Annals of Clinical Biochemistry最新文献

Background: ML predictive models have shown their capability to improve risk prediction and assist medical decision-making, nevertheless, there is a lack of accuracy systems to early identify future rapid CKD progressors in Colombia and even in South America.

Objective: The purpose of this study was to develop a series of interpretable machine learning models that predict GFR at 6-months, 9-months, and 12-months.

Study design and setting: Over 29,000 CKD patients stage 1 to 3b (estimated GFR, <60 mL/min/1.73 m²) with an average of 3-year follow-up data were included. We used the machine learning extreme gradient boosting (XGBoost) to build three models to predict the next eGFR. Models were internally and externally validated. In addition, we included SHapley Additive exPlanation (SHAP) values to offer interpretable global and local prediction models.

Results: All models showed a good performance in development and external validation. However, the 6-months XGBoost prediction model showed the best performance in internal (MAE average = 6.07; RSME = 78.87), and in external validation (MAE average = 6.45, RSME = 18.94). The top 3 most influential features that pushed the predicted eGFR value to lower values were the interpolated values for eGFR and creatinine, and eGFR at baseline.

Conclusion: In the current study we have developed and validated machine learning models to predict the next eGFR value at different intervals. Furthermore, we attempted to approach the need for prediction explanation by offering transparent predictions.

Vitamin B₁₂ (cobalamin; B₁₂) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B₁₂ deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B₁₂ status include the measurement of serum B₁₂ (also known as total B₁₂ or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B₁₂ status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B₁₂ test, which is readily available and highly automated. In some cases, the sequential use of different B₁₂ status biomarkers or the calculation of a composite B₁₂ status score, derived from a panel of B₁₂ biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B₁₂-related biomarkers and describes approaches to their application and interpretation.

Background: Lysophosphatidylethanolamines (lyso-PEs) are the partial hydrolysis products of phosphatidylethanolamine. Although lyso-PEs are important biomarkers in various diseases, their determination is limited by the lack of simple and efficient quantification methods. This study aims to develop an improved quantitative method for the determination of lyso-PEs and its application to an epidemiological study.

Methods: Single reaction monitoring channels by collision-induced dissociation for seven lyso-PEs were established using liquid chromatography-tandem mass spectrometry. Plasma lyso-PEs were extracted with a single-phase method using an isotopically labelled internal standard for quantification. The proposed method was adopted to define lyso-PEs in plasma samples of children aged 9-12 years living in Sapporo, Japan.

Results: The limit of detection and limit of quantification for each lyso-PE ranged between 0.001-0.015 and 0.002-0.031 pmol/μL, respectively. Recoveries were found to be > 91% for all the species. The analysis results of children's plasma showed that the total lyso-PE concentrations in boys (n = 181) and girls (n = 161) were 11.53 and 11.00 pmol/μL (median), respectively. Participants were further classified by the percentage of overweight and subgrouped as underweight (n = 12), normal range (n = 292), or overweight (n = 38). Interestingly, the reduction of lyso-PE 16:0 and increased lyso-PE 22:6 were observed in overweight children compared with normal range (Fold change: 0.909 and 1.174, respectively).

Conclusions: This study successfully established a simple quantitative method to determine lyso-PE concentrations. Furthermore, our method revealed the possible relation between plasma lyso-PEs and overweight status.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune condition that primarily affects the joints and periarticular soft tissues. In the past two decades, the discovery of new biomarkers has contributed to advances in the understanding of the pathogenesis and natural history of RA. These biomarkers, including genetic, clinical, serological and imaging biomarkers, play a key role in the different stages and aspects of RA, from the so called 'pre-clinical RA', which is characterized by subclinical pathological events, such as autoimmunity and inflammation, to diagnosis (including differential diagnosis), treatment decision making and disease monitoring.This review will provide an overview on the current role of traditional and newer biomarkers in the main aspects of RA management, from the identification of individuals 'at-risk' of RA who are likely to progress to clinically evident disease, to 'early' diagnosis of RA, prognosis, precision medicine, and prediction of response to treatment.

Background: Faecal calprotectin is an inflammatory marker used to triage patients for further investigation with suspected inflammatory bowel disease (IBD). Our current method requires faecal samples be sent to the laboratory, where calprotectin is extracted before analysis. This is a time-consuming, potential bottleneck in the pathway. We have recently evaluated the OC-SENSOR PLEDIA fCAL method that uses the same sampling device as used in some bowel cancer screening and symptomatic colorectal cancer programmes that detect faecal haemoglobin. The below study is a comparison of the OC-FCa method with the BÜHLMANN fCAL Turbo which is used routinely within BSPS.

Method: 150 homogenised and 110 non-homogenised faecal samples were loaded into OC-Sampling Bottle 3 and BÜHLMANN CALEX cap sampling devices. The samples were then analysed on their respective systems according to manufacturer's instructions.

Results: The OC-FCa assay had a mean positive bias of 67.3% (homogenised) and 88.4% (non-homogenised). Homogenised samples showed substantial agreement between the methods for normal (<50 µg/g) and elevated (150+µg/g) risk categories (k = 0.794, k = 0.788, respectively) and moderate agreement for borderline (51-150 µg/g) (k = 0.25) according to the current Berkshire and Surrey Pathology Service (BSPS) guidelines. Non-homogenised samples had none to slight agreement for normal and borderline values (k = 0.02 for both) and moderate agreement for elevated (k = 0.596).

