Biomarker Levels In Patients Research Articles

Inflammatory biomarkers do not distinguish between patients with sciatica and referred leg pain within a primary care population: results from a nested study within the ATLAS cohort

BackgroundThere is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica.MethodsPrimary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS). Participants underwent a standardised clinical assessment, lumbar spine MRI and a subsample (n = 119) had samples taken for biomarker analysis. Participants were classified having: a) clinically confirmed sciatica or referred leg pain, and then subdivided into those with (or without) MRI confirmed nerve root compression due to disc prolapse. Seventeen key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα and IL-6, were assayed in duplicate using commercial multiplex detection kits and measured using a Luminex suspension array system. Median biomarker levels were compared between the groups using a Mann Whitney U test. Multivariate logistic regression analysis was used to investigate the association between clinical measures and biomarker levels adjusted for possible confounders such as age, sex, and symptom duration.ResultsNo difference was found in the serum level of any of the 17 biomarkers tested in patients with (n = 93) or without (n = 26) clinically confirmed sciatica, nor between those with (n = 44) or without (n = 49) sciatica and MRI confirmed nerve root compression.ConclusionIn this cohort, no significant differences in serum levels of TNFα, IL-6 or any other biomarkers were seen between patients with sciatica and those with back pain with referred leg pain. These results suggest that in patients with low back-related leg pain, serum markers associated with inflammation do not discriminate between patients with or without clinically confirmed sciatica or between those with or without evidence of nerve root compression on MRI.

P229 The relationship between computed tomography enterography findings and levels of faecal biomarkers in patients with small bowel Crohn’s disease: A prospective study

P229 The relationship between computed tomography enterography findings and levels of faecal biomarkers in patients with small bowel Crohn’s disease: A prospective study

Prognostic significance and population dynamics of peripheral monocytes in patients with oropharyngeal squamous cell carcinoma.

Several inflammatory biomarkers are considered potential prognostic factors in various cancers. This study aimed to investigate the prognostic significance and population dynamics of pretreatment inflammatory biomarker levels in patients with oropharyngeal squamous cell carcinoma (OPSCC). The influence of neutrophil counts, lymphocyte counts, monocyte counts, platelet counts, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on progression-free survival (PFS), and overall survival (OS) was analyzed. We also analyzed the peripheral blood mononuclear cells collected from patients and healthy donors (HDs). Elevated monocyte count was an independent prognostic factor for PFS. Low LMR was an independent prognostic factor for OS. The proportion of intermediate monocytes was lower, and that of classical monocytes was higher in patients than in HDs. Furthermore, PD-L1 expression on monocytes was higher in patients than in HDs. We showed the prognostic significance and population dynamics of peripheral monocytes in patients with OPSCC.

Biomarker Profiling of Neurovascular Diseases in Patients with Stage 5 Chronic Kidney Disease.

Patients with stage 5 chronic kidney disease (CKD5D) have a higher risk of developing neurocognitive deficits. Stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD) are causes of such deficits in CKD5D. Chronic inflammation from renal failure elevates risk for these diseases through oxidative stress and vascular dysfunction. The adverse impact on the carotid and intracranial vasculatures contributes to the multifactorial pathophysiology of stroke. Eleven plasma biomarker levels in patients with CKD5D (n = 97) and healthy controls (n = 17-50) were measured using sandwich enzyme-linked immunosorbent assay (ELISA) method. Of the 97 patients with CKD5D, 24 had CCAD, 19 had ICAD, and 23 had acute stroke. Elevations in NACHT, LRR, and PYD domains-containing protein 3 (NALP3) levels in patients with CKD5D (+)CCAD (1.80 ± 0.11 ng/mL) compared to patients with (−)CCAD (1.55 ± 0.08 ng/mL) were statistically significant (P = .0299). Differences in D-dimer levels were also found to be statistically significant (P = .0258) between CKD5D (+)stroke (1.83 ± 0.42 μg/mL) and (−)stroke (0.89 ± 0.13 μg/mL) groups. The ages of the (+) neurovascular disease groups were found to be significantly elevated compared to the (−) neurovascular disease groups (P = .0002 carotid AD; P < .0001 ICAD; P = .0157 stroke). D-dimer levels were positively correlated with age in CKD5D (P = .0375). With the possible exception of NALP3 for CCAD, profiling levels of specific biomarkers for risk stratification of neurovascular diseases in the CKD5D population warrants further investigation.

