scholarly journals GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Ramu Adela ◽  
Sanjay K. Banerjee
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Clinical Decision Making ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Pathological Condition ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Clinical Decision ◽  
Protective Role

Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases.

Abstract 16873: Association of Preoperative Cell-Free DNA Levels and Outcome Following Pediatric Cardiopulmonary Bypass

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Justinn Tanem ◽  
John Scott ◽  
George M Hoffman ◽  
Robert A Niebler ◽  
Aoy TOMITA-MITCHELL ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Primary Outcome ◽  
Clinical Decision Making ◽  
Treatment Strategies ◽  
Clinical Decision ◽  
Related Factors ◽  
Cell Free Dna ◽  
Free Dna

Introduction: Preoperative risk stratification in congenital cardiac surgery includes patient and procedure related factors, which may be used in clinical decision making as well program performance evaluation. Despite these tools, unidentified factors contribute to wide variation in outcomes both within and between centers. Identification of latent physiologic risk factors may strengthen predictive models. Hypothesis: Total cell-free DNA (TCF) functions as a biomarker for cellular injury as well as a pro-inflammatory cytokine. We hypothesized that elevated preoperative TCF would be associated with poor outcome following pediatric cardiac surgery requiring cardiopulmonary bypass (CPB). Methods: Prospective observational study of children age < 18 yr and wt > 3 kg undergoing planned CPB surgery. The Children’s Wisconsin Institutional Review Board approved the protocol . A serum TCF sample was obtained after induction of anesthesia prior to surgical incision. The primary outcome measure was a composite of postoperative cardiac arrest, ECMO, or death (CAED). Association of outcome to TCF was assessed by logistic regression with a cutpoint chosen by ROC curve exploration. Odds ratios with 95% CI were calculated. Results: Data were available in 117 patients, median age 0.9 years (range 0-17.4), median weight 7.8kg (range 3.2-98). The primary outcome (CAED) was met in 6/117 (5.1%). Table 1 summarizes characteristics of patients with and without CAED. Risk of CAED was 2% with TCF<20 ng/ml, and 27% with TCF>20 ng/ml (OR=18.2, CI 2.2- 212, p<0.01). Elevated TCF was associated to fewer hospital free days (GLM p<0.01). Data in table reported as median [IQR]. Conclusions: Preoperative TCF has an important association with postoperative cardiac arrest, ECMO, and death. Alternative or intensified treatment strategies could be considered in patients with elevated preoperative TCF.

Abstract P214: Patient and Physician Factors Influence Decision-Making in Hypercholesterolemia

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Michel Krempf ◽  
Ross J Simpson ◽  
Dena R Ramey ◽  
Philippe Brudi ◽  
Hilde Giezek ◽  
...  
Keyword(s):  
Decision Making ◽  
Goal Attainment ◽  
Clinical Decision Making ◽  
Treatment Strategies ◽  
Treatment Decision ◽  
Clinical Decision ◽  
Treatment Recommendations ◽  
Treatment Choice ◽  
Treatment Recommendation ◽  
Double Blind

Objectives: Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We surveyed physicians’ treatment recommendations in high-risk patients with LDL-C not controlled on statin monotherapy. Methods: Physicians completed a questionnaire pre-randomization for each patient in a double-blind trial (NCT01154036) assessing LDL-C goal attainment rates with different treatment strategies. Patients had LDL-C ≥100 mg/dL after 5 weeks’ atorvastatin 10 mg/day and before randomization. Physicians were asked about treatment recommendations for three scenarios: (1) LDL-C near goal (100-105 mg/dL), (2) LDL-C far from goal (120 mg/dL), then (3) known baseline LDL-C of enrolled patients on atorvastatin 10 mg/day. Factors considered in their choice were specified. Physicians had been informed of projected LDL-C reductions for each treatment strategy in the trial. Regression analysis identified prognostic factors associated with each scenario, and projected LDL-C values for physicians’ treatment choices were compared to actual LDL-C values achieved in the trial. Results: Physicians at 296 sites completed questionnaires for 1535 patients. The most common treatment strategies for all three scenarios were: 1) not to change therapy, 2) double atorvastatin dose, 3) add ezetimibe, 4) double atorvastatin dose and add ezetimibe. Doubling atorvastatin dose was the most common treatment recommendation in all scenarios (43-52% of patients). ‘No change in therapy’ was recommended in 6.5% of patients when LDL-C was assumed far from goal. Treatment recommendations were more aggressive if actual LDL-C was known or considered far from goal. When compared with the ‘no change in therapy’ recommendation, CV risk factors and desire to achieve a more aggressive LDL-C goal were generally considered in decision-making for each treatment choice, regardless of LDL-C scenario. Patients randomized to a more aggressive regimen than recommended by physicians had larger reductions in LDL-C: the actual reduction in LDL-C in patients randomized to ‘add ezetimibe’ was -20.8% versus a projected reduction of -10.0% when physicians recommended ‘doubling atorvastatin dose’. Conclusions: This study provides insight into physicians’ perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. Targeting lower LDL-C and CV risk were key drivers in clinical decision-making but, generally, physicians were more conservative in their treatment choice than guidelines recommend, which may result in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose.

