Browsing by Subject "prognosis"
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Item The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma(MDPI, 2020-06-17) Kays, Joshua K.; Koniaris, Leonidas G.; Cooper, Caleb A.; Pili, Roberto; Jiang, Guanglong; Liu, Yunlong; Zimmers, Teresa A.; Medical and Molecular Genetics, School of MedicineClear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA). Skeletal muscle and fat masses measured from CT scans and tumor cytokine gene expression were compared with survival by univariate and multivariate analysis. Patients in the lowest skeletal muscle mass (SKM) quartile had significantly shorter overall survival versus the top three SKM quartiles. Patients who fell into the lowest quartiles for visceral adipose mass (VAT) and subcutaneous adipose mass (SCAT) also demonstrated significantly shorter overall survival. Multiple tumor cytokines correlated with mortality, most strongly interleukin-6 (IL-6); high IL-6 expression was associated with significantly decreased survival. The combination of low SKM/high IL-6 was associated with significantly lower overall survival compared to high SKM/low IL-6 expression (26.1 months vs. not reached; p < 0.001) and an increased risk of mortality (HR = 5.95; 95% CI = 2.86–12.38). In conclusion, tumor cytokine expression, body composition, and survival are closely related, with low SKM/high IL-6 expression portending worse prognosis in ccRCC.Item Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten Years Post-Injury(Mary Ann Liebert, 2018-09-18) Hammond, Flora M.; Giacino, Joseph T.; Nakase Richardson, Risa; Sherer, Mark; Zafonte, Ross D.; Whyte, John; Arciniegas, David B.; Tang, Xinyu; Physical Medicine and Rehabilitation, School of MedicineFew studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI.Item Efficacy of Post-Induction Therapy for High-risk Neuroblastoma Patients with End-Induction Residual Disease(Wiley, 2022) Desai, Ami V.; Applebaum, Mark A.; Karrison, Theodore G.; Oppong, Akosua; Yuan, Cindy; Berg, Katherine R.; MacQuarrie, Kyle; Sokol, Elizabeth; Hall, Anurekha G.; Pinto, Navin; Wolfe, Ian; Mody, Rajen; Shusterman, Suzanne; Smith, Valeria; Foster, Jennifer H.; Nassin, Michele; LaBelle, James L.; Bagatell, Rochelle; Cohn, Susan L.; Radiology and Imaging Sciences, School of MedicineBackground: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving response prior to autologous stem cell transplant (ASCT). We conducted a multi-center, retrospective study to investigate the efficacy of this approach. Methods: Patients diagnosed between 2008 and 2018 without progressive disease (PD) with ≤ partial response (PR) at end-induction were stratified according to post-induction treatment: i) no additional therapy prior to ASCT (Cohort 1); ii) post-induction “bridge” therapy prior to ASCT (Cohort 2); and iii) post-induction therapy without ASCT (Cohort 3). Chi-square tests were used to compare patient characteristics. Three-year event-free survival (EFS) and overall survival (OS) were estimated by the Kaplan-Meier method and survival curves were compared by log-rank test. Results: The study cohort consisted of 201 patients; Cohort 1 (n=123); Cohort 2 (n=51); and Cohort 3 (n=27). Although end-induction response was better for Cohort 1 than Cohorts 2 and 3, outcome for Cohort 1 and 2 was not significantly different (EFS; p=0.77 and OS; p=0.85). Inferior outcome was observed for Cohort 3 (EFS; p<0.001 and OS; p=0.06). Among patients with end-induction stable metastatic disease, 3-year EFS was significantly improved for Cohort 2 compared to Cohort 1 (p=0.04). Cohort 3 patients with complete response (CR) in metastatic sites following post-induction therapy had significantly better 3-year EFS compared to those with residual metastatic disease (p=0.01). Conclusions: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.Item Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications(Impact Journals, 2017-04-12) Li, Ming; Wang, Ying; Cheng, Liang; Niu, Wanting; Zhao, Guoan; Raju, Jithin K.; Huo, Jun; Wu, Bin; Yin, Bo; Song, Yongsheng; Bu, Renge; Pathology and Laboratory Medicine, School of MedicineRenal cell carcinoma is one of the most common malignancy in adults, its prognosis is poor in an advanced stage and early detection is difficult due to the lack of molecular biomarkers. The identification of novel biomarkers for RCC is an urgent and meaningful project. Long non-coding RNA (lncRNA) is transcribed from genomic regions with a minimum length of 200 bases and limited protein-coding potential. Recently, lncRNAs have been greatly studied in a variety of cancer types. They participate in a wide variety of biological processes including cancer