The Dymind automated hematology analyzer includes the five-part analyzers DF55 and DH76 and the six-part analyzer DH615, which features reticulocyte parameters and an artificial intelligence-driven analysis technology. This study evaluated the performance of these analyzers in assessing precision and conducting method comparisons to determine the diagnostic accuracy and clinical efficacy of the Dymind automated system.
Methods
We assessed precision and conducted a method comparison by analyzing complete blood count (CBC) and white blood cell (WBC) differential data from the Dymind DF55, DH76, and DH615. Results were compared with those from the Sysmex XN-3000 analyzer.
Results
The Dymind-series analyzers demonstrated high between-run precision for all CBC and WBC differential parameters. Method comparison revealed a strong correlation (r = 0.80–0.99) between the Dymind and Sysmex analyzers for most CBC parameters, except for mean corpuscular hemoglobin concentration and basophil counts.
Conclusions
The Dymind-series analyzer exhibited a strong analytical performance across all standard CBC and WBC differential count parameters, validating their precision and comparability with a reference system for routine hematological testing.
{"title":"Performance evaluation of the new Dymind automated hematology analyzer","authors":"Tipparat Penglong , Wanicha Tepakhan , Nasra Tehyoh , Yanisa Na Songkhla , Chakkrit Songnak , Kanitta Srinoun","doi":"10.1016/j.plabm.2025.e00507","DOIUrl":"10.1016/j.plabm.2025.e00507","url":null,"abstract":"<div><h3>Introduction</h3><div>The Dymind automated hematology analyzer includes the five-part analyzers DF55 and DH76 and the six-part analyzer DH615, which features reticulocyte parameters and an artificial intelligence-driven analysis technology. This study evaluated the performance of these analyzers in assessing precision and conducting method comparisons to determine the diagnostic accuracy and clinical efficacy of the Dymind automated system.</div></div><div><h3>Methods</h3><div>We assessed precision and conducted a method comparison by analyzing complete blood count (CBC) and white blood cell (WBC) differential data from the Dymind DF55, DH76, and DH615. Results were compared with those from the Sysmex XN-3000 analyzer.</div></div><div><h3>Results</h3><div>The Dymind-series analyzers demonstrated high between-run precision for all CBC and WBC differential parameters. Method comparison revealed a strong correlation (r = 0.80–0.99) between the Dymind and Sysmex analyzers for most CBC parameters, except for mean corpuscular hemoglobin concentration and basophil counts.</div></div><div><h3>Conclusions</h3><div>The Dymind-series analyzer exhibited a strong analytical performance across all standard CBC and WBC differential count parameters, validating their precision and comparability with a reference system for routine hematological testing.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00507"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-15DOI: 10.1016/j.plabm.2025.e00506
Bo Zhou , Xiaoying Li , Shitong Cheng , Zhiwei Zhou , Hui Kang
Objectives
Patient-based real-time quality control (PBRTQC) is essential for clinical laboratory management but struggles with detecting small systematic errors. This study presents the patient-based pre-classified real-time quality control with neural network (PCRTQC-NN) model, utilizing neural networks to improve error detection by extracting analytical features from testing instruments.
Methods
Using PCRTQC's clustering analysis, we pre-classified and processed Na, CHOL, ALT, and CR data from 611,031 patients. A neural network autoencoder, trained using TensorFlow with mean squared error (MSE) as the loss function, extracted the testing instrument's analytical features under error-free conditions. Systematic errors were identified by comparing reconstruction residuals between test and reconstructed data. The average number of patient samples until error detection (ANPed) evaluated the model performance.
Results
The PCRTQC-NN's error detection surpasses traditional algorithms Compared to PCRTQC, it reduced the ANPed for ALT by 37 % (constant error, CE) and 22 % (proportional error, PE) at 1 total error allowable (TEa), with comparable results for other analytes. For 0.5 TEa errors, the ANPed for CHOL decreased by 23 % (CE) and 22 % (PE), for ALT by 14 % (CE) and 6 % (PE), and for CR by 4 % (CE) and 9 % (PE), enhancing error detection capabilities for analytes with high inter-individual variability and sensitivity to smaller errors.
Conclusions
PCRTQC-NN significantly enhances systematic error detection compared to PCRTQC, leveraging autoencoders to extract analytical features as discrete signals, thus improving SNR for high-variability analytes. It promises improved laboratory efficiency and inter-laboratory standardization via robust feature models. Future multi-center studies will validate broad applicability across diverse settings.
