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Results for “Biomarker stratification”

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PubMed2026

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (≥ 90, 60-89, 30-59 mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of ≥ 125 pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values < 0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2 pg/mL, p < 0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r = 0.31, p < 0.001). However, no significant association was found between NT-Pro BNP and FMD (p = 0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p < 0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p = 0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p = 0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p < 0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT‐Pro BNP↗

PubMed2005

Prognostic value of inflammatory markers alone and in combination with blood lipids in patients with stable coronary artery disease.

BACKGROUND: Biomarkers may be helpful in improving risk stratification in cardiovascular diseases. Therefore, we assessed the prognostic value of sensitive inflammatory markers alone and in combination with lipids in patients with stable coronary artery disease (CAD). METHODS: In a prospective cohort study, we recruited 312 patients, aged 40-68 years, with angiographically proven, clinically stable CAD at the University Hospital in Ulm, Germany. C-reactive protein (CRP), interleukin-6 (IL-6), and lipoproteins were measured at baseline in all patients. After a median follow-up of 3.2 years, a fatal or non-fatal cardiovascular event (CVE) had occurred in 60 of 300 patients (20%). RESULTS: Baseline concentrations of IL-6 were significantly higher (3.27 versus 2.45 pg/ml, p=0.02) in patients with a future CVE compared to those without. After multivariate adjustment, patients with elevated baseline concentrations (4th versus 1st quartile) of inflammatory markers showed a moderately increased risk of CVE, i.e., hazard ratios (HR) were 1.3 (95% confidence interval 0.6-2.8) for CRP and 1.8 (0.9-3.6) for IL-6. The HRs increased if both inflammatory and lipid markers were simultaneously elevated (both markers>median versus<median). HR was 1.8 (0.8-4.0) for simultaneously elevated baseline concentrations of CRP and total cholesterol, and 1.9 (0.8-4.7) for simultaneously elevated concentrations of CRP and LDL cholesterol. Corresponding HRs for IL-6 and lipoproteins were 2.0 (0.9-2.7) and 2.1 (0.9-5.0). CONCLUSION: Simultaneous assessment of markers of inflammation and lipid metabolism may improve cardiovascular risk stratification in patients with stable CAD.

Journal Article↗

PubMed2026

SCLC TumorMiner: A genomics platform for small cell lung cancer precision oncology.

Small cell lung cancer (SCLC) is among the most aggressive malignancies. Unlike many other cancers, it is not represented in The Cancer Genome Atlas, and available datasets are fragmented across institutions, disease stages, and treatment settings. RNA sequencing provides a powerful and cost-effective approach, but the high dimensionality of transcriptomic data and the heterogeneity of patient cohorts pose significant challenges. To address such challenges, we developed SCLC TumorMiner (https://discover.nci.nih.gov/SclcTumorMinerCDB/), which includes 50 tumor samples from relapsed patients at the National Cancer Institute (NCI) and 154 samples from untreated patients at the University of Cologne and Tongji University. SCLC TumorMiner enables molecular classification, genomic pathway analyses, risk stratification, identification of predictive cell-surface biomarkers such as DLL3 or TROP2, and drug-response biomarkers such as SLFN11. SCLC TumorMiner illustrates profound differences between untreated and relapsed patient samples. Additionally, "MyPatient", one of SCLC TumorMiner's modules, is presented as a medical assistant application prototype.

SCLC↗

PubMed2003

The management of unstable angina and non-ST-segment elevation myocardial infartion.

Patients presenting with unstable angina and non-ST elevation myocardial infarction (UA/NSTEM) have a highly variable course. Optimal management is critical because of the high risk of death or myocardial infarction (MI) in the ensuing 30 days. In this article, we review the therapeutic options available to clinicians. Anti-ischemic therapy with beta-blockers and nitrates should be considered in all patients without contraindications. Aspirin remains a cornerstone of antiplatelet therapy and has been shown to substantially reduce the risk of death or MI. Although the data are less robust, unfractionated heparin (UFH) also appears to be efficacious, and the low-molecular-weight heparin (LMWH) enoxaparin appears to be superior to UFH. The GP IIb/IIIa inhibitors, highly beneficial in the setting of percutaneous coronary intervention (PCI), should be considered in patients with continuing ischemia or other high-risk features. The ADP receptor blocker clopidogrel has been shown to be beneficial in patients who are managed conservatively and in those who undergo PCI. Lastly, a strategy of early angiography should be considered in patients with recurrent ischemia or in those who present with high-risk features such as elevated troponins or ST deviation. Thus, early risk stratification using clinical features, electrocardiographic data, and biomarkers allows identification of subgroups of patients who are not only at high risk but also enjoy the greatest benefits from these aggressive therapies and thereby enables clinicians to target these interventions most effectively.

