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PubMed2002

Risk assignment in childhood brain tumors: the emerging role of molecular and biologic classification.

Brain tumors as a group are the most common solid tumors of childhood and currently have the highest mortality rate. A major emphasis has historically been placed on stratifying therapy for these tumors based on histologic and clinical prognostic factors. However, with the increasing application of molecular approaches to refine the categorization of these tumors, it has become apparent that histologically comparable lesions may exhibit diverse patterns of gene expression and genomic alterations, which may correspond with important prognostic distinctions. This paper summarizes these observations and discusses how they are being applied in a preliminary fashion as a foundation for risk-adapted stratification of childhood brain tumor therapy.

Biomarkers, Tumor↗
PubMed2000

Evaluation of the emergency department chest pain patient.

Patients presenting to the emergency department with chest pain are a common and perplexing problem. Because of the limitations of the initial evaluation, most patients are admitted, although many are found to have noncardiac causes of their symptoms. Recognition of these limitations has driven the investigation of newer evaluation techniques and protocols in an attempt to improve diagnostic sensitivity without increasing overall costs. These have included modifications of the standard electrocardiogram and use of newer myocardial markers of necrosis, such as mass assays for CK-MB as well as troponin T and troponin I. Use of acute rest myocardial perfusion imaging also has been shown to be a highly valuable technique for risk stratification of the intermediate- to low-risk chest pain patient.

Biomarkers↗
PubMed2005

Risk prediction in patients with chest pain: early assessment by the combination of troponin I results and electrocardiographic findings.

OBJECTIVE: To evaluate the prognostic value of point of care troponin I (TnI) results in combination with findings from the admission electrocardiogram (ECG) in patients with chest pain. METHODS: Rapid measurements of TnI were performed in 191 consecutive patients with chest pain and a non-diagnostic ECG for myocardial infarction. RESULTS: Within 6 h from admission, maximum TnI elevations of > or = 0.07 microg/l and > or = 0.1 microg/l were noted in 59 and 39% of all patients, respectively. TnI elevations in the range of 0.07-0.09 microg/l were found in many patients with diagnoses other than acute coronary syndrome. By 6-month follow-up, cardiac death had occurred in 7.1 and 11% of patients with maximum TnI > or = 0.07 microg/l and > or = 0.1 microg/l, respectively and myocardial reinfarction was documented in 12 and 15%, respectively. ST-segment depression on the admission ECG was present in 16% of all patients and was the electrocardiographic abnormality with the highest risk (cardiac death 7.7%, myocardial reinfarction 15%). The combination of TnI > or = 0.1 microg/l and ST-segment depression or an abnormal admission ECG in general allowed the identification of patients at low, intermediate and high cardiac risk, 3 h after admission. CONCLUSION: A threshold of TnI > or = 0.1 microg/l corresponding to the 10% coefficient of variation is prognostically most suitable for prediction of cardiac events in patients with chest pain. The combination of TnI results and findings from the admission ECG improves prognostic assessment and allows early and reliable risk stratification in this patient population.

Aged↗
PubMed2006

Point-of-care i-STAT cardiac troponin I for assessment of patients with symptoms suggestive of acute coronary syndrome.

BACKGROUND: Few studies have investigated the role of cardiac troponin point-of-care (POC) testing for predicting adverse outcomes in acute coronary syndrome (ACS) patients. We investigated the use of a POC cTnI assay in ACS patients. METHODS: We studied consecutive patients (n = 367) presenting with symptoms suggestive of ACS who were admitted through the emergency department. We measured plasma cTnI with the i-STAT assay. Patients were risk-stratified based on cTnI concentrations defined by the predetermined 99th percentile reference limit for plasma (0.04 microg/L). Patients were followed for 60 days. We computed survival and event curves with the Kaplan-Meier method and compared risk stratification groups with the log-rank test. RESULTS: Acute myocardial infarction (MI) was diagnosed in 8.1% of patients. Odds ratios and 95% confidence intervals for all-cause death (ACD), MI or ACD, MI or cardiac death, and cardiac death at 60 days were all statistically significant after adjustment for age, diabetes, hypertension, and history of renal failure as follows: 2.54 (1.24-5.20), P = 0.009; 2.76 (1.37-5.58), P = 0.003; 5.98 (1.65-21.7), P = 0.008; and 2.54 (1.24-5.20), P = 0.009. Kaplan-Meier curves showed early separation between patients with increased vs. reference concentrations before 30 days for ACD, MI or ACD, and MI or cardiac death. CONCLUSION: The i-STAT POC cTnI assay can be added to the list of assays for risk stratification.