The effect of group-based cognitive behavioral therapy on inflammatory biomarkers in patients with coronary heart disease—results from the SUPRIM-trial

Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.

Assessment of some hematological, biochemical parameters and cardiac biomarker levels in patients with ischemic heart disease in Erbil city

Assessment of some hematological, biochemical parameters and cardiac biomarker levels in patients with ischemic heart disease in Erbil city

Mycobacterial infection influences bone biomarker levels in patients with Crohn's disease.

Patients with Crohn's disease (CD) have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocalcin in CD patients and cow-disease model (Johne's disease). In this study, we measured ucOC, active osteocalcin, and calcium levels in sera from 42 cattle (21 infected with MAP and 21 healthy cattle), 18 CD patients, and 20 controls. The level of ucOC in MAP+ bovine samples was higher than that in MAP- controls (318 ± 57.2 nmol/mL vs. 289 ± 95.8 nmol/mL, P > 0.05). Consequently, mean calcium level in bovine MAP+ was significantly higher than that in bovine-MAP- samples (9.98 ± 0.998 mg/dL vs. 7.65 ± 2.12 mg/dL, P < 0.05). Also, the level of ucOC was higher in CD-MAP+ than in CD-MAP- (561 ± 23.7 nmol/mL vs. 285 ± 19.6 nmol/mL, P < 0.05). Interestingly, the mean osteocalcin level in MAP+ bovine was lower than that in MAP- bovine (797 ± 162 pg/mL vs. 1190 ± 43 pg/mL) and it was lower in CD-MAP+ than in CD-MAP- infection (1.89 ± 0.184 ng/mL vs. 2.19 ± 0.763 ng/mL) (P < 0.05). The correlation between MAP infection and elevation of sera ucOC, reduction of active osteocalcin and increased calcium supports MAP infection role in CD and complications with osteoporosis.

Neurotrophic and inflammatory markers in bipolar disorder: A prospective study

Altered neurotrophic signaling is thought to impair neuroplasticity in bipolar disorder (BD). Brain-derived neurotrophic factor (BDNF) is proposed as a neurotrophic marker in BD. However, the current evidence for its use in monitoring disease activity and illness progression is conflicting and an exploration of additional neurotrophic markers is needed. This prospective case-control study investigated mood-specific changes in potential neurotrophic markers and their association to inflammatory activity. Patients with BD were included during an acute mood episode, either depressive (n=35) or (hypo)manic (n=32). Fifty-nine patients (88%) and 29 healthy controls (97%) completed the study. Peripheral blood levels of BDNF, vascular endothelial growth factor A (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and tumor necrosis factor alpha (TNF-α) were measured at baseline and after 2 months. Biomarker levels in patients were compared to controls and correlated to HDRS-17 and YMRS total scores and the PANSS positive subscale scores. Linear mixed model analysis revealed no significant differences in neurotrophic markers between patients and controls. We found significantly increased TNF-α levels in patients and a subsequent normalization during euthymia. None of the biomarkers strongly correlated to mood symptom severity. Despite standardized methodological practices, BDNF and VEGF levels had a wide distribution range. We need a better understanding of methodological aspects influencing the analysis of neurotrophic factors to improve future research on markers for mood state monitoring and illness progression in BD.