Angina, Unstable↗

PubMed2002

Special report: C-reactive protein for risk stratification in coronary heart disease screening.

Explore the source record for details and available documents.

Biomarkers↗

PubMed2026

Beyond the "cold" barrier: Redefining the clinical paradigm of immune checkpoint inhibitor therapy in ovarian cancer.

Ovarian cancer remains an immunologically "cold" tumor, with early all-comer immune checkpoint inhibitor (ICI) trials largely negative despite underlying immunogenicity. This review takes a clinician-centric, stage-specific view linking regimen choice, treatment line, and tumor-immune context to observed outcomes. In the neoadjuvant and first-line settings, unselected ICI combinations with chemotherapy and anti-angiogenic agents failed to improve progression-free survival, whereas adding a poly (ADP-ribose) polymerase (PARP) inhibitor to ICI maintenance yielded modest gains in biomarker-enriched cohorts. In recurrent disease, single-agent ICIs produced objective response rates of 8-15%, and most randomized combinations were negative. The phase III KEYNOTE-B96 trial in platinum-resistant disease demonstrated a progression-free survival benefit in the intention-to-treat population and an overall survival benefit in tumors with programmed death ligand 1 (PD-L1) combined positive score ≥ 1 when pembrolizumab was paired with weekly paclitaxel with or without bevacizumab, underscoring the value of an immunomodulatory chemotherapy backbone in earlier lines. Ovarian clear cell carcinoma emerges as an immunotherapy-sensitive, chemo-resistant subtype that warrants dedicated stratification. We explain why single-analyte biomarkers-PD-L1, tumor mutational burden, homologous recombination deficiency/BRCA1/2-have not reliably enriched benefit and outline a multidimensional approach integrating genomic scars (e.g., mutational signature 3), immune functional state (Immunoscore, CD8⁺ tumor-infiltrating lymphocyte density and CD8⁺: regulatory T-cell ratio), and spatial architecture (inflamed, excluded, desert phenotypes). This framework aims to move beyond the all-comer era toward context-informed precision immunotherapy in ovarian cancer.

Humans↗

PubMed2007

Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections.

BACKGROUND: Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is co-synthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI. MATERIALS AND METHODS: Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum copeptin levels were measured with a new chemiluminescent sandwich immunoassay. RESULTS: Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0.001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0.001). In patients who died, copeptin levels on admission were significantly higher as compared to levels in survivors [70.0 (28.8-149.0) vs. 24.3 (10.8-43.8) pmol L(-1), P < 0.001]. The area under the receiver operating curve (AUC) for survival was 0.75 for copeptin, which was significantly higher as compared to C-reactive protein (AUC 0.61, P = 0.01), leukocyte count (AUC 0.59, P = 0.01) and similar to procalcitonin (AUC 0.68, P = 0.21). CONCLUSIONS: Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI.

Aged↗

PubMedDate not supplied

[Natriuretic peptides and multimarker approach to risk stratification of patients with acute coronary syndromes].

NATRIURETIC PEPTIDES IN ACUTE CORONARY SYNDROMES: Brain natriuretic peptides (BNP) and N-terminal prohormone brain natriuretic peptides (N-proBNP) have been shown to provide important prognostic information in patients with acute coronary syndrome (ACS). Ischemia may be an important stimulus for BNP release. This does not imply, however, that BNP is useful for diagnosing ischemia, and BNP is unlikely to prove sensitive or specific enough for this purpose. SIGNIFICANCE OF NATRIURETIC PEPTIDES IN ASSESSING PROGNOSIS IN PATIENTS WITH ACUTE CORONARY SYNDROMES: In patients with ST-elevation and non-ST-elevation myocardial infarction, higher BNP and N-proBNP levels have been shown to predict a greater likelihood of death or heart failure, independent of other prognostic factors. THERAPEUTIC IMPLICATIONS OF BNP ELEVATION IN ACUTE CORONARY SYNDROMES: Patients with BNP or NT-proBNP elevation following ACS are clearly at high risk for death and for developement of heart failure, but specific therapeutic implications of BNP elevation have not been defined. In particular, it is not known how patients with BNP elevation should be treated considering the fact that they have normal troponin levels and no clinical evidence of heart failure. MULTIMARKER STRATEGIES FOR RISK STRATIFICATION IN ACUTE CORONARY SYNDROMES: It has been shown recently that in patients with acute coronary syndromes the risk increased sequentially among those with one, two or three elevated biomarkers. THERAPEUTIC APPLICATIONS OF CARDIAC BIOMARKERS IN ACUTE CORONARY SYNDROMES: Multimarker strategies, that incorporate panels of cardiac biomarkers, are likely to be used in the future for risk stratification and for pathophysiologically-guided treatment of patients with ACS.

