Traditional Clinical Variables Research Articles

Abstract 248: Substance Abuse is Associated with Observation Status of Patients with Heart Failure at an Urban Academic Medical Center

Background: More than 80% of patients presenting to the emergency department (ED) with acute decompensated heart failure (ADHF) are admitted and categorized as either observation (OBS) or inpatient (IP) post discharge using Interqual criteria (severity of illness and intensity of service). Identifying patient characteristics upon admission to determine OBS or IP status may optimize hospital resource utilization. Purpose: To determine patient characteristics upon admission that are associated with the categorization (OBS vs IP) for patients with ADHF presenting to the ED of an urban academic medical center. Methods: Retrospective medical record review of 172 randomly selected adult patients from 2013 who presented to the ED with ADHF. Patients had been categorized as OBS vs IP after discharge based on Interqual Criteria. Based on the literature, we identified variables traditionally associated with an admitting diagnosis for heart failure (HF) including: symptoms (shortness of breath, paroxysmal nocturnal dyspnea, orthopnea, and lower extremity edema), physiologic measures (B-type natriuretic peptide and blood pressure), and patient characteristics (number of co-morbidities, type of HF- HF with reduced ejection fraction vs HF with preserved ejection fraction, 30 day readmission rate, gender, ethnicity, and history of substance abuse within the past 12 months). Chi square tests and student t-tests were used to compare variables between groups. Results: Of the 172 ADHF patients, 76% (n=131) were categorized as IP and 24% (n=41) were OBS. The majority of patients were African American (n = 130, 75.6%), female (n = 101, 58.7%) and had HF with a reduced ejection fraction (n = 99, 57.6%). There were no significant differences between the OBS and IP groups in terms of symptoms, B-type natriuretic peptide levels, blood pressure, number of co-morbidities, type of HF, 30 day readmission rate, gender, ethnicity, or socio-demographic characteristics. A history of substance abuse was more common among the OBS group versus the IP group ( p = 0.013). Conclusions: In this single center retrospective medical record review comparing the categorization of patients presenting to the ED with ADHF as OBS vs IP, we found no difference in the traditional clinical variables between groups. However, a history of substance abuse was associated with the patient being categorized as OBS. Substance abuse may be an important non-traditional variable to consider in resource utilization.

Radiographic size of retroperitoneal lymph nodes predicts pathological nodal involvement for patients with renal cell carcinoma: development of a risk prediction model.

To evaluate the ability of clinical and radiographic features to predict lymph node (pN1) disease among patients with renal cell carcinoma undergoing radical nephrectomy (RN), and to develop a preoperative risk prediction model. In all, 220 patients with preoperative computed tomography scans available for review underwent RN with lymph node dissection (LND) from 2000 to 2010. Radiographic features were assessed by one genitourinary radiologist blinded to pN status. Associations of features with pN1 disease were evaluated using logistic regression to develop predictive models. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and decision curve analysis. The median (interquartile range) lymph node yield was 10 (5-18). In all, 55 patients (25%) had pN1 disease at RN. On univariable analysis, the maximum lymph node (LN) short axis diameter [odds ratio (OR) 1.17; P < 0.001] predicted pN1 disease with an AUC of 0.84. Although several clinical and radiographic features were associated with pN1 disease, only two were retained in the multivariable model: maximum LN short axis diameter (OR 1.19; P <0.001) and radiographic perinephric/sinus fat invasion (OR 44.64; P = 0.01), with an AUC of 0.85. On decision curve analysis, the single variable and multivariable models showed similar net benefit. Two radiographic features, maximum LN short axis diameter and perinephric/sinus fat invasion, outperformed traditional clinical variables in predicting pN1 disease. Maximum LN short axis diameter alone showed excellent predictive performance, and, if validated externally, would provide for a simple model to guide patient selection for LND.

Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors. In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation. The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology. APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.

Systematic analysis of hematopoietic gene expression profiles for prognostic prediction in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematopoietic disorder initiated by the leukemogenic transformation of myeloid cells into leukemia stem cells (LSCs). Preexisting gene expression programs in LSCs can be used to assess their transcriptional similarity to hematopoietic cell types. While this relationship has previously been examined on a small scale, an analysis that systematically investigates this relationship throughout the hematopoietic hierarchy has yet to be implemented. We developed an integrative approach to assess the similarity between AML patient tumor profiles and a collection of 232 murine hematopoietic gene expression profiles compiled by the Immunological Genome Project. The resulting lineage similarity scores (LSS) were correlated with patient survival to assess the relationship between hematopoietic similarity and patient prognosis. This analysis demonstrated that patient tumor similarity to immature hematopoietic cell types correlated with poor survival. As a proof of concept, we highlighted one cell type identified by our analysis, the short-term reconstituting stem cell, whose LSSs were significantly correlated with patient prognosis across multiple datasets, and showed distinct patterns in patients stratified by traditional clinical variables. Finally, we validated our use of murine profiles by demonstrating similar results when applying our method to human profiles.

