Clinical biochemistry最新文献

This review provides a contemporary examination of the evolving landscape of breast cancer (BC) diagnosis, focusing on the pivotal role of novel protein-based biomarkers. The overview begins by elucidating the multifaceted nature of BC, exploring its prevalence, subtypes, and clinical complexities. A critical emphasis is placed on the transformative impact of proteomics, dissecting the proteome to unravel the molecular intricacies of BC.

Navigating through various sources of samples crucial for biomarker investigations, the review underscores the significance of robust sample processing methods and their validation in ensuring reliable outcomes. The central theme of the review revolves around the identification and evaluation of novel protein-based biomarkers. Cutting-edge discoveries are summarised, shedding light on emerging biomarkers poised for clinical application.

Nevertheless, the review candidly addresses the challenges inherent in biomarker discovery, including issues of standardisation, reproducibility, and the complex heterogeneity of BC. The future direction section envisions innovative strategies and technologies to overcome existing challenges. In conclusion, the review summarises the current state of BC biomarker research, offering insights into the intricacies of proteomic investigations.

As precision medicine gains momentum, the integration of novel protein-based biomarkers emerges as a promising avenue for enhancing the accuracy and efficacy of BC diagnosis. This review serves as a compass for researchers and clinicians navigating the evolving landscape of BC biomarker discovery, guiding them toward transformative advancements in diagnostic precision and personalised patient care.

Liquid biopsy has been investigated as a novel method to overcome the numerous challenges in gastric cancer (GC) management. This non-invasive, feasible, and easy-to-repeat method has been shown to be cost-effective and capable of increasing diagnostic sensitivity and prognostic assessment. Additionally, it is potentially accurate to aid decision-making and personalized treatment planning. MicroRNA (miRNA) and circulating tumor DNA (ctDNA) markers can enhance GC management in various aspects, including diagnosis (mainly earlier diagnosis and the ability to perform population-based screening), prognosis (more precise stratification of prognosis), and treatment (including more accurate prediction of treatment response and earlier detection of resistance to the treatment). Concerning the treatment-related application, miRNAs’ mimics and antagonists (by using two main strategies of restoring tumor suppressor miRNAs and inhibiting oncogene miRNAs) have been shown to be effective therapeutic agents. However, these need to be further validated in clinical trials. Furthermore, novel delivery systems, such as lipid-based vectors, polymeric-based vectors, and exosome-based delivery, have been developed to enhance the performance of these agents. Moreover, this paper explores the current detection and measuring methods for these markers. These approaches are categorized into direct methods (e.g., Chem-NAT, HTG EdgeSeq, and Multiplex Circulating Fireplex) and indirect methods (e.g., Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), qPCR, microarray, and NGS) for miRNA detection. For ctDNA measurement, main core technologies like NGS, digital PCR, real-time PCR, and mass spectrometry are suggested.

Background

Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension.

Methods

A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected.

Results

Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58–1.30) vs. 1.24 (0.99–1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02–0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751–0.878; P < 0.001).

Conclusion

Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..

Introduction

The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals. Pregnant HIV patients exposed to subtherapeutic doses, particularly in the last trimester of the pregnancy, have higher chances to transmit the infection to their children. Therefore, the therapeutic drug monitoring of antiretrovirals in HIV pregnant patients would be of great value.

Objectives

This study aimed to develop and validate a sensitive liquid chromatograph tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of efavirenz, raltegravir, atazanavir, and ritonavir in dried blood spots (DBS) and plasma.

Design and Methods

The analytes were extracted from the DBS punch and plasma with a mixture of methanol:zinc sulfate 200 mM (50:50, v/v) and 100 % methanol, respectively. For the chromatographic separation a Shim-pack® C18, 4.6 mm × 150 mm, 5 μm column was used. Detection was performed in a 3200-QTRAP® mass spectrometer, with a run time of 6 min.

Results

The assay was linear in the range of 15–1,000 ng/mL for raltegravir, 50–10,000 ng/mL for both atazanavir and ritonavir, 50–5,000 ng/mL for efavirenz. Precision and accuracy at these concentrations were less than 15 % for all analytes. Raltegravir, atazanavir, and ritonavir were stable for seven days at 23 °C and 40 °C, whereas efavirenz was stable for twenty-four hours at the same conditions.

Conclusions

The method was successfully applied to quantify efavirenz in DBS samples obtained from HIV-1 infected pregnant volunteers under antiretroviral therapy. The concentrations of efavirenz in DBS and plasma were comparable according to Passing-Bablok regression and Bland-Altman analysis.

