Annals of Clinical Biochemistry最新文献

Case oneA young woman presented to the Early Pregnancy Assessment Unit (EPAU) with abdominal pain, amenorrhoea and variably positive home-pregnancy tests. On review, a point-of-care test (POCT) for urine beta-HCG (β-HCG) was negative but a blood test using the Abbott i-STAT β-HCG POCT device was positive. Initial transvaginal ultrasound did not demonstrate an intra- or extra-uterine pregnancy. Over the following 2 months, weekly plasma POCT iSTAT β-HCG checks remained positive. After a further ultrasound suggesting a possible ectopic pregnancy, the patient underwent a diagnostic laparoscopy which was unremarkable. Post-operatively, POCT iSTAT β-HCG levels remained elevated, and a blood sample was sent for laboratory analysis revealing an undetectable β-HCG of <1.20 IU/L (reference interval 0-4).Case twoA middle-aged woman presented to the emergency department with mons pubis pain and swelling and was admitted to the gynaecology ward for drainage of bilateral abscesses. On review, she had raised blood β-HCG levels, measured using the Abbott i-STAT POCT device. A subsequent blood sample sent for laboratory analysis showed β-HCG levels within the post-menopausal reference interval. Discussion: In both cases, POCT immunoassay interference was confirmed by consistent results produced when contemporaneous samples were analysed by different analytical platforms. Immunoassay interference, though rare, can lead to inaccurate results from POCT devices, potentially impacting patient diagnosis and management. Clinical teams should remain vigilant for this possibility; if test results do not align with clinical expectations, it is essential to promptly send a blood sample for laboratory analysis.

Background: Heart failure (HF) is a growing global burden. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) guides diagnosis, assay cost and analyzer availability limit routine use. Routine laboratory data may offer a low-cost triage alternative.

Methods: We developed and validated an interpretable decision tree to stratify the risk of elevated NT-proBNP >300 pg/mL and assessed deployment in a diagnostic support system (DSS). We analyzed 19,889 encounters at Gifu University Hospital (Aug 2022-May 2024). All 20 candidate predictors were included without prior feature selection to capture non-linear associations. Hyperparameters were tuned by 10-fold cross-validation. Final classification used a fixed decision rule optimized for high sensitivity (≥0.90 in training) to support effective triage. Performance comprised AUROC (DeLong 95% CIs) and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy (Wilson 95% CIs) on an internal hold-out set (n=3,978) and a temporal external cohort (n=14,903; Jun 2024-Jun 2025). Analyses were complete-case with no imputation.

Results: The decision tree inherently utilized clinically relevant predictors including serum albumin, eGFR, and age. Internal test performance: AUROC 0.804 (0.791-0.818); sensitivity 0.879 (0.863-0.893); specificity 0.505 (0.484-0.526); accuracy 0.674 (0.660-0.689). External performance within the DSS: AUROC 0.806 (0.799-0.813); sensitivity 0.882 (0.874-0.890); specificity 0.518 (0.508-0.529); NPV 0.852 (0.842-0.861). Calibration and decision-curve analysis supported clinical utility.

Conclusions: An interpretable tree built from routine laboratories detects clinically relevant NT-proBNP elevation with high sensitivity and performs robustly after deployment. This scalable, low-cost approach could enable risk-directed triage and more efficient resource allocation.

Background Urinary C-peptide testing is widely used to evaluate insulin secretion capacity from pancreatic β-cells. We report a case in which urinary C-peptide showed abnormally high levels during treatment with an angiotensin receptor-neprilysin inhibitor (ARNI). Case presentation The patient was a 54-year-old man undergoing treatment for type 2 diabetes mellitus and hypertension. Following an abnormal electrocardiogram during a health check-up, he was diagnosed with aortic valve insufficiency. During admission to the diabetes and endocrinology department for preoperative glycemic control, a clinical laboratory technologist first recognized a marked discrepancy between urinary and serum C-peptide results and reported this to the attending physician, prompting further investigation. A literature review revealed reports suggesting that ARNI administration may suppress C-peptide metabolism, potentially leading to elevation of measured values. Results The patient's excreted urinary C-peptide level decreased markedly after ARNI therapy was discontinued, suggesting that ARNI influences an increase in urinary C-peptide. Conclusions When excreted urinary C-peptide is abnormally elevated and discrepant from the serum C-peptide level, it is important to confirm ARNI use and follow laboratory-driven recommendations for retesting after discontinuation if needed. Prompt reporting of this finding by the clinical laboratory is essential for the accurate assessment of insulin secretion capacity.

The presence of paraproteins in multiple myeloma can cause analytical interference, resulting in unusual and misleading biochemical outcomes. An uncommon but clinically relevant finding is the reporting of a negative direct bilirubin result on wet chemistry analyzers-an impossible outcome that strongly suggests analytical interference. A 60-year-old male presented with nonspecific symptoms. Liver function tests carried out on a wet chemistry analyzer indicated a total bilirubin of 0.39 mg/dL and a direct bilirubin of -7.67 mg/dL, which was not physiologically possible. There was no evidence of jaundice, and imaging appeared normal. Repeat testing with a dry chemistry analyzer indicated a total bilirubin of 1.0 mg/dL and a direct bilirubin of 0.1 mg/dL, aligning with the clinical picture. Further investigations confirmed the diagnosis of multiple myeloma with IgG-kappa monoclonal gammopathy. The discrepancy was attributed to paraprotein interference in the wet chemistry method. This case highlights a rare but important laboratory artifact-negative direct bilirubin due to paraprotein interference-and emphasizes the reliability of dry chemistry in such scenarios. Awareness of this interference is important for accurate diagnosis and avoiding unnecessary workup.

