Louise E Duvall, Laura Wainwright, Laura Bryant, George Sandy, Vanessa Owusu-Yeboah, Adam Hurlstone
{"title":"Immune checkpoint inhibitors in the real world: A service evaluation of immune-related adverse event incidence and blood test requesting at Portsmouth Hospitals University Trust.","authors":"Louise E Duvall, Laura Wainwright, Laura Bryant, George Sandy, Vanessa Owusu-Yeboah, Adam Hurlstone","doi":"10.1177/00045632261475616","DOIUrl":"https://doi.org/10.1177/00045632261475616","url":null,"abstract":"<p><p>BackgroundImmune checkpoint inhibitors (ICI) have revolutionised oncology care but can cause immune-related adverse events (irAE) requiring hospitalisation or lifelong treatment. Diagnosing irAE is complex, and laboratory testing is vital; however, ordering appropriate tests at appropriate intervals is challenging because of the abundance of conflicting guidelines. The burden of irAE within the NHS is not well defined, and there may be significant variation in irAE across local areas. This study seeks to inform vital local service planning.Methods1028 ICI patients were identified (2018-2023). Medical records and laboratory data were extracted and anonymised before being analysed using SQL and R to investigate the burden of irAE on hospitals and blood test request patterns by primary tumour origin.ResultsThe overall incidence of irAE was 36.8%, and the most common irAEs were skin rashes, hypothyroidism, colitis, and hepatitis. Increased prescribing of ICI across more tumour types has led to an increase in hospital inpatient days. Monitoring was inconsistent: while standard laboratory tests such as complete blood counts, liver function panel, and urea and electrolytes were frequently requested, guideline-recommended baseline tests, including AST, glucose, and thyroid testing, were significantly underutilised, with inconsistent repeat intervals.ConclusionRising ICI use at PHUT has increased irAE related hospital admissions. Blood test requests between 2018 and 2023 were found to be inconsistent across primary tumour origins, and standardised blood test profiles may help streamline the diagnosis of irAEs, leading to earlier diagnosis and interventions.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261475616"},"PeriodicalIF":1.1,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700606","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":"CORRIGENDUM to \"Standardising lipid testing and reporting in the United Kingdom; a joint statement by HEART UK and The Association for Laboratory Medicine\".","authors":"","doi":"10.1177/00045632261471456","DOIUrl":"https://doi.org/10.1177/00045632261471456","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261471456"},"PeriodicalIF":1.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676854","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":"Is improved folate status in Northern Ireland a result of improved analytical performance or the implementation of folic acid fortification of flour legislation?","authors":"Gillian Law, Kathryn Ryan, Derek McKillop","doi":"10.1177/00045632261474775","DOIUrl":"https://doi.org/10.1177/00045632261474775","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261474775"},"PeriodicalIF":1.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618097","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}
Jiya Singh, Sabyasachi Bandyopadhyay, Atanu Sen, Ravi Kant, Anindya Das, Sarama Saha
{"title":"Untargeted LC-MS/MS profiling identifies ST18 as a novel serum marker for T2DM-associated depression.","authors":"Jiya Singh, Sabyasachi Bandyopadhyay, Atanu Sen, Ravi Kant, Anindya Das, Sarama Saha","doi":"10.1177/00045632261475614","DOIUrl":"10.1177/00045632261475614","url":null,"abstract":"<p><p>Depression is a prevalent but underdiagnosed comorbidity in type 2 diabetes mellitus (T2DM), intensifying disease burden and complicating metabolic management. Reliable biomarkers for early detection remain limited. This study aimed to identify serum protein signatures associated with depression in individuals with T2DM using an untargeted proteomic approach. Methods Serum samples from healthy controls, T2DM patients, and T2DM patients with comorbid depression (n = 6 per group) were analyzed using LC-MS/MS-based untargeted proteomics (total n = 18). Differential protein abundance was assessed using MetaboAnalyst 6.0. Protein-protein interaction networks and pathway enrichment analyses were conducted using the STRING database. Candidate markers were further validated by ELISA in an independent cohort of healthy controls (n = 30), T2DM (n = 30), and T2DM with depression (n = 30). Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Results LC-MS/MS identified 242 serum proteins, of which 12 were significantly dysregulated among the groups. Nine proteins showed unique alterations in the T2DM-depression group. STRING analysis highlighted ST18 as a central regulatory protein. ELISA validation confirmed significant elevation of LRG1, APOC2, and ST18 in T2DM with depression compared to controls and T2DM without depression. Among these, ST18 demonstrated the highest diagnostic accuracy, yielding the greatest area under the ROC curve. Conclusion Untargeted proteomic profiling revealed distinct serum protein alterations in T2DM patients with comorbid depression. ST18 emerged as a robust and specific biomarker, suggesting its potential involvement in the molecular interplay between metabolic dysregulation and depressive pathology. Larger, longitudinal studies are required to validate its predictive utility and clarify its role in T2DM-associated depression.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261475614"},"PeriodicalIF":1.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576550","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":"Bayesian secondary reanalysis of published aggregate data on circulating tumor DNA for molecular residual disease detection across cancer types.","authors":"Shugo Yajima, Soichiro Yoshida, Wei Chen, Hiroshi Fukushima, Hajime Tanaka, Hiroyuki Sato, Akihiro Hirakawa, Hitoshi Masuda, Yasuhisa Fujii","doi":"10.1177/00045632261475618","DOIUrl":"10.1177/00045632261475618","url":null,"abstract":"<p><p>BackgroundCirculating tumor DNA (ctDNA)-based molecular residual disease (MRD) testing may help estimate recurrence risk after treatment. We performed a Bayesian secondary reanalysis of published aggregate data to estimate prognostic and diagnostic performance.MethodsData were extracted from Zheng et al. (80 studies, 11 cancer types). Log hazard ratios for recurrence were analyzed using Bayesian normal-normal hierarchical models. Sensitivity and specificity were analyzed using separate logit-scale random-effects models. Posterior probabilities were estimated from posterior samples.ResultsThe prognostic analysis included 109 study arms (approximately 9,980 patients). The pooled hazard ratio for recurrence associated with ctDNA positivity was 7.5 (95% credible interval [CrI], 6.4-8.8). Among cancer-type subgroups reported separately, all 95% CrIs excluded 1.0. In 70 diagnostic studies, pooled sensitivity was 57.6% (95% CrI, 53.2-61.9) and specificity was 90.5% (95% CrI, 88.5-92.3). Longitudinal monitoring had higher sensitivity than landmark testing (73.6% vs 50.0%; posterior probability >99.9%), with similar specificity (89.9% vs 90.8%). mPCR-NGS had specificity of 93.2% (95% CrI, 90.2-95.6); in separate exploratory comparisons, P(mPCR-NGS > ddPCR) and P(mPCR-NGS > hybridization capture NGS) were both 96.0%.ConclusionsThis Bayesian secondary reanalysis supports the association between ctDNA-MRD positivity and recurrence risk. Longitudinal monitoring may improve sensitivity, while assay technology comparisons should be interpreted cautiously because they were based on aggregate, non-head-to-head data.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261475618"},"PeriodicalIF":1.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576453","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":"Stability of electrolytes in whole blood at room temperature prior to centrifugation: Implications for clinical analysis.","authors":"Sayamon Janyapaisarn, Maneenooch Torngsawarng, Napaporn Inganuruksakul, Sumana Mas-Oodi, Theerawut Chanmee, Sureerut Porntadavity","doi":"10.1177/00045632261470646","DOIUrl":"10.1177/00045632261470646","url":null,"abstract":"<p><p>Background/ObjectivesThe pre-analytical stability of electrolytes in capped whole blood at room temperature remains uncertain due to limited studies and inconsistent findings. This study investigates electrolyte stability during delayed centrifugation, in accordance with recent EFLM recommendations.Materials and methodsThe stability of electrolyte concentrations (sodium, potassium, chloride, and bicarbonate) was assessed in capped whole blood samples from 40 participants stored at room temperature at three time intervals (0, 2, and 4 h) prior to centrifugation. Differences in electrolyte concentrations were expressed as percent deviation (%PD) from baseline (T0). The %PD for each analyte was calculated and compared with the maximum permissible difference (MPD), derived from intra- and inter-individual biological variation.ResultsThe calculated MPD values for sodium, potassium, chloride, and bicarbonate were 1.5%, 4.2%, 1.9%, 10.8%, respectively. The mean %PD at 2 h for sodium, potassium, chloride, and bicarbonate was 0.2, 0.1, -0.4, and -0.3, respectively. At 4 h, the mean %PD values were 0.3, 2.1, -0.7, and -0.4, respectively. All mean %PD values remained within the MPD limits at both 2 and 4 h, with potassium showing a higher mean %PD at the 4-h time point compared to 2 h.ConclusionsSodium and potassium concentrations increase over time, while chloride and bicarbonate concentrations decrease. Electrolytes in capped whole blood stored at room temperature with delayed centrifugation remained stable for up to 4 h. However, potassium appeared to be more susceptible to changes due to delayed processing. Timely sample handling is therefore critical to ensuring accurate electrolyte measurements.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261470646"},"PeriodicalIF":1.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395755","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}
Gulsum Abuşoğlu, Mohammad Ahmad Bik, Firdevs Sak, Duygu Eryavuz Onmaz, Ali Unlu, Fatma Hümeyra Yerlikaya, Sedat Abuşoğlu, Yasemin Coşkun Yavuz
{"title":"Comparison of Jaffe, Enzymatic, and Mass Spectrometric Methods for Creatinine Measurement in Protein-Positive and Hemoglobin-Positive Urine Samples.","authors":"Gulsum Abuşoğlu, Mohammad Ahmad Bik, Firdevs Sak, Duygu Eryavuz Onmaz, Ali Unlu, Fatma Hümeyra Yerlikaya, Sedat Abuşoğlu, Yasemin Coşkun Yavuz","doi":"10.1177/00045632261470633","DOIUrl":"https://doi.org/10.1177/00045632261470633","url":null,"abstract":"<p><p>Accurate measurement of urine creatinine is essential for evaluating renal function. Although the Jaffe and enzymatic methods are routinely applied in clinical laboratories, various urinary compounds can interfere with these assays. This study investigated the effects of hemoglobin and protein positivity on creatinine measurement and partially validated a mass spectrometric (LC-MS/MS) procedure. Urine samples from 136 participants were categorized based on dipstick results into three groups: negative (n = 55), hemoglobin-positive (n = 51), and protein-positive (n = 30). Creatinine concentrations were measured using Jaffe and enzymatic methods on an Architect c16000 analyzer and by LC-MS/MS on an API 3200 system. The LC-MS/MS method demonstrated linearity between 3-350 mg/dL, intra- and inter-assay coefficients of variation of 3.2-3.8% and 1.9-2.9%, and bias values ranging from 1.1% to 18.2%. Correlations among LC-MS/MS, enzymatic, and Jaffe methods ranged from 0.981 to 0.998. Bland-Altman analysis showed mean absolute biases of 0.06 to 17.33 mg/dL (1.48-19.42%) in controls, 1.44 to 4.78 mg/dL (0.79-9.59%) in hemoglobin-positive samples, and 2.18 to 9.87 mg/dL (0.52-14.39%) in protein-positive samples. Regression analysis showed slopes closer to unity in hemoglobin- and protein-positive samples compared to controls, likely reflecting higher creatinine concentrations in these groups. Despite this apparent improvement, bias values increased, particularly in protein-positive samples. Both routine methods showed acceptable agreement with LC-MS/MS, while the enzymatic method demonstrated slightly closer agreement under these conditions. LC-MS/MS maintained highest analytical specificity. These findings highlight the importance of method selection for reliable interpretation of renal function, especially in patients presenting with hematuria or proteinuria.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261470633"},"PeriodicalIF":1.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395616","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}
Katherine Birch, Maria Squires, Miles Chapman, Melanie Hart, Carrie Chadwick, John Goodfellow, Ravishankar Sargur, Bushra Zaidi, James Hoy, Michael Lunn, Dina Patel