{"title":"Patient-based pre-classified real-time quality control with neural network (PCRTQC-NN)","authors":"Bo Zhou , Xiaoying Li , Shitong Cheng , Zhiwei Zhou , Hui Kang","doi":"10.1016/j.plabm.2025.e00506","DOIUrl":"10.1016/j.plabm.2025.e00506","url":null,"abstract":"<div><h3>Objectives</h3><div>Patient-based real-time quality control (PBRTQC) is essential for clinical laboratory management but struggles with detecting small systematic errors. This study presents the patient-based pre-classified real-time quality control with neural network (PCRTQC-NN) model, utilizing neural networks to improve error detection by extracting analytical features from testing instruments.</div></div><div><h3>Methods</h3><div>Using PCRTQC's clustering analysis, we pre-classified and processed Na, CHOL, ALT, and CR data from 611,031 patients. A neural network autoencoder, trained using TensorFlow with mean squared error (MSE) as the loss function, extracted the testing instrument's analytical features under error-free conditions. Systematic errors were identified by comparing reconstruction residuals between test and reconstructed data. The average number of patient samples until error detection (ANPed) evaluated the model performance.</div></div><div><h3>Results</h3><div>The PCRTQC-NN's error detection surpasses traditional algorithms Compared to PCRTQC, it reduced the ANPed for ALT by 37 % (constant error, CE) and 22 % (proportional error, PE) at 1 total error allowable (TEa), with comparable results for other analytes. For 0.5 TEa errors, the ANPed for CHOL decreased by 23 % (CE) and 22 % (PE), for ALT by 14 % (CE) and 6 % (PE), and for CR by 4 % (CE) and 9 % (PE), enhancing error detection capabilities for analytes with high inter-individual variability and sensitivity to smaller errors.</div></div><div><h3>Conclusions</h3><div>PCRTQC-NN significantly enhances systematic error detection compared to PCRTQC, leveraging autoencoders to extract analytical features as discrete signals, thus improving SNR for high-variability analytes. It promises improved laboratory efficiency and inter-laboratory standardization via robust feature models. Future multi-center studies will validate broad applicability across diverse settings.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00506"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-22DOI: 10.1016/j.plabm.2025.e00512
Sixtus Aguree , Arthur Owora , Patricia Silveyra
Background
Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments.
Aim
To assess phase-specific variation in iron biomarkers and the prevalence of ID and IDA in non-pregnant women aged 18–44 years using 2003–2006 NHANES data.
Methods
We analyzed 1484 women with complete reproductive and iron status data. Menstrual cycle phase was categorized as menstruation (day 1–5), follicular phase (6−15), early/mid luteal phase (16–23), and late luteal phase (24–35). Eight biomarkers were analyzed: serum iron (SI), transferrin saturation (%TS), soluble transferrin receptor (sTfR), ferritin, erythrocyte protoporphyrin (EPP), hemoglobin (Hb), mean corpuscular volume (MCV) and body iron index (BII). ID and IDA were defined using ferritin-, MCV- and BII-based diagnostic models. All statistical models accounted for the complex design of the NHANES survey.
Results
SI and %TS were lowest during menstruation and increased across the cycle, peaking in the early/mid-luteal phase (SI: p = 0.001; %TS: p = 0.003). sTfR was highest during menstruation (p < 0.05) compared to other phases, consistent with increased iron requirements. Ferritin, EPP, Hb and MCV remained stable across phases. The prevalence of ID varied by model (10.5 %–22.0 %) but showed no consistent phase differences. In contrast, the prevalence of IDA decreased after menstruation, with composite IDA estimates dropping from 7.5 % during menstruation to 3.7 % in the late luteal phase (p = 0.033).
Conclusions
Iron biomarkers and IDA prevalence vary systematically across the menstrual cycle, with iron status being lowest during menstruation and recovering in the luteal phase. Consideration of menstrual phase may improve diagnostic accuracy and interpretation of iron biomarkers in women of reproductive age.
