Biomarker Profiles Of Patients Research Articles

Vulnerable plaques on CCTA and biomarker profile in patients with acute coronary syndrome (preliminary results of the Combi-LLT ACS study (NCT05624658)

Vulnerable plaques on CCTA and biomarker profile in patients with acute coronary syndrome (preliminary results of the Combi-LLT ACS study (NCT05624658)

Serum biomarkers in patients with psoriasis and coronary artery disease and their impact on hospitalization: data form a prospective, 4-year, single-center, uncontrolled study

Aim. To study serum biomarker profile in patients with coronary artery disease (CAD) and psoriasis and the impact on the incidence of hospitalization for cardiovascular reasons and psoriasis.Material and methods. The study included 90 patients divided into following 3 groups: with psoriasis (n=30), coronary artery disease (CAD) (n=30) and CAD+psoriasis (n=30) in whom serum biomarkers were determined at the beginning of the study (growth stimulation expressed gene 2, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-17 and tumor necrosis factor alpha) and hospitalization rates were monitored over 4 years.Results. There was a significant difference in the concentrations of all biomarkers between the groups (p<0,05), with the maximum values being in the CAD+psoriasis group, except for NT-proBNP. In regression analysis, risk factors for cardiovascular hospitalizations were psoriasis (p=0,049) and increased NT-proBNP concentrations (p<0,001).Conclusion. Comorbidity leads to an increase in the serum concentration of biomarkers, while the risk factors for cardiovascular hospitalization were psoriasis and serum NT-proBNP level.

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk

BackgroundAbout 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group).MethodsWe performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex.Results13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found.ConclusionsHigher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.

SAT285 Biomarkers For Cardiovascular Disease And Inflammation Are Altered In Autoimmune Addison's Disease

Abstract Disclosure: Å.B. Sævik: None. G. Ueland: None. A. Åkerman: None. P. Methlie: None. M. Quinkler: None. A. Jørgensen: None. C. Höybye: None. A.W. Debowska: None. B. Nedrebø: None. A. Dahle: None. S. Carlsen: None. A.E. Tomkowicz: None. S.T. Sollid: None. I. Nermoen: None. K. Grønning: None. P.M. Dahlqvist: None. G. Grimnes: None. J. Skov: None. T. Finnes: None. S.F. Valland: None. S.E. Holte: None. J. Wahlberg: None. O. Kämpe: None. S. Bensing: None. E.S. Husebye: None. M. Øksnes: None. Background: Population-based studies have shown a wider use of cardiovascular medications in AAD and an increased risk of ischemic heart disease, most pronounced in women. These data suggest that a subgroup of patients may be especially vulnerable, emphasizing the need for clinical tools to evaluate cardiovascular risk at an individual level in AAD. Methods: We first mapped 177 cardiovascular and inflammatory biomarkers in patients with AAD compared with healthy controls overall and stratified for sex (false discovery rate, FDR 5%). Second, we explored biomarker associations to the frequency of adrenal crises and quality of life (P<0.050), and any impact of very high ACTH exposure on biomarker profiles by change in biomarker profiles in patients without residual adrenocortical function (RAF) following injection of ACTH (FDR 5%). Results: Nineteen (11%) biomarkers significantly differed between patients with AAD and controls after correction for multiple testing, of which all but one (ST1A1) were higher in AAD. The greatest difference in biomarker value was noted for FGF21 (difference 0.80 NPX, P = 0.004). When stratified for sex, seven of the 19 biomarkers were significantly higher in female patients compared to controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9 + PGF), but no significant differences were found between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crisis (r = 0.415, P = 0.006) and AddiQoL-30 scores (r = -0.347, P = 0.028). PD-L2 and leptin significantly declined 60 minutes after injection of ACTH in AAD without RAF (-0.15 NPX, P = 0.0001 and -0.25 NPX, P = 0.0003, respectively). Conclusion: We demonstrate marked differences in cardiovascular and inflammatory biomarker profiles in patients with AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with the frequency of adrenal crises and reduced quality of life. Very high ACTH levels reduce PD-L2 and leptin in a glucocorticoid-independent manner, although the overall effect on biomarker profiles seems small. Presentation: Saturday, June 17, 2023

