Clinical biochemistry最新文献

Validation and optimization of reference intervals for serum free light chains in Chinese patients with chronic kidney disease. 中国慢性肾病患者血清游离轻链参考区间的验证与优化

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-23 DOI: 10.1016/j.clinbiochem.2026.111120

Wen Xu, Yifeng Shen, Jiayi Huang, Ying Xiong, Baishen Pan, Beili Wang, Wei Guo, Jing Zhu, Wenqi Shao

Objective: To explore the applicability of the laboratory-specific sFLC reference intervals in patients with CKD and to define new sFLC reference intervals on N-Latex platform in Chinese CKD patients.

Methods: We retrospectively analyzed clinical data from 1,700 patients at all stages of CKD who attended Zhongshan Hospital, Fudan University, between 1 January 2023 and 31 December 2025; the cohort comprised 1,066 males and 538 females with 60 (IQR49-69) years. sFLC concentrations and κ/λ ratio were characterized, and stage-specific 95% reference intervals were derived from 1135 randomly selected CKD patients and validated in other 565 patients. The clinical utility of these intervals was further validated with 36 patients initially diagnosed with LC-monoclonal gammopathy and eGFR < 60 mL/min/1.73 m².

Results: The laboratory-specific reference intervals (κFLC 9.6-23.2 mg/L, λFLC 11.6-37.5 mg/L, κ/λ ratio 0.540-1.150) showed limitations in CKD patients, with 96.2%, 85.0% and 12.2% of individuals falling outside these intervals, respectively. We derived CKD-stage-specific 95% reference intervals stratified by eGFR: eGFR 30-59 mL/min/1.73 m²: κFLC 17.9-103.0 mg/L, λFLC 20.7-112.3 mg/L, κ/λ ratio 0.489-1.401; eGFR < 30 mL/min/1.73 m²: κFLC 42.5-297.8 mg/L, λFLC 49.7-338.8 mg/L, κ/λ ratio 0.518-1.245. The novel CKD-specific reference intervals led a reduction of 11.3% and 3.9% in abnormal κ/λ ratio rates among patients with eGFR 30-59 mL/min/1.73 m² and eGFR < 30 mL/min/1.73 m², respectively. All 36 LC-monoclonal gammopathy patients with eGFR < 60 mL/min/1.73 m² exhibited an abnormal κ/λ ratio ;none fell within the novel κ/λ ratio reference interval.

Conclusion: The CKD-specific sFLC reference intervals on N-Latex platform significantly reduce the proportion of abnormal sFLC results and enhance the application value of sFLC in CKD patients.

目的：探讨实验室特异性sFLC参考区间在CKD患者中的适用性，并在N-Latex平台上定义中国CKD患者新的sFLC参考区间。方法：回顾性分析2023年1月1日至2025年12月31日在复旦大学中山医院就诊的1700例不同阶段CKD患者的临床资料；该队列包括1066名男性和538名女性，年龄为60岁（IQR49-69）。对sFLC浓度和κ/λ比值进行了表征，并从随机选择的1135例CKD患者中获得了分期特异性95%参考区间，并在其他565例患者中得到了验证。这些间隔的临床效用在36例最初诊断为lc -单克隆γ病和eGFR 2的患者中得到进一步验证。结果：实验室特异性参考区间（κ flc 9.6-23.2 mg/L, λ flc 11.6-37.5 mg/L， κ/λ比值0.54 -1.150）在CKD患者中存在局限性，分别有96.2%，85.0%和12.2%的个体不在这些区间内。我们得到了以eGFR分层的ckd分期特异性95%参考区间：eGFR 30-59 mL/min/1.73 m2; κ flc 17.9-103.0 mg/L, λ flc 20.7-112.3 mg/L， κ/λ比值0.489-1.401；表皮生长因子受体 2:κ方法42.5 - -297.8 mg / L,λ方法49.7 - -338.8 mg / L,κλ比0.518 - -1.245。在eGFR 30-59 mL/min/1.73 m2和eGFR 2的患者中，新的ckd特异性参考区间导致异常κ/λ比率分别降低11.3%和3.9%。36例伴有eGFR 2的lc -单克隆γ病患者均表现出异常的κ/λ比值；没有一个在新的κ/λ比参考区间内。结论：N-Latex平台上CKD特异性sFLC参考区间显著降低了sFLC结果异常的比例，增强了sFLC在CKD患者中的应用价值。

