Annals of Clinical Biochemistry最新文献

Background: As cortisol and metanephrine are involved in the stress response, it is often recommended that individuals are relaxed at the time of venepuncture, however, evidence behind these recommendations is lacking. We investigated the effects of acute psychological stress on serum cortisol and plasma metanephrine concentrations in healthy individuals exposed to varying levels of psychological stress and compared these results to self-reported measures of stress.

Methods: Ten medical students completed two medical in-person simulations (one low-complexity, one high-complexity) in a random order. At four times, participants completed the State-Trait Anxiety Inventory (STAI) and serum cortisol and plasma metanephrine/normetanephrine were tested.

Results: Median (interquartile range) STAI prior to the low-complexity simulation was 44 (18) versus 33 (13) afterwards (P = 0.050). STAI prior to the high-complexity simulation was 33 (10) versus 48 (17) afterwards (P = 0.007). Cortisol prior to the low-complexity simulation was 272 nmol/L (115) versus 247 (115) afterwards (P = 0.333). Prior to the high-complexity simulation, cortisol was 246 (70) versus 261 (137) afterwards (P = 0.859). Metanephrine prior to the low-complexity simulation was 242 pmol/L (79) versus 247 (93) afterwards (P = 0.515). Metanephrine prior to the high-complexity simulation was 220 (81) versus 251 pmol/L (120) afterwards (P = 0.074). Normetanephrine prior to the low-complexity simulation was 593 pmol/L (247) versus 682 (281) afterwards (P = 0.047 for the difference). Normetanephrine prior to the high-complexity simulation was 696 (123) versus 705 pmol/L (224) afterwards (P = 0.169).

Conclusions: The trend in cortisol levels largely reflected changes in STAI. We outline some implications of these findings for current practice and future research.

Background: Blood lead test is widely conducted in Chinese laboratories, while the imprecision of blood lead measurement based on internal quality control (IQC) across China has not been comprehensively evaluated nowadays.

Methods: Using the IQC data of blood lead collected through a web-based external quality assessment (EQA) reporting system, we analysed current coefficients of variation (CVs) of blood lead from 2015 to 2023 among Chinese laboratories. Two allowable total error (TEa) imprecision levels from EQA were applied to calculate the pass rates, namely percentages of laboratories meeting precision quality specifications. Besides, CV values and pass rates by different subgroups were further performed to assess potential differences.

Results: Generally, median CV values significantly declined year by year from 6.8% in February 2015 to 5.9% in March 2023. The pass rates based on 1/3 TEa showed upward trends increasing from 15.3% in February 2015 to 20.0% in March 2023, but these percentages were non-ideal with less than 25%. No significant differences in CVs were found between tertiary hospitals and non-tertiary hospitals and between accredited and non-accredited laboratories. Significant time trends were observed in tertiary hospitals and non-accredited laboratories. As for manufacturers, Bohui and self-made QC sample were most widely used with obvious interannual declining trends of CVs.

Conclusions: The CVs of blood lead demonstrated continuous overall improvements in the past twenty years. However, relatively lower pass rates indicated the non-ideal imprecision performance, and more proper performance specifications are warranted. Thus, imprecision improvement and ongoing investigation for blood lead IQC are still needed.

Background: Ethylene glycol (EG) poisoning, if not diagnosed rapidly, can lead to poor patient outcomes. Gas chromatography (GC) is primarily used for EG quantitation which is rarely available, and the turn-around time may be prolonged. Most lactate results from point-of-care (POCT) methods are falsely elevated in EG poisoning compared with automated chemistry analyser results. In combination, the lactate gap (POCT-Automated chemistry) can be used as surrogate marker in just about all laboratories to indicate likely EG toxicity and guide treatment.

Case report: A man presented by ambulance to hospital with severe agitation requiring mechanical ventilation to facilitate ongoing management. Venous blood gas analysis confirmed a high anion gap metabolic acidosis (HAGMA) with an elevated lactate. The lactate and osmolarity measured in the laboratory showed a normal lactate and high osmolarity, giving a large osmolar gap. The patient was immediately commenced on renal replacement therapy for presumed EG poisoning to minimize kidney injury, and the treatment continued for 19 hours. A very high EG concentration was confirmed by GC the next day.

Conclusion: An elevated lactate gap along with a HAGMA and osmolar gap can provide rapid surrogate laboratory data indicating EG poisoning enabling timely treatment and better patient outcomes.

Background: Symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) are naturally occurring amino acids classed as uraemic toxins by the European Uremic Toxins Work Group. SDMA is principally excreted through the kidneys and is a well-known renal function marker, and ADMA is a potent inhibitor of nitric oxide production. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry method for simultaneous measurement of SDMA, ADMA and creatinine.