Baseline Levels of Circulating Inflammatory Biomarkers Stratify Patients with Vitiligo Who Significantly Repigment after Treatment with Ruxolitinib Cream

Efficacy of ruxolitinib cream, a topical Jak1/Jak2 inhibitor, was demonstrated in a phase 2 trial in patients with vitiligo. This study aimed to characterize circulating inflammatory biomarker profiles in patients who demonstrated ≥50% improvement in facial Vitiligo Area Scoring Index scores by week 24 (group 1) and those who did not (group 2). This was a posthoc analysis of a multicenter, randomized, double-blind, vehicle-controlled, phase 2 study in which screening was conducted between June 7, 2017 and March 21, 2018. Patients aged between 18 and 75 years with vitiligo, including depigmentation affecting ≥0.5% of body surface area on the face and ≥3% of body surface area on nonfacial areas, were eligible. Patients applied 1.5% ruxolitinib cream to lesions once or twice daily for 52 weeks. Patients were grouped by achievement of ≥50% improvement in facial Vitiligo Area Scoring Index at week 24. Proteomic analysis was performed on baseline serum samples. Mean ± standard error facial Vitiligo Area Scoring Index in group 1 (n= 30) versus group 2 (n= 27) improved by 79.9 ± 4.0% versus 1.1 ± 7.3% and 91.9 ± 1.5% versus 25.1 ± 13.4% at weeks 24 and 52, respectively. Broad proteomic analysis revealed 76 proteins (of 1,104 tested) that were differentially expressed between groups 1 and 2 at baseline (P < 0.05). Ten distinct proteins were upregulated in group 1; 64 were elevated in group 2. This analysis identified potential differences between patients who achieved ≥50% improvement in facial Vitiligo Area Scoring Index at 24 weeks and those who did not that require deeper scientific interrogation and may be important in stratifying therapeutic benefit for patients with vitiligo. The original study was registered at ClinicalTrials.gov, NCT03099304.

Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients' Clinical Features.

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.

Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity.&#x0D; Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease.&#x0D; Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers.&#x0D; Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient.&#x0D; In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile.&#x0D; Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.

Biomarkers in patients with suspected obstructive sleep apnea and obstructive lung disease: Associations among polysomnographic, demographic and spirometric parameters

PURPOSE: The purpose of this study was to characterize the associations between inflammatory and oxidative stress biomarkers, demographic, polysomnographic and spirometric parameters in patients with suspected obstructive sleep apnea (OSA) and/or obstructive airway disease. METHODS: This was a cross-sectional exploratory study of patients referred to the University of British Columbia Sleep Clinic who had a diagnostic polysomnogram for suspected OSA. All patients had samples collected for measurements of IL-10, IL-6, e-selectin, endostatin, VCAM-1, ICAM-1, PDGF, thrombospondin-2, 8-OHdG, 8-isoprostane and superoxide dismutase. Spearman correlation and multiple linear regression were used to identify predictors of biomarkers. RESULTS: A total of 63 patients were included: 65% male, mean age 53 years and body mass index (BMI) 33 kg/m2. Inflammatory biomarkers were associated with female sex (IL-6, coefficient 0.51, p = 0.032), FEV1 (IL-6, coefficient −0.02, p = 0.013) and BMI (VCAM-1, coefficient 0.009, p = 0.051). The oxidative stress marker, 8-OHdG, was associated with hypoxemia in rapid eye movement (REM) sleep (coefficient 0.006, p = 0.02). Age and BMI were both independently associated with percentage of time spent below SpO2 90%. REM sleep and patients with overlap conditions and OSA had greater degree of REM and nonrapid eye movement (NREM) sleep hypoxemia than control group. Lastly, there were no differences in oxidative or inflammatory biomarkers between control, OSA, obstructive airway disease and overlap groups though the number of patients in each group were small. CONCLUSION: Female sex, lower FEV1 and increased BMI were independent predictors of increased inflammatory biomarker levels. The oxidative stress marker 8-OHdG was associated with hypoxemia indices of REM. Larger studies are warranted to delineate biomarker profiles in patients with overlap conditions.