Abstract 4627: Prognostic significance and population shift of peripheral monocytes in patients with oropharyngeal squamous cell carcinoma

Abstract Evidence has accumulated that chronic inflammation plays a critical role in carcinogenesis, tumor growth, and metastasis. To date, several inflammatory biomarkers are considered as potential prognostic factors in various cancers. The aim of the present study was to investigate the prognostic significance of the pretreatment levels of inflammatory biomarkers in patients with oropharyngeal squamous cell carcinoma (OPSCC). A total of 67 patients newly diagnosed as OPSCC was finally included. The neutrophil, lymphocyte, monocyte and platelet counts recorded before treatment was initiated, then lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. These inflammatory biomarkers and clinical parameters including age, differentiation, T-stage, N-stage, TNM-stage, smoking, and drinking were compared with progression-free survival (PFS) and overall survival (OS) using cox regression. Elevated monocyte count and advanced T-stage were significantly associated with poor PFS; in addition, these were independent prognostic factors for PFS. Elevated monocyte count and low LMR were significantly associated with poor OS; moreover, low LMR was an independent prognostic factor for OS. Of note, monocyte count and LMR were associated with prognosis more intensively in patients with p16-negative OPSCC. Following these results, we evaluated the peripheral blood mononuclear cells of 14 patients with OPSCC collected before treatments. CD14+ CD86+ HLR-DR+ cells were gated as monocytes, then divided into three subsets according to the expression of CD14 and CD16. The proportion of intermediate monocytes was lower and that of classical monocytes was higher in OPSCC patients than in healthy donors, especially in patients with elevated monocyte count. Furthermore, the expression level of PD-L1 was higher in patients than in healthy donors on all subsets. In conclusion, our data suggests that elevated monocyte count and low LMR seem to be useful biomarkers for predicting prognosis of OPSCC; furthermore, the population shift of monocytes may relate to poor prognosis of OPSCC. Citation Format: Hideyuki Takahashi, Koichi Sakakura, Kazuaki Chikamatsu. Prognostic significance and population shift of peripheral monocytes in patients with oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4627. doi:10.1158/1538-7445.AM2017-4627

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.

Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, FACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair [‡‡][1] Sana M. Al-Khatib, MD, MHS, FACC, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD,

ANGPTL3 Deficiency and Protection Against Coronary Artery Disease

BackgroundFamilial combined hypolipidemia, a Mendelian condition characterized by substantial reductions in all 3 major lipid fractions, is caused by mutations that inactivate the gene angiopoietin-like 3 (ANGPTL3). Whether ANGPTL3 deficiency reduces risk of coronary artery disease (CAD) is unknown. ObjectivesThe study goal was to leverage 3 distinct lines of evidence—a family that included individuals with complete (compound heterozygote) ANGPTL3 deficiency, a population based-study of humans with partial (heterozygote) ANGPTL3 deficiency, and biomarker levels in patients with myocardial infarction (MI)—to test whether ANGPTL3 deficiency is associated with lower risk for CAD. MethodsWe assessed coronary atherosclerotic burden in 3 individuals with complete ANGPTL3 deficiency and 3 wild-type first-degree relatives using computed tomography angiography. In the population, ANGPTL3 loss-of-function (LOF) mutations were ascertained in up to 21,980 people with CAD and 158,200 control subjects. LOF mutations were defined as nonsense, frameshift, and splice-site variants, along with missense variants resulting in <25% of wild-type ANGPTL3 activity in a mouse model. In a biomarker study, circulating ANGPTL3 concentration was measured in 1,493 people who presented with MI and 3,232 control subjects. ResultsThe 3 individuals with complete ANGPTL3 deficiency showed no evidence of coronary atherosclerotic plaque. ANGPTL3 gene sequencing demonstrated that approximately 1 in 309 people was a heterozygous carrier for an LOF mutation. Compared with those without mutation, heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol. Carrier status was associated with a 34% reduction in odds of CAD (odds ratio: 0.66; 95% confidence interval: 0.44 to 0.98; p = 0.04). Individuals in the lowest tertile of circulating ANGPTL3 concentrations, compared with the highest, had reduced odds of MI (adjusted odds ratio: 0.65; 95% confidence interval: 0.55 to 0.77; p < 0.001). ConclusionsANGPTL3 deficiency is associated with protection from CAD.

Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis

Background: The disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) vary in their mode of action and when therapies are changed, the consequences on inflammatory and degenerative processes are largely unknown. Objective: We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers. Methods: 43 RRMS patients were followed up after 4–12 months of fingolimod treatment. Concentrations of C-X-C motif chemokine 13 (CXCL13), chemokine (C-C motif) ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and neurogranin (NGRN) were analyzed by enzyme-linked immunosorbent assay (ELISA), while chitotriosidase (CHIT1) was analyzed by spectrofluorometry. Results: The levels of NFL, CXCL13, and CHI3L1 decreased (p < 0.05) after fingolimod treatment. Subgroup analysis revealed a reduction in NFL (p < 0.001), CXCL13 (p = 0.001), CHI3L1 (p < 0.001), and CHIT1 (p = 0.002) in patients previously treated with first-line therapies. In contrast, the levels of all analyzed biomarkers were essentially unchanged in patients switching from natalizumab. Conclusion: We found reduced inflammatory activity (CXCL13, CHI3L1, and CHIT1) and reduced axonal damage (NFL) in patients switching from first-line DMTs to fingolimod. Biomarker levels in patients switching from natalizumab indicate similar effects on inflammatory and degenerative processes. The CSF biomarkers provide an additional measure of treatment efficacy.

Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: How to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients

Background Changes in the level of biomarkers specific of osteoarthritis (OA) could help not only for the diagnosis but also for the monitoring of the disease progression and efficacy of a therapeutic intervention. Objectives The aim of this study was to investigate the effects of chondroitin sulfate (CS) on the serum levels of biomarkers in patients with knee OA. Methods Seventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study. Patients treated with CS (800 mg/day) were evaluated 5 times from D-30 to 6-month. The primary outcome was the % relative change in serum biomarkers (Coll2–1, Coll2–1NO2, Fib3–2). Secondary outcomes were the evaluation of pain (VAS) and function (Lequesne9s Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret variations in serum levels of Coll2–1. Results Patients from either ITT or PP populations showed no difference in the serum biomarkers levels at baseline. Most of the biomarkers levels decreased after 1 month of treatment but no significant differences were reported. However when considering responders and non-responders from the ITT population, a significant difference was found for Coll2–1 at 3 months (p=0.030) and 6 months (p=0.038) (ACA approach). A decrease in pain (VAS) and an improvement in function (LI) were recorded throughout the visits (p Conclusions CS was effective modulating the metabolic status of KOA patients trough the reduction of Coll2–1 levels in responders and the disease9s symptoms. Biomarkers are important tools for the monitoring of OA disease and of treatment. The main goal in biomarker research is to qualify them as surrogate endpoints in clinical trials. This study proposes a new approach for the analysis and the interpretation of the variation in biomarker levels and introduces the notion of metabolic responders. Disclosure of Interest None declared

Cerebrospinal fluid biomarkers for Alzheimer's disease: the role of apolipoprotein E genotype, age, and sex.