Characterizing bevacizumab use in endometrial cancer in a community medical setting

Objectives: Given that 85% of cancer patients are treated in community settings and the role of bevacizumab in the treatment of endometrial cancer is undefined, we sought to characterize the practice patterns of bevacizumab use in recurrent or persistent endometrial cancer in a community based integrated health care system. Methods: Following IRB approval, patients with endometrial cancer and prior treatment with bevacizumab were identified within the cancer registry database from our regional medical institution. Patients were excluded if they had a concurrent or prior cancer. A chart reviewof the eligible patients was performed to extract traditional clinical variables. Bevacizumab side effects were also recorded to assess tolerability. Results: Twenty-two patients were identified with recurrent or persistent endometrial cancer treated with bevacizumab. The average age was 64 years (range 38–79). Twenty-seven percent were Stage 1, 50% were Stage 3, and 23% were Stage 4. Histology types included 36% papillary serous, 32% endometriod, 9% clear cell, 5% adenosquamous, 5% carcinosarcoma, and 13% with mixed histologic components. The average time period for bevacizumab treatment was 134 days (range 22–374). The average number of chemotherapy treatments prior to bevacizumab use was 2 treatments (range 0–5). Fifty percent of patients received bevacizumab as part of a multidrug treatment regimen, 27% received it as monotherapy, and 22% received additional therapeutic agents during part of their treatment regimen with bevacizumab. Chemotherapy treatments were overseen by 13 medical oncologist and 3 gyn oncologists. Progressive diseasewas seen in 64% of patients using bevacizumab, while 27% had stable disease and 9% has partial or complete regression. Five patients (23%) had Grade 3/4 bevacizumab side effects, including three patients with hypertension, one subarachnoid hemorrhage, and one fistula. No deaths were attributed to bevacizumab. Conclusion: Bevacizumab is well tolerated in this heavily pretreated population, and utilized in varied combinations with clinical benefit. Further studies are needed to elucidate a standard treatment regimen which may optimize patient outcomes in this population with poor prognosis. Learning objective: Learners will be able to describe the role of bevacizumab in recurrent endometrial cancer in patientswho are treated in a community setting.

The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

Assessing the clinical utility of cancer genomic and proteomic data across tumor types.

Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, miRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We found that incorporating molecular data with clinical variables yielded statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2–23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data.

AB0252 Mortality in Patients with Rheumatoid Arthritis: A Prospective Cohort Study over Two Years

BackgroundRheumatoid arthritis (RA) patients have an increased risk of mortality, which has been partially attributed to higher cardiovascular mortality.ObjectivesTo determine the mortality and their risk factors over 2 years of...

Clinical and metabolomic predictors of weight loss in overweight and obese adults in an energy‐restricted controlled feeding trial (248.5)

Weight loss (WL) induced by energy restriction is highly variable even in controlled clinical trials. An integrative analysis of the plasma metabolome coupled to traditional clinical variables may reveal a WL “responder” phenotype. Therfore, we predicted WL in overweight and obese individuals on an energy‐restricted diet in a controlled feeding trial using the plasma metabolome in addition to clinical indices, body composition parameters, plasma endocrine and inflammatory markers, dietary parameters, and physical activity (PA) measurements. A total of 940 pre‐intervention (PrI) and post‐intervention (PoI) variables were assessed. Partial least squares regression accurately predicted weight loss along latent variable 1 (root mean error of prediction (RMSEP) = 1.81 kgs; Q2 = 0.43) and revealed that PrI light and moderate PA were associated with high weight loss, whereas PoI sedentary PA and 2‐ketoisocaproic acid were associated with low weight loss. Network correlation analysis revealed a direct connection between lower PrI respiratory quotient, higher PoI 3‐hydroxybutanoic acid and higher PoI citric acid (P &lt; 0.00001) in high weight losers. Our results suggest that habitual light‐to‐moderate PA are accompanied by distinct blood amino acid and lipid metabolic signatures and correlated with WL in overweight and obese individuals under controlled conditions.Grant Funding Source: Supported by: Nat. Dairy Council; CA Dairy Res. Council; USDA; NCRR (UL1 RR024146); NIH (U24 DK097154)