Method: Serum samples were prepared by protein precipitation and dilution with acetonitrile prior to injection onto a Waters TQS-Micro. SDMA, ADMA, creatinine and their corresponding internal standard transitions were detected using multiple reaction monitoring after separation with a hydrophilic interaction liquid chromatography analytical column. Sample stability and intra-individual variation studies were also assessed following ethical approval.

Results: The retention time for creatinine was 0.43, SDMA 1.10 and ADMA 1.14 min. Mean recovery for creatinine was 103%, SDMA was 100% and ADMA was 103%; matrix effects were minimal (<6%). Lower limit of quantitation for creatinine and SDMA/ADMA was 17.5 µmol/L and 0.1 µmol/L, respectively. Analytical imprecision showed a coefficient of variation <10% for all analytes across the working range of the assays. Intra-individual variation for creatinine was 4.7%, SDMA 7.5% and ADMA 7.6%.

Discussion: We have developed a rugged assay for measurement of SDMA, ADMA and creatinine by LC-MS/MS suitable for routine use. It is easy to perform owing to its simplicity and reproducibility. The stability of SDMA and ADMA pre- and post-centrifugation allows for their routine use without any special sample handling requirements.

Background: Thyroid function tests (TFTs) are routinely requested by general practitioners (GPs) in the clinical biochemistry laboratory. Hypothyroxinaemia (low fT4) accompanied by TSH within the reference interval (RI) is a discordant pattern which is seen commonly in non-thyroidal illness and also as result of medications. Hypopituitarism is a lot rarer, but a serious condition the laboratory does not want to miss.

Methods: All thyroid hormone samples from primary care meeting the discordant case definition under investigation [fT4<10 pmol/L and TSH within RI (0.3-4.2 mU/L)] had partial anterior pituitary profiles [PAPP (cortisol, oestradiol/testosterone, prolactin, gonadotrophins)] added as reflex tests and results interpreted by a chemical pathologist. From January to June 2023, we conducted structured interviews with the requesting GPs, and, where indicated, requested repeat samples for full anterior pituitary profile [FAPP (PAPP, growth hormone (GH) and insulin-like growth factor 1 (IGF-1)]. We also reviewed the laboratory records of patients with previously known hypopituitarism to determine their fT4 and TSH values at diagnosis.

Results: Over the 6 months 41,487 GP TFTs were requested; 54 (0.13%) fitted the discordant case definition and had PAPP reflexed. 13 FAPPs were requested. We identified 3 cases of hypopituitarism. The number of additional tests required to diagnose 1 case of hypopituitarism was 129. In 74% of reflex-tested cases, there was a plausible explanation for the TFT pattern (medications, known thyroid dysfunction, non-thyroidal illness, pregnancy).

Conclusion: This study highlights the importance of medical liaison and early intervention in a biochemistry laboratory in identifying cases of unsuspected hypopituitarism.

Objectives: Reports have shown that the kynurenine pathway, one of the pathways by which tryptophan is metabolized, is activated in patients with diffuse large B-cell lymphoma (DLBCL). Activation of the kynurenine pathway triggers the production of various metabolites, such as kynurenine (Kyn), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), kynurenic acid (KA), and anthranilic acid (AA), which contribute to immune tolerance. The current study aimed to investigate the changes in metabolites of kynurenine pathway in DLBCL patients and evaluate their performance predicting DLBCL.

Methods: Changes in metabolites of kynurenine pathway were examined using high-performance liquid chromatography in 35 DLBCL patients (age 61.2 ± 13.5 years) and 44 healthy controls (age 58.5 ± 12.5 years).

Results: DLBCL patients had significantly higher levels of 3-HK, AA, and 3-HAA but lower levels of tryptophan (Trp) and KA compared to healthy controls. Given that the ratio of each metabolite represents the change in the Kyn pathway, the 3-HK/KA ratio was examined. Notably, DLBCL patients had a significantly higher 3-HK/KA ratio compared to healthy controls. In DLBCL, the area under the receiver operative characteristic (ROC) curve for 3-HK/KA (0.999) was higher than that for lactate dehydrogenase (0.885) and comparable to that for soluble interleukin-2 receptor (sIL-2R) (0.997). Based on ROC curve analysis, the 3-HK/KA ratio was found to be useful biomarker for the diagnosis of DLBCL.

Conclusion: Our results suggest that the 3-HK/KA ratio is a clinically useful biomarker of DLBCL. Moreover, its combination with existing markers, such as sIL-2R, can improve its effectiveness of diagnosing DLBCL.

Objective: To evaluate the application effect of SPRi monoclonal antibody (mAb) chip in the detection of influenza virus antigen in complex mixtures.