Angina, Unstable↗

PubMed2026

Integrated metagenomic and metabolomic analysis identifies severity-specific inflammatory and metabolic signatures in post-stroke depression.

Post-stroke depression (PSD) is a common complication that significantly impacts patient prognosis. This study aimed to systematically characterize the associations among gut microbial ecology, metabolic profiles, and inflammatory responses across different severities of PSD. We conducted metagenomic sequencing, non-targeted metabolomics, and serum cytokine analysis (IL-1β, IL-6, IL-10, IL-18, TNF-α, IFN-γ, and CRP) in 91 patients with varying degrees of PSD and non-PSD controls. Bioinformatics analyzes were employed to construct multi-omics association networks and machine learning models. Results indicated that PSD patients exhibited significantly increased gut microbiota alpha-diversity, suggesting dysbiosis. Mild depression was characterized by compensatory neural signaling activation, whereas the moderate depression group exhibited abnormalities in tryptophan/indole metabolism, oxidative stress-related metabolic imbalances, and functional decompensation. Further analyzes suggested that Alistipes, Blautia_A, Evtepia gabavorous, and Lachnospira were associated with inflammatory features, GABA-related metabolic alterations, aromatic amino acid/indole metabolism, and lipid-amino acid metabolism, respectively. Under a more rigorous 10-fold cross-validation framework, the performance of different multi-omics combination models showed heterogeneity; however, some combinations still demonstrated superior discriminatory ability compared to single-omics approaches. This study provides multi-omics clues suggesting associations between different PSD severity levels and features such as increased Alistipes abundance, reduced antioxidant capacity, and altered tryptophan metabolism. It provides candidate biomarker combinations that may be useful for PSD stratification and suggests that the gut microbiome may represent a potential target for future PSD intervention. In summary, PSD may be associated with dynamic alterations along the "gut-brain-inflammation-metabolism" axis. These findings provide integrated evidence for microbial, metabolic, and inflammatory abnormalities across different PSD severity levels, but still require validation in larger samples, longitudinal cohorts, and mechanistic studies.

Humans↗

PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗

PubMed2025

Radiogenomic MRI biomarkers for noninvasive prediction of GPC3 expression and tumor microenvironment in hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC3) is frequently overexpressed in hepatocellular carcinoma (HCC) and plays a key role in immune and metabolic remodeling of the tumor microenvironment. Reliable noninvasive biomarkers for predicting GPC3 status could improve patient stratification and support precision immunotherapy. METHODS: This multicenter retrospective study included 274 patients with pathologically confirmed hepatocellular carcinoma from three institutions, 34 external cases with MRI from The Cancer Imaging Archive, and 363 transcriptomic profiles from The Cancer Genome Atlas. Contrast-enhanced T1-weighted imaging and diffusion-weighted imaging were analyzed. Tumor and peritumoral regions were segmented manually and radiomic features extracted using PyRadiomics. Feature selection was performed with correlation filtering and least absolute shrinkage and selection operator regression. Machine learning classifiers including logistic regression, random forest, support vector machine, k-nearest neighbor, and decision tree were trained with 10-fold cross-validation and tested on independent external cohorts. A radiomics score was calculated for each patient. Radiogenomic analysis correlated radiomics scores with transcriptomic data using weighted gene co-expression network analysis. Hub genes and enriched pathways were identified, and immune infiltration and predicted immunotherapy response were assessed using computational methods. RESULTS: The random forest model using contrast-enhanced T1-weighted imaging achieved an area under the curve of 0.966 in training and 0.935 in internal validation. The integrated contrast-enhanced T1-weighted imaging plus diffusion-weighted imaging model reached an internal validation area under the curve of 0.979. In external testing, the best performance was obtained with a support vector machine model (area under the curve 0.756). Radiomics scores were significantly correlated with GPC3 expression (R = 0.78, p < 0.05). Transcriptomic analysis identified a 10-gene signature enriched in hypoxia and lipid metabolism pathways that stratified patients into prognostic subgroups (concordance index 0.720, hazard ratio 4.07, p < 0.0001). High-risk patients had greater immune infiltration and a lower predicted immune evasion score, suggesting a potential benefit from immunotherapy. CONCLUSIONS: MRI-based radiomics models can noninvasively predict GPC3 expression in hepatocellular carcinoma. Radiomics scores reflect underlying hypoxia and lipid metabolism pathways and stratify patients by prognosis and predicted immunotherapy response. These findings support radiogenomics as a translational approach to imaging-guided precision treatment in hepatocellular carcinoma.

