Biomarker Insights最新文献

Background: Dyspnea is a common and diagnostically challenging symptom in the emergency department (ED), particularly among older adults with multimorbidity. Traditional risk stratification tools often perform poorly in this population. Galectin-3 (Gal-3), a biomarker of inflammation and fibrosis, may reflect biological aging and resilience, potentially improving early mortality risk assessment.

Objectives: To evaluate the independent association between Gal-3 and 30-day mortality in patients presenting with acute dyspnea; to assess its utility for identifying patients at low risk of short-term mortality; and to determine its incremental value in improving prediction of 30-day mortality when added to clinical risk models.

Design: Retrospective observational study based on the Acute Dyspnea Study (ADYS).

Methods: The study included 763 adult ED patients with acute dyspnea. Gal-3 was measured as NPX (Normalized Protein Expression) values using the Olink proximity extension assay, and NT-proBNP was measured using standard laboratory methods. The primary outcome was 30-day all-cause mortality. Multivariable logistic regression and Cox regression analyses were performed, with internal validation by bootstrap resampling. Predictive performance was evaluated using ROC curves, AUC, and the Youden index, and incremental value was assessed by AUC comparison and net reclassification improvement (NRI).

Results: Among the 763 patients, 49 (6.4%) died within 30 days. Gal-3 NPX was independently associated with 30-day mortality (OR 1.97; 95% CI: 1.16-3.36; p = 0.013). Although Gal-3 NPX alone demonstrated moderate discrimination (AUC 0.69), relatively low Gal-3 NPX levels within the cohort effectively ruled out short-term mortality, with a negative predictive value of 96%. Adding Gal-3 NPX to the clinical model modestly improved predictive performance (AUC increased from 0.803 to 0.819; NRI 0.028), primarily by enhancing identification of low-risk patients.

Conclusion: Gal-3 NPX was independently associated with 30-day mortality in patients with acute dyspnea. Although its addition yielded only a modest, non-significant improvement in overall risk prediction, Gal-3 may be useful for ruling out short-term mortality, supporting its potential role as a negative prognostic marker in the ED setting.

Background: Since the first reported case of Coronavirus Disease 2019 (COVID-19), clinicians and scientists have been challenged to contrive ideal prevention, detection, and treatment strategies. As the death toll surpasses 1 million in the United States, identifying disease risk factors, specifically those risks related to severe disease manifesting as in-hospital mortality and invasive mechanical ventilation (MV), becomes crucial.

Objectives: This study evaluated the association between abnormal blood biochemical markers, specifically albumin, alanine aminotransferase (ALT), creatinine, serum sodium, and blood urea nitrogen (BUN), to MV and in-hospital mortality in COVID-19 positive United States Veterans.

Design: We performed a retrospective cohort analysis on 298 760 US veterans admitted to any national Veterans Affairs Hospital (VHA) with a positive COVID-19 test from March 1, 2020, to August 31, 2021, resulting in a total of 30 729 patients.

Methods: A selection of patient-specific and COVID-19 test-related data was collected from the COVID-19 Shared Data Resources sourced from the VHA's Corporate Data Warehouse. These data were statistically analyzed using multivariable Cox regression models.

Results: Patients with lower albumin (<3.5 g/L); and higher BUN (>23 mg/dL), creatinine (>1.5 mg/dL), and ALT (>40 U/L) levels had increased risks for MV (29%, 40%, 20%, 26%) and in-hospital mortality (46%, 69%, 23%, 13%), respectively. Interestingly, patients with lower BUN (<11 mg/dL) values had decreased risks for both MV (22%) and in-hospital mortality (31%). Patients with sodium <135 mmol/L had an increased risk for MV and in-hospital mortality (30%, 9%), while sodium >145 mmol/L had an increased risk for in-hospital mortality (125%).

Conclusion: Overall, veterans hospitalized with COVID-19 and having abnormal albumin, ALT, BUN, and creatinine values were statistically associated with ventilatory status and case-fatality.