背景：铁缺乏症（ID）和缺铁性贫血（IDA）在育龄妇女中很常见，但月经周期对铁生物标志物的影响尚未明确，在临床和公共卫生评估中经常被忽视。目的利用2003-2006年NHANES数据，评估18-44岁非妊娠女性铁生物标志物的阶段性变化以及ID和IDA的患病率。方法对1484例女性进行完整的生殖和铁元素状况分析。月经周期阶段分为月经期（1-5天）、卵泡期（6 - 15天）、早/中黄体期（16-23天）和晚黄体期（24-35天）。分析8项生物指标：血清铁（SI）、转铁蛋白饱和度（%TS）、可溶性转铁蛋白受体（sTfR）、铁蛋白、红细胞原卟啉（EPP）、血红蛋白（Hb）、平均红细胞体积（MCV）和体铁指数（BII）。使用基于铁蛋白、MCV和bii的诊断模型来定义ID和IDA。所有统计模型都解释了NHANES调查的复杂设计。结果SI和%TS在月经期间最低，在月经周期中升高，在黄体前期/中期达到峰值（SI: p = 0.001; %TS: p = 0.003）。与其他时期相比，月经期间sTfR最高（p < 0.05），与铁需求量增加一致。铁蛋白、EPP、Hb和MCV各期均保持稳定。不同模型的ID患病率不同（10.5% - 22.0%），但没有一致的相位差异。相比之下，月经后IDA的患病率下降，综合IDA估计值从月经期间的7.5%下降到黄体晚期的3.7% （p = 0.033）。结论铁生物标志物和IDA患病率在月经周期中存在系统性变化，月经期铁水平最低，在黄体期恢复。考虑月经期可以提高诊断的准确性和对育龄妇女铁生物标志物的解释。
{"title":"Cyclical fluctuations of iron biomarkers in women: Diagnostic implications for iron deficiency","authors":"Sixtus Aguree , Arthur Owora , Patricia Silveyra","doi":"10.1016/j.plabm.2025.e00512","DOIUrl":"10.1016/j.plabm.2025.e00512","url":null,"abstract":"<div><h3>Background</h3><div>Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments.</div></div><div><h3>Aim</h3><div>To assess phase-specific variation in iron biomarkers and the prevalence of ID and IDA in non-pregnant women aged 18–44 years using 2003–2006 NHANES data.</div></div><div><h3>Methods</h3><div>We analyzed 1484 women with complete reproductive and iron status data. Menstrual cycle phase was categorized as menstruation (day 1–5), follicular phase (6−15), early/mid luteal phase (16–23), and late luteal phase (24–35). Eight biomarkers were analyzed: serum iron (SI), transferrin saturation (%TS), soluble transferrin receptor (sTfR), ferritin, erythrocyte protoporphyrin (EPP), hemoglobin (Hb), mean corpuscular volume (MCV) and body iron index (BII). ID and IDA were defined using ferritin-, MCV- and BII-based diagnostic models. All statistical models accounted for the complex design of the NHANES survey.</div></div><div><h3>Results</h3><div>SI and %TS were lowest during menstruation and increased across the cycle, peaking in the early/mid-luteal phase (SI: p = 0.001; %TS: p = 0.003). sTfR was highest during menstruation (p < 0.05) compared to other phases, consistent with increased iron requirements. Ferritin, EPP, Hb and MCV remained stable across phases. The prevalence of ID varied by model (10.5 %–22.0 %) but showed no consistent phase differences. In contrast, the prevalence of IDA decreased after menstruation, with composite IDA estimates dropping from 7.5 % during menstruation to 3.7 % in the late luteal phase (p = 0.033).</div></div><div><h3>Conclusions</h3><div>Iron biomarkers and IDA prevalence vary systematically across the menstrual cycle, with iron status being lowest during menstruation and recovering in the luteal phase. Consideration of menstrual phase may improve diagnostic accuracy and interpretation of iron biomarkers in women of reproductive age.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00512"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-30DOI: 10.1016/j.plabm.2025.e00501
Hyunji Choi , Ina Jeong , Jeongeun Cheon , Chul-Min Park , Sun Min Lee
Background
Ensuring stability in medical laboratories through quality control (QC) is crucial and requires fitted rules to prevent false alerts and identify errors. This study demonstrates how the introduction of new QC rules to align with individual total allowable error (TEa) affects laboratory efficiency and error detection.
Methods
Changes in the performance of 26 biochemical tests before and after applying new internal quality control (IQC) rules were studied. Pre-Phase utilized uniform QC rules (1–3s, 2-2s, 2/3-2s, R-4s, 4-1s, and 12-x) while Post-Phase adopted new QC rules selected using Westgard Adviser (Bio-Rad Inc., USA). Sigma metrics were calculated using TEa and precision and bias from IQC data, compared to the peer group. Efficiency was assessed by comparing QC-repeat rates, turnaround times (TAT), and proficiency test (PT) results.
Results
QC-repeats due to violations averaged 5.6 % in the Pre-Phase and decreased to 2.5 % in the Post-Phase. As a result, the rate of out-of-TAT in peak-time decreased from 29.4 % to 15.2 %. In Pre-Phase, 67 of 271 cases exceeded the 2 standard deviation index (SDI) in the PT, which was reduced to 24 cases in Post-Phase. Cases exceeding the 3 SDI significantly decreased from 27 to 4 in the Post-Phase.
Conclusion
The introduction of sigma-based rules in the internal quality control process improved laboratory efficiency by reducing QC-repeat, recalibration, and TAT while maintaining quality, demonstrating a valuable balance between efficiency and analytical performance.