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引用次数: 0

Corrigendum to "Genomic sequencing enhances metabolic newborn screening in Thailand" [Clin. Biochem. 142 (2026) 111107]. “基因组测序增强泰国新生儿代谢筛查”的勘误表[临床]。生物化学学报，2004,22(3):357 - 357。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-11 DOI: 10.1016/j.clinbiochem.2026.111110

Chulaluck Kuptanon, Pawinee Innark, Kannikar Punnapum, Supaporn Nammoonnoy, Rotjanapan Pankanjanato, Maliwan Numnuan, Orapan Sripichai, Sukanya Wattanapokayakit, Punna Kunhapan, Ekke Kunphol

引用次数: 0

Autoantibody testing in neuromuscular medicine: assay technologies, interpretation, and clinical utility 神经肌肉医学中的自身抗体检测：分析技术、解释和临床应用。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-02-01 DOI: 10.1016/j.clinbiochem.2026.111092

Tony Zhang , John R. Mills , Divyanshu Dubey , Christopher J. Klein

Neuromuscular autoantibody testing is an essential component in the diagnosis and management of autoimmune neuromuscular disorders. These immune-mediated diseases target antigens found in nerves, muscles, and neuromuscular junctions, and may occasionally involve the central nervous system, resulting in complex clinical presentations. Developments in antibody identification and validation have provided clinically relevant biomarkers for diagnostic, therapeutic, and prognostic purposes. Among antibody-associated neuromuscular disorders, paraneoplastic onconeural autoantibodies are of particular significance, as their presence may direct search for specific underlying malignancies. Appropriate ordering and interpretation of these tests should be integrated with clinical and electrodiagnostic (CEDX) findings. Given that these disorders are often rare, estimating an optimal pre-test probability is important to improve test accuracy and reduce false positive outcomes. Online clinical calculators are available to help clinicians determine appropriate testing strategies for some disorders. This review summarizes principal neuromuscular antibodies, current testing approaches, and the influence of laboratory data on patient care.

神经肌肉自身抗体检测是自身免疫性神经肌肉疾病诊断和管理的一个组成部分。这些免疫性炎症性疾病以神经、肌肉和神经肌肉连接处的抗原为靶点，偶尔也可能累及中枢神经系统，导致复杂的临床表现。抗体鉴定和验证的发展为诊断、治疗和预后提供了临床相关的生物标志物。在抗体相关的神经肌肉疾病中，副肿瘤神经自身抗体具有特别重要的意义，因为它们的存在可以指导寻找特定的潜在恶性肿瘤。这些测试的适当排序和解释应与临床和电诊断（CEDX）结果相结合。鉴于这些疾病通常是罕见的，估计一个最佳的前测试概率是重要的，以提高测试的准确性和减少假阳性结果。在线临床计算器可以帮助临床医生确定一些疾病的适当测试策略。本文综述了主要的神经肌肉抗体，目前的测试方法，以及实验室数据对患者护理的影响。

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引用次数: 0

Evidence-based extension of reagent shelf-life beyond expiry using patient-based moving averages, westgard sigma rules, and CLSI EP25 使用基于患者的移动平均线、westgard sigma规则和CLSI EP25，循证延长试剂的保质期。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-02-01 DOI: 10.1016/j.clinbiochem.2026.111094

Mohamed Mokhtar Khelil , Tony Badrick

Background

Reagent stability is a significant determinant of analytical reliability in clinical laboratories. Post-expiry reagent use is often discouraged due to the potential risk of systematic bias; however, empirical data supporting or refuting such restrictions are limited.

Methods

This study evaluated the post-expiry performance of free T3 (FT3) and free T4 (FT4) immunoassays on the Abbott Architect i1000SR analyzer using an integrated framework combining three complementary approaches: (i) a simulation-optimized moving average (MA) model based on real patient data (ii) Westgard Sigma rules quality control, and (iii) Clinical and Laboratory Standards Institute EP25-A drift analysis. The MA was optimised via Monte Carlo simulations using a step-shift bias model, which defined the optimal window size (N) for 90% detection power and 0% false rejection rate. Stability was then assessed across three reagent lots per analyte, spanning both pre- and post-expiration phases.

