{"title":"From 'replacement' to 'co-pilot': Reframing artificial intelligence in clinical biochemistry after Stevenson et al.","authors":"Mulavagili Vijayasimha","doi":"10.1177/00045632261435398","DOIUrl":"10.1177/00045632261435398","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"362-363"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Morgan Lundgren, Peter Ridefelt, Maria K Svensson, Emil Hagström, Thomas Cars, Anders Larsson
{"title":"NT-proBNP and its correlation to left ventricular ejection fraction and heart failure - The DEMONSTRATE database.","authors":"Morgan Lundgren, Peter Ridefelt, Maria K Svensson, Emil Hagström, Thomas Cars, Anders Larsson","doi":"10.1177/00045632251403397","DOIUrl":"10.1177/00045632251403397","url":null,"abstract":"<p><p>BackgroundMeasurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF) are used in diagnosing heart failure (HF). The main aim was to explore the correlation between NT-proBNP and LVEF.MethodsPatient data for 14,962 patients were extracted from medical records and national registries and compiled in the Swedish DEMONSTRATE database. HF phenotype was categorized according to LVEF level: HF with reduced EF (≤40%, HFrEF); HF with mildly reduced EF (41-49%, HFmrEF); HF with preserved EF (≥50%, HFpEF). Spearman's rank was employed for correlation analysis and ROC curves for discrimination and classification.ResultsNT-proBNP correlated negatively with LVEF level (r = -0.40) and positively with age (r = 0.49), creatinine (r = 0.35), and cystatin C (r = 0.53). Individuals with an HF diagnosis were more likely to have higher NT-proBNP levels compared to those without. The association between NT-proBNP and LVEF remained statistically significant (<i>P</i> < .0001) also after adjusting for age and kidney function estimates (r = -0.20). NT-proBNP discriminated well between HFrEF (AUC = 0.80) and HFpEF (AUC = 0.78). In discriminating the presence of an HF diagnosis, NT-proBNP (AUC = 0.81) outperformed LVEF (AUC = 0.75). However, on an individual level the correlation between LVEF and NT-proBNP was modest.ConclusionsNT-proBNP levels increase when LVEF deteriorates but with large inter-individual differences. Further research is needed, but these findings show potential in optimizing the use of LVEF with the aid of sequential analysis of NT-proBNP as a complementary diagnostic and prognostic tool to enhance assessment of cardiac function.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"308-318"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masood Moghul, Helen Berry, Freeda Millet, Amina Tran, Fiona Mutch, Elizabeth Westaway, Fionnuala Croft, Robyn Shea, Netty Kinsella, Patrick Kierkegaard, Declan Cahill, Nicholas David James
{"title":"Evaluation of a point of care prostate-specific antigen blood test on a mobile outreach service.","authors":"Masood Moghul, Helen Berry, Freeda Millet, Amina Tran, Fiona Mutch, Elizabeth Westaway, Fionnuala Croft, Robyn Shea, Netty Kinsella, Patrick Kierkegaard, Declan Cahill, Nicholas David James","doi":"10.1177/00045632251398445","DOIUrl":"10.1177/00045632251398445","url":null,"abstract":"<p><p>BackgroundPoint of care (POC) tests may improve accessibility and reduce costs of blood tests including in prostate cancer. The Man Van project was a pilot designed to address health inequalities that affect prostate cancer with novel community-based targeting of high-risk groups on a mobile clinical unit.MethodsThe i-CHROMA-II™ POC machine is a quantitative assay for the measurement of total prostate specific antigen (PSA) from capillary blood using fluorescence immunoassay technology. Laboratory based Serum PSA testing was compared with capillary blood POC testing using the i-CHROMA-II™ to determine its accuracy and impact on clinical decision making on the Man Van.Results28 men participated. The median age was 53 years (range 45-74). One POC test result was invalid. Nine POCT samples gave a result of <0.5 μg/L and were not included in the analysis. Of the remaining results (N = 18) the median PSA was 1.97 μg/L (range 0.54-31.22 μg/L). Using Lin's Concordance Correlation Coefficient of Absolute Agreement gave a value of 0.392 (N = 17). A Bland-Altman plot showed a mean difference of 0.377 μg/L.ConclusionsWe report the first testing of PSA using the i-Chroma-II™ machine, and the first real-world mobile testing using any POC PSA test. Our study did not show correlation between the laboratory and i-Chroma-II™, although it did replicate the positive bias seen in previous studies. Further testing and refinement of POC tests may help to achieve the goal to developing reliable POC PSA tests.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"301-307"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Crossley, Jonathan A Silversides, Cecilia M O'Kane, Paul K Hamilton
