Biomarker Insights[JOURNAL]
Sun
200 papers
Prognostic Value of Neutrophils-to-Lymphocytes Ratio and Platelets-to-Lymphocytes Ratio in Sepsis Patients With Lymphopenia.
Qiu X, Wang Q, Zhang Y … +3 more , Zhao Q, Jiang Z, Zhou L
Biomark Insights · 2024 · PMID 38186669 · Full text
BACKGROUND: Inflammation plays a critical role in sepsis. The integration of neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocytes ratio (PLR) from multiple cell types offers a novel approach to rapidly asses...
BACKGROUND: Inflammation plays a critical role in sepsis. The integration of neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocytes ratio (PLR) from multiple cell types offers a novel approach to rapidly assess inflammation status. However, the predictive role of NLR and PLR in sepsis with lymphopenia remains uncertain. OBJECTIVES: The purpose of this study was to explore the prognostic value of NLR and PLR in sepsis patients with lymphopenia. DESIGN AND METHODS: In this observational retrospective study, we included 172 sepsis patients with lymphopenia and collected clinical characteristics for analysis. Through binary logistic regression analysis, we identified independent factors. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were employed to assess the ability to predict hospital mortality risk. RESULTS: Our results showed a total hospital mortality rate of 53.49%. Multivariate analysis demonstrated that NLR (OR = 1.11, < .001) and PLR (OR = 1.01, = .003) were independent predictors associated with hospital mortality in sepsis patients with lymphopenia. The AUCs of NLR and PLR were 0.750 (95% CI: 0.634-0.788, < .001) and 0.662 (95% CI: 0.580-0.743, < .001), respectively. Notably, an optimal cut-off value of 18.93 for NLR displayed a sensitivity of 75.0% and specificity of 63.0% in discriminating hospital mortality in sepsis patients with lymphopenia, while the optimal cut-off value for PLR was 377.50, with a sensitivity of 67.5% and specificity of 64.1%. CONCLUSION: NLR and PLR serve as independent predictors of hospital mortality in sepsis patients with lymphopenia.
Detection of Inflammatory Biomarker suPAR in COVID-19 Disease With CHORUS TRIO Instrument.
Helena C, Giulia T, Alessandra C … +7 more , Roberto G, Caterina S, Sabrina G, Simone B, Tommaso B, Alessandra B, Roberto L
Biomark Insights · 2023 · PMID 38035182 · Full text
BACKGROUND: Deregulation in the urokinase-type plasminogen activator receptor (uPA/uPAR) system is reported in many diseases where the immune system is activated. During SARS-CoV-2 infection, a rise in soluble uPAR (suPA...
BACKGROUND: Deregulation in the urokinase-type plasminogen activator receptor (uPA/uPAR) system is reported in many diseases where the immune system is activated. During SARS-CoV-2 infection, a rise in soluble uPAR (suPAR) levels has been detected and its concentration above 6 µg/L predicts worsening to severe respiratory failure 14 days earlier, with a positive predictive value of 85.9%, and was the prerequisite for a treatment with anakinra, a recombinant IL-1 receptor antagonist that blocks the activity of both IL-1α and IL-1β. OBJECTIVES: To compare suPAR concentrations measured by CHORUS suPAR on CHORUS TRIO instrument of DIESSE with the commercially available suPARnostic (ViroGates) ELISA assay. DESIGN: A single-centre, non-pharmacological, diagnostic study was performed. RESULTS: A total of 522 serum samples from patients with COVID-19 were tested for suPAR. CHORUS suPAR resulted accurate and reliable, with a high grade of specificity (97.9%), accuracy (97.3%) and sensitivity (96.9%). The median concentration of suPAR, as determined with CHORUS suPAR, was 6.8 µg/L (interquartile range 4.5-9.7) in patients with moderate disease (n = 465) and 8.5 µg/L (interquartile range 5.4-10.6) in patients with severe disease. Among patients with moderate and severe disease, 60.6% and 71.9%, respectively, reached the cut-off concentration of suPAR ⩾6 µg/L, defining their illness severity and suggesting eligibility to anakinra treatment. CONCLUSION: CHORUS suPAR kit resulted as sensitive, specific, accurate and able to quantify suPAR concentrations in patients with moderate and severe COVID-19.
