Clinical chemistry and laboratory medicine最新文献

Objectives: Antiphospholipid antibodies (aPLs) are closely associated with recurrent spontaneous abortion (RSA) and adverse pregnancy outcomes (POs). Non-criteria aPLs may aid in diagnosing seronegative aPL-related RSA, but their limited performance often leads to missed or delayed diagnosis. This study aimed to improve diagnostic and predictive accuracy by integrating criteria and non-criteria aPLs with machine learning (ML) algorithm.

Methods: In this multicenter prospective study, 1,321 participants were recruited and 751 included. Fifteen aPLs were measured using chemiluminescence immunoassay. Six ML algorithms were trained, and the optimal model was evaluated using the area under the curve (AUC), calibration curves, decision curve analysis (DCA), and Shapley additive explanations (SHAP).

Results: Using the 95th percentile as the cut-off, aPL positivity ranged from 2.62 to 12.13 % in pregnant woman with a history of RSA and 4.29-19.74 % in non-pregnant woman with a history of RSA. The light gradient boosting machine (LGBM) model achieved AUCs of 0.875 (pregnant) and 0.778 (non-pregnant) for RSA prediction, while the random forest (RF) model achieved an AUC of 0.885 for PO prediction - surpassing all single indicators (AUC 0.516-0.647). Calibration, DCA, and SHAP analyses demonstrated strong clinical utility.

Conclusions: The ML models substantially improved diagnostic and predictive performance for RSA and PO. The LGBM and RF models showed the best accuracy and may serve as auxiliary diagnostic and early warning tools. Larger external cohorts are needed for further validation.

Objectives: Primary aldosteronism (PA) is a common cause of secondary hypertension. To address the specificity limits of immunoassays, we developed and validated an LC-MS/MS method for urinary aldosterone and tetrahydroaldosterone and established method-matched reference intervals for excretion in 24 h urine.

Methods: Urinary aldosterone, tetrahydroaldosterone and their glucuronidated metabolites were extracted in the presence of internal standards using offline solid-phase extraction (SPE), followed by enzymatic hydrolysis to release the glucuronidated fraction. Subsequently, aldosterone and tetrahydroaldosterone were analyzed by online SPE in combination with LC-MS/MS. Reference intervals were established based on 24 h urine samples from 265 individuals participating in the Lifelines Cohort study.

Results: Intra- and inter-assay imprecision ranged from 2.0-12.3 % for aldosterone, and 1.3-6.3 % for tetrahydroaldosterone. The lower limits of quantification were 0.44 nmol/L and 0.10 nmol/L, respectively. Recoveries ranged from 97-106 %, calibration was linear, with correlation coefficients greater than 0.999, and no carry-over was observed. Total aldosterone concentrations measured by LC-MS/MS were consistently higher than those obtained by radioimmunoassay. In the reference population, 24 h urinary excretion ranged from 5.4-76.7 nmol/24 h for aldosterone and 21.4-269.9 nmol/24 h for tetrahydroaldosterone.

Conclusions: This validated LC-MS/MS assay, together with a method-matched normative dataset, enables standardized urinary aldosterone profiling and defines reference intervals that will help improve the interpretability of results in the biochemical diagnosis of PA.

Introduction: Accurate assessment of T-cell clonality is key for diagnosing mature T-cell neoplasms. TRBC1-based flow cytometry provides a rapid, robust, and cost-efficient approach. This systematic review and meta-analysis assessed the diagnostic accuracy of TRBC1 flow cytometry (TRBC1-FC) for detecting T-cell clonality in mature T-cell neoplasms.

Content: We systematically searched Scopus, PubMed (MEDLINE), and Google Scholar for articles on TRBC1-FC diagnostic accuracy published up to July 1, 2025. Pooled sensitivity and specificity were estimated, between-study heterogeneity was evaluated and small-study effects were examined.

Summary: This meta-analysis included 10 studies. The pooled sensitivity was 97.6 % (95 % CI, 95.1-99.4 %) and specificity 90.7 % (95 % CI, 76.0-99.3 %). The pooled LR+ was 10.9 (95 % CI, 4.1-28.9), LR-was 0.053 (95 % CI, 0.025-0.12), and DOR 339 (95 % CI, 64-1,788). The HSROC curve demonstrated an AUC of 0.974 (partial AUC=0.970), confirming excellent global discriminatory capacity. Between-study heterogeneity was substantial (I²=83.3 %), mainly affecting specificity and DOR, while sensitivity remained highly consistent. No evidence of a threshold effect was found. Deeks' test showed significant small-study effects (p<0.001), and sensitivity analyses identified one influential study whose exclusion markedly reduced heterogeneity. These results confirm the high diagnostic performance and robustness of TRBC1-FC for T-cell clonality assessment.

Outlook: TRBC1-FC demonstrates high sensitivity and low LR-, supporting its role as a rule-out test. Variability in specificity, LR+ and DOR, mainly due to small-study effects, advises caution for rule-in use. Standardized protocols and cost-effectiveness analyses are needed before broad clinical adoption.

Objectives: Screening for primary aldosteronism (PA) using the aldosterone:renin ratio (ARR) has suboptimal diagnostic accuracy, particularly in females. We assessed whether accuracy could be improved using sex-specific relationships of aldosterone with renin.

Methods: Plasma aldosterone and renin were measured in 442 females and 491 males prospectively screened for PA. Patients were divided into test (n=717) and validation (n=216) cohorts. Sex-specific cut-offs for renin-dependent aldosterone concentrations and the ARR were developed using logistic regression models in the test cohort. Diagnostic performance of models in both cohorts was compared to that of the ARR.

Results: Females without PA had higher (p<0.001) ARRs than males due to higher plasma aldosterone and lower renin concentrations. Consequently, rates of false-positives were higher (p<0.001) in females than males. At diagnostic sensitivities close to 95 % suitable for screening, and with sex-specific cut-offs for the ARR, specificities for the test cohort were 44 % in females compared to 73 % in males. Compared to the ARR, use of formulas (termed ARRplus) for sex-specific and renin-dependent cut-offs for aldosterone resulted in increased (p≤0.005) areas under receiver operating characteristic (ROC) curves for both sexes and enhanced specificity to 71 % in females and 82 % in males. Superiority of the ARRplus compared to the ARR was confirmed in the validation cohort according to ROC curve comparisons and 47-82 % reductions in false-positive results.

Conclusions: Renin-dependent and sex-specific aldosterone cut-offs using the ARRplus offer higher diagnostic accuracy than the ARR and considerably reduced rates of false-positives to minimize follow-up of screened patients, particularly women.