biology. In this review, we provide a new insight of the profiling of lncRNAs in RCC and their roles in renal carcinogenesis, with an emphasize on their potential in diagnosis, prognosis and potential roles in RCC therapy.Item MicroRNAs: Clinical Relevance in Colorectal Cancer(MDPI, 2015) Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, HuiColorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.Item Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts(Elsevier, 2022-12-12) Strand, Siri H.; Rivero-Gutiérrez, Belén; Houlahan, Kathleen E.; Seoane, Jose A.; King, Lorraine M.; Risom, Tyler; Simpson, Lunden A.; Vennam, Sujay; Khan, Aziz; Cisneros, Luis; Hardman, Timothy; Harmon, Bryan; Couch, Fergus; Gallagher, Kristalyn; Kilgore, Mark; Wei, Shi; DeMichele, Angela; King, Tari; McAuliffe, Priscilla F.; Nangia, Julie; Lee, Joanna; Tseng, Jennifer; Storniolo, Anna Maria; Thompson, Alastair M.; Gupta, Gaorav P.; Burns, Robyn; Veis, Deborah J.; DeSchryver, Katherine; Zhu, Chunfang; Matusiak, Magdalena; Wang, Jason; Zhu, Shirley X.; Tappenden, Jen; Ding, Daisy Yi; Zhang, Dadong; Luo, Jingqin; Jiang, Shu; Varma, Sushama; Anderson, Lauren; Straub, Cody; Srivastava, Sucheta; Curtis, Christina; Tibshirani , Rob; Angelo, Robert Michael; Hall , Allison; Owzar , Kouros; Polyak , Kornelia; Maley, Carlo; Marks, Jeffrey R.; Colditz, Graham A.; Hwang, E. Shelley; West , Robert B.; Medicine, School of MedicineDuctal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.Item N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study(Elsevier, 2018-03-20) Januzzi, James L.; Chen-Tournoux, Annabel A.; Christenson, Robert H.; Doros, Gheorghe; Hollander, Judd E.; Levy, Phillip D.; Nagurney, John T.; Nowak, Richard M.; Pang, Peter S.; Patel, Darshita; Peacock, W. Franklin; Rivers, E. Joy; Walters, Elizabeth L.; Gaggin, Hanna K.; Emergency Medicine, School of MedicineBackground Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.Item A new survival model based on ferroptosis-related genes for prognostic prediction in clear cell renal cell carcinoma(Impact Journals, 2020-07-20) Wu, Guangzhen; Wang, Qifei; Xu, Yingkun; Li, Quanlin; Cheng, Liang; Pathology and Laboratory Medicine, School of MedicineIn this study, we analyzed the clinical significance of ferroptosis-related genes (FRGs) in 32 cancer types in the GSCA database. We detected a 2-82% mutation rate among 36 FRGs. In clear cell renal cell carcinoma (ccRCC; n=539) tissues from the The Cancer Genome Atlas database, 30 of 36 FRGs were differentially expressed (up- or down-regulated) compared to normal kidney tissues (n=72). Consensus clustering analysis identified two clusters of FRGs based on similar co-expression in ccRCC tissues. We then used LASSO regression analysis to build a new survival model based on five risk-related FRGs (CARS, NCOA4, FANCD2, HMGCR, and SLC7A11). Receiver operating characteristic curve analysis confirmed good prognostic performance of the new survival model with an area under the curve of 0.73. High FANCD2, CARS, and SLC7A11 expression and low HMGCR and NCOA4 expression were associated with high-risk ccRCC patients. Multivariate analysis showed that risk score, age, stage, and grade were independent risk factors associated with prognosis in ccRCC. These findings demonstrate that this five risk-related FRG-based survival model accurately predicts prognosis in ccRCC patients, and suggest FRGs are potential prognostic biomarkers and therapeutic targets in several cancer types.Item Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer(Elsevier, 2017) Wang, Lisha; Liu, Zebing; Fisher, Kurt W.; Ren, Fei; Lv, Jiaojie; Davidson, Darrell D.; Baldridge, Lee A.; Du, Xiang; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of MedicineCurrent prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P = .001) and higher Ki-67 labeling index (LI) (P = .031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P = .031), positive p53 expression (P = .031), and negative PD-L1 expression (P = .003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P < .001). In univariate analysis, negative p53 (P = .001), low Ki-67 LI (P = .006), low PD-L1 expression (P = .044), low TNM stage (P < .001), recto-sigmoid location (P = .026), and small size (P = .013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P = .004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P = .027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P < .001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score ≥ 35 and Ki-67 LI ≥ 20% identifies patients with poor clinical outcome.Item Salvage therapy for relapsed testicular cancer(Impact Journals, 2017-09-14) Adra, Nabil; Einhorn, Lawrence H.; Medicine, School of Medicine