{"title":"Interpretable laboratory-data model for risk stratification of elevated NT-proBNP and its deployment in diagnostic support middleware.","authors":"Hidekazu Ishida, Noriko Ozawa, Masaya Tachikawa, Hiroki Nagasawa, Yohei Shirakami, Takatomo Watanabe, Hiroyuki Okura, Ryosuke Kikuchi","doi":"10.1177/00045632261438009","DOIUrl":"10.1177/00045632261438009","url":null,"abstract":"<p><p>BackgroundHeart 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.MethodsWe 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 = 3978) and a temporal external cohort (n = 14,903; Jun 2024-Jun 2025). Analyses were complete-case with no imputation.ResultsThe 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); and 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); and NPV 0.852 (0.842-0.861). Calibration and decision-curve analysis supported clinical utility.ConclusionsAn 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.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"435-444"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472379","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}
Omer Ozcan, Annemieke C Heijboer, Wendy Pj den Elzen
{"title":"A survey of clinical laboratories in the Netherlands regarding pre-analytical conditions of renin measurements to prevent cryoactivation.","authors":"Omer Ozcan, Annemieke C Heijboer, Wendy Pj den Elzen","doi":"10.1177/00045632261433341","DOIUrl":"10.1177/00045632261433341","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"413-419"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343562","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}
Shahaan Shafiq, Lana Roberts, Greg Williams, Robert Shorten
{"title":"The implementation of electronic clinical decision tools to reduce inappropriate urine and swab requests: A diagnostic stewardship intervention to reduce the environmental impact of laboratory testing.","authors":"Shahaan Shafiq, Lana Roberts, Greg Williams, Robert Shorten","doi":"10.1177/00045632261433352","DOIUrl":"10.1177/00045632261433352","url":null,"abstract":"<p><p>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 CO<sub>2</sub>e 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 CO<sub>2</sub>e. Similarly, wound samples decreased by 12.9%, saving 80 kg CO<sub>2</sub>e.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.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"420-426"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324407","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}
Megan Rodney, Kelly Rankin, Jenny Butler, Simon Thompson, Chris M Florkowski, Richard I King
{"title":"Familial pseudohyperkalaemia: An unusual cause of artefactual hyperkalaemia.","authors":"Megan Rodney, Kelly Rankin, Jenny Butler, Simon Thompson, Chris M Florkowski, Richard I King","doi":"10.1177/00045632261417119","DOIUrl":"10.1177/00045632261417119","url":null,"abstract":"<p><p>Strict homoeostatic control of potassium is necessary for normal muscle and neural function, and as a result, hyperkalaemia can be life-threatening and requires timely management. Prior to treating the patient, however, it is important to determine if hyperkalaemic blood test results are authentic and not due to pre-analytical factors as treatment in this context may provoke potentially dangerous hypokalaemia. We present the case of a 47-year-old female referred for further investigation following 2 years of otherwise unexplained intermittent hyperkalaemia. Her highest recorded potassium was 8.9 mmol/L (reference interval: 3.5-5.2 mmol/L). She was otherwise healthy, not on regular medications, and asymptomatic during these episodes. There was no evidence of associated electrocardiogram (ECG) changes. She had been referred to the Emergency Department twice in 6 months due to hyperkalaemia, but these episodes resolved on repeat testing without any intervention. Further investigation revealed a significant time- and temperature-dependent increase in potassium concentration in whole blood samples, compared to a control. <i>ABCB6</i> single gene testing revealed a heterozygous variant, c.1123 C>T, p. (Arg375Trp), consistent with a diagnosis of familial pseudohyperkalaemia (FP). This is an autosomal dominant condition, which results in increased efflux of potassium from red blood cells at sub-physiological temperatures. Whilst this is an <i>ex vivo</i> phenomenon, unless recognised it poses a clinical risk to patients as they may be treated erroneously.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"448-453"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148797","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":"Inosine attenuates glycolysis in erythrocytes via glucose transporter inhibition.","authors":"Yukio Kume, Motohiro Ohkubo, Naru NaKatuka, Sayaka Aritake-Okada, Naoyuki Yoshikawa, Teruhiko Yoshida, Hideaki Isago, Makoto Kurano","doi":"10.1177/00045632261433354","DOIUrl":"10.1177/00045632261433354","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"427-434"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324476","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}