{"title":"PCSK9 in critical illness - It's not all about lipids.","authors":"Emma Crossley, Jonathan A Silversides, Cecilia M O'Kane, Paul K Hamilton","doi":"10.1177/00045632251395579","DOIUrl":"10.1177/00045632251395579","url":null,"abstract":"<p><p>Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism, binding to the low-density lipoprotein receptor (LDLR) on the cell surface and preventing its recycling, thereby reducing clearance of LDL cholesterol (LDLc) from the circulation. For this reason, it constitutes an alternative therapeutic target for the control of hypercholesterolaemia, with the development of monoclonal antibodies against PCSK9 occurring within 12 years of the protein's discovery. Recent research has also suggested an inflammatory role played by PCSK9, with elevated plasma levels identified in critical illnesses such as sepsis and Acute Respiratory Distress Syndrome, where PCSK9 is thought to reduce bacterial endotoxin clearance and may exacerbate inflammation. Further work is required in order to clarify the exact role played by PCSK9 in extra-hepatic tissues, and the potential benefits of its pharmacological inhibition.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"287-300"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susanna Reincke, Mirko Rehberg, Stefanie Stasek, Shino Junghänel-Welzing, Vera Fuessgen, Oliver Semler, Heike Hoyer-Kuhn
{"title":"Serum sclerostin levels in children with osteogenesis imperfecta.","authors":"Susanna Reincke, Mirko Rehberg, Stefanie Stasek, Shino Junghänel-Welzing, Vera Fuessgen, Oliver Semler, Heike Hoyer-Kuhn","doi":"10.1177/00045632261467690","DOIUrl":"10.1177/00045632261467690","url":null,"abstract":"<p><p>ContextSclerostin inhibits bone formation via the WNT/β-catenin pathway and is a therapeutic target in osteoporosis. Antibodies against sclerostin are currently under investigation for the treatment of osteogenesis imperfecta (OI), a rare, genetically and clinically heterogeneous bone fragility disorder. However, data on serum sclerostin levels in pediatric and adolescent patients with OI remain limited.DesignThis is a retrospective, cross-sectional analysis of serum sclerostin levels in a genetically heterogeneous cohort of children and adolescents with OI.Patients and methods80 serum samples from 74 OI patients (median age 8.9 years, range 0.1-20.7 years), classified by clinical severity and affected gene, were collected. Serum levels of sclerostin, osteoprotegerin (OPG), parathyroid hormone (PTH), alkaline phosphatase (AP) and 25-Hydroxy Vitamin D (25(OH)D) were measured and analyzed according to genotype and OI severity.ResultsThe median serum sclerostin level in this cohort was 0.35 ng/mL (IQR 0.28-0.52). Disease severity showed an inverse correlation with serum sclerostin levels (Spearman ρ = -0.4547, 95% CI [-0.62, -0.25], <i>P</i> < 0.0001). Multivariable linear regression analysis revealed genotype-specific differences in sclerostin levels, particularly in patients with <i>BMP1</i> or <i>WNT1</i> mutations compared with other mutation subgroups. No significant correlations were found between sclerostin and OPG, PTH, 25(OH)D, or AP.ConclusionsIn this cohort of children and adolescents with OI, disease severity was inversely associated with serum sclerostin levels, and genotype-specific differences may reflect distinct pathophysiological mechanisms of bone metabolism. These findings may contribute identifying patient subgroups most likely to benefit from targeted anti-sclerostin therapies.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261467690"},"PeriodicalIF":1.1,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimizing laboratory quality with sigma metrics: Application of CLIA 2024 total allowable error guidelines.","authors":"Anurag Sankhyan, Onjal Kamlakar Taywade, Sumita Sharma","doi":"10.1177/00045632261466864","DOIUrl":"10.1177/00045632261466864","url":null,"abstract":"<p><p>BackgroundStatistical quality control continues to serve as the cornerstone for ensuring the accuracy and reliability of laboratory investigations. The current research aimed to evaluate the performance of biochemistry parameters using Six Sigma metrics in light of revised CLIA (Clinical Laboratory Improvement Amendments) total allowable error (TEa) 2024 guidelines, to guide the application of appropriate quality control strategies.MethodsQuality control data for 20 chemistry parameters analyzed on the Fully Automated Biochemistry analyzer were evaluated using Six Sigma methodology. Internal quality control (IQC) and external quality assessment scheme (EQAS) data from December 2023 to May 2024 were collected. Coefficient of variation (%), bias (%) and TEa based on CLIA and Ricos biological variation guidelines were used to calculate sigma metrics. All quality control data were entered and analyzed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA).ResultsThe laboratory showed excellent (≥6 sigma) performance for direct bilirubin and HDL-cholesterol. Albumin, alkaline phosphatase, aspartate transaminase, cholesterol, glucose, iron, potassium, total iron-binding capacity and triglycerides achieved minimum sigma performance standard (>3) at one level. However, the other chemistry parameters did not meet the minimum sigma performance standard across all assay range.ConclusionThe laboratories need to reassess the performance of various biochemical parameters to redefine quality control protocols as the CLIA 2024 guidelines have tightened the total allowable error goals.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261466864"},"PeriodicalIF":1.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mustafa Kahtan Al-Bayaty, Mohammed Shamil Ali, Ragheed H Yousif
