Predictive Value Of Biomarkers Research Articles

Use of presepsin and procalcitonin for prediction of SeptiFast results in critically ill patients

PurposeThere is a need for identification of marker that could lead physicians to take the right step towards laboratory techniques for documentation of infection.The aim of this study was to investigate whether presepsin and procalcitonin (PCT) levels in patients with suspected sepsis could predict blood culture (BC) and SeptiFast (SF) results. Material and methods100 patients were included in our study. PCT, C-reactive protein (CRP), and presepsin levels were determined. Differences between groups of patients were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. Receiver operating characteristic (ROC) curves were plotted to determine predictive values of biomarkers for prediction of positive SF results. ResultsPCT (70.9±106.36 vs. 16.35±26.79) and presepsin (4899.73±5207.81 vs. 1751.59±2830.62) were significantly higher in patients with positive SF in contrast to patients with negative SF. There was no significant difference between patients who had positive and negative BC for PCT and presepsin values. PCT and presepsin showed a similar performance in predicting positive SF results with AUC of 0.75 for PCT and 0.73 for presepsin. ConclusionPresepsin can serve as good predictor of bacteremia detected by SF and it should be included with PCT in protocols for sepsis diagnosing.

Plasma biomarkers to predict or rule out early post-discharge events after hospitalization for acute heart failure.

Improved prediction of early post-discharge death or rehospitalization after admission for acute heart failure is a major unmet need. We evaluated the value of biomarkers to predict either low or high risk for early post-discharge events. A total of 1653 patients enrolled in the PROTECT trial who were discharged alive and with available blood samples were included. Forty-seven biomarkers were serially evaluated in these patients. Measurement closest to discharge was used to evaluate the predictive value of biomarkers for low and high post-discharge risk. Patients were classified as 'low risk' if post-discharge 30-day risk of death or heart failure rehospitalization was <5% while risk >20% was used to define 'high risk'. Cut-off values that yielded a 95% negative predictive value and a 20% positive predictive value were identified for each biomarker. Partial area under the receiver operating characteristic curve (pAUC) in the high-sensitivity and high-specificity regions was calculated to compare low-risk and high-risk predictive values. Of patients analysed, 193 (11.7%) patients reached the 30-day death or heart failure rehospitalization outcome. We found marked differences between low-risk and high-risk predictors. Cardiac-specific troponin I was the strongest biomarker for low-risk prediction (pAUC = 0.552, 95% confidence interval 0.52-0.58) while endothelin-1 showed better performance for high-risk prediction (pAUC = 0.560, 95% confidence interval 0.53-0.59). Several biomarkers (individually and in combination) provided added predictive value, on top of a clinical model, in both low-risk and high-risk regions. Different biomarkers predicted low risk vs. high risk of early post-discharge death or heart failure readmission in patients hospitalized for acute heart failure.

Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review.

ObjectiveTo systematically review studies addressing prediction of successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis (RA).MethodsPubMed, Embase, and Cochrane Library databases were searched for studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic agent in RA. Two reviewers independently selected studies, and extracted data and assessed the risk of bias. A biomarker was classified as a “potential predictor” if the univariate association was either strong (odds ratio or hazard ratio >2.0 or <0.5) or statistically significant. For biomarkers that were studied multiple times, qualitative best‐evidence synthesis was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥75% of the studies as potential predictors were regarded as “predictor” for the purposes of our study.ResultsOf 3,029 nonduplicate articles initially searched, 16 articles regarding 15 cohorts were included in the present study. Overall, 17 biomarkers were studied multiple times for the prediction of successful dose reduction, and 33 for the prediction of successful discontinuation of a biologic agent. Three predictors were identified: higher adalimumab trough level for successful dose reduction and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic agent for successful discontinuation.ConclusionThe predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of biologic treatment in RA has been investigated. We identified only 3 biomarkers as predictors, in just 2 studies. The strength of the evidence is limited by the low quality of the included studies and the likelihood of reporting bias and multiple testing.