Humans↗

PubMed2006

Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix.

Genome-wide microarray-based comparative genomic hybridization (array CGH) was used to identify common chromosomal alterations involved in cervical carcinogenesis as a first step towards the discovery of novel biomarkers. The genomic profiles of nine squamous cell carcinomas (SCCs) and seven adenocarcinomas (AdCAs), as well as four human papillomavirus (HPV)-immortalized keratinocyte cell lines, were assessed. On a genome-wide scale, SCCs showed significantly more gains than AdCAs. More specifically, there was a striking and highly significant difference between the two histological types for gain at 3q12.1-28, which was predominantly observed in SCC. Other frequent alterations included gains of 1q21.1-31.1 and 20q11.21-13.33, and losses of 11q22.3-25 and 13q14.3-21.33. Subsequent FISH analysis for hTR, located at 3q26, confirmed the presence of 3q gain in SCCs and HPV-immortalized cell lines. Fine mapping of chromosome 20q using multiplex ligation-dependent probe amplification (MLPA) showed copy number increases for a number of genes located at 20q11-q12, including DNMT3B and TOP1. For DNMT3B, this correlated with elevated mRNA expression in 79% of cases. In conclusion, the assessment of frequent genomic alterations resulted in the identification of potential novel biomarkers, which may ultimately enable a better risk stratification of high-risk (hr)-HPV-positive women.

Adenocarcinoma↗

PubMed2002

Acute ischemic syndromes. Early response.

The optimal treatment of patients with AIS depends on a well-run, integrated system of care involving patients and teams of health care professionals. It begins with patient education and extends to a method for accessing an efficient and effective EMS system. Medics must be well equipped and well trained to evaluate and begin initial treatment during prompt transport to an appropriate hospital. The role of out-of-hospital 12-lead ECGs and thrombolysis is reviewed and may be appropriate for some EMS systems. The initial evaluation and treatment in the ED goes on simultaneously and is a dynamic process. Prompt treatment with oxygen, nitroglycerin, morphine, and aspirin is indicated. Initial risk stratification is based on the first ECG, cardiac biomarkers, and the clinical history and physical exam. Disposition and further evaluation is individualized according to the initial work-up and risk assessment.

Acute Disease↗

PubMed2006

[The prognosis of pulmonary embolism: are there practical implications for patient management?].

There is growing evidence that outpatient treatment is safe and effective for many patients with non-massive pulmonary embolism. Despite this evidence, the vast majority of patients with non-massive pulmonary embolism continue to be treated in an inpatient setting. A major barrier to outpatient treatment has been the lack of explicit criteria to identify patients with pulmonary embolism at low-risk of adverse medical outcome. This article discusses new risk stratification tools for pulmonary embolism such as echocardiography, biomarkers, and clinical prognostic scores, and their potential application for patient management.

Anticoagulants↗

PubMed2005

Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics.

PURPOSE OF REVIEW: Patients with acute myeloid leukemia (AML) and normal karyotype constitute the single largest cytogenetic group of AML, estimated to account for 45% of adults with de novo AML. This article critically reviews the recent literature that addresses the molecular heterogeneity of this group of patients and how this relates to prognostic stratification and novel therapeutic approaches. RECENT FINDINGS: Four prognostic biomarkers-the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene-have been found to predict outcome in patients with AML and normal cytogenetics. In addition, one study using gene expression profiling identified two subgroups of AML patients with a normal karyotype whose survival differs significantly. Because mutations in FLT3 result in an autophosphorylated, leukemogenesis-driving protein, molecular targeting therapy with a new class of tyrosine kinase inhibitors is being explored in early clinical trials. SUMMARY: Considerable progress has been made in molecular characterization of AML patients with normal cytogenetics. The challenge for the future is to incorporate these biologic discoveries into novel risk-adapted therapeutic strategies that will improve the currently disappointing cure rate (approximately 25-40%) of this group of patients.

