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Full-Text Articles in Obstetrics and Gynecology

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith Feb 2026

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …


An Environmentally Relevant Phthalate Mixture Impairs Ovulatory Prostaglandin And Progesterone Receptor Pathways In Human Granulosa Cells In Vitro, Katie L. Land, Hong Xu, James W. Akin, Patrick R. Hannon Jan 2026

An Environmentally Relevant Phthalate Mixture Impairs Ovulatory Prostaglandin And Progesterone Receptor Pathways In Human Granulosa Cells In Vitro, Katie L. Land, Hong Xu, James W. Akin, Patrick R. Hannon

Obstetrics and Gynecology Faculty Publications

Ovulatory defects are the leading cause of female infertility. Widespread exposure to endocrine-disrupting chemicals, such as phthalates, may contribute to the high prevalence of failed ovulation among infertile women. Using primary ovarian granulosa cells obtained from women, we tested the hypothesis that exposure to an environmentally relevant mixture of phthalate metabolites (MPTmix) impairs essential mediators of the ovulatory process, including progesterone (P4), progesterone receptor (PGR), and prostaglandins (PGs). The composition of the MPTmix was derived from urinary phthalate levels in women. Ovarian granulosa cells, obtained from in vitro fertilization patients, were acclimated in culture to regain responsiveness to hCG (human …


Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown Feb 2025

Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown

Pediatrics Faculty Publications

BACKGROUND: Unnecessary cesarean delivery can have negative implications for both mothers and infants. In the United States, the proportion of women undergoing cesarean delivery exceeds the acceptable World Health Organization proportion. Reducing cesarean deliveries is a national goal of Centers for Disease Control and Prevention Healthy People 2030, the American College of Obstetricians and Gynecologists, and the Alliance for Innovation on Maternal Health.

OBJECTIVE: This study aimed to examine if excessive gestational weight gain is associated with increased risk of cesarean delivery across multiple body mass index categories.

STUDY DESIGN: Analysis was conducted using vital records data from the National …


A Comparison Of Adjuvant Therapy Modality And Treatment Outcomes Between Appalachian And Non-Appalachian Patients With High-Risk Endometrial Carcinoma, Josie D. Llanora, Gregory S. Hawk, Laura M. Harbin, Sara Lee, Madison Lane, Madison T. Hickey, Elizabeth Pendygraft, Lauren Baldwin, Megan L. Hutchcraft Jan 2025

A Comparison Of Adjuvant Therapy Modality And Treatment Outcomes Between Appalachian And Non-Appalachian Patients With High-Risk Endometrial Carcinoma, Josie D. Llanora, Gregory S. Hawk, Laura M. Harbin, Sara Lee, Madison Lane, Madison T. Hickey, Elizabeth Pendygraft, Lauren Baldwin, Megan L. Hutchcraft

Markey Cancer Center Faculty Publications

Objective: The incidence and mortality of endometrial cancer is increasing. After surgical staging, patients with high-risk disease often undergo adjuvant treatment, which may include systemic therapy, radiation therapy, or combined modalities. Patients in rural Appalachia have limited access to subspecialty care needed for optimal disease management. This study aims to compare adjuvant treatment regimens and outcomes among patients with high-risk endometrial cancer living in Appalachian and non-Appalachian regions.

Methods: We retrospectively identified 179 patients with high-risk endometrial carcinoma who underwent surgical staging at a single academic medical center and received adjuvant therapy between 2012 and 2019. Patients were identified as …


Environmental Sustainability In Gynecologic Oncology, Allison L. Swiecki-Sikora, Mariel V. Becker, Laura M. Harbin, Elizabeth Knapp, Rashmi T. Nair, Marcelo I. Guzman, David A. Atwood, Syed Z. Ali, Charles S. Dietrich Jan 2024

Environmental Sustainability In Gynecologic Oncology, Allison L. Swiecki-Sikora, Mariel V. Becker, Laura M. Harbin, Elizabeth Knapp, Rashmi T. Nair, Marcelo I. Guzman, David A. Atwood, Syed Z. Ali, Charles S. Dietrich

UK CARES Faculty Publications

Climate change is a complex, global issue that is impacting human health in various ways, with healthcare being a significant contributor to carbon emissions in the United States. This review discusses the environmental impact of important aspects of gynecologic oncology care, including surgery, anesthesia care, radiology, chemotherapy, and radiation oncology. Operating room energy and material use is highlighted, with a focus on the environmental impact of robotic surgery. The contribution of certain anesthetic gases in increasing green- house gas emissions is addressed. Additionally, the environmental impacts of radiologic imaging, chemotherapy, and radiation oncology are also discussed. Despite the complexity of …