Amnestic MCI Patients’ Perspectives on Volunteer Participation in a Research Context

Background: Inclusion of patients in research studies is immensely important when evaluating new biomarkers for Alzheimer’s disease (AD) and when the efficacy of possible treatment options is under trial investigation. If medical treatment is to advance in slowing the progression of AD, or even preventing it, voluntary participation of patients is not only important but also their reliable participation is key. To get closer in achieving this goal, researchers need to understand better what motivates research participants to enroll in a clinical trial and get insight into participants’ expectations about their participation. Furthermore, what researchers perceive as benefits and risks of a study can differ from participants’ view. This difference could lead to a situation in which researchers recruit fewer subjects than they expected or result in unreliable research subject participation.Method: We conducted semi-structured in-depth interviews in 38 patients with amnestic mild cognitive impairment (aMCI) as part of a clinical trial (EUDRACT no. 2013-004671-12) on the predictive value of biomarkers for AD. Patients had the option of receiving their Individual Research Results (IRR; visual binary read amyloid PET results). In this study, the motivations and perceived advantages and disadvantages of trial participation were investigated from the patients’ perspective. Before deciding to participate, patients received an information brochure describing the possible benefits and risks of participation.Results: The two most frequently mentioned reasons for volunteering for the trial were to contribute to scientific progress and to receive their IRRs. Participating to ameliorate scientific progress was not solely motivated by altruistic reasons; it was mostly mentioned along with the possibility of receiving a valuable result about their health condition, suggesting that self-interest also motivated patients to participate. The two most frequently mentioned disadvantages were the possible risks related to being subjected to invasive medical procedures and that volunteering was considered to be time consuming. Most patients felt that their partner and children supported their decision to enroll in the biomarker study.Conclusion: aMCI patients have several reasons for wanting to volunteer in a clinical trial, with the option of IRR disclosure being the primary motivation for enrolling. Most of our patients felt that family members supported their decision to volunteer. However, researchers need to be cautious when recruiting subjects for clinical trials by ensuring that they truly desire to participate in the study and those family members are not coercing them into doing so. In addition, what the information brochure mentions as possible benefits and risks of trial participation was not always perceived similarly by patients.

Biomarker-Based Scoring System for Prediction of Tumor Response After Preoperative Chemoradiotherapy in Rectal Cancer by Reverse Transcriptase Polymerase Chain Reaction Analysis.

Numerous molecular markers have been investigated to predict tumor response after preoperative chemoradiotherapy for rectal cancer. This study aimed to evaluate the predictive value of biomarkers for the prediction of tumor response after preoperative chemoradiotherapy. Tumor specimens have been collected prospectively from 80 patients with rectal cancer who underwent curative resection at 8 weeks after completing preoperative chemoradiotherapy. With the use of reverse transcriptase polymerase chain reaction analysis, mRNA expression levels of 7 candidate biomarkers (p53, p21, Ki-67, VEGF, CD133, CD24, and CD44) were evaluated from fresh tumor samples collected before preoperative chemoradiotherapy. The correlation between biomarker expression levels and the pathologic response was assessed based on histopathological staging (pTNM) and tumor regression grade. The mRNA expression levels of 4 biomarkers (p53, p21, Ki67, and CD133) significantly correlated with tumor regression grade response and pathologic complete response. Patients showing low expression of p53 and/or high expression of p21, Ki67, and CD133 exhibited a significantly greater tumor regression grade response and pathologic complete response rate. A scoring system devised so that 1 point was given for each biomarker whose expression level correlated with pathologic complete response (score range: 0-4) showed that 9 of 62 patients with scores of 0 to 2 achieved pathologic complete response, whereas 15 of 18 patients with scores of 3 to 4 achieved pathologic complete response (14.5% vs 83.3%, p < 0.001). For prediction of pathologic complete response, the scoring system showed 62.5% sensitivity, 94.6% specificity, an 83.3% positive predictive value, and an 85.5% negative predictive value. Small patient numbers have limitations related to the reproducibility and ability to provide quantitative information. In addition, this study lacks test and validation sets. The pretreatment mRNA expression levels of 4 biomarkers correlated with pathologic tumor response after intraoperative chemoradiotherapy in rectal cancer. Furthermore, the scoring system combining values of biomarker expression might have predictive power with high positive and negative predictive values.

Abstract 12577: Markers of Residual Risk in Type 2 Diabetes and Stable Ischemic Heart Disease: Insights From the BARI 2D Trial

