A novel biomarker signature to predict aggressive disease in African-American men with prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 24-24
Author(s):  
Kosj Yamoah ◽  
Michael Hiroshi Johnson ◽  
Voleak Choeurng ◽  
Kasra Yousefi ◽  
Zaid Haddad ◽  
...  
Keyword(s):  
Logistic Regression ◽  
African American ◽  
Regression Models ◽  
African American Men ◽  
Conditional Logistic Regression ◽  
Dependent Manner ◽  
Specific Expression ◽  
Significant Differential Expression ◽  
Logistic Regression Models ◽  
Increased Risk

24 Background: Numerous studies have reported a significantly higher incidence of PCa and/or adverse pathological features associated with African-American men compared to European-American men. Less however is known about the genomic disparities that exist between these two groups. In this report we compared the race-specific expression of biomarkers linked to PCa pathogenesis in a matched cohort of AA and EA men. Methods: PCa data from AA and EA patients were analyzed from four medical centers. Cases were matched based on CAPRA-S within each institution for a total sample size of 300 (121-AA; 179-EA). The distribution of mRNA expression levels of 20 validated biomarkers associated with PCa initiation and progression was compared by race using a false-discovery-rate adjusted Mann-Whitney U, and logistic regression models. Conditional logistic regression models were used to evaluate the interaction between race and biomarker expression for predicting pathologic T3 PCa. Results: Of 20 biomarkers interrogated, 6 showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include TMPRSS2-ERG (p<0.001), AMACR (p<0.001), SPINK1 (p=0.005), AR (p=0.018), SRD5A2 (p=0.005), and GSTP1 (p=0.021). Dysregulation of MYCBP (p=0.043) increases risk of pT3 disease in AA but decreases the risk in EA men, while the reverse is true for AMACR (p=0.013), TMPRSS2-ERG (p=0.026), FOXP1 (p=0.016), and GSTP1 (p=0.032). Loss-of-function mutation for tumor suppressors PTEN (p=0.046), TP53 (p=0.042), and RB1 (p=0.027), and dysregulation of AR (p=0.015), EZH2 (p=0.043), NKX3-1 (p=0.024), SRD5A2 (p=0.032), and SPOP (p=0.032) increased risk of pT3 disease for both AA and EA men. Conclusions: We have identified a subset of PCa biomarkers that predict risk of clinico-pathologic outcomes in a race-dependent manner. These biomarkers may in part explain the biological contribution to racial disparity in PCa outcomes between EA and AA men.

scholarly journals Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer

2015 ◽  
Vol 33 (25) ◽  
pp. 2789-2796 ◽  
Author(s):  
Kosj Yamoah ◽  
Michael H. Johnson ◽  
Voleak Choeurng ◽  
Farzana A. Faisal ◽  
Kasra Yousefi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Logistic Regression ◽  
African American ◽  
African American Men ◽  
Conditional Logistic Regression ◽  
Ethnic Disparities ◽  
Dependent Manner ◽  
Conditional Logistic Regression Model ◽  
Specific Expression ◽  
Significant Differential Expression

Purpose We studied the ethnicity-specific expression of prostate cancer (PC) –associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. Patients and Methods A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. Results Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). Conclusion We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients

2022 ◽  
pp. postgradmedj-2021-141204
Author(s):  
Shoujiang You ◽  
Qiao Han ◽  
Xiaofeng Dong ◽  
Chongke Zhong ◽  
Huaping Du ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischaemic Stroke ◽  
Prothrombin Time ◽  
Hospital Discharge ◽  
Acute Ischaemic Stroke ◽  
Regression Models ◽  
Logistic Regression Models ◽  
Risk Of Death ◽  
Increased Risk ◽  
International Normalised Ratio

BackgroundWe investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients.MethodsA total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92–0.98), Q3 (0.98–1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4–5) separately on discharge in AIS patients.ResultsHaving an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend=0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend=0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend=0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend=0.006) but not death or major disability (P-trend=0.240), major disability (P-trend=0.606) on discharge.ConclusionsHigh INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

scholarly journals Association of Combined Sero-Positivity to Helicobacter pylori and Streptococcus gallolyticus with Risk of Colorectal Cancer

2020 ◽  
Vol 8 (11) ◽  
pp. 1698
Author(s):  
Meira Epplein ◽  
Loïc Le Marchand ◽  
Timothy L. Cover ◽  
Mingyang Song ◽  
William J. Blot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Helicobacter Pylori ◽  
Regression Models ◽  
Conditional Logistic Regression ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Vacuolating Cytotoxin ◽  
Logistic Regression Models ◽  
Streptococcus Gallolyticus ◽  
Increased Risk

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66–1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98–1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16–2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.

scholarly journals Does Flipping the Tubercle for Improved Cartilage Repair Exposure Increase the Risk for Arthrofibrosis?