{"title":"Application of sigma-based quality control rules for the efficiency of internal quality control","authors":"Hyunji Choi , Ina Jeong , Jeongeun Cheon , Chul-Min Park , Sun Min Lee","doi":"10.1016/j.plabm.2025.e00501","DOIUrl":"10.1016/j.plabm.2025.e00501","url":null,"abstract":"<div><h3>Background</h3><div>Ensuring stability in medical laboratories through quality control (QC) is crucial and requires fitted rules to prevent false alerts and identify errors. This study demonstrates how the introduction of new QC rules to align with individual total allowable error (TEa) affects laboratory efficiency and error detection.</div></div><div><h3>Methods</h3><div>Changes in the performance of 26 biochemical tests before and after applying new internal quality control (IQC) rules were studied. Pre-Phase utilized uniform QC rules (1–3s, 2-2s, 2/3-2s, R-4s, 4-1s, and 12-x) while Post-Phase adopted new QC rules selected using Westgard Adviser (Bio-Rad Inc., USA). Sigma metrics were calculated using TEa and precision and bias from IQC data, compared to the peer group. Efficiency was assessed by comparing QC-repeat rates, turnaround times (TAT), and proficiency test (PT) results.</div></div><div><h3>Results</h3><div>QC-repeats due to violations averaged 5.6 % in the Pre-Phase and decreased to 2.5 % in the Post-Phase. As a result, the rate of out-of-TAT in peak-time decreased from 29.4 % to 15.2 %. In Pre-Phase, 67 of 271 cases exceeded the 2 standard deviation index (SDI) in the PT, which was reduced to 24 cases in Post-Phase. Cases exceeding the 3 SDI significantly decreased from 27 to 4 in the Post-Phase.</div></div><div><h3>Conclusion</h3><div>The introduction of sigma-based rules in the internal quality control process improved laboratory efficiency by reducing QC-repeat, recalibration, and TAT while maintaining quality, demonstrating a valuable balance between efficiency and analytical performance.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00501"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-01DOI: 10.1016/j.plabm.2025.e00503
Yu Li , Hongjuan Wei , Limei Sun , Dongsong Tang , Tiantian Wang , Yanhua Yu
Individuals infected with the Human Immunodeficiency Virus (HIV) face an elevated risk of Mycobacterium tuberculosis (MTB) infection. Clinical diagnosis of HIV/MTB coinfection presents substantial challenges, with co-infected patients exhibiting high mortality rates and representing a critical public health burden. The diagnostic process is complicated by atypical clinical presentations, frequent extrapulmonary tuberculosis involvement, difficulties in obtaining adequate sputum specimens, and low mycobacterial loads in samples—factors that severely limit the utility of conventional diagnostic methods such as sputum smear microscopy. Furthermore, HIV-associated immunosuppression diminishes the reliability of immunological diagnostic approaches. Recent advancements in molecular diagnostics have revolutionized tuberculosis detection in this vulnerable population. This review critically evaluates current laboratory methods for MTB detection in HIV/MTB co-infected individuals, analyzing their diagnostic performance, inherent limitations, and clinical applicability across diverse healthcare settings.
{"title":"Advancements in laboratory diagnostics for HIV/MTB coinfection: Integrating conventional methods with emerging technologies","authors":"Yu Li , Hongjuan Wei , Limei Sun , Dongsong Tang , Tiantian Wang , Yanhua Yu","doi":"10.1016/j.plabm.2025.e00503","DOIUrl":"10.1016/j.plabm.2025.e00503","url":null,"abstract":"<div><div>Individuals infected with the Human Immunodeficiency Virus (HIV) face an elevated risk of Mycobacterium tuberculosis (MTB) infection. Clinical diagnosis of HIV/MTB coinfection presents substantial challenges, with co-infected patients exhibiting high mortality rates and representing a critical public health burden. The diagnostic process is complicated by atypical clinical presentations, frequent extrapulmonary tuberculosis involvement, difficulties in obtaining adequate sputum specimens, and low mycobacterial loads in samples—factors that severely limit the utility of conventional diagnostic methods such as sputum smear microscopy. Furthermore, HIV-associated immunosuppression diminishes the reliability of immunological diagnostic approaches. Recent advancements in molecular diagnostics have revolutionized tuberculosis detection in this vulnerable population. This review critically evaluates current laboratory methods for MTB detection in HIV/MTB co-infected individuals, analyzing their diagnostic performance, inherent limitations, and clinical applicability across diverse healthcare settings.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00503"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145320997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.plabm.2025.e00509
Merve Sena Odabasi, Zeynep Mine Yalcinkaya Kara
Background
The icteric index (I-index) is a practical and low-cost method for screening hyperbilirubinemia and potentially reducing unnecessary total bilirubin (TBil) testing. This study was designed to determine a safe I-index to detect TBil above the upper reference range to avoid unnecessary TBil orders. The reflexive addition of TBil in samples where I-index is above the cut-off value and TBil measurement is not initially planned will be a secondary gain of the study.