Exposure To A Phthalate Mixture Disrupts Ovulatory Progesterone Receptor Signaling In Human Granulosa Cells In Vitro, Patrick R. Hannon, James W. Akin, Thomas E. Curry Jr Aug 2023

Exposure To A Phthalate Mixture Disrupts Ovulatory Progesterone Receptor Signaling In Human Granulosa Cells In Vitro, Patrick R. Hannon, James W. Akin, Thomas E. Curry Jr

UK CARES Faculty Publications

Exposure to phthalates disrupts ovarian function. However, limited studies have investigated the effects of phthalate mixtures on ovulation, especially in women. Human granulosa cells were used to test the hypothesis that exposure to a phthalate mixture (PHTmix) disrupts progesterone (P4)/progesterone receptor (PGR) signaling, which is a crucial pathway for ovulation. In addition, progestin and cyclic adenosine 3′, 5′-monophosphate (cAMP) supplementation were tested as methods to circumvent phthalate toxicity. Granulosa cells from women undergoing in vitro fertilization were acclimated in culture to regain responsiveness to human chorionic gonadotropin (hCG; clinical luteinizing hormone analogue). Granulosa cells were treated with or without hCG, …


A Mini-Review Of What Matters In The Management Of Nas, Is Esc The Best Care?, Enrique Gomez Pomar Jul 2023

A Mini-Review Of What Matters In The Management Of Nas, Is Esc The Best Care?, Enrique Gomez Pomar

Pediatrics Faculty Publications

As the use of opioids and polysubstance by pregnant women has increased over the years, there has also been a sharp increase in cases of neonatal abstinence syndrome (NAS). Classically, infants affected by NAS have been cared for in neonatal intensive care units resulting in an increase of healthcare expenditure and resource utilization as well as separation from the families. Consequently, the Eat, Sleep, and Console (ESC) tool was developed and promoted as a novel method that focuses on maternal/infant dyad during hospital stay while decreasing the use of pharmacological interventions and therefore decreasing the length of stay and healthcare …


County Incidence And Geospatial Trends Of Early-Onset Hypertensive Disorders Of Pregnancy In Kentucky, 2008-2017, Courtney J. Walker, Anna Kucharska-Newton, Steven R. Browning, W. Jay Christian Jun 2023

County Incidence And Geospatial Trends Of Early-Onset Hypertensive Disorders Of Pregnancy In Kentucky, 2008-2017, Courtney J. Walker, Anna Kucharska-Newton, Steven R. Browning, W. Jay Christian

UK CARES Faculty Publications

Background Early‑onset hypertensive disorders of pregnancy (eHDP) are associated with more severe maternal and infant outcomes than later‑onset disease. However, little has been done to evaluate population‑level trends. Therefore, in this paper, we seek to address this understudied area by describing the geospatial and temporal patterns of county‑level incidence of eHDP and assessing county‑level demographics that may be associated with an increased incidence of eHDP.

Methods Employing Kentucky certificates of live and stillbirth from 2008–2017, this ecological study detected county‑level clusters of early‑onset hypertensive disorders of pregnancy using SaTScan, calculated average annual percent change (AAPC) with a join point analysis, …


Lifetime Interpersonal Violence Or Abuse And Diabetes Rates By Sex And Race, Maureen Sanderson, Mekeila Cook, L. Lauren Brown, Veronica Mallett, Ann L. Coker Jan 2023

Lifetime Interpersonal Violence Or Abuse And Diabetes Rates By Sex And Race, Maureen Sanderson, Mekeila Cook, L. Lauren Brown, Veronica Mallett, Ann L. Coker

Obstetrics and Gynecology Faculty Publications

Introduction: Lifetime exposure to interpersonal violence or abuse has been associated with several chronic diseases, including adult-onset diabetes, yet this pattern has not been confirmed by sex and race within a large cohort.\Methods: Data from the Southern Community Cohort Study collected between 2002−2009 and 2012−2015 were used to explore the relationship between lifetime interpersonal violence or abuse and diabetes (N=25,251). Prospective analyses of lower-income people living in the southeastern U.S. were conducted in 2022 to examine the risk of adult-onset diabetes associated with lifetime interpersonal violence or abuse by sex and race. Lifetime interpersonal violence or abuse was defined as …


Subsequent Ultrasonographic Non-Visualization Of The Ovaries Is Hastened In Women With Only One Ovary Visualized Initially, Edward J. Pavlik, Hannah Fancher, Charles S. Dietrich, John R. Van Nagell Jr. Feb 2022

Subsequent Ultrasonographic Non-Visualization Of The Ovaries Is Hastened In Women With Only One Ovary Visualized Initially, Edward J. Pavlik, Hannah Fancher, Charles S. Dietrich, John R. Van Nagell Jr.