Results

Westgard rules provided the earliest analytical alerts, while EP25 confirmed sustained drift relative to allowable total error. The MA detected progressive instability, showing strong concordance with EP25 after lag correction (N × cadence). FT4 indicated extended stability of up to 19 months post-expiry, while FT3 showed limited stability (<4 months). These differences reflected distinct assay robustness and kinetics.

Conclusions

The combination of Westgard sigma rules, EP25, and simulation-optimized MA provides a reproducible, data-driven framework for post-expiry reagent stability assessment. Optimizing MA with real patient data enhances detection performance, bridging theoretical quality-control design and routine laboratory application. This integrated approach enables laboratories to make scientifically justified, cost-effective decisions regarding reagent reuse beyond manufacturer expiry dates.

背景：试剂稳定性是临床实验室分析可靠性的重要决定因素。由于潜在的系统性偏倚风险，通常不鼓励使用过期后的试剂；然而，支持或反驳这种限制的经验数据是有限的。方法：本研究在雅培Architect i1000SR分析仪上评估游离T3 （FT3）和游离T4 （FT4）免疫测定的过期后性能，采用结合三种互补方法的集成框架：(i)基于真实患者数据的模拟优化移动平均（MA）模型；（ii） Westgard Sigma规则质量控制；（iii）临床和实验室标准协会EP25-A漂移分析。采用步移偏置模型通过蒙特卡罗模拟对MA进行了优化，该模型定义了90%检测功率和0%误拒率的最佳窗口大小(N)。然后对每个分析物的三个试剂批次进行稳定性评估，包括过期前和过期后的阶段。结果：Westgard规则提供了最早的分析警报，而EP25则确认了相对于允许总误差的持续漂移。MA检测到进行性不稳定，滞后校正后与EP25表现出很强的一致性（N × 节拍）。FT4显示出有效期后长达19 个月的延长稳定性，而FT3显示出有限的稳定性(结论：Westgard sigma规则、EP25和模拟优化MA的组合为有效期后试剂稳定性评估提供了可重复的、数据驱动的框架。利用真实患者数据优化MA可以提高检测性能，连接理论质量控制设计和常规实验室应用。这种综合方法使实验室能够在超过制造商有效期的试剂重复使用方面做出科学合理、具有成本效益的决策。

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引用次数: 0

Corrigendum to “Improving the environmental impact paradox of clinical medical laboratories” [Clin. Biochem. 141 (2026) 111063] “改善临床医学实验室的环境影响悖论”的勘误表[临床。生物化学学报，2014,29(3):444 - 444。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.clinbiochem.2026.111091

Pernilla Sörme, Scott Weitze

引用次数: 0

Interference and failure: The challenge of high-concentration IgM monoclonal protein in capillary zone electrophoresis 干扰与失败：高浓度IgM单克隆蛋白在毛细管区带电泳中的挑战。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-02-15 DOI: 10.1016/j.clinbiochem.2026.111099

Yanhua Zhao, Minjie Zhang, Wei Gan

Background

Capillary zone electrophoresis (CZE) is a standard method for serum protein separation, but its performance can be compromised by IgM monoclonal proteins, leading to false-negative results.

Methods

We report a case of Waldenström macroglobulinemia (IgM 56.05 g/L) with repeated CZE failure. Immunofixation electrophoresis (IFE) confirmed an IgM kappa monoclonal protein. Four pretreatment protocols were evaluated: 1) 37°C incubation; 2) dilution with distilled water; 3) dilution with 0.9% saline; and 4) pretreatment with β‑mercaptoethanol (BME). Gel-based serum protein electrophoresis (SPE) and immunosubtraction CZE were also performed to investigate the interference mechanism.