Methods
This study included 267185 samples with TBil test results and corresponding I-index values. TBil and I-index values were measured with the Roche Cobas 8000 (c701) and Cobas 6000 (c501) analyzers. Statistical analyses were performed using SPSS 15.0, with ROC curve analysis used to determine the optimal I-index cut-off for TBil screening.
Results
An I-index cut-off of 34.2 μmol/L provided the lowest false negativity (0.45 %), highest specificity (97.1 %), and negative predictive value (99.5 %). Using this cut-off point, if we had reached 100 % NPV, 87.4 % of TBil tests in the group receiving inpatient/outpatient treatment with Cobas-8000 and 89.8 % in the emergency group with Cobas 6000 could have been saved.
Conclusions
This is the study with the largest sample size. The sample size is critical in determining a reliable I-index cut-off point. We conclude that I-index should not replace TBil since the NPV was not 100 %; however, it seems reasonable to reflexively add TBil testing in samples where the I-index is above the cut-off value and TBil measurement was not initially planned.
{"title":"Can the icteric index be used instead of total bilirubin in addition to being a preanalytical marker? Icteric index in the laboratory","authors":"Merve Sena Odabasi, Zeynep Mine Yalcinkaya Kara","doi":"10.1016/j.plabm.2025.e00509","DOIUrl":"10.1016/j.plabm.2025.e00509","url":null,"abstract":"<div><h3>Background</h3><div>The icteric index (I-index) is a practical and low-cost method for screening hyperbilirubinemia and potentially reducing unnecessary total bilirubin (TBil) testing. This study was designed to determine a safe I-index to detect TBil above the upper reference range to avoid unnecessary TBil orders. The reflexive addition of TBil in samples where I-index is above the cut-off value and TBil measurement is not initially planned will be a secondary gain of the study.</div></div><div><h3>Methods</h3><div>This study included 267185 samples with TBil test results and corresponding I-index values. TBil and I-index values were measured with the Roche Cobas 8000 (c701) and Cobas 6000 (c501) analyzers. Statistical analyses were performed using SPSS 15.0, with ROC curve analysis used to determine the optimal I-index cut-off for TBil screening.</div></div><div><h3>Results</h3><div>An I-index cut-off of 34.2 μmol/L provided the lowest false negativity (0.45 %), highest specificity (97.1 %), and negative predictive value (99.5 %). Using this cut-off point, if we had reached 100 % NPV, 87.4 % of TBil tests in the group receiving inpatient/outpatient treatment with Cobas-8000 and 89.8 % in the emergency group with Cobas 6000 could have been saved.</div></div><div><h3>Conclusions</h3><div>This is the study with the largest sample size. The sample size is critical in determining a reliable I-index cut-off point. We conclude that I-index should not replace TBil since the NPV was not 100 %; however, it seems reasonable to reflexively add TBil testing in samples where the I-index is above the cut-off value and TBil measurement was not initially planned.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00509"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.plabm.2025.e00511
Ariel Mundo Ortiz , Jean-Philippe Emond , Vincent Weng-Jy Cheung , Sahar Saeed , Philippe Desmarais , François Larivière , Pierre-Olivier Hétu , Robert Goulden , Quoc Dinh Nguyen
Objectives
The current criterion used to determine whether the reference interval (RI) can be used for interpretation is based on the index of individuality (II), estimated using biological variation (BV). We hypothesized that pathological variation (PV), the shift between healthy and unhealthy states, varies across biomarkers and may be considered for interpretation with BV. We explored how jointly considering PV and BV impacts the clinical interpretation (diagnostic sensitivity and specificity) of RIs.
Methods
We propose the index of pathology (IP), a ratio of within-to between-subject coefficients of variation that jointly considers PV and BV. Using a large EHR database from a tertiary care center, we obtained IP estimates for 19 laboratory tests. As a means of comparison, the II was obtained from the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) BV database. PV impact was analyzed using the absolute difference between IP and II (ΔIP-II).
Results
798,800 observations from 17,082 adult patients were analyzed. For most biomarkers, the IP (mean = 1.99, range = 0.55–8.03) differed from the II (mean = 0.54, range = 0.27–0.86). Lowest IPs were for creatinine (IP = 0.55, ΔIP-II = 0.28) and bilirubin (IP = 1.05, ΔIP-II = 0.24). Highest IPs were for aspartate transaminase (IP = 4.56, ΔIP-II = 4.13) and creatine kinase (IP = 8.03, ΔIP-II = 7.60). Hormones and proteins exhibited high PV impact (ΔIP-II>1.0).
Conclusion
Differences between variational estimates that only account for healthy states (II-BV) and those that consider healthy and unhealthy states (IP-BV + PV) vary widely among biomarkers, highlighting the differential impact of PV on their interpretation. For biomarkers where IP is high, the RI may be useful to identify unhealthy individuals.