Cartilage ◽  
2020 ◽  
pp. 194760352096820
Author(s):  
Gergo Merkely ◽  
Jakob Ackermann ◽  
Emily Sheehy ◽  
Andreas H. Gomoll
Keyword(s):  
Logistic Regression ◽  
Cartilage Repair ◽  
Regression Models ◽  
Case Control Study ◽  
Level Of Evidence ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Repair Procedure ◽  
Control Study

Objective We sought to determine whether rates of postoperative arthrofibrosis following tibial tuberosity osteotomy (TTO) with complete mobilization of the fragment (TTO-HD) are comparable to TTOs where the hinge remained intact (TTO-HI). Design Patients who underwent TTO with concomitant cartilage repair procedure between January 2007 and May 2017, with at least 2 years of follow-up were included in this study. Postoperative reinterventions following TTO-HD and TTO-HI were assessed and multivariant logistic regression models were used to identify whether postoperative reinterventions can be attributed to either technique when controlled for defect size or defect number. Results A total of 127 patients (TTO-HD, n = 80; TTO-HI, n = 47) were included in this study. Significantly more patients in the TTO-HD group (31.2%) developed postoperative arthrofibrosis compared with TTO-HI (6.4%; P < 0.05). Multivariant logistic regression revealed that TTO-HD is an independent risk factor for predicting postoperative arthrofibrosis (OR 6.5, CI = 1.7-24.2, P < 0.05). Conclusion Patients who underwent TTO with distal hinge detachment and a proximally flipped tubercle for better exposure during concomitant cartilage repair were at a significantly higher risk of postoperative arthrofibrosis than patients with similar size and number of defects treated without mobilization of the tubercle. While certain procedures can benefit from larger exposure, surgeons should be aware of the increased risk of postoperative arthrofibrosis. Level of Evidence Level III, case-control study.

scholarly journals On marginal and conditional parameters in logistic regression models

Biometrika ◽  
2019 ◽  
Vol 106 (3) ◽  
pp. 732-739
Author(s):  
Elena Stanghellini ◽  
Marco Doretti
Keyword(s):  
Logistic Regression ◽  
Regression Models ◽  
Conditional Logistic Regression ◽  
Exact Formula ◽  
Logistic Regression Models ◽  
Conditional Models ◽  
Data Generating Process ◽  
Binary Random Variables ◽  
Intermediate Variables ◽  
Relevant Covariates

Summary We derive the exact formula linking the parameters of marginal and conditional logistic regression models with binary mediators when no conditional independence assumptions can be made. The formula has the appealing property of being the sum of terms that vanish whenever parameters of the conditional models vanish, thereby recovering well-known results as particular cases. It also permits the disentangling of direct and indirect effects as well as quantifying the distortion induced by the omission of relevant covariates, opening the way to sensitivity analysis. As the parameters of the conditional models are multiplied by terms that are always bounded, the derivations may also be used to construct reasonable bounds on the parameters of interest when relevant intermediate variables are unobserved. We assume that, conditionally on a set of covariates, the data-generating process can be represented by a directed acyclic graph. We also show how the results presented here lead to the extension of path analysis to a system of binary random variables.

scholarly journals Weight Status and High Blood Pressure Among Low-Income African American Men

2010 ◽  
Vol 5 (3) ◽  
pp. 255-260 ◽  
Author(s):  
Marino A. Bruce ◽  
Bettina M. Beech ◽  
Christopher L. Edwards ◽  
Mario Sims ◽  
Isabel Scarinci ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African American ◽  
High Blood Pressure ◽  
Low Income ◽  
Regression Models ◽  
Weight Status ◽  
African American Men ◽  
Logistic Regression Models ◽  
Biological Risk Factor ◽  
West Tennessee

Obesity is a biological risk factor or comorbidity that has not received much attention from scientists studying hypertension among African American men. The purpose of this study was to examine the relationship between weight status and high blood pressure among African American men with few economic resources. The authors used surveillance data collected from low-income adults attending community- and faith-based primary care clinics in West Tennessee to estimate pooled and group-specific regression models of high blood pressure. The results from group-specific logistic regression models indicate that the factors associated with hypertension varied considerably by weight status. This study provides a glimpse into the complex relationship between weight status and high blood pressure status among African American men. Additional research is needed to identify mechanisms through which excess weight affects the development and progression of high blood pressure.

