2022 VCOM Research Retreat Program

Abstracts

Presenter: Steven Enkemann, PhD Co-Authors: Akshay B. Ratnai*; Brooke D. Escoe*

A Powerful Point-of-Care Clinical Aid in the Diagnosis of Vaginosis and STIs Vaginitis is the most common gynecological condition encountered in the OB/GYN offices today. It is diagnosed based on symptoms of abnormal discharge, pH, WHIF test, and/or observation of increased abnormal bacteria, yeast, or STIs such as trichomoniasis. The most common causes of vaginitis (90%) in symptomatic women are bacterial vaginosis (BV) (40-45%), vaginal candidiasis (CV) (20-25%), and trichomoniasis (TV) (15-20%). Yet up to 72% of women with vaginitis remain undiagnosed; 40% of yeast infections are misdiagnosed and 30% of bacterial infections require a 2nd office visit. This underlines the need for a rapid diagnostic tool that can accurately assess the health of a patient's microbiome in a cost and time effective manner. Caza Health has developed a point-of-care test (DayZ- Vaginal Health Assessment) designed to be performed in the physician office using a vaginal swab sample while the patient waits; thereby, allowing the appropriate treatment to be prescribed at the time of the office/clinic visit. The test uses the nCyte-AI automated scanning fluorescent microscope platform, which provides a fluorescence imaging processing system that measures/stores over 50 million pixels worth of data at two different magnifications. Artificial Intelligence algorithms within the nCyte-AI platform select entities of interest within an image capture area and displays multi-channel images of targets for clinician verification. We present here a comparative analysis of the performance of the point-of-care test in a side-by-side comparison to that of the physician in the clinic to verify the utility of this new test and validate its performance relative to the in-clinic diagnosis by the physician. Our goal is to complete the testing and validation phase to move toward FDA approval. Extension of this test to include sexually transmitted infections is also underway. Breast cancer is one of the most commonly diagnosed cancers with a very high mortality rate. Tamoxifen was the first selective estrogen receptor modulators (SERM) adapted for use on ER+ tumors. It is now joined by two additional SERMs (toremifene, and raloxifene) and one selective estrogen receptor downregulator (fulvestrant) as treatment options. Various enzymes have been shown to metabolize these drugs into active and inactive compounds, influence their transport out of the tumor or the body, and influence the types and intensity of side effects. Human variation in these enzymes may affect efficacy, adverse effects, and provide opportunities for drug interactions that could complicate treatment. A literature review was conducted using PubMed and Google Scholar to investigate the metabolism and common side effects of the drugs tamoxifen, toremifene, raloxifene, and fulvestrant. A table was assembled of all enzymes involved in maintaining therapeutic concentrations of these agents and all human variants that might alter this activity were identified. It is currently recognized that tamoxifen is primarily metabolized into an active metabolite by CYP3A4/3A5 and CYP2D6, with contributions from several other CYP enzymes. Enzymes from the SULT, FMO and UGT families mark it for excretion. Toremifene, Raloxifene, and Fulvestrant are active in their administered form and therefore have fewer enzymes that could influence activity. Tamoxifen has an extensive side effect profile and, because of the CYP enzymes involved in its metabolism, great potential for drug interactions, while newer agents show fewer potential complications. There is more work required to understand how genetics influences the efficacy and side effects of the newer agents in this class. The current work illustrates that a full pharmacokinetic pathway analysis of these agents is warranted and suggest that pharmacogenetic testing of an individual may allow for a more personalized and effective treatment approach. Using Pharmacogenetics to Personalize Hormone Therapy in the Treatment of Breast Cancer Presenter: James Mahaney, PhD Co-Authors: Carrie Champine, DO; Lisa Carroll, MD; Lindsey Call, DO; Peggy Robinson, John Kearney, Joe Bos, Yongjian Yu, Kent Murphy,Phd

*VCOM Student