Background: Advances in analytical techniques, including salivary proteomics and gene expression analysis, have enabled the identification of thousands of proteins and specific genetic markers, providing a comprehensive understanding of salivary composition and its dynamic changes in response to therapeutic interventions.

Objectives: To conduct the salivary proteomic analyses using the LC-MS/MS method and identify the number of proteins in the whole saliva. This study also assessed the effect of an intraoral vibration device on the expression of specific genes associated with the bone remodeling process.

Design: This pilot project is a prospective study where salivary samples were assessed at baseline (0 day), Midpoint (15 days), and Endpoint (30 days) following the intervention.

Methods: This study utilized an intraoral vibration device as a therapeutic intervention to observe the changes in the salivary proteomic analyses using the LC-MS/MS method. Salivary gene expression analysis was conducted for ALPL, OPN, IL1B, IL1RN, IL1R1, TNF alpha, RANKL, and RUNX2 genes.

Results: A total of 1119 proteins in 1059 clusters at 1 minimum peptide and a 444 proteins in 384 clusters at 2 minimum peptides were identified in saliva. Out of all of the genes included in this experiment, OPN showed significant upward change at mid point (9 fold) (15 days) followed by moving toward the baseline level (2.3-fold) toward the end point (30 days).

Conclusion: This study highlights the potential of salivary proteomics and gene expression analysis as a promising tool for biomarker discovery, emphasizing the complexity and their variability. Despite of some challenges, the advantages of whole saliva collection and the sensitivity of shotgun proteomics and gene expression analysis support its potential as a high-throughput, practical approach for future applications in the field of oral health care.

Background: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases.

Objectives: The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value.

Design: Retrospective cohort study.

Methods: Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability.

Results: Among 297 patients, 21.5% experienced extubation failure. Log₂ Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure (P < .001, P = .01, P = .01, respectively), whereas log₂ IL-6 was not (P = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (P-value for interaction = .11, P = .82, P = .31, P = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95% CI: 0.64-0.79 vs AUC 0.66, 95% CI: 0.58-0.73, P = .03).

Conclusion: Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.

Background: The blood-cerebrospinal fluid barrier (BCSFB) regulates substance exchange between the blood and cerebrospinal fluid (CSF).

Objectives: This study investigated sex-related differences in the CSF/blood quotient of albumin (QAlb), a BCSFB function biomarker, in older patients undergoing spinal anesthesia for hip fracture (HF) surgery.

Design: Seventy-eight patients aged ⩾65 years (18 males, 60 females) undergoing HF repair were enrolled.

Methods: Baseline variables, including age, sex, diagnosis of dementia, were collected. The BCSFB function was assessed using the CSF/blood quotient of albumin (QAlb).

Results: Dementia prevalence was similar in men (22.2%) and women (17.6%), as was postoperative delirium (POD) (men 27.8%, women 33.3%). Despite similar demographics, men exhibited significantly higher CSF albumin concentrations (P = .031) and QAlb values (P = .023) compared to women. No differences were found in QAlb value between patients with or without dementia in male (P = .645) and female (P = .102) subgroups. Moreover, no differences in QAlb value emerged between those with or without POD in males (P = .173) and females (P = .225).

Conclusion: Despite sample size and sex imbalance, our analyses highlight a sex-related discrepancy in BCSFB function in older patients underscoring the need for sex-specific QAlb reference ranges. Normalization of QAlb values by sex may be essential to prevent over- or underestimation of BCSFB dysfunction in the 2 sexes. Future studies with larger, balanced cohorts may clarify these differences.

Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Highly sensitive immunometric assays have enabled its reliable quantification in blood, facilitating non-invasive monitoring. Several studies demonstrated strong correlations between NfL levels and the risk of developing different neurological diseases and, in individuals already living with a neurological disease, with the risk of worsening. However, interpretation is affected by factors like age, BMI, renal function, and comorbidities. NfL is already utilized as a diagnostic and prognostic biomarker in clinical practice, particularly in specialized centers and research settings, although no FDA-cleared assay is currently available for routine use. Recent research has highlighted that NfL may represent the first of a new generation of neurological biomarkers, with many more ready to come, such as glial fibrillary acidic protein (GFAP), further improving diagnostic and prognostic accuracy. Despite its promising role in the landscape of biomarkers, challenges remain to implement NfL in daily clinical practice, including standardization of assays, defining reference values, and ensuring methodological consistency. Addressing these limitations will be essential for integrating NfL into routine clinical practice, ultimately advancing precision medicine in neurology.

Background: The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in kidney development and the progression of chronic kidney disease (CKD).

Objectives: To identify children with low birth weight (LBW) at risk of CKD who have RAAS activation.

Design: We conducted a prospective cohort study to evaluate whether a history of LBW contributes to the development of latent RAAS activation using urine samples from patients with short stature with no clinical kidney symptoms. Additionally, among children who had idiopathic nephrotic syndrome (INS), we examined how a history of LBW contributes to the development of latent RAAS activation using residual kidney biopsy samples.

Methods: We prospectively evaluated angiotensinogen (AGT) using spot urine in children with and without a history of LBW, who required evaluation for short stature without kidney symptoms at registration. We also performed immunohistochemical staining of AGT using kidney biopsy specimens of subjects with and without a history of LBW who had INS. Urinary AGT was assessed as a marker of intrarenal RAAS.

Results: In 45 children (median age 5 years), urinary AGT/creatinine (Cr) levels were significantly higher in children with a history of LBW (n = 24) than in those without (n = 21, median: 12.6 vs 6.7 µg/g･Cr, mean: 15.4 vs 9.1 µg/g･Cr, P < .01). The unadjusted mean difference between the 2 groups and the 95% confidence interval were 6.3 and (1.6, 11.1), respectively. In the immunohistochemical kidney pathological study, the positive area of AGT staining in the kidney tubules of 3 subjects with a history of LBW was more extensive than that of 3 additional subjects without a history of LBW.

Conclusion: Our results indicated that latent intrarenal RAAS activation in children with a history of LBW persists until early school age and may contribute to the progression of CKD.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with currently limited early detection options. Extracellular vesicle (EV)-derived microRNAs (miRNAs) have gained interest as non-invasive diagnostic biomarkers due to their stability in circulation and tumour-specific profiles. However, the methodological robustness of existing literature remains unclear.

Objectives: To systematically evaluate the diagnostic accuracy and methodological quality of studies investigating EV-derived miRNAs for PDAC detection, with a particular focus on adherence to established EV characterisation guidelines.

Design: Systematic review registered with PROSPERO (CRD42024501503) and conducted in accordance with PRISMA 2020 reporting standards.

Methods: We searched PubMed, EMBASE, Medline and Cochrane for original human studies published up to February 1, 2025, evaluating EV-derived miRNAs in biofluids from PDAC patients. Eligible studies reported diagnostic accuracy metrics (sensitivity, specificity, Area Under the Curve (AUC)). Methodological quality was assessed using the QUADAS-2 tool, and EV validation was scored against the Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV) 2018 checklist (updated 2023).

Results: Fifty-six studies were included. Plasma and serum were the most commonly used biofluids. The most frequently evaluated individual miRNAs were miR-21 (13 studies), miR-10b (9 studies), and miR-451a (7 studies). Although several studies reported high diagnostic performance (AUCs up to 0.99), MISEV adherence was limited: only 23.1% of miR-21 studies demonstrated strong EV validation, and >70% of all studies lacked EV quantification or protein marker analysis. Multi-miRNA panels achieved higher AUCs (often > 0.85) but typically scored poorly on EV characterisation. Only 2 of 56 studies included external validation, and 54 studies lacked blinding, contributing to substantial risk of bias.

Conclusion: EV-derived miRNAs are promising PDAC biomarkers, but progress is hindered by inconsistent methods, poor EV validation, and minimal external verification. Translation to clinical use requires robust EV characterisation, standardised workflows, and prospective multi-cohort studies.

