Browsing by Subject "Biomarkers"
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Item Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma(2016-06-23) Eskiocak, Banu; DeBerardinis, Ralph J.; White, Michael A.; Brekken, Rolf A.; Cobb, Melanie H.Genomic diversity and adaptive plasticity of melanoma tumors limit durable control with conventional and targeted therapies. Nevertheless, pathological activation of the ERK1/2 regulatory system is a linchpin tumorigenic mechanism associated with the majority of both primary and recurrent disease. To avoid common resistance mechanisms associated with perdurance of ERK1/2 signaling, we sought to identify therapeutic targets that are selectively required for tumorigenicity in the presence of pathological ERK1/2 signaling. Such targets could be leveraged in jiu jitsu fashion to breach selective pressure to engage any of the many BRAF-independent ERK1/2 pathway activation mechanisms. By integration of multi-genome chemical and genetic screens; recurrent architectural variants in melanoma tumor genomes; and patient outcome data; we identified 2 mechanistic subtypes of BRAF(V600) melanoma that inform new cancer cell biology and offer new therapeutic opportunities. Subtype membership defines sensitivity to clinical MEK inhibitors versus TBK1/IKBKE inhibitors. Importantly, subtype membership can be predicted using a robust quantitative 5-feature genetic biomarker. This biomarker, or the mechanistic relationships linked to it, can identify a cohort of best responders to clinical MEK inhibitors (detectable in 25% of melanoma patients) and identify a cohort of TBK1/IKBKE inhibitor-sensitive disease among non-responders to current targeted therapy (detectable in 9.9% of melanomas).Item Erythrocyte Sedimentation Rate and C-Reactive Protein to Monitor Treatment Outcomes in Diabetic Foot Osteomyeltis(2016-01-19) Mithani, Moez; Van Asten, Suzanne; Jupiter, Daniel; Fontaine, Javier La; Davis, Kathryn; Lavery, Lawrence; Mastro, AndrewPURPOSE: To evaluate the effectiveness of the inflammatory markers Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) in monitoring treatment of osteomyelitis in the diabetic foot. METHODOLOGY: We screened 150 charts of patients admitted to our hospital with diabetic foot osteomyelitis (DFO), confirmed by positive results of bone culture and/or histopathology. We included patients who had an initial ESR/CRP within 72 hours of admission and 2 reported follow-up values. We dichotomized patients based on the outcomes wound healing, re-infection, recurrent ulceration, re-hospitalization, additional surgery, re-amputation, death, all within 12 months, and analyzed the trajectories of the markers over time. Our primary outcome, DFO remission, was defined as wound healing within 12 months follow up without re-infection. PROCEDURES: None RESULTS: We included 122 subjects, 65 patients (53.3%) had a combination of positive culture and histopathology. Factors associated with DFO remission (n=46, 37.7%) were a lower white blood count (WBC) at admission (p=0.006), and a higher glomerular filtration rate (GFR, p=0.049). Factors associated with healing were a lower WBC (p=0.004), a higher GFR (p=0.01), longer wound duration before admission (p=0.01), location of the ulcer on the great toe (p=0.01), and higher glycated haemoglobin (p=0.03). Logistic regression analysis demonstrated no associations between DFO remission and other variables collected. Trajectories of the inflammatory markers showed an association between stagnating values of ESR and CRP and poor clinical outcomes. DISCUSSION: In this study population, the trajectories of both ESR and CRP during the 12-month follow-up suggest a predictive role of inflammatory markers when monitoring treatment of DFO.Item Factors That Alter the Relationship Between Peak Postoperative CKMB and Troponin T After CABG(2019-04-02) Mehta, Kinjal Mukesh; Jessen, Michael; Pruszynski, Jessica; Huffman, LynnBACKGROUND: Peak postoperative creatine kinase MB fraction (CKMB) and Troponin T (TnT) levels have been measured after cardiac surgery to assess perioperative myocardial damage, evaluate myocardial protective strategies and predict adverse events. However, the relationship between peak levels of both enzymes has not been fully established in this setting. We compared peak levels of CKMB and TnT in patients after CABG to test the hypothesis that patient and operative characteristics influence the correlation between the values of these biomarkers. OBJECTIVE: To examine the relationship between peak levels of cTnT and CKMB following CABG in defined subsets of patients with pre-defined comorbidities to test the hypothesis that patient and operative characteristics influence the correlation between the values of these biomarkers. METHODS: Data were prospectively collected