New Insights from Major Prospective Cohort Studies with Cardiac Nuclear Imaging

For more than two decades, radionuclide imaging has prevailed as a cornerstone in the diagnosis and treatment of patients with cardiac disease. From this experience, large cohort studies have emerged that demonstrate the prognostic value of cardiac radionuclide imaging in a variety of patient groups and conditions. Myocardial perfusion imaging has accrued the most robust evidence for accurate and independent risk stratification over traditional clinical variables. In a variety of patient populations, the presence of myocardial ischemia is a strong predictor of cardiac events on follow-up. In patients with heart failure, smaller observations have similarly established the prognostic value of viability imaging and imaging of cardiac sympathetic activity. The present review provides a summary of recent cohort studies with radionuclide imaging and a critical appraisal of their clinical implications. Its purpose is to put the available evidence into a clinical context, analyze its potential impact on patient management and identify gaps in knowledge and unanswered questions to be addressed in future randomized trials.

FRI0450 The enthesitis ultrasonographic assessment is associated with clinical assessments and responsive to improvements in patients with ankylosing spondylitis starting enbrel treatment

BackgroundEnthesitis is a hallmark of ankylosing spondylitis (AS), while entheseal involvement in AS is not always detected by clinical examination. Ultrasonography (US) has proved to be a highly sensitive and...

SAT0474 Predictors of Early Inactive Disease and Health-Related Quality of Life in Children with Juvenile Idiopathic Arthritis

BackgroundThe outcomes of children with juvenile idiopathic arthritis (JIA) have improved over the last decades. Numerous studies reported traditional clinical predictors like pain and functional status for a better outome...

Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: The Multinational Observational Cohort on Acute Heart Failure (MOCA) study

This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60 mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF.

Mood instability and functional recovery in bipolar disorders

The aim of this study was to identify psychopathological factors associated with long-term functional outcome in euthymic bipolar disorder patients and to test new measures of mood instability and symptoms intensity. Fifty-five patients with more than 12 months of follow-up were included. In addition to traditional clinical variables, the time spent ill was documented using a modified life-charting technique based on NIHM life-charting method. New measures, Mood Instability Factor, and Mood Intensity Factor were defined and assessed. Functioning Assessment Short Test (FAST) was used to assess disability. The follow-up period was 3.00 ± 1.51 years. Weeks with subsyndromal depressive symptoms (β = 0.133, t = 2.556, P = 0.014), weeks with mild manic symptoms (β = 1.441, t = 3.10, P = 0.003), and the Mood Instability Factor (β = 0.105, t = 3.593, P = 0.001) contributed to approximately 46% of the FAST total score variance. New methodologies including subsyndromal symptoms and mood instability parameters might contribute to understand the worse long-term functional outcome that affects a considerable percentage of BD patients even after episode remission. Concerns about therapeutic approaches are discussed.

Clinical and Genetic Association of Serum Paraoxonase and Arylesterase Activities With Cardiovascular Risk

Diminished serum paraoxonase and arylesterase activities (measures of paraoxonase-1 [PON-1] function) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk. The clinical prognostic use of measuring distinct PON-1 activities has not been established, and the genetic determinants of PON-1 activities are not known. We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospectively followed for major adverse cardiovascular events (MACE= death, myocardial infarction, stroke) over 3 years. Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE, with arylesterase activity showing greatest prognostic value (quartile 4 versus quartile 1; hazard ratio 2.63; 95% CI, 1.97-3.50; P<0.01). Arylesterase remained significant after adjusting for traditional risk factors, C-reactive protein, and creatinine clearance (hazard ratio, 2.20; 95% CI, 1.60-3.02; P<0.01), predicted future development of MACE in both primary and secondary prevention populations, and reclassified risk categories incrementally to traditional clinical variables. A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase (1.18×10(-303)) or arylesterase (4.99×10(-116)) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort (n=2136) or history of either coronary artery disease or myocardial infarction in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis consortium (n≈80 000 subjects). Diminished serum arylesterase activity, but not the genetic determinants of PON-1 functional measures, provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE.

Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer

Detection of fusion gene TMPRSS2:ERG transcripts in urine have been recently described in order to refine urine-based detection of prostate cancer (PCa), but data its clinical impact remain scarce. We aimed at investigating the correlation of TMPRSS2:ERG, prostate cancer antigen 3 (PCA3), prostate specific antigen (PSA) density, genetic variants, and androgenic status with outcome and pathological findings at prostatic biopsy. Between 2007 and 2011, 291 patients at risk of PCa because of PSA > 3.0 ng/ml (55%) or candidate to active surveillance protocol justifying restaging biopsy management (45%) were recruited. TMPRSS2:ERG was detected by urine assay (Progensa™). PCA3-score, PSA level, bioavailable testosterone level, prostate volume, rs1447295 and rs6983267 genotypes were prospectively assessed. Univariate and multivariate analysis by logistic regression model (logit) were conducted to study the correlation of TMPRSS2:ERG status, PCA3, and PSA density with biopsy results, and Gleason score. Of 291 patients, 173 had PCa and 118 had negative biopsy. PCA3 score, PSA density and TMPRSS2:ERG-score were correlated with presence of PCa (P < 0.0001, P = 0.046, and P < 0.0001, respectively). This correlation remained strong on multivariable analysis model (area under curve 0.743). PCA3 score and PSA density were significantly associated with presence of Grade 4 through multivariable analysis. PCA3 score was also correlated to the percentage of positive cores at biopsy (P = 0.008). Integration of levels TMPRSS2:ERG transcripts in urine, with PCA3-score, androgenic status, genetic status and traditional clinical variables could significantly increase detection of high risk localized PCa.

Health-Related Quality of Life is Associated with Positive Affect in Patients with Coronary Heart Disease Entering Cardiac Rehabilitation

Health-related quality of life (QoL) is an important and widely used outcome measure in cardiac populations. We examined the relationship between positive affect and health-related quality of life, controlling for traditional cardiovascular risk factors, clinical variables and negative affect. We further investigated the role of gender in this relationship given the well-known gender differences in cardiovascular health. We enrolled 746 patients with coronary heart disease (CHD) before they entered outpatient cardiac rehabilitation. All patients completed the Global Mood Scale and the SF-36 Health Survey. Positive affect was independently associated with mental (p<.001) and physical QoL (p<.001) after controlling for control variables. Gender moderated the relationship between positive affect and physical QoL (p=.009) but not mental QoL (p=.60). Positive affect was positively associated with physical QoL in men (p<.001) but not in women (p=.44). The health-related QoL of patients with CHD is associated with a person's level of positive affect.

Deceased-donor kidney perfusate and urine biomarkers for kidney allograft outcomes: a systematic review

Accurate and reliable assessment of kidney quality before transplantation is needed to predict recipient outcomes and to optimize management and allocation of the allograft. The aim of this study was to systematically review the published literature on biomarkers in two mediums (the perfusate from deceased-donor kidneys receiving machine perfusion and deceased-donor urine) that were evaluated for their possible association with outcomes after kidney transplantation. We searched the Ovid Medline and Scopus databases using broad keywords related to deceased-donor biomarkers in kidney transplantation (limited to humans and the English language). Studies were included if they involved deceased-donor kidneys, measured perfusate or urine biomarkers and studied a possible relationship between biomarker concentrations and kidney allograft outcomes. Each included article was assessed for methodological quality. Of 1430 abstracts screened, 29 studies met the inclusion criteria. Of these, 23 were studies of perfusate (16 biomarkers examined) and 6 were studies of urine (18 biomarkers examined). Only 3 studies (two perfusate) met the criteria of 'good' quality and only 12 were published since 2000. Perfusate lactate dehydrogenase, glutathione-S-transferase (GST) and aspartate transaminase were all found to be significantly associated with delayed graft function in a majority of their respective studies (6/9, 4/6 and 2/2 studies, respectively). Urine neutrophil gelatinase-associated lipocalin, GST, Trolox-equivalent antioxidant capacity and kidney injury molecule-1 were found to be significantly associated with allograft outcomes in single studies that examined diverse end points. Higher quality studies are needed to investigate modern kidney injury biomarkers, to validate novel biomarkers in larger donor populations and to determine the incremental predictive value of biomarkers over traditional clinical variables.

