Pub Date : 2024-07-01Epub Date: 2024-07-02DOI: 10.1080/00365513.2024.2369993
Viktor Schutz Taune, Michal Zabczyk, Shu He, Anna Ågren, Margareta Blombäck, Håkan Wallén, Mika Skeppholm
Introduction: There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable.
Materials and methods: Blood samples from patients on dabigatran (n = 23), rivaroxaban (n = 26), or apixaban (n = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin.
Results: Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors.
Conclusions: Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.
{"title":"Effects of dabigatran, rivaroxaban, and apixaban on fibrin network permeability, thrombin generation, and fibrinolysis.","authors":"Viktor Schutz Taune, Michal Zabczyk, Shu He, Anna Ågren, Margareta Blombäck, Håkan Wallén, Mika Skeppholm","doi":"10.1080/00365513.2024.2369993","DOIUrl":"10.1080/00365513.2024.2369993","url":null,"abstract":"<p><strong>Introduction: </strong>There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable.</p><p><strong>Materials and methods: </strong>Blood samples from patients on dabigatran (<i>n</i> = 23), rivaroxaban (<i>n</i> = 26), or apixaban (<i>n</i> = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin.</p><p><strong>Results: </strong>Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors.</p><p><strong>Conclusions: </strong>Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493237","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}
Pub Date : 2024-07-01Epub Date: 2024-05-28DOI: 10.1080/00365513.2024.2359085
Arne Åsberg, Bjørn Johan Bolann
Internal quality control in clinical chemistry laboratories are based on analyzing samples of stable control materials among the patient samples. The control results are interpreted by using quality control rules that usually are designed to detect systematic errors. The best rules have a high probability of error detection (Ped), i.e. to detect the maximal allowable (critical) systematic error and a low probability of false rejection (Pfr, false alarm). In this work we show that quality control rules can be represented by points on a ROC curve which appears when Ped is plotted against Pfrand only the control limit is varied. Further, we introduce a new method for choosing the optimal control limit, analogous to choosing the optimal operating point on the ROC curve of a diagnostic test. This decision needs knowledge of the pretest probability of a critical systematic error, the benefit of detecting it when it occurs and the cost of false alarm. The ROC curve analysis showed that if rules based on N = 2 are used, mean rules outperform Westgard rules because the ROC curve of the mean rules was lying above the ROC curves of the Westgard rules. A mean rule also had a lower maximum expected increase in the number of unacceptable patient results reported during the presence of an out-of-control error condition (Max E(NUF)) than comparable Westgard rules.
{"title":"The diagnostic accuracy of quality control rules.","authors":"Arne Åsberg, Bjørn Johan Bolann","doi":"10.1080/00365513.2024.2359085","DOIUrl":"10.1080/00365513.2024.2359085","url":null,"abstract":"<p><p>Internal quality control in clinical chemistry laboratories are based on analyzing samples of stable control materials among the patient samples. The control results are interpreted by using quality control rules that usually are designed to detect systematic errors. The best rules have a high probability of error detection (P<sub>ed</sub>), i.e. to detect the maximal allowable (critical) systematic error and a low probability of false rejection (P<sub>fr</sub>, false alarm). In this work we show that quality control rules can be represented by points on a ROC curve which appears when P<sub>ed</sub> is plotted against P<sub>fr</sub> <i>and only the control limit is varied</i>. Further, we introduce a new method for choosing the optimal control limit, analogous to choosing the optimal operating point on the ROC curve of a diagnostic test. This decision needs knowledge of the pretest probability of a critical systematic error, the benefit of detecting it when it occurs and the cost of false alarm. The ROC curve analysis showed that if rules based on <i>N</i> = 2 are used, mean rules outperform Westgard rules because the ROC curve of the mean rules was lying above the ROC curves of the Westgard rules. A mean rule also had a lower maximum expected increase in the number of unacceptable patient results reported during the presence of an out-of-control error condition (Max E(N<sub>UF</sub>)) than comparable Westgard rules.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158245","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}
Pub Date : 2024-07-01Epub Date: 2024-06-27DOI: 10.1080/00365513.2024.2369982
Milan Dastych, Miloš Holánek, Jana Gottwaldová, Zdenka Čermáková, Alena Mikušková
Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.