from 885 consecutive patients undergoing on-pump CABG at a single institution between July 2011 and June 2017. Peak values were selected from all serum levels of CKMB and TnT collected during the hospital stay following surgery. Clinical variables were collected based on definitions in the STS Adult Cardiac Surgery Database version 2.181. Analysis of covariance (ANCOVA) and linear regression models were used to statistically compare the slope of the linear relationship between peak postoperative CKMB and TnT for the patient cohort. Models were created to compare the slopes by pre-defined clinical variables including (1) age, (2) sex, (3) race, (4) current smoking status (5) hypertension, (6) dyslipidemia, (7) ejection fraction (EF), (8) diabetes, (9) renal dysfunction (GFR<60), (10) recent MI, preoperative use of (11) ACE-inhibitors, (12) beta-blockers, and (13) anticoagulants; and operative variables including (1) cross clamp time (< or > 70 min), (2) CPB time (< or > 100 min), and (3) intra-operative blood products transfusion. RESULTS: Overall, the correlation between peak postoperative CKMB and TnT was robust in patients undergoing CABG. However, the slope of the relationship was significantly lower in males, diabetics, patients with dyslipidemia, patients with hypertension, patients with lower EF, patients who received red blood cell transfusions, and patients receiving beta-blockers. The slope was significantly greater in patients with renal dysfunction, current smokers, patients with a recent MI, patients with longer cross clamp times, patients with longer CPB time, and patients receiving ACE inhibitors. CONCLUSION: The relationship between CKMB and TnT following CABG appears to be influenced by patient and operative characteristics. These data do not assess which enzyme more accurately reflects myocardial injury, but does suggest conclusions about myocardial damage may be affected by the biomarker selected in the presence of certain variables. Further study to assess the association between these biomarkers and patient outcomes is warranted.Item [Southwestern News](2007-02-01) Piloto, ConnieItem Tear Biomarkers and Corneal Sensitivity as an Indicator of Neuropathy in Type 2 Diabetes(2020-05-01T05:00:00.000Z) Iyengar, Meera Farzana; Chang, Mary; Lingvay, Ildiko; Rajora, NilumBACKGROUND: Diabetic peripheral neuropathy (DPN) is a debilitating, progressive complication of type 2 diabetes. The high cost of management leads to amputations in approximately 6% of individuals with DPN in poor-resource settings due to medical noncompliance or lack of finances. Having an effective means of early detection of DPN is crucial for early intervention, which would have a major impact in alleviating its social, economic, and medical burden. OBJECTIVES: To explore the potential of 31 tear biomarkers involved in both corneal growth and development and inflammatory pathways in screening for diabetic peripheral neuropathy (DPN). Additionally, the utility of aesthesiometry for measuring corneal damage in DPN was assessed. METHODS: This screening test pilot study recruited 90 participants from a tertiary hospital in Lima, Peru. Participants were categorized into three groups based on diabetes and neuropathy status. Tears were collected on Schirmer strips, and proteins were measured by both ELISA and multiplex-bead assay. Corneal sensitivity was measured by aesthesiometry, and DPN was measured through vibration perception threshold testing. RESULTS: A total of 89 participants were included in the analysis. The mean age was 55.7+1.46, and 58.4% were female. After adjusting for potential confounders, MMP-9 and TGF-alpha levels showed a strong upward trend in participants with DPN when compared to those with diabetes alone, though not significant. Decreased corneal sensitivity, as measured by aesthesiometry, was negatively correlated with MMP-9 levels (p<0.01) in individuals with DPN. Aesthesiometry was significantly decreased in individuals with DPN when compared to participants with diabetes alone (p<0.01) and normal controls (p<0.01). CONCLUSIONS: Although tears are a simple and inexpensive resource with promise to help detect DPN, it is an insufficient standalone tool for detecting DPN based on the present study. Aesthesiometry is a simple, inexpensive, and accurate method to assess corneal damage associated with DPN, and its integration into screening practices has potential to improve detection of DPN in poor-resource settings.Item Using biomarkers to add precision to cardiovascular medicine, prevention and population health: hype or hope?(2021-07-30) de Lemos, JamesItem [UT Southwestern Medical Center News](2012-05-15) Rian, RussellItem [UT Southwestern Medical Center News](2008-06-15) Piloto, ConnieItem [UT Southwestern Medical Center News](2009-07-21) Piloto, Connie