Conclusion: The OC-FCa method is a viable alternative for faecal calprotectin testing, but requires an adjustment to clinical cut-off values due to the lack of standardisation and strong positive bias. A clinical comparative study is required to assess the impact of patients collecting their own samples into the devices, as this may negate any potential degradation samples may exhibit during transit to the laboratory.

This is a case of a 61-year-old lady who presented to the lipid clinic with possible familial hypercholesterolaemia (Simon Broome Criteria). She was commenced on atorvastatin; however, 4 weeks later, she developed hepatitis, and therefore her atorvastatin was discontinued. Following that, her liver function tests normalized, and she was diagnosed with statin-induced hepatitis. Three years later, she was seen again in the lipid clinic with an uncontrolled lipid profile, and she was commenced on alirocumab, a Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor. A few days later, she developed hepatitis, and subsequently, the alirocumab was discontinued. She underwent a liver biopsy, which confirmed that she had Autoimmune Hepatitis (AIH) with presumed superimposed drug injury. This is the first reported case of autoimmune hepatitis associated with alirocumab.

Background: Immune checkpoint inhibitors (ICIs) have revolutionised oncology care, by enhancing the body's T cell lymphocyte response against tumour cells. ICIs block the inhibitory signalling between tumour cells and the immune system, but consequently reduce immunological tolerance. Subsequently for some, this leads to immune-related adverse events (irAE), a spectrum term for autoimmune-like toxicities induced by ICIs that affects various tissues and organs. This limited narrative review will give a brief overview of immune checkpoint inhibitors and immune related adverse events for laboratory professionals and review the current evidence for predictive biomarkers.

Methods: A limited narrative review was conducted by accessing Pubmed and Google from June 2023 to January 2024 to identify references published from database inception to January 2024. Language was restricted to English.

Results/findings: Professional guidance does not recommend any biomarkers for irAE prediction. Some studies have found an association between the prediction of irAE and interleukin six (IL-6), C-reactive protein (CRP), thyroid stimulating hormone (TSH), albumin, ferritin, full blood count metrics, and lactate dehydrogenase (LDH). However, these have often been single-centre retrospective studies. While an abundance of societal guidance has been produced, it is unclear what blood tests should be included within a baseline profile.

Conclusions: Presently, there is no singular biomarker routinely available in clinical laboratories that can predict the onset of irAE. A custom battery of tests may be more predictive, but evidence is currently lacking. In the meantime, due to the clinical significance of these complications, laboratory professionals should proactively support prospective studies.

A case involving the incidental diagnosis of multiple myeloma (MM) due to interference in the 25-hydroxy-vitamin D (25(OH) vitamin D) immunoassay is presented. The patient, under the care of rheumatology and receiving treatment with alendronic acid and vitamin D supplements, was referred to endocrinology for investigation of acromegaly. Acromegaly was subsequently ruled out; however, during the investigations, consistently elevated levels of 25(OH) vitamin D were noted, raising suspicion of vitamin D resistance syndrome. The laboratory and endocrinology teams engaged in discussions, and following the cessation of medication, repeated analyses for 25(OH) vitamin D and a single analysis of 1,25-dihydroxy-vitamin D levels were requested, yielding high and normal results, respectively. The laboratory conducted a three-step interference investigation, ultimately identifying a high molecular weight molecule responsible for the initially elevated 25(OH) vitamin D levels. Due to the clinical presentation of back pain, a proteinogram was requested, revealing a monoclonal band of 36 g/L. Subsequent free light chain analysis indicated an elevated ratio. With three risk factors identified, this was classified as an established MM and urgently referred to haematology for correct management. Laboratory assay interferences have the potential to disrupt the accurate diagnostic workup of patients. Collaborative discussions between laboratory and clinical teams regarding such cases aid in directing the diagnostic pathway appropriately, facilitating prompt and proper diagnosis and management.

Introduction: The aim of our study was to determine reference intervals for serum pentraxin 3 and calprotectin, as well as for urine calprotectin according to the CLSI EP28-A3C guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory.

Materials and methods: A total of 120 serum and urine samples from either healthy volunteers or outpatients were used for reference interval establishment. The participants had CRP levels, leucocyte counts, serum urea levels, creatinine levels, and estimated glomerular filtration rates (CKD-EPI eGFRs) within the reference range and no medical history of acute/chronic inflammatory diseases/conditions or cancer. Calprotectin was measured via a commercially available turbidimetric method - the Bühhlmann fCAL® Turbo Reagent Kit - while pentraxin 3 was measured using the Human Pentraxin 3 ELISA Kit from the BioVendor Group.

Results: The serum calprotectin reference range was ≤3.6 mg/L, the 90% CI for the upper reference range was 3.1-4.1 mg/L, while the serum pentraxin 3 reference concentration was ≤3.0 µg/L, and the 90% CI for the upper reference range being 2.7-3.2 µg/L. Additionally, the urinary calprotectin concentration was ≤1.4 mg/L, with a 90% CI for the upper reference range of 1.0-1.7 mg/L.

Conclusion: This study reports sample and method-specific reference intervals for the detection of various inflammatory conditions.