Methods: A total of 115 strains of mAbs against different subtypes (H1N1, H5N1, A1, A3, B, H7N9, H9N2, and H3N2) of influenza virus were prepared. The chip of mAbs against influenza virus was prepared by surface plasmonic resonance imaging (SPRi) technology, which was used for the detection of influenza virus supernatant, and compared with the traditional antigen capture ELISA method.

Results: Comparative studies have shown that traditional antigen capture ELISA methods have a higher sensitivity (86.8% (46/53) vs. 46.5% (46/99); z = 4.84, P < .001), while the SPRi chip methods present a significantly higher specificity (56.3% (9/16) vs. 14.5% (9/62); z = 3.54, P < .001). The SPRi chip detection method for influenza virus antibodies can well reflect the specific binding characteristics of influenza virus antigens and antibodies.

Conclusion: The SPRi mAb chip can be used for the detection of specific pathogenic microorganisms or viral proteins in complex mixtures such as influenza virus supernatant. It has significant advantages of label free, real-time, high-throughput, and good specificity, and can play an important role in disease diagnosis and infectious disease prevention and control.

Background: The Dutch guideline algorithm for the analysis of anaemia in patients of general practitioners (GPs) was programmed in a Clinical Decision Support system (CDS-anaemia) to support the process of diagnosing the cause of anaemia in the laboratory. This research aims to assess the supplementary benefit provided by the automated algorithm in various demographic categories, including different sexes, age groups and severities of anaemia, in comparison to the manual diagnostic approach employed by GPs.

Methods: This was a retrospective cohort study of 5399 primary care patients where the cause of anaemia was diagnosed by GPs with or without the aid of CDS-anaemia within the age groups 18-44, 45-64, 65-79 and 80 and older. Anaemia was defined according to the Dutch College of General Practitioners (DCGP) guideline. Causes of anaemia were based on the DCGP guidelines with the corresponding blood tests. By calculation of rate ratios and percentage differences of the determined cause of anaemia we evaluated the effect of the diagnostic algorithm.

Results and conclusion: The percentage patients in which an underlying cause of anaemia was found increased 34 and 46 percentage points in females and males, respectively, when GPs were supported by CDS-anaemia compared to GPs who were not supported by CDS-anaemia. The highest increase in percentage points when CDS-anaemia was used, was found in younger- and middle-aged males and mild or moderate anaemia.

Background: This study examines the association between the coefficient of variation (%CV) of lithium levels and episode risk and frequency in bipolar patients maintaining serum lithium levels within the therapeutic range.

Methods: We retrospectively reviewed patients with bipolar disorder under care from 2018 to 2022. Inclusion criteria were at least 2 years of follow-up, a minimum of three annual lithium level measurements within the therapeutic range. Patients were categorized based on seizure status. We calculated mean lithium levels, standard deviation (SD), and %CV.

Results: The study included 75 patients (patients with-without episodes, 39-36). Demographic data revealed no significant differences. While mean lithium levels showed no significant disparity between groups, SD and %CV were notably higher in patients with episodes (P < .05). ROC analysis demonstrated AUC values of 0.722 (95% CI: 0.607-0.836 P = .001) for %CV and 0.709 (95% CI: 0.593-0.826; P = .002) for SD. The optimal %CV cutoff was 17.39, with 67% sensitivity and 69% specificity. A weak correlation was found between %CV and the number of episodes (P = .001, r = 0.376). The post-hoc power analysis for this study was 0.78.

Conclusions: Despite acceptable lithium levels, patients with recent episodes exhibited significant lithium level fluctuations. Integrating %CV with real-time lithium measurements during bipolar disorder follow-up may enhance clinical monitoring and seizure prediction.

Background: The detection of deficiencies in B₁₂ and folate children is important. However, despite the availability of various markers to assess B₁₂ and folate metabolism, there are limited studies describing the reference intervals (RIs) and changes during growth and development for these markers in healthy children.

Methods: Using samples collected from 378 children aged 30 days-< 18 years, we derived continuous RIs for holotranscobalamin, homocysteine and red cell folate.

Results: The lower RI for holotranscobalamin was lowest at birth, rising during early childhood and then declining following ages 4-6 years whereas red cell folate was highest early in life and then declined steadily towards adulthood. Total homocysteine, reflective of both B₁₂ and folate status was elevated early in life, reaching a nadir at age 2 and then increasing towards adulthood.

Conclusions: Continuous central 95^th percentile RI for holotranscobalamin, homocysteine and red cell folate for children ages 30 days to <18 years were established. Each marker shows dynamic changes throughout childhood and adolescence which will assist clinicians in more appropriately assessing B₁₂ and folate status in this population.