Results

Initial CZE failed to yield an interpretable electrophoretogram. Incubation at 37°C showed no improvement. Dilution with distilled water induced visible precipitation and resulted in a false-negative electrophoretic pattern with a marked drop in measured total protein. Dilution with saline prevented precipitation but still failed to reveal a distinct monoclonal spike, despite biochemical measurements consistent with high globulin levels. In contrast, pretreatment with BME successfully restored a clear monoclonal spike in the β‑γ region on CZE, demonstrating restored solubility and proper migration. IFE corroborated the presence of the IgM kappa monoclonal protein. Gel-based SPE successfully showed a distinct M-protein band without interference, while immunosubtraction CZE failed under both temperature conditions, supporting cryoglobulin-related interference.

Conclusions

Very high IgM concentrations, particularly with cryoglobulin activity, can cause complete CZE failure not resolved by standard dilution or heating. The interference likely involves capillary obstruction from protein aggregation or temperature-dependent re-precipitation within the capillary. BME pretreatment is a critical intervention for unmasking IgM monoclonal proteins when CZE results are inconsistent with other laboratory findings, thereby preventing diagnostic errors.

背景：毛细管区带电泳（CZE）是血清蛋白分离的标准方法，但其性能可能受到IgM单克隆蛋白的影响，导致假阴性结果。方法：我们报告一例Waldenström巨球蛋白血症（IgM 56.05 g/L）伴有反复CZE失败。免疫固定电泳（IFE）证实了IgM kappa单克隆蛋白。评估4种预处理方案：1)37℃孵育；2)用蒸馏水稀释；3) 0.9%生理盐水稀释；4) β -巯基乙醇（BME）预处理。同时采用凝胶型血清蛋白电泳（SPE）和免疫减影CZE （CZE）研究其干扰机制。结果：初始CZE未能产生可解释的电泳图。37℃孵育无明显改善。用蒸馏水稀释诱导可见的沉淀，并导致假阴性电泳模式与测量的总蛋白显著下降。用生理盐水稀释防止沉淀，但仍未能显示出明显的单克隆尖峰，尽管生化测量与高球蛋白水平一致。相比之下，BME预处理成功地恢复了CZE β - γ区一个清晰的单克隆峰，显示了恢复的溶解度和适当的迁移。IFE证实了IgM kappa单克隆蛋白的存在。凝胶型SPE在无干扰的情况下成功显示出明显的m蛋白条带，而免疫减相法CZE在两种温度条件下均失败，支持冷球蛋白相关干扰。结论：非常高的IgM浓度，特别是具有低温球蛋白活性的IgM浓度，可导致CZE完全失效，而不能通过标准稀释或加热解决。这种干扰可能与毛细管内蛋白质聚集或温度依赖性再沉淀引起的毛细血管阻塞有关。当CZE结果与其他实验室结果不一致时，BME预处理是揭示IgM单克隆蛋白的关键干预措施，从而防止诊断错误。

{"title":"Interference and failure: The challenge of high-concentration IgM monoclonal protein in capillary zone electrophoresis","authors":"Yanhua Zhao, Minjie Zhang, Wei Gan","doi":"10.1016/j.clinbiochem.2026.111099","DOIUrl":"10.1016/j.clinbiochem.2026.111099","url":null,"abstract":"<div><h3>Background</h3><div>Capillary zone electrophoresis (CZE) is a standard method for serum protein separation, but its performance can be compromised by IgM monoclonal proteins, leading to false-negative results.</div></div><div><h3>Methods</h3><div>We report a case of Waldenström macroglobulinemia (IgM 56.05 g/L) with repeated CZE failure. Immunofixation electrophoresis (IFE) confirmed an IgM kappa monoclonal protein. Four pretreatment protocols were evaluated: 1) 37°C incubation; 2) dilution with distilled water; 3) dilution with 0.9% saline; and 4) pretreatment with β‑mercaptoethanol (BME). Gel-based serum protein electrophoresis (SPE) and immunosubtraction CZE were also performed to investigate the interference mechanism.</div></div><div><h3>Results</h3><div>Initial CZE failed to yield an interpretable electrophoretogram. Incubation at 37°C showed no improvement. Dilution with distilled water induced visible precipitation and resulted in a false-negative electrophoretic pattern with a marked drop in measured total protein. Dilution with saline prevented precipitation but still failed to reveal a distinct monoclonal spike, despite biochemical measurements consistent with high globulin levels. In contrast, pretreatment with BME successfully restored a clear monoclonal spike in the β‑γ region on CZE, demonstrating restored solubility and proper migration. IFE corroborated the presence of the IgM kappa monoclonal protein. Gel-based SPE successfully showed a distinct M-protein band without interference, while immunosubtraction CZE failed under both temperature conditions, supporting cryoglobulin-related interference.</div></div><div><h3>Conclusions</h3><div>Very high IgM concentrations, particularly with cryoglobulin activity, can cause complete CZE failure not resolved by standard dilution or heating. The interference likely involves capillary obstruction from protein aggregation or temperature-dependent re-precipitation within the capillary. BME pretreatment is a critical intervention for unmasking IgM monoclonal proteins when CZE results are inconsistent with other laboratory findings, thereby preventing diagnostic errors.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111099"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing precision, bias, and sigma metrics of 22 measurands using Ricos and EFLM specifications and implementation of internal quality control procedure in clinical chemistry laboratory 使用Ricos和EFLM规范评估22种测量方法的精度、偏差和西格玛指标，并在临床化学实验室实施内部质量控制程序。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-02-28 DOI: 10.1016/j.clinbiochem.2026.111108