Obstetrics and Gynecology Faculty Publications

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries when one or both ovaries are visualized on the first ultrasound exam. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams and 9703 women that had only one ovary visualized on their first exam were followed over 63,702 ultrasonography exams. All images were reviewed by a physician. While non-visualization of both ovaries increased with …


Management Of Infective Endocarditis In Pregnancy By A Multidisciplinary Team: A Case Series, Kayle S. Shapero, Varidhi Nauriyal, Christina Megli, Kathryn Berlacher, Sami El-Dalati Feb 2022

Management Of Infective Endocarditis In Pregnancy By A Multidisciplinary Team: A Case Series, Kayle S. Shapero, Varidhi Nauriyal, Christina Megli, Kathryn Berlacher, Sami El-Dalati

Internal Medicine Faculty Publications

Introduction: The incidence of infective endocarditis (IE) in pregnancy is rare and has been increasing during the opioid epidemic. IE in pregnancy is associated with high rates of maternal and fetal morbidity and mortality. Multidisciplinary endocarditis teams for management of IE have been shown to reduce in-hospital and 1-year mortality. We present a single-center experience managing IE in pregnancy utilizing a multidisciplinary endocarditis team.

Methods: Patients diagnosed with IE while pregnant or within 30 days post-partum were identified. All patients discussed at the institution's weekly multidisciplinary endocarditis meeting were included. Demographic and clinical data and outcome-related variables were retrospectively reviewed …


Significance Of Pelvic Fluid Observed During Ovarian Cancer Screening With Transvaginal Sonogram, Justin W. Gorski, Charles S. Dietrich Iii, Caeli Davis, Lindsay Erol, Hayley Dietrich, Nicholas J. Per, Emily Lenk Ferrell, Anthony B. Mcdowell, Mckayla J. Riggs, Megan L. Hutchcraft, Lauren A. Baldwin-Branch, Rachel W. Miller, Christopher P. Desimone, Holly H. Gallion, Frederick R. Ueland, John R. Van Nagell Jr., Edward J. Pavlik Jan 2022

Significance Of Pelvic Fluid Observed During Ovarian Cancer Screening With Transvaginal Sonogram, Justin W. Gorski, Charles S. Dietrich Iii, Caeli Davis, Lindsay Erol, Hayley Dietrich, Nicholas J. Per, Emily Lenk Ferrell, Anthony B. Mcdowell, Mckayla J. Riggs, Megan L. Hutchcraft, Lauren A. Baldwin-Branch, Rachel W. Miller, Christopher P. Desimone, Holly H. Gallion, Frederick R. Ueland, John R. Van Nagell Jr., Edward J. Pavlik

Markey Cancer Center Faculty Publications

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison …


Ultrasonographic Visualization Of The Ovaries To Detect Ovarian Cancer According To Age, Menopausal Status And Body Type, Edward J. Pavlik, Emily Brekke, Justin Gorski, Lauren Baldwin-Branch, Rachel Miller, Christopher P. Desimone, Charles S. Dietrich, Holly S. Gallion, Frederick Rand Ueland, John R. Van Nagell, Jr. Jan 2022

Ultrasonographic Visualization Of The Ovaries To Detect Ovarian Cancer According To Age, Menopausal Status And Body Type, Edward J. Pavlik, Emily Brekke, Justin Gorski, Lauren Baldwin-Branch, Rachel Miller, Christopher P. Desimone, Charles S. Dietrich, Holly S. Gallion, Frederick Rand Ueland, John R. Van Nagell, Jr.

Obstetrics and Gynecology Faculty Publications

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams. All images were reviewed by a physician. While visualization of both ovaries decreased with age, one or both ovaries could be visualized in two of every three women over 80 years of age. Around 93% of pre-menopausal women and ~69% of post-menopausal women had both …


Social And Biological Determinants Of Pregnancy-Related Mortality And Morbidity In A Rural, Underserved Population, Anna Hansen Jan 2022

Social And Biological Determinants Of Pregnancy-Related Mortality And Morbidity In A Rural, Underserved Population, Anna Hansen

Theses and Dissertations--Sociology

Cases of severe maternal morbidity (SMM) and pregnancy-related mortality (PRM) are increasing in the US. Research concerning SMM and PRM has neglected women in Central Appalachia; a largely rural, health-disparate population. The aims of this study are two-fold: (1) Examine patient-level and place-based predictors of SMM/PRM via hierarchical logistic regression modeling, and (2) Elucidate Appalachian healthcare patients’ and providers’ experiences with SMM/PRM, perceptions of contributing factors, and insights on points of intervention.