BackgroundExposure of plasma to low temperatures induces the conversion of prorenin to renin, causing falsely elevated levels of renin. This also happens at storage temperatures of -20°C. Our survey evaluated the pre-analytical procedures used by clinical laboratories in the Netherlands for renin testing and assessed their awareness of recent studies on cryoactivation and their impact on pre-analytical procedures.MethodsA nine-question online survey about pre-analytical conditions for renin measurements in clinical laboratories was distributed by the Foundation for Quality Assessment in Medical Laboratory Diagnostics (SKML) to 106 clinical laboratories in the Netherlands participating in the external quality assessment scheme for hormone measurements.ResultsOf the 42 labs that responded, pre-analytical practices varied considerably. Time limits for sample receipt ranged from none (31%, n = 13) to <4 h (57%, n = 24) or >4 h (5%, n = 2). Most laboratories transported and centrifuged samples at room temperature (90% and 93%; n = 38 and 39). Storage conditions differed: 79% (n = 33) stored at -20°C, 17% (n = 7) at -80°C, 2% (n = 1) at -40°C, and 2% (n = 1) at room temperature. Twenty-two respondents (52%) were aware of recent literature, and 8 (36%) had changed or planned to change procedures accordingly. Overall, only eight laboratories (19%) followed all recommended steps to minimize cryoactivation.ConclusionsThis survey shows considerable inconsistency in pre-analytical procedures of renin testing in clinical laboratories in the Netherlands. Despite moderate awareness of recent evidence, implementation of optimal preanalytical procedures remains limited. The survey results show that guidelines and scientific evidence have not been fully implemented, and that awareness of the latest evidence does not directly lead to a change in practice.

BackgroundThe NHS accounts for approximately 4-5% of England's total carbon footprint and was the first healthcare organisation to commit to a net-zero target. Reducing the inappropriate use of diagnostic tests could play a meaningful role in reaching this goal. In 2024, the microbiology laboratory at Lancashire Teaching Hospitals NHS Foundation Trust received >90,000 urine and >15,000 wound samples. Local audit data highlights samples are sent for testing in the absence of clinical signs and symptoms of infection. Furthermore, 25 % of superficial swabs and 10% of urines grew mixed-faecal organisms.PurposeThe aim was to implement a diagnostic stewardship intervention to reduce inappropriate urine and wound swab submissions from primary care and estimate associated carbon savings.Research DesignA pre-analytical stage diagnostic stewardship intervention was implemented consisting of a computerised clinical decision support tool (CCDS). The tool prompts clinicians, using evidence-based guidance, on when to obtain samples for testing. Study Sample: 3-month intervention period data was compared with two 3-month pre-intervention periods (I and II).Data AnalysisThe UK Government 2024 greenhouse gas conversion factors were used to calculate the total CO₂e associated with testing urine and wound samples. ResultsComparing number of samples received during the intervention period with pre-intervention II, urine samples decreased by 10.2%, saving 190.5 kg CO₂e. Similarly, wound samples decreased by 12.9%, saving 80 kg CO₂e.ConclusionThe CCDS tool effectively reduced unnecessary testing and associated carbon emissions, supporting the NHS's net-zero ambitions. Similar tools can be employed in other areas of pathology to reduce the impact of inappropriate testing whilst supporting sustainable healthcare.

BackgroundBlood glucose concentrations decrease after blood collection. We recently developed novel blood collection tubes containing inosine added to sodium fluoride (NaF; FI tubes), which effectively inhibits post-collection blood glucose decline. However, the underlying mechanism remains unclear. In this study, we examined the mechanism by which inosine inhibits blood glucose consumption by erythrocytes and assessed glucose transporter (GLUT) activity.MethodsATP levels were measured in erythrocytes treated with inosine, and metabolomic changes were analyzed using GC-MS. In addition, glucose uptake tests were performed.ResultsIn patients' blood samples, FI tubes suppressed the post-collection decline in blood glucose levels more effectively than conventional NaF tubes, regardless of baseline blood glucose levels. FI tubes attenuated the time-dependent decrease in ATP levels; however, similar to that in conventional NaF tubes, ATP levels in erythrocytes in FI tubes were nearly zero after 4 h. Metabolic analysis demonstrated a decrease in the levels of glucose and glycolytic metabolites, such as 2-phosphoglycerate and phosphoenolpyruvate, in inosine-treated erythrocytes. Glucose uptake assays revealed that inosine significantly inhibited glucose uptake, indicating suppression of GLUT activity.ConclusionsInosine inhibits glucose uptake in erythrocytes primarily via the suppression of GLUT activity. It also inhibits erythrocyte hemolysis by temporarily maintaining intracellular ATP levels.