{"title":"The impact of pathological fluctuations versus biological variation on the interpretation of laboratory values","authors":"Ariel Mundo Ortiz , Jean-Philippe Emond , Vincent Weng-Jy Cheung , Sahar Saeed , Philippe Desmarais , François Larivière , Pierre-Olivier Hétu , Robert Goulden , Quoc Dinh Nguyen","doi":"10.1016/j.plabm.2025.e00511","DOIUrl":"10.1016/j.plabm.2025.e00511","url":null,"abstract":"<div><h3>Objectives</h3><div>The current criterion used to determine whether the reference interval (RI) can be used for interpretation is based on the index of individuality (II), estimated using biological variation (BV). We hypothesized that pathological variation (PV), the shift between healthy and unhealthy states, varies across biomarkers and may be considered for interpretation with BV. We explored how jointly considering PV and BV impacts the clinical interpretation (diagnostic sensitivity and specificity) of RIs.</div></div><div><h3>Methods</h3><div>We propose the index of pathology (IP), a ratio of within-to between-subject coefficients of variation that jointly considers PV and BV. Using a large EHR database from a tertiary care center, we obtained IP estimates for 19 laboratory tests. As a means of comparison, the II was obtained from the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) BV database. PV impact was analyzed using the absolute difference between IP and II (Δ<sub>IP-II</sub>).</div></div><div><h3>Results</h3><div>798,800 observations from 17,082 adult patients were analyzed. For most biomarkers, the IP (mean = 1.99, range = 0.55–8.03) differed from the II (mean = 0.54, range = 0.27–0.86). Lowest IPs were for creatinine (IP = 0.55, Δ<sub>IP-II</sub> = 0.28) and bilirubin (IP = 1.05, Δ<sub>IP-II</sub> = 0.24). Highest IPs were for aspartate transaminase (IP = 4.56, Δ<sub>IP-II</sub> = 4.13) and creatine kinase (IP = 8.03, Δ<sub>IP-II</sub> = 7.60). Hormones and proteins exhibited high PV impact (Δ<sub>IP-II</sub>>1.0).</div></div><div><h3>Conclusion</h3><div>Differences between variational estimates that only account for healthy states (II-BV) and those that consider healthy and unhealthy states (IP-BV + PV) vary widely among biomarkers, highlighting the differential impact of PV on their interpretation. For biomarkers where IP is high, the RI may be useful to identify unhealthy individuals.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00511"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.plabm.2025.e00500
Sung Wan Kang , Ok-Ju Kang , Young-Jae Lee , Hee Jung Jung , Min-Seo Lee , Ji-Young Lee , Yong-Man Kim , Shin-Wha Lee
Background
Circulating tumor DNA (ctDNA) has emerged as a valuable biomarker in liquid biopsies for monitoring treatment responses in cancer patients. However, detecting ctDNA in epithelial ovarian cancer (EOC) is challenging due to its high heterogeneity and the absence of hotspot driver mutations. Therefore, a personalized approach to ctDNA analysis is essential, tailored to the specific tumor mutations of each EOC patient. In this study, we aimed to evaluate a droplet digital PCR (ddPCR) method targeting various genetic alterations in ctDNA identified through a targeted next-generation sequencing (NGS) panel in EOC tumors.
Methods
EOC tumor tissues were sequenced using a targeted NGS panel to identify oncogenic mutations. ddPCR assays were subsequently designed and optimized to detect these tumor-specific mutations in ctDNA. ctDNA levels were monitored and compared with CA-125 for EOC.
Results
Fourteen pathogenic mutations, including TP53, PIK3CA, PTEN, KRAS, and RB1, were identified in 13 patients with EOC and selected as targets for ctDNA detection. The performance of ddPCR assays was validated for 10 mutations, and mutated ctDNA was successfully detected for 8 mutations in 7 patients. In most cases, ctDNA levels showed trends consistent with CA-125 levels, reflecting the treatment response. However, in one case, PTEN (E91∗) mutated ctDNA was detected during recurrence, while CA-125 levels remained within the normal range.
Conclusion
This study demonstrates the clinical utility of ddPCR for monitoring treatment responses in EOC by targeting patient-specific mutations. Integrating ddPCR with NGS-based mutation identification offers an effective approach for assessing therapeutic outcomes in EOC patients.