Multiomic Approaches for Cancer Biomarker Discovery in Liquid Biopsies: Advances and Challenges.
Diaz PM, Leehans A, Ravishankar P … +1 more , Daily A
Biomark Insights · 2023 · PMID 37846373 · Full text
Cancer is a complex and heterogeneous disease that poses a significant threat to global health. Early diagnosis and treatment are critical for improving patient outcomes, and the use of liquid biopsies has emerged as a p...
Cancer is a complex and heterogeneous disease that poses a significant threat to global health. Early diagnosis and treatment are critical for improving patient outcomes, and the use of liquid biopsies has emerged as a promising approach for cancer detection and monitoring. Traditionally, cancer diagnosis has relied on invasive tissue biopsies, the collection of which can prove challenging for patients and the results of which may not always provide accurate results due to tumor heterogeneity. Liquid biopsies have gained increasing attention as they provide a non-invasive and accessible source of cancer biomarkers, which can be used to diagnose cancer, monitor treatment response, and detect relapse. The integration of -omics technologies, such as proteomics, genomics, and metabolomics, has further enhanced the capabilities of liquid biopsies by introducing precision oncology and enabling the tailoring of treatment for individual patients based on their unique tumor biology. In this review, we will discuss the challenges and advances in the field of cancer liquid biopsies and the integration of -omics technologies for different types of liquid biopsies, including blood, tear, urine, sweat, saliva, and cerebrospinal fluid.
The Latest Developments in Using Proteomic Biomarkers from Urine and Serum for Non-Invasive Disease Diagnosis and Prognosis.
Shama A, Soni T, Jawanda IK … +3 more , Upadhyay G, Sharma A, Prabha V
Biomark Insights · 2023 · PMID 37528936 · Full text
Due to diagnostic improvements, medical diagnostics is demanding non-invasive or minimally invasive methods. Non-invasively obtained body fluids (eg., Urine, serum) can replace cerebral fluid, amniotic fluid, synovial fl...
Due to diagnostic improvements, medical diagnostics is demanding non-invasive or minimally invasive methods. Non-invasively obtained body fluids (eg., Urine, serum) can replace cerebral fluid, amniotic fluid, synovial fluid, bronchoalveolar lavage fluid, and others for diagnostic reasons. Many illnesses are induced by perturbations of cellular signaling pathways and associated pathway networks as a result of genetic abnormalities. These disturbances are represented by a shift in the protein composition of the fluids surrounding the tissues and organs that is, tissue interstitial fluid (TIF). These variant proteins may serve as diagnostic "signatures" for a variety of disorders. This review provides a concise summary of urine and serum biomarkers that may be used for the diagnosis and prognosis of a variety of disorders, including cancer, brain diseases, kidney diseases, and other system diseases. The studies reviewed in this article suggest that serum and urine biomarkers of various illnesses may be therapeutically useful for future diagnostics. Correct illness management is crucial for disease prognosis, hence non-invasive serum and urine biomarkers have been extensively studied for diagnosis, subclassification, monitoring disease activity, and predicting treatment results and consequences.
Implementation of a Customized Tertiary Analysis Platform for the Reporting of Somatic Variants.
Schilter KF, Dubay S, Stachowiak M … +3 more , Kaplan A, Stauffenger A, Reddi HV
Biomark Insights · 2023 · PMID 37313115 · Full text
Precision medicine for oncology requires the evaluation of variants identified in molecular profiling of solid tumors and hematologic malignancies. This includes evaluation of pre-analytical and postanalytical quality me...
Precision medicine for oncology requires the evaluation of variants identified in molecular profiling of solid tumors and hematologic malignancies. This includes evaluation of pre-analytical and postanalytical quality metrics, variant interpretation, classification, and tiering as outlined in established guidelines, association with clinical significance such as FDA approved drugs and clinical trials, and finally comprehensive reporting. This study documents our experience with the customization and implementation of a software platform that facilitates these requirements for effective reporting of somatic variants.
Caveat Medicus: It's Time to Re-Think Stratification, You May Not Be Helping.