This study uses a mixed methods approach guided by the WHO’s conceptual framework for action on social determinants of health to identify determinants of SMM and PRM among …


Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky Oct 2021

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …


Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar Sep 2021

Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with …


Elevated Lipid Oxidation Is Associated With Exceeding Gestational Weight Gain Recommendations And Increased Neonatal Anthropometrics: A Cross-Sectional Analysis, Jill M. Maples, Samantha F. Ehrlich, Nikki B. Zite, Kevin J. Pearson, W. Todd Cade, Courtney J. Riedinger, Maire M. Blankenship, Rachel A. Tinius Aug 2021

Elevated Lipid Oxidation Is Associated With Exceeding Gestational Weight Gain Recommendations And Increased Neonatal Anthropometrics: A Cross-Sectional Analysis, Jill M. Maples, Samantha F. Ehrlich, Nikki B. Zite, Kevin J. Pearson, W. Todd Cade, Courtney J. Riedinger, Maire M. Blankenship, Rachel A. Tinius

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes.

METHODS: Women (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly …


Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar Aug 2021

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values …


Salvaging Detection Of Early-Stage Ovarian Malignancies When Ca125 Is Not Informative, Charles J. Dunton, Megan L. Hutchcraft, Rowan G. Bullock, Lesley E. Northrop, Frederick R. Ueland Aug 2021

Salvaging Detection Of Early-Stage Ovarian Malignancies When Ca125 Is Not Informative, Charles J. Dunton, Megan L. Hutchcraft, Rowan G. Bullock, Lesley E. Northrop, Frederick R. Ueland

Markey Cancer Center Faculty Publications

Background: Ovarian cancer is the deadliest gynecologic cancer, with no recommended screening test to assist with early detection. Cancer antigen 125 (CA125) is a serum biomarker commonly used by clinicians to assess preoperative cancer risk, but it underperforms in premenopausal women, early-stage malignancies, and several histologic subtypes. OVA1 is a multivariate index assay that combines CA125 and four other serum proteins to assess the malignant risk of an adnexal mass. Objective: To evaluate the performance of OVA1 in a cohort of patients with low-risk serum CA125 values. Study Design: We analyzed patient data from previous collections (N = 2305, prevalence …


Lapatinib And Poziotinib Overcome Abcb1-Mediated Paclitaxel Resistance In Ovarian Cancer, J. Robert Mccorkle, Justin W. Gorski, Jinpeng Liu, Mckayla J. Riggs, Anthony B. Mcdowell Jr., Nan Lin, Chi Wang, Frederick R. Ueland, Jill M. Kolesar Aug 2021

Lapatinib And Poziotinib Overcome Abcb1-Mediated Paclitaxel Resistance In Ovarian Cancer, J. Robert Mccorkle, Justin W. Gorski, Jinpeng Liu, Mckayla J. Riggs, Anthony B. Mcdowell Jr., Nan Lin, Chi Wang, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We established in vitro paclitaxel-resistant ovarian cancer cell line and organoid models. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing. We manipulated candidate genes associated with paclitaxel resistance using siRNA or small molecule inhibitors, and then screened the cells for paclitaxel sensitivity using cell viability assays. …


Primary Bilateral Ovarian Artery Embolization For Uterine Leiomyomatosis In The Setting Of A Rare Anatomic Variant - Hypoplastic Uterine Arteries, Merve Ozen, Shezaan Momin, Charles Ben Myers, Mark Hoffman, Driss Raissi Jul 2021

Primary Bilateral Ovarian Artery Embolization For Uterine Leiomyomatosis In The Setting Of A Rare Anatomic Variant - Hypoplastic Uterine Arteries, Merve Ozen, Shezaan Momin, Charles Ben Myers, Mark Hoffman, Driss Raissi

Radiology Faculty Publications

We present the case of a 50-year-old female who underwent bilateral ovarian artery embolization for uterine fibroids in the setting of hypoplastic uterine arteries. Ovarian artery embolization is usually conducted during uterine artery embolization for fibroids to increase the procedure success when ovarian feeders are seen. The bilateral ovarian artery embolization is rarely performed due to fears of amenorrhea and early menopause from decreased blood supply to both ovaries. According to our knowledge, this the first case report describing primary bilateral ovarian artery embolization in the setting of a rare anatomic variant- hypoplastic uterine arteries. The patient had complete resolution …


Loss Of Obstetric Services In Rural Appalachia: A Qualitative Study Of Community Perceptions, Caroline R. Efird, David Dry, Rachel F. Seidman May 2021

Loss Of Obstetric Services In Rural Appalachia: A Qualitative Study Of Community Perceptions, Caroline R. Efird, David Dry, Rachel F. Seidman

Journal of Appalachian Health

Background: As rural hospitals across the United States increasingly downsize or close, the availability of inpatient obstetric services continues to decline in rural areas. In rural Appalachia, the termination of obstetric services threatens to exacerbate the existing risk of adverse birth outcomes for women and infants, yet less is known about how the cessation of these services affects the broader community.