scholarly journals Prevalence and population structure of Staphylococcus aureus nasal carriage in healthcare workers in a general population. The Tromsø Staph and Skin Study

2012 ◽  
Vol 141 (1) ◽  
pp. 143-152 ◽  
Author(s):  
K. OLSEN ◽  
M. SANGVIK ◽  
G. S. SIMONSEN ◽  
J. U. E. SOLLID ◽  
A. SUNDSFJORD ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Logistic Regression ◽  
Population Structure ◽  
Regression Models ◽  
Healthcare Workers ◽  
Nasal Carriage ◽  
Population Based ◽  
Family Status ◽  
Logistic Regression Models ◽  
Increased Risk

SUMMARYHealthcare workers (HCWs) may be a reservoir for Staphylococcus aureus transmission to patients. We examined whether HCW status is associated with S. aureus nasal carriage and population structure (spa types) in 1302 women (334 HCWs) and 977 men (71 HCWs) aged 30–69 years participating in the population-based Tromsø Study in 2007–2008. Multivariable logistic regression models were used. While no methicillin-resistant S. aureus (MRSA) was isolated, overall, 26·2% of HCWs and 26·0% of non-HCWs were S. aureus nasal carriers. For women overall and women residing with children, the odds ratios for nasal carriage were 1·54 [95% confidence interval (CI) 1·09–2·19] and 1·86 (95% CI 1·14–3·04), respectively, in HCWs compared to non-HCWs. Moreover, HCWs vs. non-HCWs had a 2·17 and 3·16 times higher risk of spa types t012 and t015, respectively. This supports the view that HCWs have an increased risk of S. aureus nasal carriage depending on gender, family status and spa type.

scholarly journals Plasmatic Extracellular Vesicles in Acute Graft-Versus-Host Disease after Haplo-Identical Allografting with Post-Transplant Cyclophosphamide

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 598-598
Author(s):  
Giuseppe Lia ◽  
Clara Di Vito ◽  
Marta Tapparo ◽  
Stefania Bruno ◽  
Elisa Zaghi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Extracellular Vesicles ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Regression Models ◽  
Logistic Regression Models ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