{"title":"Impact of breast cancer neoadjuvant chemotherapy on plasma and urine amino acid profile, plasma proteins and nitrogen metabolism.","authors":"Milan Dastych, Miloš Holánek, Jana Gottwaldová, Zdenka Čermáková, Alena Mikušková","doi":"10.1080/00365513.2024.2369982","DOIUrl":"10.1080/00365513.2024.2369982","url":null,"abstract":"<p><p>Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459060","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}
Chimeric antigen receptor-T (CAR-T) cell therapy is currently the best-known type of immune effector cells therapy. For CAR T-cell therapy, the determination of CD3+ T cells is necessary for the quality control of fresh leukapheresis product as starting material. The aim was to validate analytical method for quantification of percentage and absolute count of T lymphocyte subtypes (CD3+, CD4+ and CD8+ cells) in fresh apheresis products using single-platform method on flow cytometer BD FACS Canto II. Validation study included determination of precision, trueness (bias), assessment of linearity, carryover, comparison of results obtained with two different protocols on flow cytometer for CD3+ cells determination and stability study. For between-run precision coefficients of variation (CVs) were <20%, as well as bias for all T-lymphocyte subtypes. For within-run precision, CVs were <10%, except for low CD8+ cell (percentage 10.51% and viable absolute count 12.37%). Comparison of results obtained with two different protocols for CD3+ cells determination shows no statistically significant difference. Statistically significant differences between results of the analysis of CD4+ cells in fresh samples and results obtained after storage at 4 °C (p = .004) and at room temperature (p = .018) were found. In conclusion, method for enumeration of T-lymphocyte subtypes can be used in routine work on BD FACS Canto II instrument for quality assessment of fresh cell products collected by leukapheresis procedure.
嵌合抗原受体-T(CAR-T)细胞疗法是目前最著名的免疫效应细胞疗法。对于 CAR T 细胞疗法来说,CD3+ T 细胞的测定对于作为起始材料的新鲜白细胞产品的质量控制是必要的。目的是在 BD FACS Canto II 流式细胞仪上使用单平台方法验证定量新鲜白细胞采集产物中 T 淋巴细胞亚型(CD3+、CD4+ 和 CD8+ 细胞)百分比和绝对计数的分析方法。验证研究包括测定精确度、真实度(偏差)、线性评估、携带、比较两种不同的流式细胞仪测定 CD3+ 细胞的方案所获得的结果以及稳定性研究。结果发现,运行间精密度(CVs)为 p = .004,室温下精密度(CVs)为 p = .018。总之,T淋巴细胞亚型的计数方法可用于 BD FACS Canto II 仪器的常规工作中,以评估通过白细胞清除程序收集的新鲜细胞产品的质量。
{"title":"Evaluation of a flow cytometry-based method for determination of T-lymphocyte subtypes for quality assessment of cell therapy products.","authors":"Vladimira Rimac, Ines Bojanić, Nikolina Blažević, Koraljka Gojčeta","doi":"10.1080/00365513.2024.2377961","DOIUrl":"10.1080/00365513.2024.2377961","url":null,"abstract":"<p><p>Chimeric antigen receptor-T (CAR-T) cell therapy is currently the best-known type of immune effector cells therapy. For CAR T-cell therapy, the determination of CD3+ T cells is necessary for the quality control of fresh leukapheresis product as starting material. The aim was to validate analytical method for quantification of percentage and absolute count of T lymphocyte subtypes (CD3+, CD4+ and CD8+ cells) in fresh apheresis products using single-platform method on flow cytometer BD FACS Canto II. Validation study included determination of precision, trueness (bias), assessment of linearity, carryover, comparison of results obtained with two different protocols on flow cytometer for CD3+ cells determination and stability study. For between-run precision coefficients of variation (CVs) were <20%, as well as bias for all T-lymphocyte subtypes. For within-run precision, CVs were <10%, except for low CD8+ cell (percentage 10.51% and viable absolute count 12.37%). Comparison of results obtained with two different protocols for CD3+ cells determination shows no statistically significant difference. Statistically significant differences between results of the analysis of CD4+ cells in fresh samples and results obtained after storage at 4 °C (<i>p</i> = .004) and at room temperature (<i>p</i> = .018) were found. In conclusion, method for enumeration of T-lymphocyte subtypes can be used in routine work on BD FACS Canto II instrument for quality assessment of fresh cell products collected by leukapheresis procedure.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604087","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}
Pub Date : 2024-07-01Epub Date: 2024-07-10DOI: 10.1080/00365513.2024.2377960
Hanna Fjeldheim Dale, Milada Hagen, Chirajyoti Deb, Viggo Skar, Jørgen Valeur
Background: Reduced activity of the sucrase-isomaltase (SI) enzyme can cause gastrointestinal symptoms. Biochemical measurement of SI activity in small intestinal biopsies is presently considered the gold standard for the diagnosis of SI deficiency, but this invasive test is not suitable as a routine diagnostic tool.
