Annals of Clinical Biochemistry最新文献

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.

The presence of latent fibrin clots is a recognised pre-analytical factor that causes inaccurate immunoassay results. This report details a case of a patient with Graves' disease and congenital dysfibrinogenemia (CD) that had serum thyroid function test results (TFTs) that were not in keeping with clinical signs or symptoms. Analysis of plasma samples taken from the patient was shown to provide more accurate results than those obtained using serum samples. Further cases of patients with CD, all sharing the same genetic mutation of fibrinogen, and discordant TFTs are described, where TFTs measurement in serum samples proved to be unreliable. Despite evidence of fibrin effecting immunoassays, this is the first report of its kind linking CD to erroneous immunoassay results. The mechanism is postulated to be related to atypical forms of fibrinogen resulting in latent fibrin in serum samples blocking the antigen binding site and leading to incorrect results. Congenital dysfibrinogenemia is asymptomatic in most patients and therefore abnormal, albeit inaccurate, TFTs may be the first finding. Recognition of CD as a cause of discordant results is important when interpreting TFTs to avoid unnecessary investigations and inappropriate clinical interventions to those with the disorder and potentially identify undiagnosed cases.

Background: Examining the distribution of biochemical and haematological tests in different age groups of rural population is necessary to ensure that health care facilities are equipped to address the prevalent health conditions and manage age-related illness effectively. Hence, this study is aimed at seeing the distributions of blood biochemical and haematological parameters in rural population.

Methods: This cross-sectional study investigated the distribution of 26 different haematological and biochemical parameters in longitudinal cohort study (Srinivaspura Aging, NeuoSenescence and COGnition - SANSCOG), from the villages of Srinivaspura, Kolar district, India. A total of 2592 participants (1240 males and 1352 females), aged ≥45 years who are cognitively healthy were included for the analysis. Mean, 2.5^th, 5^th, 25^th, 50^th, 75^th, 95^th and 97.5^th percentiles were calculated for the entire sample. Additionally, median and percentiles were determined for both gender and age categories (45-54, 55-64, 65-74, and ≥75 years).

Results: We observed the distinct distributions of various haematological and biochemical parameters, with elevated levels of glycaemic, lipid, liver, and thyroid parameters.

Conclusion: Findings revealed the notable variations from the established reference ranges, indicating the potential undiagnosed cases and highlighting the gaps in health awareness and health seeking behaviour.

Background: Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g. positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e. levels of antibodies), quantitative laboratory test data are needed.

Method: 36 data attributes were collected from 3 NHS laboratories and 29 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results: A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions: This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.