Arandjelović O
Biomark Insights · 2023 · PMID 37200865 · Full text
BACKGROUND: The focus of the present Letter is on the large and seemingly fertile body of work captured under the umbrella of 'patient stratification'. OBJECTIVES: I identify and explain a fundamental methodological flaw...
BACKGROUND: The focus of the present Letter is on the large and seemingly fertile body of work captured under the umbrella of 'patient stratification'. OBJECTIVES: I identify and explain a fundamental methodological flaw underlying the manner in which the development of an increasingly large number of new stratification strategies is approached. DESIGN: I show an inherent conflict between the assumptions made, and the very purpose of stratification and its application in practice. METHODS: I analyse the methodological underpinnings of stratification as presently done and draw parallels with conceptually similarly flawed precedents which are now widely recognized. RESULTS: The highlighted flaw is shown to undermine the overarching ultimate goal of improved patient outcomes by undue fixation on an ill-founded proxy. CONCLUSION: I issue a call for a re-think of the problem and the processes leading to the adoption of new stratification strategies in the clinic.
Copeptin Reflect Left Ventricular Systolic Function at Early Stage of Acute Myocardial Infarction in a Pig Model.
Li W, Sun W, Lyu L … +7 more , Wang G, Yang W, An H, Chen L, Fan J, Yue Y, Zhang R
Biomark Insights · 2023 · PMID 37151758 · Full text
INTRODUCTION: Measurement of biomarkers early after acute myocardial infarction (AMI) might provide a cost-effective and widely available tool to assess infarct severity, myocardial dysfunction, and clinical outcomes. We...
INTRODUCTION: Measurement of biomarkers early after acute myocardial infarction (AMI) might provide a cost-effective and widely available tool to assess infarct severity, myocardial dysfunction, and clinical outcomes. We aimed to induce AMI in miniature pigs, measure the levels of serum biomarkers and global LV function dynamically and explore the release kinetics and optimal sampling time points of copeptin and its correlation with global LV function. METHODS: We induced AMI in the experimental group using a closed-chest model. Left ventricular (LV) function was detected by dual-source computed tomography (DSCT) and serum copeptin was determined by ELISA. RESULTS: The serum copeptin levels were increased at 1 hour, peaked at 3 hours, gradually decreased after 6 hours, and returned to baseline 3 days after AMI. At 3 to 6 hours, the copeptin cutoff of 16.97 to 17.44 pmol/l had 100% sensitivity and 100% specificity ( ⩽ .001) for AMI. Serum copeptin levels at 3 hours and 3 days were negatively correlated with the 3-hours LVEF ( ⩽ .001), respectively. CONCLUSION: Serum copeptin levels change in time, and measurements at 3 to 6 hours after AMI had the highest predictive value.
The Use of Biomarkers in Pharmacovigilance: A Systematic Review of the Literature.
Salas M, Gossell-Williams M, Yalamanchili P … +4 more , Dhingra S, Malikova MA, Aimer O, Junaid T
Biomark Insights · 2023 · PMID 37077840 · Full text
BACKGROUND: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the u...
BACKGROUND: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs). OBJECTIVE: The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area. DESIGN: This is a systematic review of the literature. DATA SOURCES AND METHODS: Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance. RESULTS: Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories. CONCLUSION: Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.
Validation of Prognostic Club Cell Secretory Protein (CC16) Cut-point in an Independent ALTA Cohort.
Almuntashiri S, Chase A, Sikora A … +1 more , Zhang D
Biomark Insights · 2023 · PMID 36814995 · Full text
BACKGROUND: Club cell secretory protein (CC16) has demonstrated utility as a lung-specific biomarker in predicting mortality in acute respiratory distress syndrome (ARDS). These findings have been observed in pre-clinica...