{"title":"Limitations of spectrophotometry in the analysis of cerebrospinal fluid bilirubin.","authors":"Katherine Birch, Maria Squires, Miles Chapman, Melanie Hart, Carrie Chadwick, John Goodfellow, Ravishankar Sargur, Bushra Zaidi, James Hoy, Michael Lunn, Dina Patel","doi":"10.1177/00045632261466866","DOIUrl":"https://doi.org/10.1177/00045632261466866","url":null,"abstract":"<p><p>BackgroundCerebrospinal fluid (CSF) spectrophotometry is well-established in the UK for measuring CSF bilirubin and oxyhaemoglobin to aid in the diagnosis of subarachnoid haemorrhage. Although it is known that some antibiotics and large amounts of oxyhaemoglobin interfere in the spectrophotometric analysis of CSF bilirubin, there is little published evidence about the impact of such interferences.MethodsExperimental samples were distributed to participants in the UK National External Quality Assessment Service (NEQAS) for Immunology, Immunochemistry and Allergy EQA programme for CSF haem pigments. Distribution 244 consisted of a pair of matched samples but with sample 244-2 containing an increased amount of oxyhaemoglobin compared to sample 244-1. Distribution 251 consisted of a pair of matched samples but with sample 251-2 containing additional doxycycline at a concentration of 0.5 µg/mL compared to sample 251-1. Participants analysed the samples spectrophotometrically and absorbance values were returned to UK NEQAS.ResultsThe net bilirubin absorbance (NBA) was significantly reduced in the presence of both interferants; adding 0.6% oxyhaemoglobin decreased the NBA by a mean of 55.9% and adding 0.5 µg/mL doxycycline decreased the NBA by a mean of 14.3%. Wilcoxon signed rank tests showed the NBA was significantly different for sample 2 compared to sample 1 for both distributions.ConclusionsIncreased amounts of oxyhaemoglobin and the presence of doxycycline can both negatively interfere with NBA. The interference is subtle and difficult to detect but has the potential to change a true positive result to a false negative, highlighting a significant limitation of the CSF spectrophotometry technique.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261466866"},"PeriodicalIF":1.1,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389901","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":"Commentary on the impact of lithium heparin vacutainer tubes on daily cerebrospinal fluid analysis.","authors":"Valery Brunel","doi":"10.1177/00045632261466862","DOIUrl":"https://doi.org/10.1177/00045632261466862","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261466862"},"PeriodicalIF":1.1,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389863","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}
Johan Bjerner, Michael Sovershaev, Elisabeth Wiik Vigerust, Thor Hilberg, Johannes Østrem Fjøse, Tom Rune Karlsen
{"title":"Estimation of half-life with confidence interval for phosphatidylethanol (PEth) in blood based on two consecutive measurements.","authors":"Johan Bjerner, Michael Sovershaev, Elisabeth Wiik Vigerust, Thor Hilberg, Johannes Østrem Fjøse, Tom Rune Karlsen","doi":"10.1177/00045632251411787","DOIUrl":"10.1177/00045632251411787","url":null,"abstract":"<p><p>BackgroundPhosphatidylethanol (PEth) is formed in erythrocyte membranes after alcohol consumption. When abstaining, the PEth level falls with a rate proportional to its concentration, and a short apparent PEth half-life supports abstinence. We here derive algorithms for calculating unbiased half-lives and confidence intervals (CIs).MethodsPEth was measured using Acquity UPC2-MS/MS systems in clinical blood samples from out-patients. We identified 6989 individuals having taken two or more PEth samples within 28 days. One measurement pair was randomly selected from everyone. We derived methods for and calculated PEth half-lives and corresponding 95% CIs for exact, rounded, and truncated data, on closed form, Monte Carlo methods and No-U-turn sampling.ResultsThe peak of the PEth half-life was at 8.62 days. Peak PEth half-life was 8.72 days for men and 8.47 days for women (<i>P</i> = 0.028) and on age: 8.55 days for age 18-39 years, 8.56 for age 40-59 years and 8.87 for 60+ years (<i>P</i> = 0.026). PEth concentration did not significantly affect half-life. CIs on a closed form performed excellently on exact data, with misclassification of abstinence for 16 out of 6989 observations (0.23%). When rounding or truncating data, misclassification occurred using Monte Carlo methods in 104 (1.5%) and 127 (1.8%) of the observations and using closed form algorithms in 855 (12.2%) and 777 (11.1%).ConclusionUnbiased PEth half-lives and CIs can be calculated and put into use in laboratory information systems. Rounding or truncating data used for PEth half-life calculation widened CIs with misinterpretations of alcohol abstinence.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"319-326"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761892","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}