Background: Measurement of chemokine CXCL10 is a novel approach to assess the transplant rejection risk and to detect the rejection. While CXCL10 has shown itself to be useful in renal transplants, there are only a few studies on the association between pancreas transplantation and CXCL10. Furthermore, the importance of autoantibodies associated with type I diabetes in pancreas transplantation are relatively poorly understood.

Objectives: To determine whether there is an association between CXCL10 plasma levels and graft rejection in simultaneous pancreas and kidney transplant recipients, and to assess the effects of pancreas autoantibodies on pancreatic transplant rejection.

Design: A retrospective case-control study was conducted.

Methods: In total of 23 individuals (11 male and 12 female, mean age 39.5 (SD ± 7.6) years) who underwent simultaneous pancreas and kidney transplantation, and in 8 healthy controls (evenly distributed in terms of gender, mean age 26.1 (SD ± 1.5) years) plasma samples were analyzed for CXCL10 and autoantibody levels using ELISA. The data was categorized into preoperative, perioperative and postoperative samples and were further juxtaposed in relation to rejection episodes.

Results: Preoperative CXCL10 levels did not differ from those for healthy individuals, but they rose postoperatively (P = .02). The median preoperative plasma concentration of CXCL10 was 68 pg/ml and increased to 123 pg/ml postoperatively. A postoperative plasma CXCL10 cut-off value of 297 pg/ml was indicative of rejection. Postoperative autoantibodies were detected in 10 recipients, 4 of whom were positive for anti-ZnT8 autoantibodies, and 2 were positive for more than 1 type autoantibody. All recipients who were positive for anti-ZnT8 autoantibodies or for more than 1 type autoantibody experienced rejection.

Conclusion: Elevated CXCL10 levels during the first 3 months after transplantation seem to be a risk factor for rejection. The post transplant presence of anti-ZnT8 autoantibodies was associated with transplant rejection.

Background: Patients with inborn errors of metabolism related to Methylenetetrahydrofolate reductase (MTHFR) gene variants are at an increased risk for microvascular complications resulting from diabetic retinopathy. Early intervention with targeted nutritional support, particularly folate supplementation, may help stabilize metabolic function and slow the progression of diseases such as diabetes and hypertension, especially before irreversible structural damage occurs.

Objectives: To assess the effects of the folate supplement Ocufolin^® on serum markers in patients with Type 2 diabetes (T2D) and mild diabetic retinopathy (MDR).

Design: Prospective Cohort Study.

Methods: Ten patients with both MDR and MTHFR polymorphisms (C677T or A1298C) were enrolled in the present study and received Ocufolin^® to address errors in folate methylation metabolism. Patients were excluded if they had a history of other ocular or systemic diseases. Serum biomarkers associated with clinical chemistry (homocysteine, high-sensitivity C-reactive protein [hs-CRP], myeloperoxidase [MPO], fasting insulin, triglycerides, total cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL], Oxidized-LDL [Ox-LDL], vascular endothelial growth factor [VEGF], D-Dimer, hemoglobin A1c [HbA1c] and glutathione) were measured pre-and post-intervention.

Result: Treatment with Ocufolin^® resulted in a 23% decrease in serum homocysteine (P = .005), an 18% decrease in hsCRP, a 13% decrease in fasting insulin, a 15% increase in D-Dimer (P = .03) and a 47% decrease in VEGF (P = .04). Additionally, there was a 9% increase in glutathione, a 2% increase in MPO, a 6% reduction in triglycerides, a 3% increase in total cholesterol, a 4% increase in HDL, a 4% increase in LDL, an 8% increase in Ox-LDL. HbA1c did not change.

Conclusion: Normalizing folate metabolism through Ocufolin^® significantly improved key blood-based biomarkers in patients with diabetic retinopathy. These metabolic improvements may underlie enhanced retinal perfusion and reduced oxidative stress, suggesting potential adjunctive therapeutic benefits for managing vascular retinopathies in this population.