BACKGROUND: Club cell secretory protein (CC16) has demonstrated utility as a lung-specific biomarker in predicting mortality in acute respiratory distress syndrome (ARDS). These findings have been observed in pre-clinical trials and a re-analysis of a large, randomized controlled trial of ARDS (Fluid and Catheter Treatment Trial (FACTT)). OBJECTIVES: The purpose of this study was to validate previous findings by evaluating CC16 level as a mortality predictor in patients from the albuterol to treat acute lung injury (ALTA) trial. DESIGN AND METHOD: In this secondary biomarker analysis, plasma CC16 level was measured from 100 ALTA subjects using enzyme-linked immunosorbent assay (ELISA). The rate of mortality was assessed in patients with high (⩾45 ng/mL) versus low CC16 (<45 ng/mL) levels. This cut-off level was applied based on our previous analysis from FACTT trial. Significance was assessed using Kaplan-Meier curves and a log-rank test. RESULTS: Subjects were an average of 50 years old and 46% of them were females. Patients with high CC16 levels had higher 90-day mortality compared to those with low CC16 levels, (37.73% vs 8.95%, < .001). Other clinical outcomes including ICU-free days, ventilator-free days, and organ failure free days were significantly different between the groups (All < .05). CONCLUSION: In this validation study, we demonstrated that ARDS patients with high plasma CC16 concentration had a higher mortality rate than those with low CC16 levels, confirming previous findings that CC16 levels are associated with ARDS mortality.
What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?
Edwards G, Seeley A, Carter A … +7 more , Patrick Smith M, Cross E, Hughes K, Van den Bruel A, Llewelyn MJ, Verbakel JY, Hayward G
Biomark Insights · 2023 · PMID 36761839 · Full text
BACKGROUND: Urinary tract infection (UTI) affects half of women at least once in their lifetime. Current diagnosis involves urinary dipstick and urine culture, yet both methods have modest diagnostic accuracy, and cannot...
BACKGROUND: Urinary tract infection (UTI) affects half of women at least once in their lifetime. Current diagnosis involves urinary dipstick and urine culture, yet both methods have modest diagnostic accuracy, and cannot support decision-making in patient populations with high prevalence of asymptomatic bacteriuria, such as older adults. Detecting biomarkers of host response in the urine of hosts has the potential to improve diagnosis. OBJECTIVES: To synthesise the evidence of the diagnostic accuracy of novel biomarkers for UTI, and of their ability to differentiate UTI from asymptomatic bacteriuria. DESIGN: A systematic review. DATA SOURCES AND METHODS: We searched MEDLINE, EMBASE, CINAHL and Web of Science for studies of novel biomarkers for the diagnosis of UTI. We excluded studies assessing biomarkers included in urine dipsticks as these have been well described previously. We included studies of adult patients (≥16 years) with a suspected or confirmed urinary tract infection using microscopy and culture as the reference standard. We excluded studies using clinical signs and symptoms, or urine dipstick only as a reference standard. Quality appraisal was performed using QUADAS-2. We summarised our data using point estimates and data accuracy statistics. RESULTS: We included 37 studies on 4009 adults measuring 66 biomarkers. Study quality was limited by case-control design and study size; only 4 included studies had a prospective cohort design. IL-6 and IL-8 were the most studied biomarkers. We found plausible evidence to suggest that IL-8, IL-6, GRO-a, sTNF-1, sTNF-2 and MCR may benefit from more rigorous evaluation of their potential diagnostic value for UTI. CONCLUSIONS: There is insufficient evidence to recommend the use of any novel biomarker for UTI diagnosis at present. Further evaluation of the more promising candidates, is needed before they can be recommended for clinical use.
Advantages and Limitations of Monitoring Circulating Tumor DNA Levels to Predict the Prognosis of Patients Diagnosed With Gastric Cancer.
He W, Yang J, Sun X … +8 more , Jiang S, Jiang J, Liu M, Mu T, Li Y, Zhang X, Duan J, Xu R
Biomark Insights · 2022 · PMID 36533271 · Full text
Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disp...
Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disputed. We investigated 24 patients with gastric cancer in this study, using a 605-gene sequencing panel to sequence their plasma cfDNA and tumor tissue DNA. The mutation concordance between plasma cfDNA and tumor tissue DNA was 70.6% in stage IV gastric cancer and 30.2% in stage III gastric cancer, indicating insufficient mutation detection rates in stage III and early-stage cancer. When compared with total cfDNA load and blood tumor mutation burden (bTMB), the variant allele frequencies (VAF) of commonly mutated genes are highly accurate in representing disease burden. Further, VAF are a better prognostic indicator compared with serum biomarkers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP). The use of cfDNA in molecular profiling of patients allows prediction of patient survival and clinical response, as well as the development of personalized therapy regimens.