Aim: To evaluate a 13C-sucrose-breath test (13CSBT) as a diagnostic tool for SI deficiency in an adult population.
Methods: 13CSBT results were compared to sucrase activity measured in duodenal biopsies.
Results: Forty patients with gastrointestinal symptoms were included in the study, 4 of whom had celiac disease and the rest (n = 36) had normal histological findings. Nine patients (22.5%) had low sucrase activity measured using duodenal biopsies. No correlation was observed between enzymatic sucrase activity and the 13CSBT results. The 13CSBT-curves for the celiac patients versus patients with normal duodenal histology demonstrated that the patients with celiac disease were within the lower range of the distribution.
Conclusion: We observed a mismatch between the 13CSBT results and the biochemically measured sucrase activity, suggesting that SI activity is not uniformly distributed throughout the small intestines. This methodological discrepancy should be acknowledged when diagnosing SI deficiency.
背景:蔗糖异麦芽糖酶(SI)活性降低可导致胃肠道症状。目的:评估 13C-蔗糖呼气试验(13CSBT)作为诊断成人 SI 缺乏症的工具的效果。方法:将 13CSBT 结果与十二指肠活检中测得的蔗糖酶活性进行比较:研究共纳入了 40 名有胃肠道症状的患者,其中 4 人患有乳糜泻,其余患者(n = 36)的组织学检查结果正常。九名患者(22.5%)的十二指肠活检结果显示蔗糖酶活性较低。酶促蔗糖酶活性与 13CSBT 结果之间没有相关性。乳糜泻患者与十二指肠组织学正常患者的 13CSBT 曲线显示,乳糜泻患者的分布范围较低:我们观察到 13CSBT 结果与生化测定的蔗糖酶活性不匹配,这表明蔗糖酶活性在整个小肠的分布并不均匀。在诊断 SI 缺乏症时,应认识到这一方法上的差异。
{"title":"Diagnosing sucrase-isomaltase deficiency: a comparison of a <sup>13</sup>C-sucrose breath test and a duodenal enzyme assay.","authors":"Hanna Fjeldheim Dale, Milada Hagen, Chirajyoti Deb, Viggo Skar, Jørgen Valeur","doi":"10.1080/00365513.2024.2377960","DOIUrl":"10.1080/00365513.2024.2377960","url":null,"abstract":"<p><strong>Background: </strong>Reduced activity of the sucrase-isomaltase (SI) enzyme can cause gastrointestinal symptoms. Biochemical measurement of SI activity in small intestinal biopsies is presently considered the gold standard for the diagnosis of SI deficiency, but this invasive test is not suitable as a routine diagnostic tool.</p><p><strong>Aim: </strong>To evaluate a <sup>13</sup>C-sucrose-breath test (<sup>13</sup>CSBT) as a diagnostic tool for SI deficiency in an adult population.</p><p><strong>Methods: </strong><sup>13</sup>CSBT results were compared to sucrase activity measured in duodenal biopsies.</p><p><strong>Results: </strong>Forty patients with gastrointestinal symptoms were included in the study, 4 of whom had celiac disease and the rest (<i>n</i> = 36) had normal histological findings. Nine patients (22.5%) had low sucrase activity measured using duodenal biopsies. No correlation was observed between enzymatic sucrase activity and the <sup>13</sup>CSBT results. The <sup>13</sup>CSBT-curves for the celiac patients versus patients with normal duodenal histology demonstrated that the patients with celiac disease were within the lower range of the distribution.</p><p><strong>Conclusion: </strong>We observed a mismatch between the <sup>13</sup>CSBT results and the biochemically measured sucrase activity, suggesting that SI activity is not uniformly distributed throughout the small intestines. This methodological discrepancy should be acknowledged when diagnosing SI deficiency.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564244","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}
Pub Date : 2024-05-01Epub Date: 2024-05-06DOI: 10.1080/00365513.2024.2346908
Andreas Ingebrigtsen, Sahrai Saeed, Terje Hjalmar Larsen, Håkon Reikvam