Quality in laboratory medicine encompasses multiple components related to total quality management, including quality control (QC), quality assurance (QA), quality indicators, and quality improvement (QI). Together, they contribute to minimizing errors (pre-analytical, analytical, or post-analytical) in clinical service delivery and improving process appropriateness and efficiency. In contrast to static quality benchmarks (QC, QA, quality indicators), the QI paradigm is a continuous approach to systemic process improvement for optimizing patient safety, timeliness, effectiveness, and efficiency. Healthcare institutions have placed emphasis on applying the QI framework to identify and improve healthcare delivery. Despite QI’s increasing importance, there is a lack of guidance on preparing, executing, and sustaining QI initiatives in the field of laboratory medicine. This has presented a significant barrier for clinical laboratorians to participate in and lead QI initiatives. This three-part primer series will bridge this knowledge gap by providing a guide for clinical laboratories to implement a QI project that is successful and sustainable. In the first article, we introduce the steps needed to prepare a QI project with focus on relevant methodology and tools related to problem identification, stakeholder engagement, root cause analysis (e.g., fishbone diagrams, Pareto charts and process mapping), and SMART aim establishment. Throughout, we describe a clinical vignette of a real QI project completed at our institution focused on serum protein electrophoresis (SPEP) utilization. This primer series is the first of its kind in laboratory medicine and will serve as a useful resource for future engagement of clinical laboratory leaders in QI initiatives.

Objectives

Contamination with intravenous (IV) fluids is a common cause of specimen rejection or erroneous results in hospitalized patients. Identification of contaminated samples can be difficult. Common measures such as failed delta checks may not be adequately sensitive nor specific. This study aimed to determine detection criteria using commonly ordered tests to identify IV fluid contamination and validate the use of these criteria.

Methods

Confirmed contaminated and non-contaminated samples were used to identify patterns in laboratory results to develop criteria to detect IV fluid contamination. The proposed criteria were implemented at a tertiary care hospital laboratory to assess performance prospectively for 6 months, and applied to retrospective chemistry results from 3 hospitals and 1 community lab to determine feasibility and flagging rates. The algorithm was also tested at an external institution for transferability.

Results

The proposed algorithm had a positive predictive value of 92 %, negative predictive value of 91 % and overall agreement of 92 % when two or more criteria are met (n = 214). The flagging rates were 0.03 % to 0.07 % for hospital and 0.003 % for community laboratories.

Conclusions

The proposed algorithm identified true contamination with low false flagging rates in tertiary care urban hospital laboratories. Retrospective and prospective analysis suggest the algorithm is suitable for implementation in clinical laboratories to identify samples with possible IV fluid contamination for further investigation.

Introduction

The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI).

Material and methods

We enrolled 204 patients with suspected PCa. For each patient, a blood sample was collected before mpMRI to measure PHI. Findings on mpMRI were assessed according to the Prostate Imaging Reporting & Data System version 2.0 (PI-RADSv2) category scale.

Results

According to PI-RADSv2, patients were classified into two groups: PI-RADS < 3 (48 %) and ≥ 3 (52 %). PHI showed the best performance for predicting PI-RADS ≥ 3 [AUC: 0,747 (0,679–0,815), 0,680(0,607–0,754), and 0,613 (0,535–0,690) for PHI, PSA ratio, and total PSA, respectively]. The best PHI cut-off was 30, with a sensitivity of 90%.

At the univariate logistic regression, total PSA (p = 0.007), PSA ratio (p = 0.001), [-2]proPSA (p = 0.019) and PHI (p < 0.001) were associated with PI-RADS ≥ 3; however, at the multivariate analysis, only PHI (p < 0.001) was found to be an independent predictor of PI-RADS ≥ 3.

Conclusion

PHI could represent a reliable noninvasive tool for selecting patients to undergo mpMRI.

Background

This study aims to investigate the impact of age and sex on high-sensitivity cardiac troponin T (hs-cTnT) and establish 99th percentile upper reference limits (URLs) in older individuals utilizing large-scale real-world data.

Methods

40,530 outpatient hs-cTnT results were obtained from the laboratory database from January 1, 2018, to December 31, 2023. Our study included 4,199 elderly outpatients (aged ≥ 60) without cardiovascular disease or other heart-related chronic conditions. Nested analysis of variance was used to explore the necessity of partitioning reference intervals (RIs) by sex and age groups. RIs were established by the refineR algorithm and assessed based on ≤ 10% test results of validation data set outside the new RIs.