Hyun-Woo Lee, Sang-Mi Kim, Hyun-Young Kim, Soo-Youn Lee, Hyung-Doo Park
{"title":"Evaluation of sample integrity and turnaround time upon implementation of a high-speed carrier-free pneumatic tube system.","authors":"Hyun-Woo Lee, Sang-Mi Kim, Hyun-Young Kim, Soo-Youn Lee, Hyung-Doo Park","doi":"10.1177/00045632261428924","DOIUrl":"10.1177/00045632261428924","url":null,"abstract":"<p><p>BackgroundPneumatic tube systems (PTSs) have revolutionized sample transport efficiency, yet concerns about sample integrity remain unresolved. This study evaluated the AirLab system (PazKorea, Hanam-si, Korea), a novel high-speed carrier-free PTS, for its impact on sample integrity and turnaround time (TAT) under controlled pre-analytical conditions.MethodsBlood specimens were collected in duplicate from 42 participants (30 healthy volunteers and 12 outpatients with chronic alcohol use) and randomly assigned to PTS or manual transport. Multiple laboratory parameters were analysed, including chemistry, hematology, coagulation, and heavy metal tests. Sample integrity was assessed by comparing test results between transport methods using both statistical analysis and clinical significance criteria based on total allowable error (TAE). Pre-analytical, analytical and total TATs were compared between transport methods.ResultsAmong 20 measurands, four showed statistically significant differences: glucose, potassium (K), lactate dehydrogenase (LD), and mean corpuscular volume (MCV). PTS yielded higher results for glucose, K and LD (average percentage biases: 1.88%, 2.01%, and 15.80%, respectively), while producing lower results for MCV (average percentage bias: -0.47%). Only LD showed clinically significant differences, as its average percentage bias exceeded its desirable TAE. PTS significantly reduced both pre-analytical and total TATs for all test types, with reductions ranging from 12.12% to 22.82% and 7.32% to 8.98%, respectively, whereas analytical TATs remained unchanged.ConclusionsThe AirLab system effectively preserves sample integrity for most laboratory parameters while improving operational efficiency through TAT reduction. However, the clinically significant elevation in LD levels necessitates careful interpretation when employing this system in clinical laboratories.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"403-412"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199962","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}
Kosuke Koyano, Makoto Arioka, Yuta Noguchi, Yuta Shinabe, Tomoaki Kusaka, Hirosuke Morita, Katsufumi Nishioka, Yasuhiro Nakao, Kota Inoue, Aya Morimoto, Shinji Nakamura, Sonoko Kondo, Yukihiko Konishi, Saneyuki Yasuda, Hitoshi Okada, Konomu Hirao, Takashi Kusaka
{"title":"Improved transcutaneous bilirubinometer for enhanced measurement accuracy in neonatal hyperbilirubinemia.","authors":"Kosuke Koyano, Makoto Arioka, Yuta Noguchi, Yuta Shinabe, Tomoaki Kusaka, Hirosuke Morita, Katsufumi Nishioka, Yasuhiro Nakao, Kota Inoue, Aya Morimoto, Shinji Nakamura, Sonoko Kondo, Yukihiko Konishi, Saneyuki Yasuda, Hitoshi Okada, Konomu Hirao, Takashi Kusaka","doi":"10.1177/00045632261424727","DOIUrl":"10.1177/00045632261424727","url":null,"abstract":"<p><p>BackgroundConventional transcutaneous bilirubinometers often underestimate total bilirubin (TB) levels at high concentrations, limiting their clinical utility in cases of neonatal hyperbilirubinemia. We aimed to address this shortcoming by developing and testing a novel type of advanced transcutaneous bilirubinometer that may enhance the early identification of severe hyperbilirubinemia, potentially reducing the need for invasive testing and exchange transfusions.MethodsWe developed a novel transcutaneous bilirubinometer with adjustable light intensity and detection distances. Transcutaneous bilirubin (TcB) measurements were obtained using both the novel device and a conventional JM-105 bilirubinometer in 66 instances in 62 neonates (≥36 weeks gestation). TB values measured in patient blood samples were used as reference values for calculating correlations and error metrics (i.e. mean squared error [MSE] and mean absolute error [MAE]).ResultsThe novel device showed strong correlation with TB values across all concentrations (R<sup>2</sup> = 0.96), including those ≥15 mg/dL (R<sup>2</sup> = 0.84), outperforming the JM-105 device (R<sup>2</sup> = 0.60 for TBs ≥15 mg/dL). The novel device also yielded lower MSE (1.53 vs 2.95) and MAE values (1.00 vs 1.39) than the JM-105.ConclusionsOur novel transcutaneous bilirubinometer demonstrated improved accuracy at higher bilirubin concentrations compared with a conventional JM-105 device.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"369-374"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103604","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}