Khouloud Hkimi , Sonia Gara

Background

The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) biological variation (BV) database is currently the reference source for BV-based specifications, providing evidence-based and more stringent limits than the historical Ricos database.

Objective

This study aimed to assess the impact of the transition from old to updated BV goals on sigma metrics in our laboratory.

Methods

The study was conducted at the National Institute of Salah Azaiz medical biology laboratory over an 8-month period. It included 22 biological parameters for which coefficients of variation and biases were calculated using internal and external quality control materials. Sigma metrics were determined using Ricos and the EFLM desirable specifications.

Results

Using Ricos desirable specifications, 27.3% of analytes (ALT, CK, iron, total bilirubin, triglycerides, and CA19-9) achieved sigma ≥ 6, 36.4% had sigma between 3 and 6 (AST, LDH, urea, uric acid, AFP, CEA, CA125, and CA15-3), and 36.4% had sigma < 3 (calcium, creatinine, glucose, magnesium, potassium, sodium, total cholesterol, total protein). With the stricter EFLM targets, 6 sigma performers decreased to 19.1% (CK, iron, total bilirubin, triglycerides). 28.5% of analytes had sigma between 3 and 6 (ALT, AST, urea, uric acid, CEA, CA19-9), and 52.4% had sigma < 3 (calcium, creatinine, glucose, LDH, magnesium, potassium, sodium, total cholesterol, total protein, AFP and CA125). The resulting internal quality control strategy hence differed. The quality goal index indicated that imprecision was the main limitation for most analytes.

Conclusions

Updating performance specifications from the historical Ricos database to the evidence-based EFLM resulted in more stringent BV goals that are challenging to achieve with current routine technologies. Intensified root-cause analysis, closer collaboration with manufacturers, and ongoing performance reassessment are necessary for poor performers.

背景：欧洲临床化学和检验医学联合会（EFLM）生物变异（BV）数据库是目前基于BV规范的参考来源，提供了比历史上的Ricos数据库更严格的循证限制。目的：本研究旨在评估我们实验室从旧的BV目标到更新的BV目标的转变对西格玛指标的影响。方法：研究在Salah Azaiz国家研究所医学生物学实验室进行，为期8个月。它包括22个生物参数，使用内部和外部质量控制材料计算变异系数和偏差。使用Ricos和EFLM理想规格确定Sigma指标。结果：使用Ricos理想的规格，27.3%的分析物（ALT、CK、铁、总胆红素、甘油三酯和CA19-9）达到sigma ≥ 6,36.4%的sigma在3到6之间（AST、LDH、尿素、尿酸、AFP、CEA、CA125和CA15-3）， 36.4%达到sigma 结论：将Ricos历史数据库的性能规格更新到循证EFLM导致更严格的BV目标，这是目前常规技术难以实现的。加强根本原因分析，与制造商更密切的合作，以及持续的绩效重新评估对表现不佳是必要的。