Analysis of Sex-Specific Prostanoid Production Using a Mouse Model of Selective Cyclooxygenase-2 Inhibition.
Upmacis RK, Becker WL, Rattendi DM … +4 more , Bell RS, Jordan KD, Saniei S, Mejia E
Biomark Insights · 2022 · PMID 36533270 · Full text
BACKGROUND: Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females ind...
BACKGROUND: Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females indicating that different therapeutic approaches may be required during disease. OBJECTIVES: We examined sex-dependent differences in COX-related metabolites in genetically modified mice that produce a cyclooxygenase-2 (COX2) enzyme containing a tyrosine 385 to phenylalanine (Y385F) mutation. This mutation renders the COX2 enzyme unable to form a key intermediate radical required for complete arachidonic acid metabolism and provides a model of selective COX2 inhibition. DESIGN AND METHODS: Mice heterozygous for the Y385F mutation in COX2 were mated to produce cohorts of wild-type, heterozygous, and COX2 mutant mice. We investigated whether the genotype distribution followed Mendelian genetics and studied whether sex-specific differences could be found in certain prostanoid levels measured in peritoneal macrophages and in urinary samples. RESULTS: The inheritance of the COX2 mutation displayed a significant deviation with respect to Mendel's laws of genetics, with a lower-than-expected progeny of weaned COX2 mutant pups. In macrophages, prostaglandin E (PGE) production following lipopolysaccharide (LPS) and interferon gamma (IFNγ) stimulation was COX2-dependent in both males and females, and data indicated that crosstalk between the nitric oxide (NO) and COX2 pathways may be sex specific. We observed significant differences in urinary PGE production by male and female COX2 mutant mice, with the loss of COX2 activity in male mice decreasing their ability to produce urinary PGE. Finally, female mice across all 3 genotypes produced similar levels of urinary thromboxane (measured as 11-dehydro TxB) at significantly higher levels than males, indicating a sex-related difference that is likely COX1-derived. CONCLUSIONS: Our findings clearly demonstrate that sex-related differences in COX-derived metabolites can be observed, and that other pathways (such as the NO pathway) are affected.
Aberrant expression of miR-138 as a novel diagnostic biomarker in systemic sclerosis.
Bayati P, Poormoghim H, Mojtabavi N
Biomark Insights · 2022 · PMID 36518749 · Full text
BACKGROUND: MicroRNAs are short nucleotide sequences that contribute to the regulation of various biological functions and therefore their roles have been investigated in many pathologic conditions such as epithelial to...
BACKGROUND: MicroRNAs are short nucleotide sequences that contribute to the regulation of various biological functions and therefore their roles have been investigated in many pathologic conditions such as epithelial to mesenchymal transition in cancer and fibrosis; among them, miR-138 has been mostly studied in cancer biology and is well-known for its suppressing effect on cancer progression. Being able to suppress major pathways involved in EMT, miR-138 could be a good candidate to be investigated in fibrotic responses too. Based on our previous studies, and the capability of miR-138 to target and regulate several components of the EMT pathway; we hypothesized a role for miR-138 in systemic sclerosis. Accordingly, the gene expression of miR-138 was assessed to find any alterations in the whole blood of the SSc patients. METHODS: Blood was collected from 70 patients with systemic sclerosis (equally divided between 2 groups of limited and diffuse categories) and 30 healthy individuals as controls. RNA was immediately isolated from the fresh whole blood; afterward, the resulting RNA was reverse transcribed into cDNA and then the relative expression of miR-138 was compared between the patients and the controls by the means of qPCR, and specific TaqMan primer and probes. RESULTS: The relative expression of miR-138 was significantly lower in patients with systemic sclerosis compared to the controls. No significant difference was observed between the limited and diffuse patient groups. ROC curve analysis showed an appropriate diagnostic value of miR-138 in effectively differentiating SSc patients from the healthy controls. CONCLUSION: miR-138 is likely involved in the pathogenesis of SSc and with further evaluations may be utilized as a diagnostic biomarker in SSc. Also, targeting miR-138 in future studies could be promising for finding a novel treatment option for patients with SSc.
