scholarly journals Incremental Prognostic Value of Ankle-Brachial Index in High Atherosclerosis Risk Patients: Prediction model assessment on ABILITIES Study

2020 ◽  
Author(s):  
Yan Cang ◽  
Shaojie Xu ◽  
Jingyi Ju ◽  
Jingyin Zhang ◽  
Zijun Chen ◽  
...  

Abstract Background Previous studies have demonstrated association between ankle–brachial index (ABI) and cardiovascular disease (CVD), and confirmed patients with high atherosclerotic risk (AR) had worse prognosis. But after controlling traditional risks, the prognostic value of ABI with all-cause mortality and CVD-cause mortality remains unclarified, especially lack of prediction model assessment. Methods 2988 valid participants were separated into 0-0.40, 0.41–0.89, 0.90–0.99, and 1.00-1.40 four ABI subgroups, and followed up by six year. Factors related to all-cause mortality and CVD-cause mortality were observed by multivariate Cox regression analysis, log-rank test and nomogram. Restricted cubic splines (RCS) were used to explore relationship with ABI and mortality. Incremental discrimination was evaluated by net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Results RCS and Kaplan–Meier survival curve all manifested abnormal ABI levels increased mortality. Compare with normal value, among 0-0.40 and 0.41–0.89 subgroup, adjusted HR of all-cause mortality was 2.12, 95% CI (1.63–3.17), and 2.06, 95% CI (1.35–2.90), respectively. HR of CVD-cuase mortality was 2.39, 95% CI (2.41–3.09), and 2.29, 95% CI (1.83–2.87), respectively. RCS presented reverse J-shaped relationship with ABI and mortality. Nomogram indicated ABI as a strong risk, occupied the second weight. Adding ABI to traditional AR model, NRI, IDI, and DCA was 0.11, 0.12, and 0.18, respectively. Conclusion Combining ABI with traditional AR can improve all-cause mortality and CVD mortality prediction. Routine ABI evaluation and intensive intervention were pressing needed, especially in high AR patients.

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is a prevent malignancy with high mortality. Long noncoding RNAs (lncRNAs) have been reported to play important roles in tumorigenesis. The purpose of this study was to explore the prognostic value of lncRNA HOTTIP in lung cancer.Methods: The expression of HOTTIP in lung cancer tissues was measured by quantitative real-time PCR (qRT-PCR). Chi-square test was applied to assess the correlation of HOTTIP with clinicopathological features. Overall survival curve was built by Kaplan-Meier method with log rank test. Cox regression analysis was used to explore the prognostic value of HOTTIP in lung cancer.Results: The expression of HOTTIP was significantly increased in lung cancer samples compared with paired noncancerous samples (P<0.001). Moreover, its expression patterns were correlated with lymph node metastasis (P=0.039) and TNM stage (P=0.007). Survival curve demonstrated that lung cancer patients with high level of HOTTIP had poor survival rate (log-rank P=0.011). HOTTIP might be an independent prognostic factor for lung cancer (HR=1.916, 95%CI=1.133-3.238, P=0.015).Conclusions: HOTTIP is up-regulated in lung cancer, and associated with aggressive tumor progression. HOTTIP may be a potential prognostic biomarker for lung cancer.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  

Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lu Lu ◽  
Le-Ping Liu ◽  
Qiang-Qiang Zhao ◽  
Rong Gui ◽  
Qin-Yu Zhao

Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Amanda Lemos Barros Martins Portela ◽  
Rafael Neves Moreno ◽  
Maria Helena Madruga Lima Ribeiro ◽  
Fernanda Miguel de Andrade ◽  
Yale Viana Alves ◽  
...  

Abstract Background To investigate the effect of nicergoline on the rate of complete corneal ulcer reepithelialization (CCUR) in diabetic rats with diabetic keratopathy. Methods Forty-eight streptozotocin-induced diabetic rats were randomly divided into two groups. The experimental group (n = 24) received nicergoline (10 mg.kg− 1.day− 1), while the control group (n = 24) received a placebo. A corneal epithelial defect was induced using a corneal diamond burr, and defect area was compared at time points of 0, 12, 24, 48 and 72 h after the injury using image analysis software. The probability of CCUR within 72 h was assessed using the Kaplan–Meier survival analysis log-rank test. Results When compared, 4 of the 24 rats (17%) in the placebo group and 12 of the 24 rats (50%) in the nicergoline group were found to have CCUR within 72 h (log-rank = 0.027). Cox regression analysis found no effect of the covariates blood glucose (P = 0.601) or weight (P = 0.322) on the corneal reepithelialization (survival) curve. Conclusions Nicergoline increased wound healing rates relative to placebo and may therefore be investigated as a treatment option in diabetic keratopathy.