Acute Disease↗
PubMed2004

[Brain natriuretic peptide in acute coronary syndromes: utility of NT-pro BNP assay].

Better risk stratification strategies are required for patients with acute coronary syndromes. Plasma myocardial troponin is a specific but poorly sensitive marker. Levels of B natriuretic peptide, a 32-amino-acid peptide synthesized and released by left ventricular myocytes, correlate strongly both with the presence of acute myocardial lesions and with vital outcome. To address the possible influence of the sampling time, we measured NT-pro BNP plasma concentrations on emergency admission and 8 and 24 hours later in 64 patients with acute coronary syndromes. Troponin levels were abnormal in respectively 44%, 51% and 52% of patients, while NT-pro BNP levels were abnormal in 75%, 83% and 79% of patients (p < 10(-4)). Both troponin and NT-pro BNP levels were abnormal in patients with ST elevation MI (n = 15; 93% and 87%, NS) and in patients with non ST elevation MI (n = 19; 73% and 68%). In contrast, among 30 patients with unstable angina, troponin levels were always normal whereas NT-pro BNP levels were elevated in 73% of cases (p < 10(-4)). This suggests that more than 50% patients with acute coronary syndromes who have normal troponin levels 8 hours after admission--and would therefore be discharged--would qualify for further investigations on the basis of natriuretic peptide levels. NT-pro BNP is thus more sensitive than troponin as a marker of myocardial damage. In addition, its clinical significance is not influenced by the precise sampling time within 24 hours following emergency admission. NT-pro BNP therefore adds important information for patient stratification.

Acute Disease↗
PubMed2026

Machine learning-guided risk stratification in elderly AML based on genomic, immunophenotypic and therapeutic profiles.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) exhibit considerable biological and clinical heterogeneity, hindering precise prognosis. Existing prognostic systems inadequately capture the complexity of elderly AML due to their reliance on data from younger cohorts and omission of key factors like immunophenotypic markers and therapeutic profiles. This study aimed to develop and internally validate a machine learning-based prognostic model specifically tailored to elderly AML patients. METHODS: A total of 156 patients were analyzed using a two-stage modeling strategy. Clinical and genomic variables were modeled first, followed by independent analysis of immunophenotypic features. Feature selection was performed using multilayer perceptron (MLP) and random forest (RF), while multivariate Cox regression was used for final model construction. Internal validation was conducted using 1000 bootstrap iterations to assess model stability and performance. RESULTS: The model demonstrated strong predictive performance, with a concordance index (C-index) of 0.702. Time-dependent area under the curve (AUC) and calibration plots confirmed accurate prediction of 1-, 3-, and 5-year overall survival. Decision curve analysis indicated favorable net benefit across a range of threshold probabilities. Key independent prognostic factors identified included TP53 mutations, high CD13 expression, and IDH2 mutations. CONCLUSION: This model provides a robust and interpretable tool for individualized risk stratification in elderly AML. By integrating genomic, immunophenotypic, and therapeutic variables, it may help optimize treatment decisions and improve outcomes for this vulnerable population. Future efforts should focus on external validation and integration of dynamic biomarkers.

Humans↗
PubMed2006

Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department.

BACKGROUND: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification. METHODS: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA. RESULTS: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively. CONCLUSIONS: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Angina, Unstable↗
PubMed2025

UALCAN Mobile, an app for cancer proteogenomic data analysis.

Cancer is a complex disease affecting various organs and is a major cause of death worldwide. During cancer initiation, disease progression, and tumor metastasis, various genomic and proteomic alterations are observed. Recent technological advances have led to the generation of large amounts of molecular data, including genomics and transcriptomics. These large-scale datasets can be utilized to analyze and identify sub-class-specific cancer biomarkers and targets. However, there is a need for the development of user-friendly tools for large-scale data analysis, disseminating the analyzed data in a visualizable format to cancer researchers with no programming skills. We developed UALCAN, a comprehensive platform that allows users to integrate disparate data to better understand the genes, proteins, and pathways perturbed in cancer and make discoveries of potential biomarkers and targets. In the current study, we describe the development of the UALCAN Mobile application (app) that will provide cancer transcriptomic data obtained from The Cancer Genome Atlas (TCGA) project to evaluate protein-coding gene expression based on various stratifications, including stage, grade, race, gender, and molecular-subtypes across over 30 types of cancers. In addition, the UALCAN mobile provides data analysis options for epigenetic changes due to DNA promoter methylation and Clinical Proteomic Tumor Analysis Consortium (CPTAC) cancer proteomic data. The app provides access to large cancer molecular datasets on the go. To find changes in the expression of causative genes and proteins and to identify biomarkers and therapeutic targets, UALCAN mobile app will be extremely valuable. The "UALCAN Mobile" app is free to use and can be downloaded from both the iOS/Apple and the Android Play Store and has been downloaded over 100 times in each of iOS and android app stores.