Amyloidosis is a disease characterized by the deposition of protein fibrils. Cardiac involvement is a significant factor in determining prognosis. This study aimed to examine the clinical profile, outcomes, and long-term mortality rates in patients with transthyretin (ATTR) and amyloid light-chain (AL) amyloidosis. The retrospective cohort study included 94 patients with amyloidosis (69 with AL and 25 with ATTR amyloidosis) diagnosed between 2010 and 2022. The study involved multimodality imaging (ECG, echocardiography and cardiac magnetic resonance (CMR) data and survival analyses. Patients with ATTR amyloidosis were older and had a higher proportion of males compared to those with AL amyloidosis. Cardiac involvement was more prevalent in the ATTR group, including atrial fibrillation (AF), while pleural and pericardial effusion were more frequent in the AL group. Biomarkers such as NT-proBNP and troponin T were significantly elevated in both groups and were associated with all-cause mortality only in univariate analyses. CMR data, especially typical late gadolinium enhancement (LGE) was not associated with increased mortality, while pleural effusion and left atrial dilatation on echocardiography were identified as powerful predictors of mortality. In conclusion, both AL and ATTR amyloidosis exhibited poor outcomes. Cardiac involvement, particularly dilated left atrium and pleural effusion on echocardiography were associated with an increased risk of mortality, while typical LGE on CMR was not.
{"title":"Clinical and imaging characteristics of patients with cardiac amyloidosis- a single center observational study.","authors":"Andreas Ingebrigtsen, Sahrai Saeed, Terje Hjalmar Larsen, Håkon Reikvam","doi":"10.1080/00365513.2024.2346908","DOIUrl":"10.1080/00365513.2024.2346908","url":null,"abstract":"<p><p>Amyloidosis is a disease characterized by the deposition of protein fibrils. Cardiac involvement is a significant factor in determining prognosis. This study aimed to examine the clinical profile, outcomes, and long-term mortality rates in patients with transthyretin (ATTR) and amyloid light-chain (AL) amyloidosis. The retrospective cohort study included 94 patients with amyloidosis (69 with AL and 25 with ATTR amyloidosis) diagnosed between 2010 and 2022. The study involved multimodality imaging (ECG, echocardiography and cardiac magnetic resonance (CMR) data and survival analyses. Patients with ATTR amyloidosis were older and had a higher proportion of males compared to those with AL amyloidosis. Cardiac involvement was more prevalent in the ATTR group, including atrial fibrillation (AF), while pleural and pericardial effusion were more frequent in the AL group. Biomarkers such as NT-proBNP and troponin T were significantly elevated in both groups and were associated with all-cause mortality only in univariate analyses. CMR data, especially typical late gadolinium enhancement (LGE) was not associated with increased mortality, while pleural effusion and left atrial dilatation on echocardiography were identified as powerful predictors of mortality. In conclusion, both AL and ATTR amyloidosis exhibited poor outcomes. Cardiac involvement, particularly dilated left atrium and pleural effusion on echocardiography were associated with an increased risk of mortality, while typical LGE on CMR was not.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862507","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}
Pub Date : 2024-05-01Epub Date: 2024-05-14DOI: 10.1080/00365513.2024.2338738
Nilhan Nurlu, Abdulkadir Cat, Kamil Taha Ucar
Aim: Measuring uncertainty (MU) is crucial to ensure the accuracy and precision of laboratory results. This study compares the ISO 20914 and Nordtest guidelines to analyze the MU values for 20 clinical chemistry analytes over six months.
Methods: The researchers calculated MU components, including within-laboratory reproducibility (Rw), laboratory analytical performance bias (u(bias)), and combined standard uncertainty (uc), based on internal quality control and external quality assessment data. The final expanded uncertainty (U) values were determined by multiplying the combined uncertainty with a coverage factor (k = 2 for 95% Confidence Interval), following each guideline's respective procedures. Clinical chemistry analytes were analyzed on Roche Cobas 6000 c501 auto analyzer (Roche Diagnostics, Mannheim, Germany) and manufacturer's kits were used analysis.