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引用次数: 0

Advantages and application of a decision tree algorithm combined with the Harris-Boyd criterion in the construction of dynamic reference intervals for coagulation indicators during pregnancy 决策树算法结合Harris-Boyd准则在构建妊娠凝血指标动态参考区间中的优势及应用

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.clinbiochem.2026.111087

Xiaosong Lin , Zhi Lin , Liangjie Xu , Feng Zhao , Yuying Weng

Introduction

Reference intervals (RIs) based on fixed gestationals may not accurately reflect the dynamic changes of the hypercoagulable state. This study aimed to evaluate the rationality of integrating a decision tree algorithm (DTA) with the Harris-Boyd criterion (DTAHBC) to establish dynamic RIs for coagulation indicators during pregnancy.

Materials and methods

Dynamic data of prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer (D-d), and fibrin degradation product (FDP) were retrospectively analyzed in 4,698 healthy pregnant women. Scatter plots were drawn to observe changes regarding each indicator during pregnancy. DTAs were used to identify dynamic inflection points, which were validated using the Harris-Boyd criterion. Moreover, 2.5th and 97.5th percentiles and their 90% confidence intervals were calculated. New RIs were compared to traditional trimester-based RIs and validated by coincidence rates within the cohort.

Results

The study showed that PT, INR, APTT, and TT values were stable across gestation weeks. However, Fib, D-d, and FDP values increased rapidly. The DTA analysis found inflection points misaligned with traditional trimester-based nodes. Compared to traditional methods, the new method identified the initial stage of coagulation activation in the second trimester (FDP exceeding non-pregnant ranges at 14–21 weeks) and the aggravation stage of hypercoagulability in the late trimester (median FDP exceeding non-pregnant upper limits at 34–40 weeks). Validation in the same cohort revealed compliance rates >90% for new RIs, whereas traditional TT (82.11%) and D-d (87.89%) measurements obtained at 14–27 weeks failed validation.

Conclusion

DTAHBC-based RIs do not follow the traditional trimester division, can effectively reflect dynamic changes in coagulation indicators, and provide a new solution for coagulation-function evaluation during pregnancy.

基于固定胎位的参考间隔（RIs）可能不能准确反映高凝状态的动态变化。本研究旨在评价将决策树算法（DTA）与Harris-Boyd准则（DTAHBC）相结合建立妊娠凝血指标动态RIs的合理性。材料与方法：回顾性分析4698例健康孕妇凝血酶原时间（PT）、国际标准化比值（INR）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（Fib）、d -二聚体（D-d）、纤维蛋白降解产物（FDP）的动态数据。绘制散点图，观察妊娠期间各指标的变化。dta用于识别动态拐点，并使用Harris-Boyd准则进行验证。计算2.5和97.5%百分位及其90%置信区间。将新的RIs与传统的基于妊娠期的RIs进行比较，并通过队列内的符合率进行验证。结果：PT、INR、APTT、TT值在妊娠周内稳定。Fib、D-d、FDP值增加较快。DTA分析发现拐点与传统的妊娠期节点不一致。与传统方法相比，新方法确定了妊娠中期凝血激活的初始阶段（FDP在14-21 周超过非妊娠范围）和妊娠晚期高凝性加重阶段（FDP中位数在34-40 周超过非妊娠上限）。在同一队列中的验证显示，新RIs的依从率为bb90 %，而在14-27 周获得的传统TT（82.11%）和D-d（87.89%）测量未能验证。结论：基于dtahbc的RIs不遵循传统的孕期划分，能有效反映凝血指标的动态变化，为妊娠期凝血功能评价提供新的解决方案。

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引用次数: 0

Prognostic value of human serum alpha-klotho concentrations in patients with heart failure with reduced ejection fraction 人血清α -克洛索浓度对心力衰竭伴射血分数降低患者的预后价值。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.clinbiochem.2026.111086

Ajay Mahenthiran , Silvio Augusto Nunes Jr , Chia-Feng Liu , Steven Leon , Jennifer Wilcox , W.H. Wilson Tang

Objective

Heart Failure (HF) is a major health problem with high prevalence and mortality. Identifying new biomarkers involved in controlling heart failure progression has become particularly important. This study evaluated the association between serum α-klotho concentrations and long-term all-cause mortality in patients with stable HF.