Purpose: The purpose of this paper is to explain how the loss of local obstetric services affects perceptions of healthcare among multi-generational residents of a remote, rural Appalachian community in western North Carolina.

Methods: An interdisciplinary team of researchers …


Preclinical Evaluation Of Artesunate As An Antineoplastic Agent In Ovarian Cancer Treatment, Anthony Mcdowell Jr., Kristen S. Hill, Joseph Robert Mccorkle, Justin W. Gorski, Yilin Zhang, Ameen A. Salahudeen, Frederick R. Ueland, Jill M. Kolesar Feb 2021

Preclinical Evaluation Of Artesunate As An Antineoplastic Agent In Ovarian Cancer Treatment, Anthony Mcdowell Jr., Kristen S. Hill, Joseph Robert Mccorkle, Justin W. Gorski, Yilin Zhang, Ameen A. Salahudeen, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

BACKGROUND: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment.

METHODS: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq …


Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar Jan 2021

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …


Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar Jan 2021

Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian …


Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski Jan 2021

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …


Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley Jan 2021

Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

BACKGROUND/ OBJECTIVE: Cervical cancer is the fourth most commonly occurring malignancy in women worldwide, with an estimated 530,000 new cases and 270,000 new deaths each year (Small et al, 2017). While the incidence of cervical cancer has decreased by approximately 1.9% per year between 2007 and 2011, the death rate has remained stable (Bernard et al, 2014). Studies have shown that nearly all cervical cancer cases are associated with the Human Papilloma Virus (HPV). Many studies support the association of smoking with increased risk of invasive cervical cancer in women with high-risk HPV (Castle et al, 2002; Fang et al, …


Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar Dec 2020

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …


Behavioral And Enhanced Perinatal Intervention (B-Epic): A Randomized Trial Targeting Tobacco Use Among Opioid Dependent Pregnant Women, Amanda Fallin-Bennett, Michelle R. Lofwall, Teresa M. Waters, Paul Nuzzo, Janine Barnett, Letitia Ducas, Andrea Mccubbin, Niraj R. Chavan, Lisa Blair, Kristin Ashford Dec 2020

Behavioral And Enhanced Perinatal Intervention (B-Epic): A Randomized Trial Targeting Tobacco Use Among Opioid Dependent Pregnant Women, Amanda Fallin-Bennett, Michelle R. Lofwall, Teresa M. Waters, Paul Nuzzo, Janine Barnett, Letitia Ducas, Andrea Mccubbin, Niraj R. Chavan, Lisa Blair, Kristin Ashford

Nursing Faculty Publications

Background

Opioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD.

Aims

The aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine …


Preterm Birth Prevention In Appalachian Kentucky: Understanding Barriers And Facilitators Related To Transvaginal Ultrasound Cervical Length Surveillance Among Prenatal Care Providers, Anna Hansen, Mairead E. Moloney, Cynthia Cockerham-Morris, Jing Li, Niraj R. Chavan Sep 2020

Preterm Birth Prevention In Appalachian Kentucky: Understanding Barriers And Facilitators Related To Transvaginal Ultrasound Cervical Length Surveillance Among Prenatal Care Providers, Anna Hansen, Mairead E. Moloney, Cynthia Cockerham-Morris, Jing Li, Niraj R. Chavan

Sociology Faculty Publications

Background: Appalachian Kentucky has higher-than-average rates of preterm birth (PTB)—a health disparity associated with increased maternal and fetal/neonatal morbidity and neonatal mortality. Transvaginal ultrasound (TVU) cervical length measurement is the best predictor of PTB risk, but is underutilized in Appalachia. This study explores prenatal care providers' TVU-related knowledge and practices, and identifies barriers and facilitators, which impact the adoption of this evidence-based technology.

Materials and Methods: This study recruited providers from three Appalachian Kentucky health care sites. Prenatal care providers took part in semistructured interviews and completed brief survey scales. Questions focused on PTB knowledge, TVU-related barriers, and suggestions for …