{"title":"Tumor-informed circulating tumor DNA detection for personalized monitoring of treatment response in epithelial ovarian cancer","authors":"Sung Wan Kang , Ok-Ju Kang , Young-Jae Lee , Hee Jung Jung , Min-Seo Lee , Ji-Young Lee , Yong-Man Kim , Shin-Wha Lee","doi":"10.1016/j.plabm.2025.e00500","DOIUrl":"10.1016/j.plabm.2025.e00500","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) has emerged as a valuable biomarker in liquid biopsies for monitoring treatment responses in cancer patients. However, detecting ctDNA in epithelial ovarian cancer (EOC) is challenging due to its high heterogeneity and the absence of hotspot driver mutations. Therefore, a personalized approach to ctDNA analysis is essential, tailored to the specific tumor mutations of each EOC patient. In this study, we aimed to evaluate a droplet digital PCR (ddPCR) method targeting various genetic alterations in ctDNA identified through a targeted next-generation sequencing (NGS) panel in EOC tumors.</div></div><div><h3>Methods</h3><div>EOC tumor tissues were sequenced using a targeted NGS panel to identify oncogenic mutations. ddPCR assays were subsequently designed and optimized to detect these tumor-specific mutations in ctDNA. ctDNA levels were monitored and compared with CA-125 for EOC.</div></div><div><h3>Results</h3><div>Fourteen pathogenic mutations, including <em>TP53, PIK3CA, PTEN, KRAS,</em> and <em>RB1</em>, were identified in 13 patients with EOC and selected as targets for ctDNA detection. The performance of ddPCR assays was validated for 10 mutations, and mutated ctDNA was successfully detected for 8 mutations in 7 patients. In most cases, ctDNA levels showed trends consistent with CA-125 levels, reflecting the treatment response. However, in one case, <em>PTEN</em> (E91∗) mutated ctDNA was detected during recurrence, while CA-125 levels remained within the normal range.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the clinical utility of ddPCR for monitoring treatment responses in EOC by targeting patient-specific mutations. Integrating ddPCR with NGS-based mutation identification offers an effective approach for assessing therapeutic outcomes in EOC patients.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00500"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-28DOI: 10.1016/j.plabm.2025.e00513
Qichuan Fu , Jie Wang , Liya Yue , Tianyu Lu , Wenyu Shi , Cuidan Li , Xiaoyuan Jiang , Peihan Wang , Fei Chen
Background
Bloodstream infections (BSIs) caused by bacteria, viruses, and parasites pose a global health challenge, with high mortality rates. Traditional blood cultures are considered the gold standard but are limited by long turnaround times, low sensitivity, and reliance on culturable pathogens. Cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker for rapid pathogen detection.
Materials and methods
In this study, we analyzed plasma cfDNA from 102 BSI patients (42 bacterial, 34 viral, and 23 parasitic infections) using next-generation sequencing to examine the differences in cfDNA fragmentation patterns across pathogen types.
Results
Pathogen-derived cfDNA fragments were shorter than human-derived cfDNA (median: 166 bp), with bacterial cfDNA averaging 126 bp and viral cfDNA 140 bp. Bacterial cfDNA fragments were typically shorter than viral ones, revealing distinctive patterns that could differentiate bacterial from viral infections. Fragment lengths varied among bacterial and viral species, suggesting the potential for pathogen-specific detection. EBV-derived cfDNA, at 163 bp, resembled human cfDNA possibly due to its nucleosome-bound form, while parasite-derived cfDNA had a broader distribution (median: 165 bp), indicating limitations in using cfDNA length for detecting parasitic infections.
Conclusions
Our findings demonstrate that pathogen-derived cfDNA exhibits distinct fragmentation patterns, providing a potential non-invasive tool to complement traditional diagnostic methods, particularly for hard-to-culture pathogens. However, further studies with larger sample sizes are needed to refine pathogen-specific fragment length ranges and validate its clinical applicability.