Results: The results show that 11 out of 20 clinical chemistry analytes met the targeted maximum allowable measurement uncertainty (MAU) values when calculated according to ISO 20914 guideline. Also, 11 out of 20 clinical chemistry analytes' MU values met the MAU values with the Nordtest guideline's recommended calculations. However, some tests met the MAU in the ISO 20914 approach but not in the Nordtest guideline, and vice versa.
Conclusions: The study found that intermediate precision (uRw) in the ISO 20914 approach and performance bias (u(bias)) in the Nordtest approach significantly impacted MU values. The research highlights the importance of standardization in MU calculation approaches across clinical laboratories. These findings have implications for patient care and clinical decision-making, emphasizing the importance of selecting appropriate laboratory guidelines for routine use.
目的:测量不确定性(MU)对于确保实验室结果的准确性和精确性至关重要。本研究比较了 ISO 20914 和 Nordtest 准则,分析了 20 种临床化学分析物在六个月内的不确定度值:研究人员根据内部质量控制和外部质量评估数据计算了MU的组成部分,包括实验室内重现性(Rw)、实验室分析性能偏差(u(bias))和综合标准不确定度(uc)。最终的扩展不确定度 (U) 值是按照每份指南各自的程序,将综合不确定度乘以覆盖因子(k = 2,95% 置信区间)确定的。使用罗氏 Cobas 6000 c501 自动分析仪(罗氏诊断公司,德国曼海姆)分析临床化学分析物,并使用制造商提供的试剂盒进行分析:结果表明,根据 ISO 20914 准则计算,20 种临床化学分析物中有 11 种达到了最大允许测量不确定度 (MAU) 的目标值。此外,在 20 个临床化学分析项目中,有 11 个项目的 MU 值符合 Nordtest 指南推荐的 MAU 值。然而,有些检测项目在 ISO 20914 方法中符合 MAU 值,但在 Nordtest 指南中却不符合,反之亦然:研究发现,ISO 20914 方法中的中间精度(uRw)和 Nordtest 方法中的性能偏差(u(bias))对 MAU 值有很大影响。这项研究强调了临床实验室MU计算方法标准化的重要性。这些发现对患者护理和临床决策具有重要意义,强调了选择合适的实验室指南作为常规使用的重要性。
{"title":"Measurement uncertainty in clinical chemistry: ISO 20914 versus nordtest or intermediate precision versus bias.","authors":"Nilhan Nurlu, Abdulkadir Cat, Kamil Taha Ucar","doi":"10.1080/00365513.2024.2338738","DOIUrl":"10.1080/00365513.2024.2338738","url":null,"abstract":"<p><strong>Aim: </strong>Measuring uncertainty (MU) is crucial to ensure the accuracy and precision of laboratory results. This study compares the ISO 20914 and Nordtest guidelines to analyze the MU values for 20 clinical chemistry analytes over six months.</p><p><strong>Methods: </strong>The researchers calculated MU components, including within-laboratory reproducibility (Rw), laboratory analytical performance bias (<i>u</i>(bias)), and combined standard uncertainty (<i>u</i><sub>c</sub>), based on internal quality control and external quality assessment data. The final expanded uncertainty (<i>U</i>) values were determined by multiplying the combined uncertainty with a coverage factor (<i>k</i> = 2 for 95% Confidence Interval), following each guideline's respective procedures. Clinical chemistry analytes were analyzed on Roche Cobas 6000 c501 auto analyzer (Roche Diagnostics, Mannheim, Germany) and manufacturer's kits were used analysis.</p><p><strong>Results: </strong>The results show that 11 out of 20 clinical chemistry analytes met the targeted maximum allowable measurement uncertainty (MAU) values when calculated according to ISO 20914 guideline. Also, 11 out of 20 clinical chemistry analytes' MU values met the MAU values with the Nordtest guideline's recommended calculations. However, some tests met the MAU in the ISO 20914 approach but not in the Nordtest guideline, and vice versa.</p><p><strong>Conclusions: </strong>The study found that intermediate precision (<i>u</i><sub>Rw</sub>) in the ISO 20914 approach and performance bias (<i>u</i>(bias)) in the Nordtest approach significantly impacted MU values. The research highlights the importance of standardization in MU calculation approaches across clinical laboratories. These findings have implications for patient care and clinical decision-making, emphasizing the importance of selecting appropriate laboratory guidelines for routine use.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923152","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}
Pub Date : 2024-05-01Epub Date: 2024-05-20DOI: 10.1080/00365513.2024.2352844
Marina Slobodkin, Ari Polachek, Victoria Furer, Ori Elkayam, Smadar Gertel
