Associations Between Oncogenic Risk Markers and Clinical Outcomes among Black and White Colorectal Cancer Patients

Introduction: Blacks have a 25% higher incidence of colorectal cancer compared to their white societal counterparts. Additionally, the overall mortality rate among black colorectal cancer patients is 50% higher than that of whites. However, little is known about the biomarkers prevalent among blacks and their possible correlation to treatment response and patient outcomes. Objective: The objective of this study is to explore disease trends that may unveil a correlation between molecular markers and poor clinical outcomes among black colorectal cancer patients. Methods: De-identified patient data was obtained from The Oncology Data Services Department (Cancer Registry) of TJUH. The population cohort included newly diagnosed colorectal cancer patients treated at TJUH from 2000-2019, and included information regarding patient race, sex, age at presentation, stage at presentation, histological code, tumor markers: KRAS, NRAS, BRAF, MS1, treatment received, surgical findings: tumor size, lymph node involvement, presence of distant metastases at first surgery, response to chemotherapy & disease-free survival. Results: Preliminary data on the analyzed population demonstrates that biomarker profiles did not correlate with patient race. Therefore, racial disparities seen among colorectal cancer patients cannot be attributed to these findings. Conclusion: Biomarker trends among newly diagnosed colorectal cancer patients at TJUH do not correlate with racial identity. Additional data is needed regarding possible etiologies for the comparatively higher incidence and mortality rates among black colorectal cancer patients. Health professionals should continue to explore possible etiologies for this racial disparity in future studies

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

A Comparison of Heterotroph Isolation and Sequencing Methods From Various Cyanobacterial and Algal Microbiomes

Cyanobacteria have provided a vast, new source of natural products to be utilized in drug development. Because of their non-axenic nature, cyanobacteria typically have an abundance of symbiotic heterotrophs living in association with them. These bacteria can play significant roles in the survival of its cyanobacterial host as well as provide the potential production of unique compounds. The possibility of unknown natural products is only increased by the flexible nature of these bacteria, as altering its environmental state can change the activity of biosynthetic pathways and even activate novel production. Our research team’s intent is to isolate cyanobacterial strains from diverse sources and investigate for the production of unique compounds. Furthermore, the team aims to isolate individual heterotrophic symbionts from the cyanobacterial culture and determine their identity through sequencing. To date, the lab has collected 49 heterotrophic bacteria strains from local sources as well as 45 from various library strains. Furthermore, the lab has conducted many methods of heterotrophic isolation and sequencing preparation and has determined the effectiveness of each approach. Future work on identifying heterotrophic sources of unique compounds and understanding their potential uses will provide novel resources to be utilized in drug development. Overall, the goal of the lab is to identify and harness unique natural products to inspire production of new treatments to improve human health

Evaluating Fidelity to the Primary Care Behavioral Health Model Among Pediatric Subspecialty Clinics in Rural Appalachia

Pediatric patients in rural areas face unique challenges in managing chronic illness. Furthermore, unmet mental health needs or lifestyle factors impact health. Primary Care Behavioral Health (PCBH) is an integrated team-based care approach that places behavioral health providers in medical settings to see patients same-day for identified needs and follow up for short-term care. The principles of this model are summarized by the GATHER acronym: Generalist, Accessible, Team-based, High productivity, Educator, and Routine. PCBH acknowledges the psychosocial aspects of chronic illnesses and overcomes barriers to care for rural communities. We evaluated fidelity to the PCBH model by examining trends in utilization of services that may have implications for accessibility and productivity of an integrated behavioral health provider in pediatric subspecialty clinics in rural northeast Tennessee. De-identified data was collected over the first year of the integrated behavioral health program. Among other variables, the number of warm handoffs (WHO), scheduled visits, monthly totals by subspecialty, medical diagnoses, and visit duration were collected. Descriptive statistics were calculated utilizing Excel. Over a one-year period, behavioral health saw 518 patients, of which 35.6% required subsequent visits. Within this subset of patients, the average number of visits with behavioral health was 2.8. Of these, 67.7% of patients saw behavioral health first as a WHO as opposed to 32.3% having an initial scheduled visit on a different day than their medical appointment. Differences were identified across subspecialties of endocrinology (endo), gastroenterology (GI), and neurology (neuro) for how patients initially connected with behavioral health; 64%, 78%, and 56% had a WHO first and 36%, 22% and 44% had a scheduled visit respectively. Average duration of WHOs were consistent across subspecialities; visits were an average of 29.7, 27.1, and 26.1 minutes, respectively. The average times for scheduled visits were 35.1, 32.7, and 34.3 minutes respectively. Findings yield preliminary results for fidelity to the PCBH model, while also highlighting areas for growth. There were high rates of provider use of same-day service accessibility (WHOs). Subspecialty differences with WHOs versus scheduled initial visits may reflect needing additional behavioral health providers to fulfill the same day demand for services or disparities across disciplines regarding desire for PCBH (warm handoffs) versus a co-located model of integration (referral for consultation). Despite novelty of the program, average visit duration was close to the recommended 15-30 minute consults by the PCBH model. Longer visits may be due to the complex patient population or need for additional training to enhance efficiency and potential productivity. Addressing these factors may enhance fidelity and have positive implications for the health of medically complex pediatric patients in rural areas

MANAGEMENT OF LDL-C IN HIGH RISK FEMALE PATIENTS WITH ASCVD- A CROSS-SECTIONAL STUDY

Therapeutic Area: ASCD/CVD in Women Background: The 2018 ACC/AHA guidelines recommend an LDL-C of 70mg/dL as a threshold to initiate non-statin medications in patients with a history of a major ASCVD event. Analysis of the PINNACLE Registry and the TRANSFORM LDL-C Risk Initiative identified female patients as a high risk population with a low likelihood of achieving an LDL-C 70mg/dL despite having a history of a major ASCVD event, of which only 27% were on the max dose of a high intensity statin. Only 10.4% were noted to be on additional non-statin lipid lowering therapies, of which Ezetimibe was the most prescribed (76.9%) while PCSK9 inhibitors were the least prescribed (7.7%). CVA was the most common observed major ASCVD event (45.8%), while HTN and HLD were the most common associated comorbidities (85.9%, 83.4%). Conclusion: Although the 2018 ACC/AHA guidelines recommend initiating non-statin medications in patients with a major ASCVD event, clinical implementation of these guidelines has not yet become widespread. In this study, we identify female patients as a high risk population that does not meet these guidelines at our institution. Further studies will focus on implementing a quality initiative program to improve the prescribing practices of non-statin medications in this population

Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus

SummaryHereditary hemochromatosis, an iron overload disease caused by a deficiency in the iron-regulatory hormone hepcidin, is associated with lethal infections by siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we infected wild-type and hepcidin-deficient mice with the siderophilic bacterium Vibrio vulnificus and found that hepcidin deficiency results in increased bacteremia and decreased survival of infected mice, which can be partially ameliorated by dietary iron depletion. Additionally, timely administration of hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases bacterial loads and rescues these mice from death, regardless of initial iron levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from hepcidin-deficient mice support extraordinarily rapid bacterial growth and that this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin-mediated hypoferremia is a host defense mechanism against siderophilic pathogens and suggest that hepcidin agonists may improve infection outcomes in patients with hereditary hemochromatosis or thalassemia