M H Elise van Driel, Alan Han, Dirk J Grünhagen, Christian Ramakers
{"title":"Exploring the stability of whole blood samples for remote health care applications towards reliable home-based blood testing.","authors":"M H Elise van Driel, Alan Han, Dirk J Grünhagen, Christian Ramakers","doi":"10.1177/00045632261424746","DOIUrl":"10.1177/00045632261424746","url":null,"abstract":"<p><p>ObjectivesTo evaluate the stability of commonly used biomarkers in whole blood under various storage conditions, in order to assess their suitability for home-based blood collection in remote care settings.MethodsWhole blood samples were stored at 4-8°C, 20-25°C and 37°C for up to 72 h. Six pooled samples and two healthy volunteer samples were aliquoted and analysed at four time points (T0, T24, T48 and T72 h). A panel of 47 routine chemistry and immunochemistry biomarkers was measured in all samples. Recoveries relative to T0 were compared to within subject coefficients of variation of the individual biomarkers.ResultsMost biomarkers remained stable at refrigerated and room temperature conditions up to 72 h with a subset of biomarkers, mostly proteins and tumour markers also showing good to acceptable stability at 37°C. Several biomarkers, including potassium, inorganic phosphate and iron, consistently fell outside acceptable limits under multiple conditions. Others, such as sodium, calcium, ferritin, aspartate aminotransferase and cytokeratin fragment 21-1, were unstable only at 37°C. A few transient deviations were observed, but these were not consistent over time.ConclusionsHome-based blood sampling is feasible for a broad range of biomarkers, provided that heat exposure during transport is minimised. These findings are a first step in the further validation of selected analytes under real-world, capillary blood sampling conditions.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"375-381"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103598","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}
Sarah R Meadows, Amanda McKillion, Damon A Parkington, Albert Koulman, Kerry S Jones
{"title":"Comparability of serum folate concentration measured by a microbiological method, LC-MS/MS and immunoassay.","authors":"Sarah R Meadows, Amanda McKillion, Damon A Parkington, Albert Koulman, Kerry S Jones","doi":"10.1177/00045632261488256","DOIUrl":"10.1177/00045632261488256","url":null,"abstract":"<p><p>BackgroundFolate, vitamin B9, is an essential micronutrient for DNA replication and repair. Deficiency is associated with megaloblastic anaemia and fetal neural tube defects. Serum folate measurement provides a convenient biomarker of folate status in clinical and research settings, including nutritional surveys. The overall aim of this evaluation was to compare serum folate results measured from three different technologies within the same laboratory to determine systematic biases and equivalence between methods.Methods58 serum samples from the UK National Diet and Nutrition Survey were used to compare a microbiological method, a liquid chromatography tandem mass spectrometry method (LC-MS/MS) and a commercial immunoassay (Tosoh CL1200).ResultsThe within-run imprecision of all three assays was ≤7%, measured at two concentrations. The microbiological and LC-MS/MS methods were accurate against NIST Standard Reference Material and VITAL External Quality Assessment (EQA) target values. The plasma-based sample used for the NIST Standard Reference Material (SRM) was unsuitable for analysis by the Tosoh immunoassay; however, comparison with the VITAL EQA target values showed good accuracy. Using the serum samples, both the LC-MS/MS and Tosoh immunoassay methods showed a slight positive proportional bias compared to the microbiological method, whilst the Tosoh method also had an additional constant bias of 3-4 nmol/L compared to the other methods.ConclusionsThis data shows that the microbiological method, LC-MS/MS and Tosoh CL1200 immunoassay have acceptable accuracy, imprecision and agreement. The small concentration dependant bias is likely explainable by the expected characteristics of the individual methods and ability to detect and respond to different circulating forms of folate.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632261488256"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862775","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}