Adult↗

PubMed2004

Biomarker discovery and validation: technologies and integrative approaches.

The emerging field of biomarkers has applications in the diagnosis, staging, prognosis and monitoring of disease progression, as well as in the monitoring of clinical responses to a therapeutic intervention and the development and delivery of personalized treatments to reduce attrition in clinical trials. Moreover, biomarkers have a positive impact on health economics. The word "biomarker" has been used extensively across therapeutic areas and many disciplines, and its nature takes into consideration clinical, physiological, biochemical, developmental, morphological and molecular measures. In drug trials, biomarkers have been proposed for use in efficacy determination and patient population stratification, in deducing pharmacokinetic-pharmacodynamic relationships and in safety monitoring. The interfacing and integration of different technologies for data collection and analysis are pivotal to biomarker identification, characterization, validation and application. "Integrative functional informatics" represents a novel direction in such technology integration.

Biomarkers↗

PubMed2004

Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer.

Biomarkers have the potential to significantly change diagnostic strategies and influence therapeutic management. We developed a MALDI-TOF protein expression profiling platform for biomarker discovery and a proof-of-principle study identified two proteins, cyclophilin A (CyPA) and macrophage migration inhibitory factor (MIF), that were overexpressed in non-small cell lung cancer (NSCLC). The current study focused on evaluating the potential of CyPA and MIF as prognostic markers in patients with a new diagnosis of lung cancer for rapid translation into clinical practice. Two hundred and thirty-four primary NSCLC specimens reflecting a broad range of histologies and stages were examined for CyPA and MIF reactivity by tissue microarray immunohistochemistry (TMA-IHC). The percent tumor cell reactivity, staining intensity and a composite staining score were compared with overall patient survival by Kaplan-Meier curves, log rank test and Cox model statistics. Although both proteins were overexpressed in most NSCLC tumors, neither CypA nor MIF showed a correlation with outcome. This pilot project approach can expedite integration of newly discovered biomarkers into clinical practice, with the goal of improving stratification of patients into appropriate treatment regimens. While both proteins considered in this study were overexpressed in the vast majority of NSCLCs, they were not found to be of prognostic significance.

Adult↗

PubMed2006

D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism.

BACKGROUND: Elevated plasma D-dimer and factor VIII coagulant activity (FVIIIc) may be associated with the risk of recurrent venous thromboembolism (VTE). OBJECTIVES: To evaluate D-dimer and FVIIIc as risk factors for recurrent VTE and assess the efficacy of extended low-intensity warfarin (target International Normalized Ratio 1.5-2.0) in preventing recurrence by biomarker level. PATIENTS AND METHODS: In the Prevention of Recurrent Venous Thromboembolism trial, 508 idiopathic VTE patients treated for > or = 3 months with full-intensity warfarin, and who had stopped warfarin for 7 weeks on average, were randomized to low-intensity warfarin or placebo and followed for 2.1 years for recurrent VTE. Prerandomization blood samples were analysed for D-dimer and FVIIIc. RESULTS: One-third of participants had elevated baseline D-dimer (> or = 500 ng mL(-1)) and one-fourth, elevated FVIIIc (> or = 150 IU dL(-1)). Adjusting for other risk factors, the hazard ratios (HRs) for recurrent VTE with elevated D-dimer or FVIIIc were 2.0 [95% confidence interval (CI) 1.2-3.4] and 1.5 (95% CI 0.8-2.8), respectively. The association of elevated D-dimer with recurrence was larger among patients with one prior VTE (HR 3.2, 95% CI 1.3-8.0) than in patients with more than one event (HR 1.4, 95% CI 0.7-2.2). For patients with one prior VTE on placebo, the annual recurrence incidence was 10.9% with elevated D-dimer and 2.9% with normal values. Low-intensity warfarin was equally effective in recurrence risk reduction in those with normal or elevated biomarkers. CONCLUSIONS: Among patients with idiopathic VTE, measurement of D-dimer, but not FVIIIc, might be useful for risk stratification. The efficacy of extended low-intensity warfarin therapy did not vary by biomarker level.

Adult↗