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study.

Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. NT-proBNP level was significantly higher in patients with AHF (p &lt; 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma.

BackgroundTezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER.MethodsAdults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)‐5, IL‐13, periostin, thymus and activation‐regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels.ResultsPositive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL‐5, IL‐13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55–83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL‐5, IL‐13, periostin, TARC, or TSLP, when these biomarkers were assessed individually.ConclusionAt baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.

Correlation between tumor voxel dose response matrix and tumor biomarker profile in patients with head and neck squamous cell carcinoma

BackgroundWe have developed a novel imaging analysis procedure that is highly predictive of local failure after chemoradiation in head and neck cancer. In this study we investigated whether any pretreatment biomarkers correlated with key imaging parameters. MethodsPretreatment biopsy material was available for 28 patients entered into an institutional trial of adaptive radiotherapy in which FDG-PET images were collected weekly during treatment. The biopsies were immunohistochemically stained for CD44, EGFR, GLUT1, ALDH1, Ki-67 and p53 and quantified using image analysis. Expression levels were correlated with previously derived imaging parameters, the pretreatment SUVmax and the dose response matrix (DRM). ResultsThe different parameters of the SUVmax and DRM did not correlate with each other. We observed a positive and highly significant (p = 0.0088) correlation between CD44 expression and volume of tumor with a DRM greater than 0.8. We found no correlation between any DRM parameter and GLUT1, p53, Ki-67 and EGFR or ALDH1. GLUT1 expression did correlate with the maximum SUV0 and the volume of tumor with an SUV0 greater than 20. ConclusionsThe pretreatment SUVmax and DRM are independent imaging parameters that combine to predict local recurrence. The significant correlation between CD44 expression, a known cancer stem cell (CSC) marker, and volume of tumor with a DRM greater than 0.8 is consistent with concept that specific foci of cells are responsible for tumor recurrence and that CSCs may be randomly distributed in tumors in specific niches. Dose painting these small areas may lead to improved tumor control.

The Mutation Matters: CSF Profiles of GCase, Sphingolipids, α-Synuclein in PDGBA.

With pathway-specific trials in PD associated with variants in the glucocerebrosidase gene (PDGBA ) under way, we need markers that confirm the impact of genetic variants in patient-derived biofluids in order to allow patient stratification merely based on genetics and that might serve as biochemical read-out for target engagement. To explore GBA-pathway-specific biomarker profiles cross-sectionally (TUEPAC-MIGAP, PPMI) and longitudinally (PPMI). We measured enzyme activity of the lysosomal glucocerebrosidase, CSF levels of glucosylceramides (upstream substrate of glucocerebrosidase), CSF levels of ceramides (downstream product of glucocerebrosidase), lactosylceramides, sphingosines, sphingomyelin (by-products) and CSF levels of total α-synuclein in PDGBA patients compared to PDGBA_wildtype patients. Cross-sectionally in both cohorts and longitudinally in PPMI: (1) glucocerebrosidase activity was significantly lower in PDGBA compared to PDGBA_wildtype . (2) CSF levels of upstream substrates (glucosylceramides species) were higher in PDGBA compared to PDGBA_wildtype . (3) CSF levels of total α-synuclein were lower in PDGBA compared to PDGBA_wildtype . All of these findings were most pronounced in PDGBA with severe mutations (PDGBA_severe ). Cross-sectionally in TUEPAC-MIGAP and longitudinally in PPMI, CSF levels of downstream-products (ceramides) were higher in PDGBA_severe . Cross-sectionally in TUEPAC-MIGAP by-products sphinganine and sphingosine-1-phosphate and longitudinally in PPMI species of by-products lactosylceramides and sphingomyelin were higher in PDGBA_severe . These findings confirm that GBA mutations have a relevant functional impact on biomarker profiles in patients. Bridging the gap between genetics and biochemical profiles now allows patient stratification for clinical trials merely based on mutation status. Importantly, all findings were most prominent in PDGBA with severe variants. © 2021 International Parkinson and Movement Disorder Society.