2106 URINE TMPRSS2:ERG FUSION TRANSCRIPT INTEGRATED WITH PCA3 SCORE, GENOTYPING, AND BIOLOGICAL FEATURES ARE CORRELATED TO THE RESULTS OF PROSTATIC BIOPSIES IN MEN AT RISK OF PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20122106 URINE TMPRSS2:ERG FUSION TRANSCRIPT INTEGRATED WITH PCA3 SCORE, GENOTYPING, AND BIOLOGICAL FEATURES ARE CORRELATED TO THE RESULTS OF PROSTATIC BIOPSIES IN MEN AT RISK OF PROSTATE CANCER Jean-Nicolas Cornu, Géraldine Cancel-Tassin, Chirstophe Egrot, Cecile Gaffory, François Haab, and Olivier Cussenot Jean-Nicolas CornuJean-Nicolas Cornu Paris, France More articles by this author , Géraldine Cancel-TassinGéraldine Cancel-Tassin Paris, France More articles by this author , Chirstophe EgrotChirstophe Egrot Paris, France More articles by this author , Cecile GafforyCecile Gaffory Paris, France More articles by this author , François HaabFrançois Haab Paris, France More articles by this author , and Olivier CussenotOlivier Cussenot Paris, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2274AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Detection of fusion gene TMPRSS2:ERG transcripts in urine have been recently described in order to refine urine-based detection of prostate cancer (PCa). Our objective was to investigate the correlation of TMPRSS2:ERG urine detection, Prostate Cancer Antigen 3 (PCA3), Prostate Specific Antigen (PSA) density, 8q24 PCa susceptibility genotypes and androgenic status with outcome and pathological findings at prostatic biopsy. METHODS Between 2007 and 2011, 291 patients at risk of PCa because of PSA>3.0 ng/mL (55%) or candidate to active surveillance protocol justifying restaging biopsy management (45%) were recruited. TMPRSS2:ERG fusion transcript (T2-score) was detected by urine assay (GenProbe, San Diego, CA, USA). PCA3-score, PSA level, bioavailable testosterone (baT) level, prostate volume, genotypes for 8q24 single nucleotide polymorphisms rs1447295 and 6983267, and usual clinical data were assessed for all patients. Univariate and multivariate analysis by logistic regression model (logit) evaluated the correlation of T2-score, PCA3, PSA density, genotype, baT level, age and familial history with biopsy results, and Gleason score. RESULTS Of 291 patients, 173 had PCa and 118 had negative biopsy. PCA3-score, PSA density and T2-score were correlated with presence of PCa (p<0.0001, p=0.046, and p<0.0001 respectively). This correlation remained strong on multivariable analysis prediction model (figure and table). PCA3-score and PSA density were significantly associated with presence of grade 4 through multivariable model (p=0.029 and p=0.03, respectively), with a trend for an association with T2-score (p=0.052). AUC for grade 4 prediction was 0.804. PCA3 score was also correlated to the percentage of positive cores at biopsy (p=0.008). CONCLUSIONS Integration of T2-score, with PCA3-score, androgenic status, genetic status and traditional clinical variables could significantly increase detection of high risk localized PCa. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e849-e850 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jean-Nicolas Cornu Paris, France More articles by this author Géraldine Cancel-Tassin Paris, France More articles by this author Chirstophe Egrot Paris, France More articles by this author Cecile Gaffory Paris, France More articles by this author François Haab Paris, France More articles by this author Olivier Cussenot Paris, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Importance of Biomarkers for Long-Term Mortality Prediction in Acutely Dyspneic Patients

Although numerous biomarkers may be prognostically meaningful in patients with acute dyspnea, few comparative analyses have addressed possible associations between a wide range of candidate biomarkers and clinical variables. Vital status was obtained for 517 acutely dyspneic patients at 4 years after emergency department presentation. A wide array of biomarkers was measured in this cohort, including natriuretic peptides, necrosis markers, inflammatory markers, hematologic markers, and renal markers. We performed statistical evaluation by using minimization of the Bayesian information criterion to evaluate predictors of 4-year mortality. Cox proportional hazards analysis was used to confirm results from the Bayesian information criterion. A final risk model was derived, and this model was then validated by applying it to patients from a separate cohort of acutely dyspneic patients. By 4 years, there were 186 deaths (36%). In addition to several clinical variables, several biomarkers were significant predictors of death, including log-transformed concentrations of hemoglobin (hazard ratio=0.77; P < 0.001), soluble ST2 (hazard ratio=1.38; P < 0.001), and amino-terminal pro-B-type natriuretic peptide (hazard ratio=1.19; P < 0.001). Risk models that used these significant variables were accurate in predicting 4-year mortality in both the training and validation sets. When added to traditional clinical variables, selected biomarkers added significant value for long-term prognostication in acute dyspnea.