Results

RIs for hs-cTnT in the older population needed to be partitioned by sex and age groups ([standard deviation ratio] SDR_age = 0.75; SDR_sex = 0.49). URLs in older Chinese adults were 21.8 ng/L for males, 16.5 ng/L for females, and 20.7 ng/L for the overall participant group. URLs for males aged 60–69, 70–79, and ≥ 80 were 13.7, 19.4, and 31.0 ng/L, respectively. Female values were 10.1, 17.2, and 22.0 ng/L. Importantly, manufacturer-reported RIs do not suffice for Chinese individuals aged ≥ 70. Validation data showed that 2.7–5.2% of test results fell outside the new RIs, confirming the validity of the results.

Conclusion

This study establishes age- and sex-specific 99th percentile URLs for hs-cTnT in Chinese older individuals, thereby enhancing the accuracy of clinical assessments.

Objectives

Some therapeutic monoclonal antibodies, like daratumumab and elotuzumab, produce interfering monoclonal bands on serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Whether other common therapeutic antibodies also produce interference has not been systematically evaluated.

Design and methods

SPEP/IFE from patients receiving isatuximab (48 patients), belantamab mafodotin (BM; 41), and denosumab (41) were retrospectively reviewed for therapeutic antibody interference. Cases exhibiting isatuximab interference were quantified and the maximum duration of isatuximab effect was evaluated. To characterize band position, neat human serum was spiked with BM or denosumab at supratherapeutic concentrations. Band migration patterns were compared on SPEP and IFE, with band position expressed relative to other constant protein fractions.

Results

Isatuximab-induced IFE interference was common (81.3 % of evaluated patients) with a maximum observed duration of 8 weeks. 10.4 % of isatuximab patients had IgG kappa monoclonal gammopathies that co-migrated with the drug; this subset could benefit from HYDRASHIFT 2/4 isatuximab testing. 8.3 % of IFE cases were negative for an isatuximab band but showed large, endogenous M-spikes migrating elsewhere. All patients in this group expired within 1 year of this finding. We hypothesize that an inability to detect isatuximab in this setting corresponds to a large residual myeloma burden that reduces isatuximab serum concentration. This observation may serve as a negative prognostic factor. Spiking studies demonstrated that BM and denosumab produce interference in vitro, but sustained interference was not observed in >40 treated patients.

Conclusions

Therapeutic antibody interference in patients receiving isatuximab is common, and can persist for at least 8 weeks after administration. >10 % of patients receiving isatuximab may benefit from HYDRASHIFT testing post-therapy. In contrast, BM and denosumab fail to produce sustained interference in treated patients.

Background

Recent data show that netrin-1 has a role in development of pulmonary fibrosis. This study was aimed to investigate serum netrin-1 level and its relation to interstitial lung disease(ILD) in patients with rheumatoid arthritis (RA).

Method

42 RA patients with RA-ILD, 58 RA patients without RA-ILD (RA non-ILD group), and 61 healthy volunteers were included in this study. The modified DAS28-ESR score was used to calculate disease activity in RA patients. Using the quantitative immunoassay method, Serum netrin-1 levels were measured with an ELISA kit (Catalog number: E-EL-H2328; lab science, lot number: GZWTKZ5SWK, Texas, USA).

Results

The median value of netrin-1 was found to be significantly higher in the RA-ILD group (82.9 [59.9–124]) compared to both the RA non-ILD group(52.9 [49.5–73.1])(B = −0.006, OR = 0.994, CI 95 %=0.989–0.999, P = 0.018) and the control group(53.5 [49.5–87.5]) (B: −0.005, OR: 0.994, CI 95 %: 0.990–0.999, p: 0.022). A cut-off value of 61.78 for netrin-1 was found to have a sensitivity of 73.8 % and a specificity of 69 % for the diagnosis of RA-ILD (AUC [95 %Cl] = 0.771 [0.679–0.862], p < 0.0001).It was found that high serum netrin-1 level was strongly associated with the RA-usual interstitial pneumonia(UIP) pattern and poorly related to the RA-nonspecific interstitial pneumonia(NSIP) pattern compared to the RA non-ILD group.

Conclusions

Netrin-1 is elevated in the serum of patients with RA-ILD, especially in the UIP pattern. Netrin-1 may be a potential candidate for predicting the development of RA-ILD that should be investigated in the pathophysiological and therapeutic fields..