Intrinsic functional connectivity, CSF biomarker profiles and their relation to cognitive function in mild cognitive impairment.

Mild cognitive impairment (MCI) often precedes Alzheimer's Dementia (AD), and in a high proportion of individuals affected by MCI, there are already neuropathological processes ongoing that become more evident when patients progress to AD. Accordingly, there is a need for reliable biomarkers to distinguish between normal aging and incipient AD. Recent research suggests that, in addition to established biomarkers such as CSF Aß42, total tau and hyperphosphorylated tau, resting state connectivity established by functional magnetic resonance imaging might also be a feasible biomarker for prodromal stages of AD. In order to explore this possibility, we investigated resting state functional connectivity as well as cerebrospinal fluid (CSF) biomarker profiles in patients with MCI (n = 30; age 66.43 ± 7.06 years) and cognitively healthy controls (n = 38; age 66.89 ± 7.12 years). CSF Aß42, total tau and hyperphosphorylated tau concentrations were correlated with measures of cognitive performance (immediate and delayed recall, global cognition, processing speed). Moreover, MCI-related alterations in intrinsic functional connectivity within the default mode network were investigated using functional resting state MRI. As expected, MCI patients showed decreased CSF Aß42 and increased total tau concentrations. These alterations were associated with cognitive performance. However, there were no differences between MCI patients and cognitively healthy controls regarding intrinsic functional connectivity. In conclusion, our results indicate that CSF protein profiles seem to be more closely related to cognitive decline than alterations in resting state activity. Thus, resting state connectivity might not be a reliable biomarker for early stages of AD.

P4606Comparing biomarker profiles in patients with stable atherosclerosis treated with anacetrapib versus placebo: a nested proteomic study from HPS3/TIMI 55-REVEAL

Abstract Background The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib improves cardiovascular outcomes in patients with stable atherosclerosis; however, the potential interaction of HDL-C-, LDL-C-, and non-lipid-mediated effects remains incompletely understood. Purpose The aim of this study was to identify biological pathways that are influenced by treatment with anacetrapib. Methods HPS3/TIMI 55-REVEAL was a randomized, double-blind, placebo-controlled trial of anacetrapib in patients with stable atherosclerotic cardiovascular disease. We performed a nested prospective biomarker study in 500 patients, analyzing 274 candidate biomarkers. We compared changes in biomarker levels between randomization and mid-study (∼2 years) in patients treated with anacetrapib vs. placebo using a stringent threshold for statistical significance. We evaluated associations between changes in selected biomarkers and changes in HDL-C and LDL-C from baseline to mid-study in each treatment group. Results Eleven biomarkers were significantly modified by anacetrapib vs. placebo (Figure). These proteins represent pathways implicated in inflammation, lipid metabolism, and hematopoiesis. Among anacetrapib-treated patients, changes in 5/11 biomarkers were not significantly correlated with changes in either serum HDL-C or serum LDL-C. Conclusion(s) In patients with stable atherosclerosis, treatment with anacetrapib results in changes in protein expression extending beyond lipid metabolism. Some of these changes appear to be independent of anacetrapib-mediated effects on HDL-C and LDL-C. Acknowledgement/Funding HPS3/TIMI 55-REVEAL was sponsored by Merck.

