A 17-gene genomic prostate score as a predictor of adverse pathology for men on active surveillance.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 97-97
Author(s):  
Zachary Kornberg ◽  
Matthew R. Cooperberg ◽  
Janet E. Cowan ◽  
Jeffry Simko ◽  
June M. Chan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Active Surveillance ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Short Period

97 Background: The OncotypeDX Genomic Prostate Score (GPS) test is a RNA expression assay that can be performed on needle-core biopsies from men with prostate cancer (PCa). GPS has previously been validated as a predictor of adverse pathology in men with low-risk prostate cancer who undergo primary radical prostatectomy (RP). We sought to determine whether GPS was associated with increased risk of adverse pathology for men enrolled on active surveillance (AS) who undergo delayed RP. Methods: Of 1,662 men enrolled on AS at the University of California San Francisco (UCSF) who consented for prospective data collection, we evaluated 215 men on AS with Gleason score (GS) 3+3 and GS 3+4 PCa who underwent GPS testing at diagnostic or confirmatory biopsy (ie. within 1 year). Patients had at least 6 biopsy cores sampled and ≤ 33% positive cores, stage T1 or T2 disease, PSA < 20, and clinical Cancer of the Prostate Risk Assessment (CAPRA) score < 6. The primary outcome was adverse pathology at delayed RP, defined as GS ≥ 4+3, stage ≥ pT3a or pN1. We performed Cox proportional hazards regression, and inverse probability censored weights (IPCW) models to evaluate association between GPS and adverse pathology, adjusting for CAPRA score. Results: 72 percent (N=154) of the cohort had GS 3+3, and 28 percent (N=61) had GS 3+4. 83 percent of men (N=179) were low risk, and 17 percent of men (N=36) were intermediate risk by CAPRA scoring. Median GPS was 26.4 (interquartile range [IQR]: 18.8, 34.6). Median time from diagnosis to RP was 23 months (IQR: 15, 40). 121 men had adverse pathology on delayed RP at a median time of 27 months (IQR 16, 43) to prostatectomy. In a Cox-proportional hazards regression adjusted for CAPRA, GPS was associated with increased risk of adverse pathology at delayed RP (Hazard Ratio [HR] per 5 units: 1.12, 95 Confidence Interval [CI]: 1.05, 1.20, p < 0.01). CAPRA score was not associated with adverse pathology (p=0.09). IPCW model findings were very similar to Cox results. Conclusions: In patients who undergo RP after a relatively short period of AS, a higher GPS is associated with increased risk for adverse pathology on delayed RP.

scholarly journals Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

2014 ◽  
Vol 58 (12) ◽  
pp. 7468-7474 ◽  
Author(s):  
W. Picard ◽  
F. Bazin ◽  
B. Clouzeau ◽  
H.-N. Bui ◽  
M. Soulat ◽  
...  
Keyword(s):  
Septic Shock ◽  
Renal Failure ◽  
Regression Analysis ◽  
Severe Sepsis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Adjusted Relative Risk ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Increased Risk

ABSTRACTTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.

scholarly journals Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12070
Author(s):  
Yujia Lan ◽  
Erjie Zhao ◽  
Xinxin Zhang ◽  
Xiaojing Zhu ◽  
Linyun Wan ◽  
...  
Keyword(s):  
Regression Models ◽  
Proportional Hazards ◽  
Lymphocyte Activation ◽  
Risk Groups ◽  
Gene Signature ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Training Dataset ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Background Glioblastoma multiforme (GBM) is a highly, malignant tumor of the primary central nervous system. Patients diagnosed with this type of tumor have a poor prognosis. Lymphocyte activation plays important roles in the development of cancers and its therapeutic treatments. Objective We sought to identify an efficient lymphocyte activation-associated gene signature that could predict the progression and prognosis of GBM. Methods We used univariate Cox proportional hazards regression and stepwise regression algorithm to develop a lymphocyte activation-associated gene signature in the training dataset (TCGA, n = 525). Then, the signature was validated in two datasets, including GSE16011 (n = 150) and GSE13041 (n = 191) using the Kaplan Meier method. Univariate and multivariate Cox proportional hazards regression models were used to adjust for clinicopathological factors. Results We identified a lymphocyte activation-associated gene signature (TCF3, IGFBP2, TYRO3 and NOD2) in the training dataset and classified the patients into high-risk and low-risk groups with significant differences in overall survival (median survival 15.33 months vs 12.57 months, HR = 1.55, 95% CI [1.28–1.87], log-rank test P < 0.001). This signature showed similar prognostic values in the other two datasets. Further, univariate and multivariate Cox proportional hazards regression models analysis indicated that the signature was an independent prognostic factor for GBM patients. Moreover, we determined that there were differences in lymphocyte activity between the high- and low-risk groups of GBM patients among all datasets. Furthermore, the lymphocyte activation-associated gene signature could significantly predict the survival of patients with certain features, including IDH-wildtype patients and patients undergoing radiotherapy. In addition, the signature may also improve the prognostic power of age. Conclusions In summary, our results suggested that the lymphocyte activation-associated gene signature is a promising factor for the survival of patients, which is helpful for the prognosis of GBM patients.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Antibiotic and acid-suppression medications during early childhood are associated with obesity

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Christopher M Stark ◽  
Apryl Susi ◽  
Jill Emerick ◽  
Cade M Nylund
Keyword(s):  
Early Childhood ◽  
Department Of Defense ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Analysis ◽  
Early Exposure ◽  
Single Event ◽  
Inclusion Criteria ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

scholarly journals Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

scholarly journals Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer’s Disease

2018 ◽  
Vol 31 (2) ◽  
pp. 322-342 ◽  
Author(s):  
Shanna L. Burke ◽  
Tianyan Hu ◽  
Christine E. Spadola ◽  
Aaron Burgess ◽  
Tan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disturbance ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Data Set ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Research Questions

Objective: This study explored two research questions: (a) Does sleep medication neutralize or provide a protective effect against the hazard of Alzheimer’s disease (AD)? (b) Do apolipoprotein (APOE) e4 carriers reporting a sleep disturbance experience an increased risk of AD? Method: This study is a secondary analysis of the National Alzheimer’s Coordinating Center’s Uniform Data Set ( n = 6,782) using Cox proportional hazards regression. Results: Sleep disturbance was significantly associated with eventual AD development. Among the subset of participants taking general sleep medications, no relationship between sleep disturbance and eventual AD was observed. Among individuals not taking sleep medications, the increased hazard between the two variables remained. Among APOE e4 carriers, sleep disturbance and AD were significant, except among those taking zolpidem. Discussion: Our findings support the emerging link between sleep disturbance and AD. Our findings also suggest a continued need to elucidate the mechanisms that offer protective factors against AD development.

Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease

Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Regression Analysis ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Artery Disease

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.

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