INTRODUCTION: Acute Graft-versus-Host-Disease (aGVHD) is a frequent complication where the endothelium may play a pivotal role. We recently investigated the potential role of extracellular vesicles (EVs) as novel biomarkers of aGVHD (Lia G. et al. Leukemia 2018). In this study we further investigated the correlation of plasma EVs and their content in miRNAs with the risk of developing aGVHD in the setting of post-transplant cyclophosphamide (PTCY) haploidentical-stem cell transplantation (Haplo-SCT). METHODS: Thirty-two patients who underwent a Haplo-SCT were included. Plasma samples were collected from peripheral blood at given time-points (pre-transplant, on day 0, 3, 7, 14, 21, 28, 35, 45, 60, 75 and 90 after transplant). EVs were extracted by a protamine-based precipitation method and were characterized by Nano-tracking Particle Analysis (Nanosight). EVs were then analyzed by flow-cytometry (Guava EasyCyte Flow Cytometer) with a panel of 14 antibodies (CD44, CD138, CD146, KRT18, CD120a, CD8, CD30, CD106, CD25, CD26, CD31, CD144, CD86, and CD140a). MiRNAs were extracted from EVs by miRNeasy Mini Kit (Qiagen) and retrotranscribed by miScript II RT Kit (Qiagen). Three miRNAs (miR100, miR194, miR155) were studied and quantified by qRT-PCR using the miScript SYBR Green PCR Kit (Qiagen). Concomitant plasma concentrations of human Tumor Necrosis Factor Receptor I (TNFR1) and human ST2 were also evaluated using a commercially available sandwich enzyme-linked immunosorbent assay (DualSET® ELISA R&D Systems). The risk of aGVHD was evaluated by logistic regression models and Odds Ratios (ORs) were estimated as absolute levels and as proportional changes compared with pre-transplant baseline levels of each marker. Moreover, among biomarkers significantly associated with a higher risk of aGVHD, a multivariable logistic regression model using Akaike's information criteria (AIC) was estimated to define a biomarker combination. Ors were reported for 1-unit increase of standardized variables. RESULTS: AGVHD (grade II-IV) was observed in 7/32 patients (22%) at a median of 41 (range 33-90) days after transplant. Logistic regression models showed that CD146 fluorescence was associated with a significantly increased risk of acute GVHD (OR 2.93 p&lt;0.001) as well as expression changes in miR100, miR155 and miR194 (OR 3.90 p&lt;0.001; OR 1.84 p=0.008; OR 2.68 p&lt;0.001, respectively). Concentrations of plasmatic hTNFR1 and ST2 were also confirmed to be associated with increased risk of aGVHD (OR 1.47 p=0.04; OR 1.55 p=0.05, respectively) as previously described. Of note, all biomarkers associated with risk of aGVHD showed a consensual change in signal levels before the onset of aGVHD (Figure 1). By applying a backward selection on a multivariable logistic model using the AICapproach, we found that the combination of CD146-miR100-TNFR1 with an individual AUROC of 0.858, 0.923, and 0.794, respectively, increased their discrimination ability to predict aGVHD (multivariable AUROC = 0.987). CONCLUSIONS: This study, in the setting of haplo-transplant, confirms the association of CD146, a cell adhesion molecule, and the risk of aGVHD suggesting an important role of endothelium damage in the pathogenesis of aGVHD. The association of miRNA100, miRNA155 and miRNA194, carried by EVs, and aGVHD was also significant. Interestingly, MiRNA100 was reported to regulate inflammatory neovascularization during GvHD while miR-155 plays a role in donor T cell expansion. We have also found that using three markers in combination (CD146-miR100-TNFR1) could greatly improve aGVHD predictivity. To translate our results into an in vivo model, we have recently designed preclinical mouse models to evaluate if a) antagomir (against miRNA100 and/or miRNA155) injections or b) pre-emptive treatments with endothelium protective agents such as defibrinotide or OMS721 (Anti-Masp2) may reduce the risk of aGVHD. Figure1 a) Signal variation from baseline level (preTx) of CD146 fluorescence, miR100 expression, and TNFR1 concentration before aGVHD onset. Disclosures Boccadoro: Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding.

scholarly journals Identifying Household Level Risk Factors for Unintentional House Fire Incidents, Injuries and Fatalities

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Samantha Turner ◽  
Sarah Rodgers ◽  
Ronan Lyons
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Large Scale ◽  
Conditional Logistic Regression ◽  
Household Composition ◽  
Health Concern ◽  
Logistic Regression Models ◽  
Household Level ◽  
Increased Risk ◽  
The Uk

ABSTRACTObjectivesUnintentional house fire incidents, injuries and deaths are a serious public health concern in the UK, which disproportionally affect certain groups in the population. Whilst house fires have decreased in recent years; growing financial pressures in the Fire and Rescue Services (FRSs) have resulted in funds dedicated to fire preventative activities becoming increasingly limited. To ensure ever limiting resources are targeted towards those households at greatest risk, it is essential the FRSs’ are accurately informed about the types of household at increased risk. The aim of this project is to undertake a large-scale case-control study, to identify the distinguishing household level risk factors associated with unintentional house fire incidents, injuries and deaths. ApproachUnintentional house fire incidents reported to the Welsh FRS between the years 2003-2008, were anonymised and incorporated into the Secure Anonymised Information Linkage (SAIL) Databank at the Farr Institute, Swansea University. 6943 case households (households which reported a fire to the FRS) were time-matched to 347,150 control households (case:control ratio 1:50). Individuals registered as living at these properties on the date of the fire were established using the Welsh Demographic Service (WDS) dataset. Household level variables will be created by linking case and control households to other demographic, health, educational and environmental datasets in SAIL. Conditional Logistic Regression will be used to estimate matched odds ratios and 95% confidence intervals. ResultsPotential risk factor variables were selected on the basis of a systematic review and theoretically plausible variables. Covariates include: household composition (e.g. age and gender of residents), socioeconomic status, educational attainment, smoking, alcohol consumption, mental health conditions, other health related conditions, mobility and sensory impairments and property related characteristics. Fire related circumstances (e.g. fire ignition source, presence of a smoke alarm) will also be investigated in logistic regression models exploring risk factors for injury and death. Results will be presented at the conference. ConclusionThis is the first large-scale analysis of risk factors for unintentional house fire incidents, injuries and deaths. The findings from this project will be translated into comprehensible infographics, designed to support the FRSs, other partner organisations and the general public, recognise high risk households in need of preventative interventions.

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