Background: In spite of aggressive preventive therapy, patients with type 2 diabetes (T2D) and stable ischemic heart disease (SIHD) remain at high risk for major cardiovascular events and death. Understanding the pathophysiologic determinants of that residual risk could help identify effective preventive therapies. Methods and Results: In this Ancillary Study of the BARI 2D trial, we examined the predictive value of biomarkers from 6 distinct pathophysiologic pathways in 2285 men and women with T2D and SIHD who were followed for a median (IQR) of 5.0 (4.1-6.0) years. The endpoint for this Ancillary Study was a composite of myocardial infarction, stroke, heart failure, or all-cause mortality. The 5-year Kaplan-Meier event rate was 31%. The pathophysiologic processes evaluated included dysglycemia (HbA1c), dyslipidemia (LDL-C), myocardial strain (NT-proBNP), myocardial injury (high-sensitivity cardiac troponin T [hsTnT]), subclinical inflammation (high-sensitivity C-reactive protein [hsCRP]), and nephropathy (presence/absence of macroalbuminuria). In Cox proportional hazards models adjusted for baseline risk factors, angiographic severity of disease, and ejection fraction, each marker except LDL-C was a significant predictor of outcome (Figure) in this population with 74% baseline statin use. After mutual adjustment for all 6 markers and baseline risk factors, the hazard ratio (95% CI) per 1-SD of natural logarithm transformed concentration was largest for NT-proBNP [1.29 (1.17, 1.42)], followed by hsTnT [1.16 (1.07, 1.26)], HbA1c [1.12 (1.03, 1.21)], and hsCRP [1.11 (1.03, 1.20). Macroalbuminuria was not a significant predictor after adjustment for the other markers (Figure). Conclusions: In this high-risk population of patients with type 2 diabetes and stable ischemic heart disease, strategies to target myocardial strain, myocardial injury, and subclinical inflammation may lead to improvements in cardiovascular outcome.

Predictive value of biomarkers of hepatic fibrosis in adult Fontan patients

Hepatic fibrosis is highly prevalent in individuals with Fontan circulation. FibroSure (LabCorp, Burlington, NC) and hyaluronic acid (HA) have been validated for assessment of hepatic fibrosis in several forms of liver disease. We sought to determine whether these tests could identify Fontan patients with advanced hepatic fibrosis or cirrhosis. Subjects who had liver biopsy and FibroSure or HA testing within 6 months of biopsy were identified from the Alliance for Adult Research in Congenital Cardiology Fontan Liver Health study. Biopsy specimens were scored for degree of sinusoidal and portal fibrosis on a 3- and 5-point scale, respectively. Histologic findings were correlated with FibroSure and HA results. The study included 27 subjects. Median age was 26.8 years (range, 17.4-59.8 years), and the median time since the Fontan surgery was 20.4 years (range, 12.0-31.3 years). FibroSure scores were elevated (>0.21) in 21 of 23 subjects (91%), and the scores for 3 (13%) suggested cirrhosis (>0.74). HA suggested cirrhosis (>46 ng/mL) in 3 of 17 subjects (18%). One subject died during the collection period. Eleven of 26 subjects (42%) had 4/5 or 5/5 portal fibrosis, consistent with cirrhosis; 17 (63%) had 3/3 sinusoidal fibrosis involving >66% of sinusoids. The FibroSure score and HA levels did not correlate with the degree of hepatic fibrosis and did not predict cirrhosis. Abnormal biomarkers of hepatic fibrosis and specimen-proven hepatic fibrosis are common in adults with Fontan circulation. However, FibroSure and HA do not accurately predict the degree of histologic hepatic fibrosis. Further studies are needed to guide strategies for surveillance of liver disease in this population.

Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use

Early diagnosis and timely treatment of early onset neonatal sepsis (EOS) are essential to prevent life threatening complications. Subtle, nonspecific clinical presentation and low predictive values of biomarkers complicate early diagnosis. This uncertainty commonly results in unnecessary and prolonged empiric antibiotic treatment. Annually, approximately 395,000 neonates (7.9% of live term births) are treated for suspected EOS in the European Union, while the incidence of proven EOS varies between 0.01 and 0.53 per 1000 live births. Adherence to guidelines for the management of suspicion of EOS is poor. Pragmatic approaches to minimise overtreatment in neonates with suspected EOS, using combined stratified risk algorithms, based on maternal and perinatal risk factors, clinical characteristics of the neonate and sequential biomarkers are promising.

Prediction of Appropriate Shocks Using 24-Hour Holter Variables and T-Wave Alternans After First Implantable Cardioverter-Defibrillator Implantation in Patients With Ischemic or Nonischemic Cardiomyopathy

In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T-wave alternans testing and 24-hour Holter variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holter for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 ± 15months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT-proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (≥1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p= 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p= 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks (clinicaltrials.gov: NCT02010515).

The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study

The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. We developed and internally validated a new biomarker-based risk score for major bleeding in 14,537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively. The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 [95% CI 0·66-0·70] vs 0·61 [0·59-0·63] vs 0·65 [0·62-0·67], respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 [95% CI 0·68-0·73] vs 0·62 [0·59-0·64] for HAS-BLED vs 0·68 [0·65-0·70] for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores. The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation. BMS, Pfizer, Boehringer Ingelheim, Roche Diagnostics.