PsoP27 is an antigen expressed in psoriatic lesions. It plays an inflammatory role in psoriasis. This study objective was to characterize antibodies (Abs) against PsoP27 in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Levels of Abs against native and citrullinated PsoP27 in PsA and RA patients' synovial fluid (SF) and sera were determined by ELISA. SF of osteoarthritis (OA) patients and sera of healthy donors were used as controls. Levels of Abs against PsoP27 were correlated with disease activity scores. Abs against native and citrullinated PsoP27 levels in SF of PsA (n = 48; 0.38 ± 0.03 and 0.44 ± 0.04, respectively) and RA (n = 22; 0.57 ± 0.1 and 0.62 ± 0.09, respectively) were significantly higher than in OA patients (n = 23; 0.14 ± 0.01 and 0.15 ± 0.01, respectively) (p < .0001). For both Abs, there were no significant differences between their level in PsA and RA patients. There was no difference in the level of Abs against citrullinated PsoP27 in SF of seronegative versus seropositive RA patients. Levels of Abs against both native and citrullinated PsoP27 in the SF and level of systemic C-reactive protein in PsA correlated positively, while in RA there were no significant correlations with disease activity scores. No differences in level of Abs against PsoP27 were found in the sera of all three study groups. Abs against native and citrullinated PsoP27 are present in PsA and RA SF but not in those of OA patients, suggesting a potential role of those Abs in inflammatory joint diseases.
{"title":"Identification of autoantibodies against PsoP27 in synovial fluid derived from psoriatic arthritis and rheumatoid arthritis patients.","authors":"Marina Slobodkin, Ari Polachek, Victoria Furer, Ori Elkayam, Smadar Gertel","doi":"10.1080/00365513.2024.2352844","DOIUrl":"10.1080/00365513.2024.2352844","url":null,"abstract":"<p><p>PsoP27 is an antigen expressed in psoriatic lesions. It plays an inflammatory role in psoriasis. This study objective was to characterize antibodies (Abs) against PsoP27 in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Levels of Abs against native and citrullinated PsoP27 in PsA and RA patients' synovial fluid (SF) and sera were determined by ELISA. SF of osteoarthritis (OA) patients and sera of healthy donors were used as controls. Levels of Abs against PsoP27 were correlated with disease activity scores. Abs against native and citrullinated PsoP27 levels in SF of PsA (<i>n</i> = 48; 0.38 ± 0.03 and 0.44 ± 0.04, respectively) and RA (<i>n</i> = 22; 0.57 ± 0.1 and 0.62 ± 0.09, respectively) were significantly higher than in OA patients (<i>n</i> = 23; 0.14 ± 0.01 and 0.15 ± 0.01, respectively) (<i>p</i> < .0001). For both Abs, there were no significant differences between their level in PsA and RA patients. There was no difference in the level of Abs against citrullinated PsoP27 in SF of seronegative versus seropositive RA patients. Levels of Abs against both native and citrullinated PsoP27 in the SF and level of systemic C-reactive protein in PsA correlated positively, while in RA there were no significant correlations with disease activity scores. No differences in level of Abs against PsoP27 were found in the sera of all three study groups. Abs against native and citrullinated PsoP27 are present in PsA and RA SF but not in those of OA patients, suggesting a potential role of those Abs in inflammatory joint diseases.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066116","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}
Pub Date : 2024-05-01Epub Date: 2024-04-29DOI: 10.1080/00365513.2024.2346914
Mingkuan Su, Haiying Wu, Hongbin Chen, Jianfeng Guo, Zongyun Chen, Jie Qiu, Jiancheng Huang
Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.
{"title":"Early prediction of sepsis-induced respiratory tract infection using a biomarker-based machine-learning algorithm.","authors":"Mingkuan Su, Haiying Wu, Hongbin Chen, Jianfeng Guo, Zongyun Chen, Jie Qiu, Jiancheng Huang","doi":"10.1080/00365513.2024.2346914","DOIUrl":"10.1080/00365513.2024.2346914","url":null,"abstract":"<p><p>Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859581","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}