{"title":"Fragmentation patterns of pathogen-derived cell-free DNA as a promising non-invasive biomarker for bloodstream infection diagnosis","authors":"Qichuan Fu , Jie Wang , Liya Yue , Tianyu Lu , Wenyu Shi , Cuidan Li , Xiaoyuan Jiang , Peihan Wang , Fei Chen","doi":"10.1016/j.plabm.2025.e00513","DOIUrl":"10.1016/j.plabm.2025.e00513","url":null,"abstract":"<div><h3>Background</h3><div>Bloodstream infections (BSIs) caused by bacteria, viruses, and parasites pose a global health challenge, with high mortality rates. Traditional blood cultures are considered the gold standard but are limited by long turnaround times, low sensitivity, and reliance on culturable pathogens. Cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker for rapid pathogen detection.</div></div><div><h3>Materials and methods</h3><div>In this study, we analyzed plasma cfDNA from 102 BSI patients (42 bacterial, 34 viral, and 23 parasitic infections) using next-generation sequencing to examine the differences in cfDNA fragmentation patterns across pathogen types.</div></div><div><h3>Results</h3><div>Pathogen-derived cfDNA fragments were shorter than human-derived cfDNA (median: 166 bp), with bacterial cfDNA averaging 126 bp and viral cfDNA 140 bp. Bacterial cfDNA fragments were typically shorter than viral ones, revealing distinctive patterns that could differentiate bacterial from viral infections. Fragment lengths varied among bacterial and viral species, suggesting the potential for pathogen-specific detection. EBV-derived cfDNA, at 163 bp, resembled human cfDNA possibly due to its nucleosome-bound form, while parasite-derived cfDNA had a broader distribution (median: 165 bp), indicating limitations in using cfDNA length for detecting parasitic infections.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that pathogen-derived cfDNA exhibits distinct fragmentation patterns, providing a potential non-invasive tool to complement traditional diagnostic methods, particularly for hard-to-culture pathogens. However, further studies with larger sample sizes are needed to refine pathogen-specific fragment length ranges and validate its clinical applicability.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00513"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-03DOI: 10.1016/j.plabm.2025.e00502
Erica K. Barnell , Kimberly Kruse , Elizabeth M. Wurtzler , Maya Crowder Scott , Andrew R. Barnell , Eric J. Duncavage
Background & aims
Traditional stool-based colorectal cancer (CRC) screening tests require patients to collect and swab their own stool, which can reduce adherence due to aversion and introduce variability from user error. A novel multitarget stool RNA test (mt-sRNA, ColoSense) eliminates the need for scraping or swabbing stool. Instead, patients merely deposit and ship a sample to the lab. Once recieved, laboratory technologists swab the sample and quantify hemoglobin concentrations using the fecal immunochemical test (FIT). This study evaluates the reliability and reproducibility of this in-laboratory fecal sampling method.
Methods
Analytical validation was performed by generating stool pools with known hemoglobin concentrations and exposing pools to various conditions prior to testing with the in-lab FIT. Analytical validation assessed freeze thaw stability, interfering substances, stool input volume, precision, and in-transit stability. Clinical equivalency was also evaluated.
Results
All studies met predefined acceptance criteria. The assay demonstrated stability for up to three freeze-thaw cycles. Interference testing with nine dietary substances showed no impact on assay performance. The in-lab FIT maintained accuracy across five different stool input volumes and demonstrated high precision. In-transit stability was confirmed for up to 120 hours, supporting sample robustness during shipping and handling. Clinical equivalency demonstrated in-lab FIT sensitivity of 78 % for CRC and 33 % for advanced adenomas, aligning with previously reported performance of the at-home FIT method.
Conclusions
Analytical validation of the in-lab FIT demonstrates the reliability and robustness of this streamlined, single-sample collection method. This improvement could enhance adherence and patient ease-of-use in stool-based CRC screening.
{"title":"Analytical validation of a scrape-free multitarget stool RNA test for colorectal cancer screening","authors":"Erica K. Barnell , Kimberly Kruse , Elizabeth M. Wurtzler , Maya Crowder Scott , Andrew R. Barnell , Eric J. Duncavage","doi":"10.1016/j.plabm.2025.e00502","DOIUrl":"10.1016/j.plabm.2025.e00502","url":null,"abstract":"<div><h3>Background & aims</h3><div>Traditional stool-based colorectal cancer (CRC) screening tests require patients to collect and swab their own stool, which can reduce adherence due to aversion and introduce variability from user error. A novel multitarget stool RNA test (mt-sRNA, ColoSense) eliminates the need for scraping or swabbing stool. Instead, patients merely deposit and ship a sample to the lab. Once recieved, laboratory technologists swab the sample and quantify hemoglobin concentrations using the fecal immunochemical test (FIT). This study evaluates the reliability and reproducibility of this in-laboratory fecal sampling method.</div></div><div><h3>Methods</h3><div>Analytical validation was performed by generating stool pools with known hemoglobin concentrations and exposing pools to various conditions prior to testing with the in-lab FIT. Analytical validation assessed freeze thaw stability, interfering substances, stool input volume, precision, and in-transit stability. Clinical equivalency was also evaluated.</div></div><div><h3>Results</h3><div>All studies met predefined acceptance criteria. The assay demonstrated stability for up to three freeze-thaw cycles. Interference testing with nine dietary substances showed no impact on assay performance. The in-lab FIT maintained accuracy across five different stool input volumes and demonstrated high precision. In-transit stability was confirmed for up to 120 hours, supporting sample robustness during shipping and handling. Clinical equivalency demonstrated in-lab FIT sensitivity of 78 % for CRC and 33 % for advanced adenomas, aligning with previously reported performance of the at-home FIT method.</div></div><div><h3>Conclusions</h3><div>Analytical validation of the in-lab FIT demonstrates the reliability and robustness of this streamlined, single-sample collection method. This improvement could enhance adherence and patient ease-of-use in stool-based CRC screening.</div></div>","PeriodicalId":20421,"journal":{"name":"Practical Laboratory Medicine","volume":"47 ","pages":"Article e00502"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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