XPA–A Biomarker With Potential Prognostic Value in Patients With Oropharyngeal Head and Neck Squamous Cell Carcinoma

Platinum-based chemotherapy resistance has been under investigation for a long time, looking at the nucleotide excision repair (NER) pathway, which is responsible for DNA adduct repair. One of the participating proteins in that pathway is XPA. There is little information about this protein regarding its prognostic value in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we investigated XPA expression as a prognostic factor by retrospectively looking at overall survival, time to recurrence, and correlation with clinical parameters. Tissue microarrays were constructed from 453 cases of HNSCC including 222 oral (49%), 126 pharyngeal (27.8%), and 105 laryngeal (23.2%) tumors. Two hundred ninety-three tumor blocks were evaluable for XPA immunohistochemistry. Expression levels were dichotomized into a high and low XPA expressing group followed by a comparison of age, gender, TNM status, grading, and UICC stage. Outcomes for overall survival and time to recurrence were analyzed by using the Kaplan-Meier method and performed for different subsites of the head and neck. Analysis of overall survival and time to recurrence showed no difference between both expression levels of XPA in the overall patient cohort. However, superior overall survival in patients with oropharyngeal SCC and a high XPA expression could be observed (P=.0386). Looking at SCCs of the oral cavity, a trend toward an inferior overall survival in patients with a high XPA expression was seen, whereas investigations in the hypopharynx and larynx showed no significant differences between high and low XPA expressing tumors. Looking generally at gender, M stage, and grading, no statistical correlation was found. Analyzing T and N stage in all tumors, a trend toward a lower XPA expression in advanced tumors (>pT4 P=.0543 and >pN1 P=.0546) could be seen. This trend was confirmed by statistical lower expression of XPA in patients with UICC stage IV looking at the overall patient cohort (P=.035). The shown results suggest that XPA might be a novel predictive marker for overall survival in patients with oropharyngeal SCC with a superior survival in tumors with a high XPA expression. Furthermore, this study shows that subsites in the head and neck will have to be looked at separately in the future to determine the predictive value of biomarkers for therapy outcome and pretherapeutic risk stratification of patients. To increase statistical power of this study and to evaluate the effect on platinum-based chemotherapy resistance, further studies with even larger patient cohorts will be needed and are ongoing.

Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke.

Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23, 1.45-3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients.

Biomarkers Investigation for In-Hospital Death in Patients With Stanford Type A Acute Aortic Dissection.

This retrospective study aimed to investigate the predictive value of biomarkers for in-hospital mortality of patients with Stanford type A acute aortic dissection (AAD).AAD is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year.A total of 67 consecutive Stanford type A AAD patients admitted to hospital were divided into a deceased group and survival group. The baseline information of the patients between two groups was systematically compared, followed by examination of the electrocardiograms (ECG). Based on the follow-up during hospitalization, we investigated the simultaneous assessment of indexes like fragmented QRS complex (fQRS), admission systolic blood pressure (SBP), aortic diameter, surgical management, troponin I (TnI), white blood cell (WBC) count, N-terminal pro-brain natriuretic peptide (NT-proBNP), and D-dimer.The levels of TnI and NT-proBNP, WBC counts, and rate of fQRS (+) in patients of the deceased group were significantly higher than those in the survival group. The male sex (hazard ratio, 10.88; P = 0.001), admission SBP (hazard ratio, 0.98; P = 0.012), NT-proBNP (hazard ratio, 1.00; P = 0.001), and WBC count (hazard ratio, 1.10; P = 0.033) were independently related with in-hospital death. As a single marker, WBC count had the highest sensitivity at 84.6% (specificity 65.9%).Admission SBP, NT-proBNP, and WBC count were potential independent risk factors of in-hospital death in Stanford type A AAD patients. WBC count may be a more accurate predictor of type A AAD than either alone.

Predictive Value of Biomarkers for Normal and Pathological Ageing in a Rat Model

Sub-optimal diets are widely known to be associated with disease. This study investigated two questions: first, whether a Western affluent diet affects long-term health in the rat, and second, whether, and to what extent, early changes in blood biomarkers can predict specific pathologies. A rat model was used in which animals were fed from weaning either a control diet or a high fat, low protein, energy dense Western affluent diet. Rats were harvested at either 12 or 18 months, and at these time points blood samples were taken and various clinical biomarkers measured using a hospital analyser or by ELISA. Predictive biomarkers should show small changes at early time points and larger changes at later time-points, and be associated with disease(s). Tissues were examined for overt pathology, and data were mined to establish links between pathologies and specific blood markers that might be used predictively. Results showed that the Western affluent diet is associated with ill-health, with a relative risk of developing disease 4.5 times higher than for the control diet. Furthermore we conclude that triacylglycerol, HDL cholesterol, the ratio of total cholesterol to HDL cholesterol, creatinine and alanine aminotransferase were good predictors of disease as across the cohorts they showed altered levels before the clinical development of pathologies, in agreement with our hypothesis.

