provide robust biological variation (BV) data for cardiac biomarkers in athletes, specifically focusing on those applied to detect or exclude MI, such as myoglobin, creatine kinase-myocardial band (CK-MB) and cardiac troponins (cTn), and those related to heart failure and cardiac dysfunction, brain natriuretic peptide (BNP) and N-terminal brain natriuretic pro-peptide (NT-proBNP).

Methods: Thirty athletes participated, providing monthly fasting blood samples over 11 months. Samples were analyzed using chemiluminescent immunoassays and statistical analyses were conducted using the classical ANOVA method, a linear mixed model and a Bayesian approach.

Results: The study observed significant gender differences in biomarker concentrations, with higher BNP and NT-proBNP in females and higher myoglobin and CK-MB in males. Physical activity within 24 h before sampling notably affected CK-MB, myoglobin, and hs-cTnI variability. The BV estimates demonstrated high individuality for most biomarkers, suggesting their potential for personalized monitoring. The study also revealed substantial heterogeneity for NT-proBNP and BNP within the population.

Conclusions: These findings underscore the importance of considering gender-specific reference intervals and the impact of recent physical activity when interpreting cardiac biomarkers in athletes. The study delivers new BV estimates for CK-MB and myoglobin while emphasizing the need for tailored clinical assessments in athlete populations.

Objectives: The aim of the study was to evaluate the predictive value of cell population data (CPD) parameters in comparison with procalcitonin (PCT) and C-reactive protein (CRP) for an early diagnosis of sepsis in intensive care unit (ICU). The effect of renal function on CPD, PCT and CRP, in septic and non-septic patients was also investigated.

Methods: This is a retrospective, observational and single-center study, performed with data collected from patients consecutively admitted to the ICU of the Edoardo Bassini Hospital in Milan. Patients were divided in septic and non-septic according to Sepsis-III criteria. The control group was formed by critically ill patients without sepsis. Patients with sepsis were further divided in patients with sepsis and patients with septic shock.

Results: A significant difference between septic and non-septic patients was found for neutrophils complexity (NE-SSC), neutrophils fluorescence intensity (NE-SFL), width of dispersion of neutrophils fluorescence (NE-WY), monocytes complexity (MO-X), monocytes fluorescence intensity (MO-Y), PCT and CRP parameters. PCT, neutrophils sixe (NE-FSC), NE-WY, width of dispersion of neutrophils size (NE-WZ) and MO-X discriminated sepsis and septic-shock patients. CPD parameters were not influenced by renal function. CPD, PCT and CRP had a heterogeneous diagnostic performance efficiency in the prediction of sepsis. Overall, NE-SSC, NE-SFL, width of dispersion of neutrophils complexity (NE-WX), MO-X, MO-Y, PCT and CRP displayed the best diagnostic performance for sepsis.

Conclusions: This study suggested that some CPD parameters (i.e., NE-SFL and MO-X) might provide useful information for diagnosis and management of sepsis.