app↗
PubMed2026

Cell-free DNA genomic and fragmentomic features for early outcome prediction in large B cell lymphoma.

Curative-intent immunochemotherapy fails in &#x223c;30% of patients with large B cell lymphoma (LBCL), yet no validated molecular tool enables early identification of high-risk individuals to guide treatment intensification. Using shallow whole-genome sequencing (sWGS) of plasma cell-free DNA from 190 LBCL patients, we develop and validate the ACT score (aberrations, composition of fragments, and terminal motif analyses), a composite classifier integrating genomic and fragmentomic features from a single post-cycle-1 sample. ACT-positive patients have worse 2-year outcomes versus ACT-negative patients: time-to-progression 29% vs. 83% (hazard ratio [HR]: 4.4, 95% confidence interval [CI]: 1.9-10.0; p = 1.5 &#xd7; 10-4) and overall survival 47% vs. 93% (HR: 8.7, 95% CI: 3.0-25.4; p = 1.8 &#xd7; 10-6). The ACT score is independently prognostic of the International Prognostic Index, and their combination identifies the highest risk patients. Unlike mutation-based approaches, this assay requires neither tumor tissue, germline control, nor a baseline plasma sample. Built on open-source tools and sWGS, the ACT score offers a feasible, scalable strategy for early risk stratification in aggressive LBCL.

Humans↗
PubMed2026

Discovery and validation of novel plasma protein biomarkers for severe tuberculosis patients.

OBJECTIVE: Severe tuberculosis (STB) imposes a substantial disease burden, yet reliable biomarkers for distinguishing STB from mild/moderate tuberculosis (MTB) remain scarce. This study aimed to identify and independently validate plasma protein biomarkers associated with tuberculosis severity. METHODS: In this multicenter prospective study, 298 adults with confirmed pulmonary tuberculosis were enrolled into screening (n&#x2009;=&#x2009;128) and independent validation (n&#x2009;=&#x2009;170) cohorts. Plasma samples were analysed using data-independent acquisition proteomics. Differentially expressed proteins were screened via Limma and four machine-learning algorithms, with candidate proteins measured by enzyme-linked immunosorbent assays. Receiver operating characteristic analysis assessed individual and combined diagnostic performance. RESULTS: STB patients were older and presented with lymphopenia, hypoalbuminemia, neutrophilia, and elevated lactate dehydrogenase. Among 166 differentially expressed proteins, HSPA5, HSP90B1, EEF1D, and SULT1A1 were selected for validation. In STB patients, HSPA5, HSP90B1, and EEF1D were upregulated, whereas SULT1A1 was downregulated. The four-protein panel achieved an AUC of 0.908 (95% CI 0.864-0.952), with 87.5% sensitivity and 83.8% specificity, modestly outperforming HSPA5 alone (AUC&#x2009;=&#x2009;0.894). Functional enrichment implicated cholesterol metabolism, immune-inflammatory pathways, and endoplasmic reticulum stress. CONCLUSIONS: The four-protein panel effectively discriminated STB from MTB; however, its marginal improvement over HSPA5 alone suggests that an HSPA5-based assay may offer a simpler, more practical, and potentially cost-effective strategy for severity stratification.

Humans↗
PubMed2026

Pan-cancer landscape of APEX1 expression and genomic alterations: Associations with clinical outcomes and functional validation in lung cancer.