{"title":"Population-specific HOMA-IR reference ranges in Iraq: Defining insulin sensitivity in a Middle Eastern cohort.","authors":"Mustafa Kahtan Al-Bayaty, Mohammed Shamil Ali, Ragheed H Yousif","doi":"10.1177/00045632261466856","DOIUrl":"10.1177/00045632261466856","url":null,"abstract":"<p><p>The homeostatic model assessment for insulin resistance (HOMA-IR) is one of the most commonly applied surrogate markers for the measurement of insulin resistance; however, the use of this metric does require sex-specific, age-specific, and body mass index (BMI)-specific reference ranges due to variations among populations and there is a lack of data in countries like Iraq on such reference ranges. The purpose of this investigation was to develop sex-, age-, and BMI-specific reference ranges for HOMA-IR in apparently healthy Iraqi adults aged 18 to 60 years. There were 2,160 participants enrolled in the study who were equally divided into sex-specific groups and age groups (18-30, 31-45, and 46-60 years) and BMI categories (normal weight, overweight, and obesity). In addition to measuring fasting glucose and insulin levels, the HOMA-IR was calculated. Reference ranges, which included the 2.5th and 97.5th percentiles of HOMA-IR, were developed using non-parametric statistical methods based on CLSI EP28-A3c guidelines. The results demonstrated that HOMA-IR values increased as both age and BMI increased (<i>p</i> < 0.001). Also, males consistently had higher HOMA-IR values compared to females within similar subgroups. All between-group comparisons were statistically significant. It is important to use sex-, age-, and BMI-specific reference intervals when interpreting HOMA-IR to avoid misclassifying subjects in clinical and epidemiologic studies. This investigation represents the first large-scale study to identify such reference intervals in Iraq and adds relevant regional data to the global research on the prevalence of insulin resistance.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261466856"},"PeriodicalIF":1.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Senan Shortall, Aaron Niblock, Philip Logue, Kathryn Maguire
{"title":"Suspected thermal amplitude of cryoglobulin likely more clinically significant than size detected: A case report.","authors":"Senan Shortall, Aaron Niblock, Philip Logue, Kathryn Maguire","doi":"10.1177/00045632261454289","DOIUrl":"https://doi.org/10.1177/00045632261454289","url":null,"abstract":"<p><p>Cryoglobulins are proteins that are temperature sensitive, precipitating at temperatures below 37°C, and dissolve upon rewarming. However, at lower temperatures cryoglobulins can result in damage subsequently leading to vascular compromise. We present a case of a patient with a known lymphoplasmacytic lymphoma. The patient developed extensive finger necrosis and toe necrosis. Cryoglobulin was requested and a small type I was found. Given how common type I cryoglobulins are, more evidence was needed that this was the underlying aetiology of the necrosis. A biopsy of the tissue immediately proximal to the necrosis was performed. Histological evaluation confirmed cryoglobulin occlusions. Given the small cryoglobulin level, we assume the thermal amplitude of this resulted in this degree of vascular damage. Thermal amplitude of cryoglobulins is not generally performed. However, we know from testing the thermal amplitude of the red cell agglutination that the more active the antibody is at higher temperatures like those experienced in both the central and peripheral circulation, the more clinically significant the haemolysis. As this lady had chronic stable haemolysis, we sent the sample to the red cell reference lab to investigate the thermal range of the red cell antibody. This was checked at 4°C, room temperature, and 37°C. The cold antibody titre was 65536 at 4°C, 2048 at room temperature, and 1 at 37°C. This activity, despite having large titres at the cold range, demonstrated a wide thermal amplitude. Therefore, given these findings it is likely that the cryoprecipitate within the plasma had a similarly high thermal range.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261454289"},"PeriodicalIF":1.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systematic identification of human anti-mouse antibody interference causing falsely elevated B-type natriuretic peptide: A case study.","authors":"Shunchang Li, Jifei Yao","doi":"10.1177/00045632261458983","DOIUrl":"https://doi.org/10.1177/00045632261458983","url":null,"abstract":"<p><p>B-type natriuretic peptide (BNP) is crucial for heart failure diagnosis. However, immunoassays are vulnerable to heterophilic antibody interference, which may lead to false-positive results and significant clinical mismanagement. Studies suggest such interference may account for a notable proportion of unexplained biomarker elevations. This report describes a case of a 36-year-old female with a markedly elevated BNP (2735.7 ± 54.3 pg/mL) incongruent with her clinical presentation. Therefore, we conducted a detailed analysis through a stepwise investigation, including serial dilution (showing non-linear recovery), cross-platform comparison (normal result on an alternative platform), and heterophilic blocking reagent treatment (partial correction). Ultimately, the addition of purified mouse IgG, but not anti-goat IgG or IgM blockers, normalized the BNP level in a dose-dependent manner, confirming human anti-mouse antibody (HAMA) interference. This case demonstrates that such interference is one of the potential causes of unexplained elevations in clinical immunoassay results. A systematic workflow was established in the case, ranging from suspicion to confirmation and ultimately to laboratory-adoptable conclusions. This process facilitates accurate diagnosis and helps clinicians avoid unnecessary interventions.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261458983"},"PeriodicalIF":1.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}