Purpose, Partnership, and Possibilities: The Implementation of the Dog Aging Project Biobank.
Mouttham L, Castelhano MG
Biomark Insights · 2022 · PMID 36468152 · Full text
BACKGROUND: Biobanks have been supporting longitudinal prospective and retrospective studies by providing standardized services for the acquisition, transport, processing, storage, and distribution of high-quality biolog...
BACKGROUND: Biobanks have been supporting longitudinal prospective and retrospective studies by providing standardized services for the acquisition, transport, processing, storage, and distribution of high-quality biological material and associated data. Here, we describe how the Dog Aging Project (DAP), a large-scale longitudinal study of the domestic dog () with translational applications for humans, developed a biobank of canine biospecimens and associated data. DESIGN AND METHODS: This was accomplished by working with the Cornell Veterinary Biobank, the first biobank in the world to receive accreditation to ISO 20387:2018-General Requirements for Biobanking. The biobank research team was involved in the early collection stages of the DAP, contributing to the development of appropriate workflows and processing fit-for-purpose biospecimens. In support of a dynamic strategy for real-time adjustment of processes, a pilot phase was implemented to develop, test, and optimize the biospecimen workflows, followed by an early phase of collection, processing, and banking of specimens from DAP participants. RESULTS: During the pilot and early phases of collection, the DAP Biobank stored 164 aliquots of whole blood, 273 aliquots of peripheral blood mononuclear cells, 130 aliquots of plasma, and 70 aliquots of serum, and extracted high molecular weight genomic DNA suitable for whole-genome sequencing from 109 whole blood specimens. These specimens, along with their associated preanalytical data, have been made available for distribution to researchers. CONCLUSION: We discuss the challenges and opportunities encountered during the implementation of the DAP Biobank, along with novel strategies for promoting biobanking sustainability such as partnering with a DAP quality assurance manager and a DAP marketing and communication specialist and developing a pilot grant structure to fund small innovative research projects.
Evaluation of Genetic Polymorphisms of the Antioxidant Enzymes and Biomarkers of Oxidative Stress in Preterm Neonates With Respiratory Distress Syndrome Receiving External Surfactant.
Sridharan K, Al Jufairi M, Hejab AAM … +10 more , Al Madhoob A, Al Marzooq R, Taha S, Jaber Mulla Aljishi M, Abdulhadi A, Al Ansari E, Ali MA, Naser MAA, Al Segai O, Dunne K
Biomark Insights · 2022 · PMID 36386121 · Full text
BACKGROUND: Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influen...
BACKGROUND: Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules. OBJECTIVES: To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS. DESIGN: Observational, cross-sectional study. METHODS: Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI). RESULTS: GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in , , and (rs1799983) were significantly associated with differences in oxidative stress biomarkers. (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; = .01) with an optimal cut-off value of 88.78 µmol/L. CONCLUSION: We observed that SNPs in and significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.
The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-β1, FGF-2 in COVID-19 Patients.
Karadeniz H, Avanoğlu Güler A, Özger HS … +9 more , Yıldız PA, Erbaş G, Bozdayı G, Deveci Bulut T, Gülbahar Ö, Yapar D, Küçük H, Öztürk MA, Tufan A
Biomark Insights · 2022 · PMID 36380740 · Full text
BACKGROUND: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects dire...
BACKGROUND: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed. RESULTS: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis. CONCLUSIONS: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.
MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation.
Crow J, Samuel G, Farrow E … +10 more , Gibson M, Johnston J, Guest E, Miller N, Pei D, Koestler D, Pathak H, Liang X, Mangels C, Godwin AK
Biomark Insights · 2022 · PMID 36341281 · Full text
Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the...
Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the pathognomonic chimeric transcripts and their corresponding oncoproteins. It has been suggested that the EWS-ETS oncogenic action can mediate microRNA (miRNA) processing. Importantly, small extracellular vesicles (sEVs), including those frequently referred to as exosomes have been shown to be highly enriched with tumor-derived small RNAs such as miRNAs. We hypothesized that ESFT-specific sEVs are enriched with certain miRNAs which could be utilized toward an exo-miRNA biomarker signature specific to this disease. We performed miRNAseq to compare both the exo-derived and cell-derived miRNA content from 8 ESFT, 2 osteosarcoma, 2 non-cancerous cell lines, and pediatric plasma samples. We found that sEVs derived from ESFT cells contained nearly 2-fold more number of unique individual miRNAs as compared to non-ESFT samples. Quantitative analysis of the differential enrichment of sEV miRNAs resulted in the identification of 62 sEV-miRNAs (exo-miRNAs) with significant ( < .05) enrichment variation between ESFT and non-ESFT sEV samples. To determine if we could utilize this miRNA signature to diagnose ESFT patients via a liquid biopsy, we analyzed the RNA content of total circulating sEVs isolated from 500 µL plasma from 5 pediatric ESFT patients, 2 pediatric osteosarcoma patients, 2 pediatric rhabdomyosarcoma patients, and 4 non-cancer pediatric controls. Pearson's clustering of 60 of the 62 candidate exo-miRNAs correctly identified 80% (4 of 5) of pathology confirmed ESFT patients. Importantly, RNAseq analysis of tumor tissue from the 1 outlier, revealed a previously uncharacterized translocation. Taken together, these findings support the development and validation of an exo-miRNA-based liquid biopsy to aid in the diagnosis and monitoring of ESFT.
Monitoring of Post-Brain Injuries By Measuring Plasma Levels of Neuron-Derived Extracellular Vesicles.
Hotta N, Tadokoro T, Henry J … +7 more , Koga D, Kawata K, Ishida H, Oguma Y, Hirata A, Mitsuhashi M, Yoshitani K
Biomark Insights · 2022 · PMID 36324609 · Full text
BACKGROUND: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. METHODS: A sandwich...
BACKGROUND: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. METHODS: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 CD9]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36). RESULTS: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 CD9]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly ( = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23). CONCLUSIONS: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.
The Behaviour of Serum Survivin in Patients With Lupus Nephritis.
Lisboa RV, de Oliveira FR, Quaresma TO … +3 more , de Almeida RM, Ribeiro Oliveira RD, Junior PL
Biomark Insights · 2022 · PMID 36311208 · Full text
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multi phenotypic, autoimmune inflammatory disease and renal involvement significantly worsens its prognosis. Apoptosis dysregulation plays a key pathogenic rol...
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multi phenotypic, autoimmune inflammatory disease and renal involvement significantly worsens its prognosis. Apoptosis dysregulation plays a key pathogenic role. Survivin, a protein from the apoptosis inhibitors family, has been considered a promising strategy in cancer therapy and evaluated as one of the regulatory pathways in the scenario of immune-mediated disorders. OBJECTIVE: This study aims to explore survivin behaviour in SLE patients with lupus nephritis (LN), assessing its potential as a therapeutic and prognostic biomarker. METHODS: 297 SLE patients were classified based on the American College of Rheumatology (ACR) 1997 criteria, from 2000 to 2015. In a cross-sectional study, the serum level of survivin was measured by an ELISA test and compared between 200 SLE individuals and healthy controls. In a longitudinal cohort, 97 patients with active LN had the concentration of survinin measured, before and after treatment with cyclophosphamide pulse therapy. RESULTS: The serum concentration of survivin was significantly lower in the SLE group than in healthy controls, regardless of concomitant NL or disease activity. The longitudinal evaluation revealed a significant reduction in survivin serum level after treatment. However, survivin rates were not able to discriminate groups that achieved remission from those that maintained nephritis activity. CONCLUSION: Our study suggests that survivin levels in SLE patients are lower than in the general population. Even so, its use as a biomarker in SLE seems limited, not reflecting disease activity or response to LN treatment, as in other contexts.
FRailty and Arterial stiffness - the role of oXidative stress and Inflammation (FRAXI study).
Mensah E, Ali K, Banya W … +4 more , Kirkham FA, Mengozzi M, Ghezzi P, Rajkumar C
Biomark Insights · 2022 · PMID 36275839 · Full text
OBJECTIVE: There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute t...
OBJECTIVE: There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states. METHODS: An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita. Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2'-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin. RESULTS DATA ANALYSIS PLAN: Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at < .05. CONCLUSION: This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.
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