Musculoskeletal health and osteoarthritis in the UK army – the ADVANCE study (Armed Services Trauma Rehabilitation Outcome Study)

Trauma is a well recognised risk factor for the future development of osteoarthritis (OA). The Armed Services Trauma and Rehabilitation outcome study (The ADVANCE study) is a 20 year cohort study comparing medical and psychosocial outcomes of military personnel both exposed and not exposed, to significant trauma. The Bio-Mil-OA study, a sub-study of the ADVANCE study, is an ideal opportunity to investigate the predictive value of biomarkers in joint pain and osteoarthritis. The ADVANCE study is a 20 year cohort study of 600 combat casualties and 600 matched non exposed participants investigating the predictive value of biomarkers and trauma on the long term development of pain and OA in the hip and knee. Validated serum biomarkers for OA, knee and hip radiographs and patient reported outcomes for pain and function will be taken at baseline and at 5 years. The predictive value of the biomarkers in predicting OA development and progression and joint pain in those exposed to different levels of trauma will be investigated using quantitative immunoassays for catabolic markers of cartilage matrix degradation.

NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys.

With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study

ObjectivesNeutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic...

Mir-661: A key Factor in Embryo-Maternal dialog With Potential Clinical Application to Predict Implantation Outcome?

Mir-661: A key Factor in Embryo-Maternal dialog With Potential Clinical Application to Predict Implantation Outcome?

Effect of the timing of sunitinib administration on the predictive value of biomarkers in renal cell cancer (mRCC).

11096 Background: Angiogenic cytokines influence tumor growth in mRCC patients (pts) and are modulated by diurnal fluctuations. The timing of antiangiogenic tyrosine kinase inhibitor (TKIs) administration may impact efficacy, toxicity and biomarker expression. Methods: 34 mRCC pts, randomized to receive sunitinib at 8 AM or 8 PM on a 28 days (d) on/14 d off schedule, had blood sampling before and during Rx on the first cycle for potential biomarkers including: sunitinib and metabolite blood levels, 18 circulating angiogenic factors (CAFs) and 4 circulating angiogenic cell types including circulating endothelial cells (CECs). Results: Spearman analysis of the 24 biomarkers obtained on d 14 showed significantly better correlations with OS and PFS in PM-treated pts. Three CAFs in PM-treated pts significantly correlated with both OS and PFS. These included Leptin (r = 0.7182, p = 0.0128 and r = 0.8364, p = 0.0022, respectively), IL-8 (r = -0.635, p = 0.0485 and r = -0.5735, p = 0.031, respectively) and PDGF-β...

Predictive value of biomarkers for the prognosis of acute pulmonary embolism in Japanese patients: Results of the Tokyo CCU Network registry

BackgroundSeveral studies from Western countries have reported associations between cardiac troponin and B-type natriuretic peptide (BNP) levels and acute pulmonary embolism prognosis; however, the number of such reports from Asian countries, including Japan, is limited. Thus, we evaluated the relationship between blood biochemical findings and acute-phase pulmonary embolism prognosis in Japanese patients. MethodsThe subjects included 441 patients with acute pulmonary embolism (191 men, 250 women; average age, 65.8±16.0 years) treated at Tokyo CCU Network Institutions from 2009 to 2011 and registered via survey forms. The association between blood biochemical findings at admission and 30-day mortality was investigated. ResultsThe median BNP value was 186.5pg/mL (25th to 75th interquartile range: 49.8–500pg/mL) of 210 cases. No deaths were recorded among those with BNP levels <90pg/mL (n=70), whereas significantly higher mortality (10 deaths/140 cases, 7.1%; p=0.033) was observed among those with BNP levels ≥90pg/mL. A qualitative cardiac troponin test was positive in 58 of the 204 cases (28.4%), with a significantly higher mortality incidence (p=0.017) among the troponin-positive cases [6 (10.3%) versus 3 (2.1%) deaths among the 146 troponin-negative cases]. The overall mean blood glucose level at admission of 331 cases was 152.0±74.0mg/dL, and 30-day mortality significantly increased with blood glucose values (p=0.048). ConclusionsTroponin, BNP, and blood glucose levels are useful prognostic biomarkers for acute pulmonary embolism in Japanese patients.