This pan-cancer study systematically evaluated APEX1 expression, genomic alteration status, and prognostic value across 13,270 tumors and 2544 normal tissues from TCGA and GTEx. APEX1 overexpression was prominent in bladder, breast, and colon adenocarcinomas and correlated with advanced tumor stages and survival outcomes in a cancer-type-specific manner, with unfavorable associations in selected tumor contexts and an opposite favorable association in KIRC. Low-frequency APEX1 genomic alterations require cautious interpretation and may be associated with adverse outcomes in selected tumor contexts. Statistical methods including t-tests, ANOVA, Cox regression, Benjamini-Hochberg false-discovery rate correction for cohort-wise OS analyses, and log-rank tests were used to correlate APEX1 expression or alteration status with survival outcomes. The findings suggest that APEX1 expression and low-frequency genomic alterations are associated with tumor progression and worse patient outcomes in selected cancer contexts. This study supports APEX1 as a candidate prognostic indicator requiring further validation and suggests its potential value for future clinical stratification research. The pan-cancer approach improves contextual breadth, and the large sample size adds robustness. The observed relevance of APEX1 across malignancies supports further evaluation of its value for risk stratification and treatment planning. Future prospective studies are needed to validate its clinical utility. This work contributes to the growing field of DNA repair-related biomarkers and may inform future studies of APEX1-targeted therapeutic strategies.

Apurinic/Apyrimidinic Endonuclease 1↗
PubMed2005

Adoption of array technologies into the clinical laboratory.

Array-based methods are making substantial contributions to the discovery of disease biomarkers and are fueling the growth of multianalyte testing for disease diagnosis and treatment. The distillation of high-density array results into sets of signature markers promises to improve disease staging, risk stratification and treatment decisions. To accommodate the growing requirement for multiplex testing, clinical laboratories are converting several single-analyte tests into array-based formats. However, adoption of array technologies provides several challenges to the laboratory, which must evaluate these new formats, train laboratory personnel, market the new services and obtain reimbursement for new analytes. Liquid-bead arrays are an attractive format for routine clinical diagnostics due to a combination of appropriate analyte density, simultaneous array decoding and detection, and flexibility for rapid customization. In this review, the suitability of several array platforms to diagnostic testing and applications of liquid-bead arrays for cystic fibrosis testing, multidisease carrier status assays and leukemia subtyping are discussed. As our understanding of the clinical utility of new or established biomarkers and recommendations for testing change, flexibility and adaptability of array platforms will be imperative. Future development of novel assay formats and improved quantitation will expand the number of diseases tested and lead to further integration into the diagnostic laboratory.

Genetic Testing↗
PubMed2006

Association of B-type natriuretic peptide activation to left ventricular end-systolic remodeling in organic and functional mitral regurgitation.

B-type natriuretic peptide (BNP) is activated with mitral regurgitation (MR), but it is unclear whether BNP activation is uniform in organic and functional MR and whether it merely reflects symptoms or is a biomarker of left ventricular (LV) geometric and functional alterations. Comprehensive Doppler echocardiography and hormonal measurements were performed prospectively in 99 patients, 50 with organic MR, 28 with functional MR (with similar LV enlargement 130 +/- 21 vs 141 +/- 40, p = 0.18, and age 64 +/- 13 vs 66 +/- 12 years, p = 0.56) and 21 controls subjects of similar age. Compared with the controls, the patients with MR displayed LV remodeling and BNP activation. In those with functional MR compared with those with organic MR, despite a lower regurgitant volume (25 +/- 25 vs 96 +/- 29 ml), higher BNP levels were noted (385 +/- 388 vs 70 +/- 97 pg/ml, p <0.0001), even after stratification by functional class (class I 120 +/- 122 vs 33 +/- 40, class II 318 +/- 470 vs 74 +/- 69, class III to IV 487 +/- 383 vs 268 +/- 165 pg/ml, p = 0.006). The major determinant of BNP activation was the LV end-systolic volume index (p <0.0001), independent of MR etiology, symptoms, other hormonal activation, and hemodynamic characteristics. The BNP level is a biomarker of LV alteration in patients with MR, independent of MR etiology. With BNP >90 pg/ml, the odds ratio of an end-systolic volume index value of >/=60 ml/m(2) was 16 (95% confidence interval 5.5 to 45). In conclusion, BNP activation with MR is more pronounced in those with functional than those with organic MR, even after stratification for functional class, and independently reflects the severity of the LV alteration. Pronounced BNP activation is linked to a higher end-systolic volume index, for which it is a biomarker, irrespective of MR etiology and symptoms.

Aged↗
PubMed2005

Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population.