Determining the stress biomarker profile in patients undergoing total knee replacement and the relationship with outcome at 12 months

BackgroundTotal knee replacement (TKR) is the commonest joint arthroplasty procedure worldwide. Despite excellent outcomes, some studies have reported dissatisfaction in up to 20% of patients.There is evidence of an association between the biochemical stress response to surgery and outcomes. The objective of this study is to describe the stress biomarker profile for TKR, and correlate this with patient outcomes. MethodsA prospective cohort study of 50 patients undergoing primary TKR was conducted. Serum IL-6, TNF-α, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were measured immediately pre- and post-operatively, and on Days 1 and 3. Follow-up questionnaires including the Oxford Knee Score (OKS) and EuroQol five dimensions (EQ-5D) were completed at 12-months.Univariate analysis was completed using a linear regression model (p < 0.05). ResultsSerum IL-6, NLR, and PLR all increased to Day 1 post-operatively, and decreased by Day 3. TNF-α values increased across all time points.Statistical analysis found a significant negative correlation (r = −0.414; p = 0.005) between pre-operative IL-6 and 12-month OKS. There was a significant positive correlation between pre-operative NLR and 12 month OKS (r = 0.272; p = 0.039) and 12 month EQ5D (r = 0.268; p = 0.043). ConclusionThis is the first study to describe the biochemical stress response to TKR. The results raise the potential for a pre-operative risk stratification tool for patients based on IL-6 and NLR measurements.Further research should be conducted to explore the underlying mechanisms involved, and investigate interventions to reduce pre-operative physiological stress with a view to improving post-operative outcomes.

LUMIPULSE G® CSF AD BIOMARKER CONCORDANCE TO PET IN THE KBASE COHORT

Accurate, reliable, and highly standardized measurement of cerebrospinal fluid (CSF) biomarker profiles in patients suspected to suffer from Alzheimer's Disease (AD), can help in setting correct diagnosis and enrichment of AD-drug clinical trials, as of early stages. Compared to Position Emission Tomography (PET) these measurements are relatively cheap and applicable on large scale. As part of an immunoassay platform comparison study, CSF samples of the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD study (KBASE) were analyzed for the AD CSF core biomarkers on the LUMIPULSE G platform. Here we present cut-point determinations for the Lumipulse CSF biomarkers based on PET amyloid positivity. A total of 126 CSF samples of the KBASE study with known PET status (visual reading) were analyzed on the fully automated Lumipulse G AD biomarker panel (β-Amyloid 1–42 (CRM standardized), β-Amyloid 1-40, Total Tau, and pTau 181). For each individual analyte and ratio using Aβ1-42, a cut-point was determined using ROC curve analysis and Youden index. Concordance with amyloid PET was reported as Positive, Negative, and Overall Percentage Agreement (OPA). All samples were successfully analyzed on the LUMIPULSE G1200 instrument. For the 39 PET-positive and 87 PET-negative samples, analyte concentrations were within the assay's measurement range, except for 11 Total Tau measurements. Compared to other cohorts, Total Tau concentrations were found to be lower, impacting the study cut-point determination. For the ratios using Aβ1-42, the Positive Percentage Agreement was above or equal to 85%, whilst Negative Percentage Agreement was at least 89%, illustrating high concordance with PET dichotomous classification of amyloid status. Based on the results of this cohort, for each analyte (excluding Aβ1-40) and ratio using Aβ1-42, a cut-point was identified, which aligned well with amyloid PET status. The discriminatory capacity of single analyte concentrations was lower compared to that of a ratio (single analyte OPA > 75%; ratio OPA > 85%), confirming results of similar studies. Although additional independent studies are needed to further validate the clinical performance of the identified cut-points, they can be applied in the context of studies using the same set-up.