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: A novel antioxidative mechanism

2007 ◽  
Vol 97 (01) ◽  
pp. 88-98 ◽  
Author(s):  
Christina Barja-Fidalgo ◽  
Vany Nascimento-Silva ◽  
Maria Arruda ◽  
Iolanda Fierro
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Ros Generation ◽  
Oxygen Species ◽  
Lipoxin A4 ◽  
Pre Treatment

SummaryLipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A4 analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1–100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47phox to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF-κB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

scholarly journals Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements towards Individualizing the Treatment

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3481
Author(s):  
Rebecca A. Shuford ◽  
Ashley L. Cairns ◽  
Omeed Moaven
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Clinical Decision Making ◽  
Growth Factor Receptor ◽  
Clinical Decision ◽  
Current Evidence ◽  
Therapeutic Modalities ◽  
Clinically Significant

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.

scholarly journals Direct current electrocorticography for clinical neuromonitoring of spreading depolarizations

2016 ◽  
Vol 37 (5) ◽  
pp. 1857-1870 ◽  
Author(s):  
Jed A Hartings ◽  
Chunyan Li ◽  
Jason M Hinzman ◽  
C William Shuttleworth ◽  
Griffin L Ernst ◽  
...  
Keyword(s):  
Direct Current ◽  
Clinical Decision Making ◽  
Tissue Injury ◽  
Interobserver Reliability ◽  
Electrical Potential ◽  
Training Session ◽  
Clinical Decision ◽  
Platinum Electrodes ◽  
Slow Potentials ◽  
The Impact

Spreading depolarizations cause cortical electrical potential changes over a wide spectral range that includes slow potentials approaching the direct current (or 0 Hz) level. The negative direct current shift (<0.05 Hz) is an important identifier of cortical depolarization and its duration is a measure of potential tissue injury associated with longer lasting depolarizations. To determine the feasibility of monitoring the full signal bandwidth of spreading depolarizations in patients, we performed subdural electrocorticography using platinum electrode strips and direct current-coupled amplifiers in 27 patients with acute brain injury at two neurosurgical centers. While large baseline direct current offsets developed, loss of data due to amplifier saturation was minimal and rates of baseline drift throughout recordings were generally low. Transient negative direct current shifts of spreading depolarizations were easily recognized and in 306/551 (56%) cases had stereotyped, measurable characteristics. Following a standardized training session, novice scorers achieved a high degree of accuracy and interobserver reliability in identifying depolarizations, suggesting that direct current-coupled recordings can facilitate bedside diagnosis for future trials or clinical decision-making. We conclude that intracranial monitoring of slow potentials can be achieved with platinum electrodes and that unfiltered, direct current-coupled recordings are advantageous for identifying and assessing the impact of spreading depolarizations.

scholarly journals The Agony of Choice—Where to Place the Wave of BCMA-Targeted Therapies in the Multiple Myeloma Treatment Puzzle in 2022 and Beyond

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4701
Author(s):  
Irene Strassl ◽  
Martin Schreder ◽  
Normann Steiner ◽  
Jakob Rudzki ◽  
Hermine Agis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Decision Making ◽  
Nk Cell ◽  
Clinical Stage ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Clinical Trial Data ◽  
Clinical Decision ◽  
Preclinical Development ◽  
Comprehensive Overview

Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody–drug conjugates, bispecific and trispecific antibodies, autologous and allogeneic CAR-T cell as well as CAR-NK cell constructs are either approved or in different stages of clinical and preclinical development for the treatment of MM. This armamentarium of treatment choices raises several challenges for clinical decision making, particularly in the absence of head-to-head comparisons. In this review, we provide a comprehensive overview of BCMA-targeting therapeutics, deliver latest updates on clinical trial data, and focus on potential patient selection criteria for different BCMA-targeting immunotherapeutic strategies.

Di'ao Xinxuekang: Therapeutic Potential in Cardiovascular Diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Shengyu Zhang ◽  
Lingli Li ◽  
Mingying Deng ◽  
Yanan Wang ◽  
AiZong Shen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Blood Lipids ◽  
Clinical Decision Making ◽  
Therapeutic Potential ◽  
Clinical Decision ◽  
Pharmacological Effects ◽  
Herbal Preparation ◽  
Pharmacological Studies

Background: Cardiovascular disease is the leading cause of death in both developed and developing countries. Di'ao Xinxuekang (DAXXK) is a pure Chinese medicine herbal preparation refined from dioscin extracted from the roots of Dioscorea panthaica Prain et Burk and Diosorea nipponica Makino. Objective: To evaluate the application of DAXXK in Cardiovascular disease. Methods: : We searched and summarized all the studies on DAXXK and Cardiovascular disease in pumend, Google, and CNKI. Results: Modern pharmacological studies have shown that DAXXK has pharmacological effects such as dilating blood vessels, lowering blood pressure and cardiac load, improving hemodynamics, lowering blood lipids and anti-platelet aggregation, and is widely used for the therapy of various kinds of cardiovascular diseases, including hypertension, atherosclerosis, coronary heart disease (CHD), angina pectoris (AP) and myocardial infarction. We provide an overview of the clinical efficacy, molecular mechanisms, safety and therapeutic potential of DAXXK in the treatment of cardiovascular disease, aiming to provide clues and evidence for clinical decision-making. Conclusion: DAXXK exerts cardiovascular protection by regulating a variety of cardiovascular disease-related signaling pathways.

scholarly journals Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Stella Bernardi ◽  
Fleur Bossi ◽  
Barbara Toffoli ◽  
Bruno Fabris
Keyword(s):  
Cardiovascular Disease ◽  
Decision Making ◽  
Cardiovascular Diseases ◽  
Cause Of Death ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Clinical Applications ◽  
Nuclear Factor ◽  
Potential Utility ◽  
Receptor Activator

Cardiovascular diseases (CVD) remain the major cause of death and premature disability in Western societies. Assessing the risk of CVD is an important aspect in clinical decision-making. Among the growing number of molecules that are studied for their potential utility as CVD biomarkers, a lot of attention has been focused on osteoprotegerin (OPG) and its ligands, which are receptor activator of nuclear factorκB ligand (RANKL) and TNF-related apoptosis-inducing ligand. Based on the existing literature and on our experience in this field, here we review what the possible roles of OPG and TRAIL in CVD are and their potential utility as CVD biomarkers.

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