Design and methods

We analyzed serum α-klotho levels in 230 adults (135 patients with HF with reduced ejection fraction and 95 age and sex-matched healthy controls). A classification and regression tree analysis was used to stratify patients by α-klotho concentration, using all-cause mortality within a 5-year follow-up as the primary endpoint. Differences in log-NT-proBNP levels across α-klotho groups were assessed using the Kruskal-Wallis test with Dunn’s post-hoc comparisons. Kaplan-Meier survival analysis evaluated the association between α-klotho stratified groups and 5-year all-cause mortality.

Results

Patients with higher serum α-klotho levels had significantly lower mortality and lower log NT-proBNP across α-klotho groups (χ²(2) = 8.05, p = 0.018) when compared to lower α-klotho concentration levels. Kaplan-Meier curves show the significant difference in survival across α-klotho stratification (log-rank p < 0.01).

Conclusion

Patients with higher serum α-klotho concentrations were associated with lower log-NT-proBNP levels and better 5-year survival in all patients as well as in patients with heart failure, compared to those with lower. These findings support the role of α-klotho as a promising cardioprotective biomarker for risk stratification in patients with HF.

目的：心力衰竭（HF）是一种发病率高、死亡率高的主要健康问题。识别与控制心力衰竭进展相关的新生物标志物变得尤为重要。本研究评估了稳定型心衰患者血清α-克洛索浓度与长期全因死亡率之间的关系。设计和方法：我们分析了230名成人（135名伴有射血分数降低的心衰患者和95名年龄和性别匹配的健康对照）的血清α-klotho水平。采用分类和回归树分析，以5年随访期间的全因死亡率为主要终点，按α-克洛索浓度对患者进行分层。α-klotho组间log-NT-proBNP水平的差异采用Kruskal-Wallis测试和Dunn’s事后比较进行评估。Kaplan-Meier生存分析评估α-klotho分层组与5年全因死亡率之间的关系。结果：血清α-klotho水平较高的患者死亡率显著低于α-klotho水平较低的患者（χ2(2) = 8.05,p = 0.018），α-klotho水平组的NT-proBNP对数显著低于α-klotho水平组。Kaplan-Meier曲线显示不同α-klotho浓度患者的生存率有显著差异（log-rank p ）结论：血清α-klotho浓度较高的患者与所有患者以及心力衰竭患者的log-NT-proBNP水平较低相关，且与较低的患者相比，其5年生存率更高。这些发现支持α-klotho作为心衰患者危险分层的有希望的心脏保护生物标志物的作用。

{"title":"Prognostic value of human serum alpha-klotho concentrations in patients with heart failure with reduced ejection fraction","authors":"Ajay Mahenthiran , Silvio Augusto Nunes Jr , Chia-Feng Liu , Steven Leon , Jennifer Wilcox , W.H. Wilson Tang","doi":"10.1016/j.clinbiochem.2026.111086","DOIUrl":"10.1016/j.clinbiochem.2026.111086","url":null,"abstract":"<div><h3>Objective</h3><div>Heart Failure (HF) is a major health problem with high prevalence and mortality. Identifying new biomarkers involved in controlling heart failure progression has become particularly important. This study evaluated the association between serum α-klotho concentrations and long-term all-cause mortality in patients with stable HF.</div></div><div><h3>Design and methods</h3><div>We analyzed serum α-klotho levels in 230 adults (135 patients with HF with reduced ejection fraction and 95 age and sex-matched healthy controls). A classification and regression tree analysis was used to stratify patients by α-klotho concentration, using all-cause mortality within a 5-year follow-up as the primary endpoint. Differences in log-NT-proBNP levels across α-klotho groups were assessed using the Kruskal-Wallis test with Dunn’s post-hoc comparisons. Kaplan-Meier survival analysis evaluated the association between α-klotho stratified groups and 5-year all-cause mortality.</div></div><div><h3>Results</h3><div>Patients with higher serum α-klotho levels had significantly lower mortality and lower log NT-proBNP across α-klotho groups (χ<sup>2</sup>(2) = 8.05, p = 0.018) when compared to lower α-klotho concentration levels. Kaplan-Meier curves show the significant difference in survival across α-klotho stratification (log-rank p < 0.01).</div></div><div><h3>Conclusion</h3><div>Patients with higher serum α-klotho concentrations were associated with lower log-NT-proBNP levels and better 5-year survival in all patients as well as in patients with heart failure, compared to those with lower. These findings support the role of α-klotho as a promising cardioprotective biomarker for risk stratification in patients with HF.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111086"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibroblast growth factor 23-induced hypophosphatemia in a malignant phosphaturic mesenchymal tumor: presentation of a rare case 成纤维细胞生长因子23在恶性磷质间充质肿瘤中诱导低磷血症：一例罕见病例。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2026-03-01 Epub Date: 2026-01-25 DOI: 10.1016/j.clinbiochem.2026.111090