OBJECTIVES: Patients presenting with chest pain or related symptoms suggestive of myocardial ischemia, without ST-segment elevation (NSTE) on their presenting electrocardiograms, often present a diagnostic challenge in the emergency department (ED). Prompt and accurate risk stratification to identify those patients with NSTE chest pain who are at highest risk for adverse events is essential, however, to optimal management. Although validated and used frequently in patients already enrolled in acute coronary syndrome trials, the Thrombolysis in Myocardial Infarction (TIMI) risk score never has been examined for its value in risk stratification in an all-comers, non-trial-based ED chest pain population. METHODS: An analysis of an ED-based prospective observational cohort study was conducted in 3,929 adult patients presenting with chest pain syndrome and warranting evaluation with an electrocardiogram. These patients had TIMI risk scores determined at ED presentation. The main outcome was the composite of death, acute myocardial infarction (MI), and revascularization within 30 days. RESULTS: The TIMI risk score at ED presentation successfully risk-stratified this unselected cohort of chest pain patients with respect to 30-day adverse outcome, with a range from 2.1%, with a score of 0, to 100%, with a score of 7. The highest correlation of an individual TIMI risk indicator to adverse outcome was for elevated cardiac biomarker at admission. Overall, the score had similar performance characteristics to that seen when applied to other databases of patients enrolled in clinical trials and registries using a 14-day end point. CONCLUSIONS: The TIMI risk score may be a useful tool for risk stratification of ED patients with chest pain syndrome.

Angina, Unstable↗
PubMed2005

Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma.

Diffuse malignant gliomas, the most common type of brain tumor, carry a dire prognosis and are poorly responsive to initial treatment. The response to treatment is typically evaluated by measurements obtained from radiographic images several months after the start of treatment; therefore, an early biomarker of tumor response would be useful for making early treatment decisions and for prognostic information. Thirty-four patients with malignant glioma were examined by diffusion MRI before treatment and 3 weeks later. These images were coregistered, and differences in tumor-water diffusion values were calculated as functional diffusion maps (fDM), which were correlated with the radiographic response, time-to-progression (TTP), and overall survival (OS). Changes in fDM at 3 weeks were closely associated with the radiographic response at 10 weeks. The percentage of the tumor undergoing a significant change in the diffusion of water (V(T)) was different between patients with progressive disease (PD) vs. stable disease (SD) (P < 0.001). Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter TTP compared with SD (median TTP, 4.3 vs. 7.3 months; P < 0.04). By using fDM, early patient stratification also was correlated with shorter OS in the PD group compared with SD patients (median survival, 8.0 vs. 18.2 months; P < 0.01). On the basis of fDM, tumor assessment provided an early biomarker for response, TTP, and OS in patients with malignant glioma. Further evaluation of this technique is warranted to determine whether it may be useful in the individualization of treatment or evaluation of the response in clinical protocols.

Adult↗
PubMed2006

Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results.

BACKGROUND: B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing. METHODS AND RESULTS: The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy. CONCLUSIONS: Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Adult↗
PubMed2006

Prognostic value of plasma N-terminal pro-brain natriuretic peptide in children with congenital heart defects and open-heart surgery.

OBJECTIVE: To assess whether preoperative and postoperative plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) predict postoperative outcome of open-heart surgery in children. STUDY DESIGN: A prospective observational study was conducted with 40 children with congenital heart defects who were undergoing elective open-heart surgery. Plasma levels of NT-proBNP, troponin T, lactate, C-reactive protein, and total neutrophil cell counts were measured before, during, and 1 and 3 hours after the end of cardiopulmonary bypass grafting (CPB). Outcomes were assessed by means of the kind, dosage, and duration of inotropic drug use during the postoperative period, lactate concentrations, and the duration of mechanical ventilation. RESULTS: Preoperative levels of NT-proBNP were significantly increased irrespective of the type of congenital heart defect and the age of the patient. Preoperative NT-proBNP levels were higher in patients receiving prolonged postoperative inotropic drug therapy (r = 0.56, P = .0003). By means of multivariate analysis with the duration of inotropic therapy as the dependent variable, a significant impact of preoperative NT-proBNP levels, the presence of a cyanotic heart defect, the risk adjustment for congenital heart surgery score, duration of CPB time, and postoperative lactate levels were demonstrated (R squared = 76.8%, P <.0001). CONCLUSION: Preoperative NT-proBNP levels were associated with complicated postoperative outcome in children who underwent low-risk open-heart surgery. This marker may therefore be a useful tool in risk stratification of patients with congenital heart defects.

Biomarkers↗