2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Piqiang Zhang ◽  
Deyun Sun ◽  
Xuemei Sun ◽  
Hongjuan Li

Abstract Background microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance. Methods The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan–Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay. Results Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P < 0.001). ROC curve showed that miR-381 could distinguish pediatric AML cases from normal controls. At the same time, the downregulation of miR-381 was associated with M7 in the French–American–British (FAB) classifications and unfavorable cytogenetic risks (P < 0.05). Low serum miR-381 levels were associated with poor overall survival of pediatric AML (log-rank test, P = 0.011) and poor relapse-free survival (log-rank test, P = 0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR = 3.794, 95% CI 1.3633–10.559, P = 0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P < 0.05). Conclusion All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhong Zheng ◽  
Jun Li ◽  
Junyan An ◽  
Yikuan Feng ◽  
Lirong Wang

Abstract Background Gastric cancer (GCa) is one of the six major malignancies in the world with low survival rate. Although there are advances in therapeutic approaches, the prognosis of patients with GCa remains not optimistic. Therefore, this study aimed to evaluate the prognostic value of miR-324-5p, as well as its functional role in GCa progression. Methods The expression of miR-324-5p in tumor tissues and cell lines was examined using real-time quantitative PCR. The prognostic value of miR-324-5p in patients with GCa was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Gain- and loss-of-function experiments were performed to evaluate the biological function of miR-324-5p during the progression of GCa, and a target gene of miR-324-5p was proposed. Results The expression of miR-324-5p was up-regulated in GCa tissues and cell lines. Patients with high expression of miR-324-5p had more cases with positive lymph node metastasis, advanced TNM stage, and worse overall survival compared with patients with low expression. The elevated miR-324-5p was an independent prognostic indicator of GCa. In addition, the inhibition of miR-324-5p could suppress GCa cell proliferation, migration and invasion and promote cell apoptosis, and PTEN was demonstrated to serve as a direct target of miR-324-5p in GCa progression. Conclusion The present study indicates that miR-324-5p overexpression predicts poor prognosis in GCa patients, and the reduction of miR-324-5p can inhibit GCa biological processes. PTEN is a target gene of GCa, which may mediate the biological function of miR-324-5p in GCa progression.


2020 ◽  
Author(s):  
Amanda Portela ◽  
Rafael Moreno ◽  
Maria Helena Ribeiro ◽  
Fernanda de Andrade ◽  
Yale Alves ◽  
...  

Abstract Background: To investigate the effect of nicergoline on the rate of complete corneal ulcer reepithelialization (CCUR) in diabetic rats with diabetic keratopathy.Methods: Forty-eight streptozotocin-induced diabetic rats were randomly divided into two groups. The experimental group (n=24) received nicergoline (10 mg.kg-1.day-1), while the control group (n=24) received a placebo. A corneal epithelial defect was induced using a corneal diamond burr, and defect area was compared at timepoints of 0, 12, 24, 48 and 72 hours after the injury using image analysis software. The probability of CCUR within 72 hours was assessed using the Kaplan–Meier survival analysis log-rank test. Results: When compared, 4 of the 24 rats (17%) in the placebo group and 12 of the 24 rats (50%) in the nicergoline group were found to have CCUR within 72 hours (log-rank = 0.027). Cox regression analysis found no effect of the covariates blood glucose (P=0.601) or weight (P=0.322) on the corneal reepithelialization (survival) curve. Conclusions: Nicergoline increased wound healing rates relative to placebo and may therefore be investigated as a treatment option in diabetic keratopathy.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Fortuni ◽  
M.F Dietz ◽  
E.A Prihadi ◽  
S.G Priori ◽  
J.J Bax ◽  
...  

Abstract Background Functional tricuspid regurgitation (FTR) can be caused by right ventricular (RV) and/or right atrial (RA) dilation, and it leads in turn to further RV and RA remodeling. While it is known that in these patients RV dilation is associated with worse prognosis, there are no data on the prognostic value of RA enlargement. Purpose To assess the prognostic impact of RA dilation in patients with significant (≥ moderate) FTR taking into account the presence of atrial fibrillation (AF). Methods 1382 patients (mean age: 69±13 year; 50% male) with moderate or severe FTR were included. Patients with congenital heart disease were excluded. Significant RA enlargement was identified by the value of RA area associated with excess of mortality according to spline curve analysis in the overall population (30 cm2 – Figure: Left Panel). The prognostic value of RA enlargement was investigated separately in patients with sinus rhythm (SR) and AF. The primary endpoint was all-cause mortality. Results A total of 987 (71%) patients were in SR while the remaining 395 (29%) had AF at the time of significant FTR diagnosis. Patients in SR with RA enlargement were more likely to present with RV failure symptoms and to receive diuretics compared with patients in SR with non-enlarged RA, whereas these differences were not detected in patients with AF. During a median follow-up of 53 (interquartile range, 20–89) months, 698 (51%) patients died. The survival rates of patients in SR with RA enlargement were significantly worse compared to the ones of patients in SR with normal RA size (Figure: Right Panel). In contrast, RA enlargement did not affect the prognosis of patients in AF (Log-rank χ2: 0.41; P=0.522). RA enlargement was associated with 33% increase risk of all-cause mortality in patients with SR and this association was retained on a multivariable Cox regression analysis (HR 1.27; 95% CI 1.04–1.56; P=0.022) together with older age, coronary artery disease, diabetes, severe renal impairment, reduced left ventricular or RV systolic function, and increased pulmonary artery pressures. Conclusion RA enlargement has an independent prognostic value for all-cause mortality in patients with FTR and SR, and therefore its evaluation might be useful to further improve their risk stratification. Funding Acknowledgement Type of funding source: None


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