IntroductionCerebrospinal fluid (CSF) biomarkers improve the diagnostic accuracy for Alzheimer’s disease (AD), even at the predementia stage of the disease. The ε4-allele of apolipoprotein E (ApoE ε4), female sex, and older age are well-known risk factors for AD. It is unclear how these risk factors affect the CSF biomarkers in patients with AD.AimThe objective of this study was to investigate the associations of ApoE ε4, sex, and age with CSF biomarker levels in a unicenter sample of patients with AD that includes a high proportion of patients with early-onset AD (EOAD).MethodsThe CSF levels of amyloid-β 1-42 (Aβ1-42) and total-tau of 117 subjects with mild to moderate AD (55 late-onset AD and 62 EOAD) were assessed. All subjects underwent ApoE genotyping, clinical evaluation, comprehensive neuropsychological assessments, and neuroimaging. Associations between CSF biomarker levels, ApoE ε4 allele frequency, age, and sex were evaluated.ResultsIn the whole patient sample and in the late-onset AD subgroup ε4 homozygous subjects had significantly lower CSF Aβ1-42 levels compared with ε4 heterozygous subjects and ε4 noncarriers. This association was not detected in the EOAD group. Age group, sex, and severity of cognitive decline did not have a significant impact on CSF Aβ1-42 levels. No significant associations were found between ApoE ε4 allele frequency and CSF total-tau levels.ConclusionApoE ε4 allele is associated with a reduction of CSF Aβ1-42 levels. This result is consistent with the findings of several previous studies. In the subgroup of patients with EOAD this association was not replicated. Larger studies are necessary to further investigate associations between ApoE ε4 allele frequency and CSF biomarker levels in patients with EOAD.

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

Effect of Diabetes Mellitus on Metabolic Biomarker Levels in Patients with End Stage Renal Disease or Undergoing Total Joint Arthroplasty

Aim: Diabetes mellitus (DM) is a proven risk factor for diseases such as end stage renal disease (ESRD) and osteoarthritis (OA). Thus, it is not unreasonable to assume that some of the ESRD/ OA pathogenesis, namely inflammation and metabolic dysfunction, could be attributed to DM as a comorbititiy. This study aims to investigate DM's effect on metabolic biomarker levels in patients with ESRD or undergoing total joint arthroplasty. Methods: Under IRB approval, plasma samples were collected from 82 patients with ESRD prior to hemodialysis and from 39 patients prior to total hip and knee arthroplasty. Normal human plasma samples (female & male, 18-35 years old) were purchased from George King Biomedical Inc. (Overland Park, KS). Samples were stored at -80°C. Metabolic biochips were purchased from RANDOX (Co. Antrim, Northern Ireland) to test c-peptide, ferritin, IL-6, resistin, insulin, TNF-α, IL-1α, leptin and PAI-1. These biomarkers were tested in two batches: 82 ESRD and 17 normals, and 39 TJA and 25 normals. Results & Conclusions: All biomarkers, except insulin, were significantly elevated in ESRD+DM compared to normal. For TJA+DM vs. normal, all biomarkers were increased except c-peptide and insulin, which were decreased, and ferritin, which showed no significant change. The only biomarker significantly increased in ESRD+DM compared to ESRD-DM, was leptin. Furthermore, ESRD+DM vs. normal were significant for leptin, but ESRD-DM vs. normal was not. This pattern is consistent with the leptin pattern seen in patients with ESRD+MetS. This suggests that elevated leptin levels seen in patients with ESRD may be due to DM and/or MetS, which are both highly prevalent in the ESRD population. For all other biomarkers, there was lack of significance in ESRD+DM vs. ESRD-DM, as well as in TJA+DM vs. TJA-DM. This suggests that the presence of DM may not substantially further alter the metabolic profiles seen in patients with ESRD or undergoing TJA.

Alterations in the cholinesterase and adenosine deaminase activities and inflammation biomarker levels in patients with multiple sclerosis

Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the CNS that cause functional disability in young adults. It has unknown etiology characterized by the infiltration of lymphocytes and macrophages into the brain. The aim of this study was to evaluate the acetylcholinesterase (AChE) activity in lymphocytes and whole blood, as well as butyrylcholinesterase (BChE) and adenosine deaminase (ADA) activities in serum. We also checked the levels of nucleotides, nucleosides, biomarkers of inflammation such as cytokines (interleukin (IL)-1, IL-6, interferon (IFN)-γ, tumor necrosis factor-alpha (TNF-α) and IL-10) and C-reactive protein (CRP) in serum from 29 patients with the relapsing-remitting form of MS (RRMS) and 29 healthy subjects as the control group. Results showed that AChE in lymphocytes and whole blood as well as BChE, and ADA activities in serum were significantly increased in RRMS patients when compared to the control group (P<0.05). In addition, we observed a decrease in ATP levels and a significant increase in the levels of ADP, AMP, adenosine and inosine in serum from RRMS patients in relation to the healthy subjects (P<0.05). Results also demonstrated an increase in the IFN-γ, TNF-α, IL-1, IL-6 and CRP (P<0.05) and a significant decrease in the IL-10 (P<0.0001) in RRMS patients when compared to control. Our results suggest that alterations in the biomarkers of inflammation and hydrolysis of nucleotides and nucleosides may contribute to the understanding of the neurological dysfunction of RRMS patients.

CXCL10 and neopterin in CSF are candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis

Human T-lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease. Since the disease course of HAM/TSP varies among patients, there is a dire need for biomarkers capable of predicting the rate of disease progression for earlier detection of high-risk patients. However, there have been no studies to date that have compared the prognostic values of multiple potential biomarkers for HAM/TSP. Peripheral blood and cerebrospinal fluid (CSF) samples from HAM/TSP patients and HTLV-1-infected control subjects were obtained and tested for several potential biomarkers, including chemokines and other cytokines, and 8 optimal candidates were selected based on receiver operating characteristic (ROC) analysis. Next, we evaluated the relationship between these candidates and the rate of disease progression in HAM/TSP patients, beginning with a Training Set of 30 patients and proceeding to a Test Set of 23 patients. We defined “deteriorating HAM/TSP” as distinctly worsening function (≥ 3 grades on Osame’s Motor Disability Score (OMDS)) over 4 y and “stable HAM/TSP” as unchanged or only slightly worsened function (1 grade on OMDS) over 4 y, and we compared the levels of the candidate biomarkers in patients divided into these 2 groups. The CSF levels of chemokine (C-X-C motif) ligand 10 (CXCL10), neopterin and the CSF cell count were well-correlated with disease progression, better even than HTLV-1 proviral load in PBMCs. Importantly, these results were cross-validated using the Test Set. Therefore, the CSF levels of CXCL10 and neopterin represent the most viable candidates for HAM/TSP prognostic biomarkers.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study

BackgroundThe purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis.MethodsPatients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3.ResultsPaired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted.ConclusionsThere were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers’ release.

Serum Biomarkers in Severe Refractory Cardiogenic Shock

The aim of this study was to characterize levels of serum biomarkers in patients with severe refractory cardiogenic shock (SRCS) and to document temporal changes in these levels during restoration of circulation. Patients with SRCS have been challenging to study because of their rapidly changing clinical condition while undergoing multiple simultaneous interventions. Twenty-one patients with SRCS received circulatory support via a percutaneously implanted ventricular assist device (PVAD). Serum samples obtained prior to PVAD support initiation, at 24 h of PVAD support, and at 7 days of PVAD support were assayed for B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor receptor-1 (sTNFR1), soluble Fas (sFas), soluble Fas ligand (sFasL), endothelin-1, and procollagen III N-terminal peptide (PIIINP). Baseline biomarker levels were qualitatively compared to reference values; levels at 24 h of PVAD support and at 7 days of PVAD support were compared to baseline using 2-tailed Wilcoxon matched pair signed rank tests with Bonferroni correction for multiple comparisons. These patients with SRCS had elevated serum levels of BNP, hsCRP, sTNFR1, endothelin-1, and PIIINP. Ventricular unloading and restoration of circulation via PVAD support in patients with SRCS were associated with reductions in serum BNP, sFas, and endothelin-1 levels and increases in serum sFasL and PIIINP levels. This study characterizes several important baseline serum biomarker levels in patients with SRCS and introduces a novel PVAD-based protocol with the potential to "reverse"-model the pathophysiology of cardiogenic shock.