Diver Alexis Chicangana Tuquerres , Andrés David Sastre Martínez , Carlos Mário Barrios Herrera , Paula Andrea Torres Pérez , Carlos Fernando Acuña Roldán , Gabriel Jaime Varela Aguirre , Andres Felipe García Ramos

Introduction

Tumor-induced osteomalacia is a rare paraneoplastic disorder caused by excess fibroblast growth factor 23 (FGF23), most often produced by phosphaturic mesenchymal tumors. Delayed diagnosis may result in severe metabolic and skeletal complications.

Case presentation

We report the case of a 32-year-old woman with a three-year history of progressive weakness and a rapidly enlarging thoracic mass. Imaging revealed an 18 × 13 cm highly vascularized thoracic lesion with multiple lytic bone metastases. Laboratory evaluation showed severe hypophosphatemia (0.9 mg/dL), renal phosphate wasting (fractional excretion of phosphate 24.5%), elevated intact parathyroid hormone, low vitamin D levels, and markedly increased serum FGF23 (7926 kRU/L). Histopathological examination and immunohistochemistry demonstrated a malignant phosphaturic mesenchymal tumor with positivity for CD56, SATB2, and SSTR2A.

Discussion

This case highlights the aggressive clinical behavior that malignant phosphaturic mesenchymal tumors may exhibit, including extensive local invasion, metastatic disease, and profound metabolic derangements. The diagnosis of tumor-induced osteomalacia requires a high index of suspicion and an integrated approach combining biochemical evaluation, functional imaging, and detailed pathological assessment.

Conclusions

Tumor-induced osteomalacia should be considered in patients with persistent hypophosphatemia and phosphate wasting. Early recognition is essential, as complete surgical resection remains the only curative option. In advanced or unresectable disease, management is challenging and may be limited by tumor burden and access to targeted therapies, including anti-FGF23 agents, which offer biochemical and symptomatic benefit in selected cases.

肿瘤诱导的骨软化症是一种罕见的副肿瘤疾病，由过量的成纤维细胞生长因子23 （FGF23）引起，最常由磷化间充质肿瘤产生。延迟诊断可能导致严重的代谢和骨骼并发症。病例介绍：我们报告一位32岁的女性，有三年的进行性虚弱史和迅速扩大的胸部肿块。影像学显示18 × 13 cm高度血管化的胸椎病变伴多发溶解性骨转移。实验室评估显示严重的低磷血症（0.9 mg/dL），肾脏磷酸盐消耗（磷酸盐部分排泄24.5%），完整甲状旁腺激素升高，维生素D水平低，血清FGF23显著升高（7926 kRU/L）。组织病理学检查和免疫组化证实为恶性磷化间充质瘤，CD56、SATB2和SSTR2A阳性。讨论：本病例突出了恶性磷质间充质肿瘤可能表现出的侵袭性临床行为，包括广泛的局部侵袭、转移性疾病和严重的代谢紊乱。肿瘤性骨软化症的诊断需要高度的怀疑指数和生化评价、功能影像学和详细的病理评估相结合的综合方法。结论：持续性低磷血症和磷酸盐消耗患者应考虑肿瘤诱导的骨软化。早期识别是必要的，因为完全的手术切除仍然是唯一的治疗选择。在晚期或不可切除的疾病中，治疗是具有挑战性的，可能受到肿瘤负担和靶向治疗的限制，包括抗fgf23药物，这些药物在选定的病例中提供生化和症状方面的益处。

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