Analysis of distant cardiovascular events depending on the biomarker profile in patients with myocardial infarction

Acute coronary syndrome (ACS) and its complications is one of the main reasons of mortality and invalidation in the world. New biomarkers, such as ST2, NT-proBNP и Pentraxin-3 (Ptx-3) present much more opportunities in the diagnostics of diseases and risk of its development.Aim.To investigate standards and “new” biomarkers in different variants of MI and cardiovascular events in 1 year after MI.Material and methods.In 180 patients with MI (61,4±1,7 years) we determined the serum concentration of standard and “new” (ST2, NT-proBNP, Ptx-3) biomarkers in groups with Q/non-Q, STEMI and NSTEMI and the endpoints (MI, strokes, repeated hospitalizations and sudden deaths) in 1 year (384,3±21,2 days) after MI.Results.Patients with Q-MI and STEMI had higher risk of unfavorable cardiovascular events (p&lt;0,05). Ptx-3 &gt;43,9 ng/ml was shown to be risk factor for sudden death (sensitivity 70,0%, specificity 52,9%), and &gt;125,9±0,06 ng/ml (74,1% and 44,1%) — of recurrent MI.Conclusion.NT-proBNP, ST2 and Ptx-3 showed prognostic value in the diagnostics of unfavorable cardiovascular endpoints.

Tumor necrosis factor-alpha −308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis

BackgroundTakayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA. Hence, the present study investigates the contribution of TNF-α polymorphism toward the complex etiology of TA. MethodsA cross-sectional study was performed in 87 patients with TA and 90 controls. A promoter region polymorphism of TNF-α, rs1800629 G/A, or −308G/A was genotyped in all the study subjects followed by a case–control association study. Furthermore, to understand the biomarker profile, levels of specific markers such as erythrocyte sedimentation rate, serum high-sensitivity C-reactive protein, interleukin-18, interleukin-6, and TNF-α were measured in all the study subjects. ResultsAll the inflammatory markers were significantly higher in the TA patients than in the controls. The genetic study (available for 57 TA patients and 36 controls) revealed that the TNF-α −308A allele was overrepresented in the TA patients (12% vs 7%). The TNF-α −308A allele correlated with the increased TNF-α levels, but it could not attain significance because of a small sample size. ConclusionThe TNF-α −308G/A polymorphism is associated with TNF-α levels in Indian population, which might have implications for clinical risk stratification and treatment. The different TNF-α gene promoter polymorphism might contribute to the molecular pathogenesis of TA. However, further study of the underlying mechanism is warranted.

Host Gene Expression Kinetics During Treatment of Tuberculosis in HIV-Coinfected Individuals Is Independent of Highly Active Antiretroviral Therapy.

Limitations in diagnostic tools to discriminate between active tuberculosis and latent Mycobacterium tuberculosis infection and for monitoring antituberculosis treatment responses are major challenges in tuberculosis control, especially in human immunodeficiency virus (HIV)-coinfected individuals. Expression levels of 105 immune-related genes were determined in 131 HIV-infected patients with active tuberculosis (n = 48), patients with latent M. tuberculosis infection (LTBI; n = 37), and controls with no M. tuberculosis infection (n = 46) in Addis Ababa, Ethiopia, using focused gene expression profiling with a dual-color reverse-transcription multiplex ligation-dependent probe amplification assay. Within the cohort of HIV-positive subjects, the expression profiles of 7 genes at baseline (FCGR1A, RAB24, TLR1, TLR4, MMP9, NLRC4, and IL1B) could accurately discriminate between active tuberculosis and both latent and no M. tuberculosis infection, largely independently of (in)eligibility for highly active antiretroviral therapy (HAART). Six months after antituberculosis treatment, biomarker profiles of patients with tuberculosis became indistinguishable from those of patients with LTBI and controls. Importantly, host gene expression kinetics during antituberculosis treatment in HIV-coinfected individuals was found to be independent of HAART use. Blood transcriptomic profiles can potentially be used as biomarkers to discriminate the different clinical stages of tuberculosis in HIV-coinfected individuals and to monitor tuberculosis treatment responses in both HAART recipients and untreated individuals.