Women's Health Commons^™

Analysis Of East Asia Subgroup In Study 309/Keynote-775: Lenvatinib Plus Pembrolizumab Versus Treatment Of Physician's Choice Chemotherapy In Patients With Previously Treated Advanced Or Recurrent Endometrial Cancer, Kan Yonemori, Keiichi Fujiwara, Kosei Hasegawa, Mayu Yunokawa, Kimio Ushijima, Shiro Suzuki, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Jae-Weon Kim, Byoung-Gie Kim, Peng-Hui Wang, Ting-Chang Chang, Keiko Yamamoto, Shirong Han, Jodi Mckenzie, Robert J Orlowski, Takuma Miura, Vicky Makker, Yong Man Kim

Faculty, Staff and Student Publications

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.

METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Breastfeeding Initiation, Duration, And Associated Factors Among People With Hepatitis C Virus Infection, Jennifer L Grasch, Jessica A De Voest, George R Saade, Brenna L Hughes, Uma M Reddy, Maged M Costantine, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection.

METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

A Systematic Review Of Measures Of Healthcare Workers’ Vaccine Confidence, Kofoworola Akinsola, Ayobami Bakare, Elisa Gobbo, Carina King, Claudia Hanson, Adegoke Falade, Sibylle Herzig Van Wees

Centre of Excellence in Women and Child Health

Healthcare workers (HCW) perceptions toward vaccines influence patient and community vaccine decision making. In an era of rising vaccine hesitancy, understanding HCW vaccine confidence is critical. This systematic review aims to review instruments that have been validated to measure HCW vaccine confidence. We conducted a search in five databases in June 2023. Data was descriptively synthesized. Twelve articles describing 10 different tools were included. Most tools included dimensions or items on vaccine knowledge (n = 9), safety (n = 8), vaccine usefulness (n = 8), recommendation behavior (n = 8), and self-vaccination practice (n = 7). All, except one study, …

Dhea: A Neglected Biological Signal That May Affect Fetal And Child Development, Natasha A. Bailey, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

The stress-sensitive maternal hypothalamic–pituitary–adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study …

Covid-19 Prevalence And Trends Among Pregnant And Postpartum Persons In Maine By Rurality And Pregnancy Conditions, Charlie O. Grantham, Christina M. Ackerman-Banks Md, Heather S. Lipkind Md, Ms, Kristin Palmsten Scd, Katherine A. Ahrens Mph, Phd

Journal of Maine Medical Center

No abstract provided.

A Pharmacist’S Central Role In Improving Hormonal Contraceptive Access, Aleese Smith, Urvi Patel, Alexandra Arledge, Josie Young, Erin Johanson

Annual Research Symposium

In 2019, the roles of Utah pharmacists grew with the implementation of a statewide standing order allowing prescribing abilities for hormonal contraceptives. With the rates of unplanned pregnancies in Utah up to 1 in every 5; pharmacists have a new role in birth control distribution. Pharmacists and pharmacy interns across the state of Utah are able to prescribe self-administered hormonal contraceptive medications including: oral pills, vaginal insertion medications, and birth control patches. Pharmacists are entrusted with the responsibility to evaluate the patient and their needs to ensure all women receiving birth control are educated about the risks and side effects …

The National Status Of Pharmacists’ Ability To Prescribe Hormonal Contraceptives, Aleese Smith, Urvi Patel, Alexandra Arledge, Josie Young, Erin Johanson

Annual Research Symposium

The scope of practice for pharmacists first expanded in California and Oregon with the ability to prescribe hormonal contraceptives to patients in their communities. Since 2016, over 33 states now allow for pharmacist prescribing of birth control in their pharmacy practice laws.

90% of Americans live within 5 miles of a retail pharmacy, making community pharmacies an accessible resource who may otherwise be unable to access contraceptives. The gap in care experienced by certain patient populations is now being filled by pharmacists with their ability to prescribe birth control.

Uterine Leiomyomata As A Cause Of Abdominal Compartment Syndrome In The Postpartum Period, Mason Hui, Baha Sibai, Alvaro Montealegre, Mateo G Leon

Faculty, Staff and Student Publications

Uterine leiomyomas are common benign smooth muscle tumors that often occur during the reproductive years. Although many cases may not result in significant complications, negative pregnancy outcomes have been associated with the size and location of the fibroids. Degeneration of fibroids can occur as early as the late first trimester when they undergo significant volumetric growth, contributing to pain during pregnancy. While myomectomy is typically avoided during pregnancy, conservative management with anti-inflammatory medications may be effective. Surgical removal or preterm delivery may be necessary if symptoms persist. Abdominal compartment syndrome (ACS) is a rare condition characterized by sustained elevated intra-abdominal …

Black Women Have The Highest Maternal Mortality Rate In The United States, Tori-Ann Haywood

Population Health Research Brief Series

The U.S. maternal mortality rate is consistently higher than its high-income peer countries. Since 2018 maternal mortality rates in the U.S. have steadily increased for all ethnoracial groups. This data slice uses data from the U.S. National Center for Health Statistics to describe U.S. maternity mortality rates for women ages 15-45 across different ethnoracial groups between 2018-2022. Results show that, except for non-Hispanic (NH) Asian women, ethnoracial minority women have higher maternal death rates than NH White women.

Response To The Letter To The Editor: Surgical Delay Of Thoracodorsal Artery Perforator Flaps For Bilateral Autologous Breast Reconstruction, Robert J. Allen, Mark A. Maier

School of Medicine Faculty Publications

No abstract provided.

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Impact Of Point-Of-Care Ultrasound Use On Patient Referral Decisions In Rural Kenya: A Mixed Methods Study., Grace Wanjiku, Gregory Bell, Sonja Kapadia, Benjamin Wachira

Emergency Medicine, East Africa

Background: Point-of-care ultrasound (POCUS) is recognized as a key imaging modality to bridge the diagnostic imaging gap in Low- and Middle-Income Countries (LMICs). POCUS use has been shown to impact patient management decisions including referral for specialist care. This study explored the impact of POCUS use on referral decisions among trained healthcare providers working in primary rural and peri-urban health facilities in Kenya.

Methods: A concurrent mixed methods approach was used, including a locally developed survey (N=38) and semistructured interviews of POCUS trained healthcare providers (N=12). Data from the survey was descriptively analyzed and interviews were evaluated through the framework …

Women In Health And Their Economic, Equity And Livelihood Statuses During Emergency Preparedness And Response (Wheeler) Protocol: A Mixed Methods Study In Kenya., Evaline Chepchirchir Langat, Bilali Yusuf Mazoya, Pauline Oginga, Ferdinand Okwaro, Norah Matheka, Irene Kibara, Rhoda Otieno, Michaela Mantel, Robert Lorway, Marleen Temmerman

Centre of Excellence in Women and Child Health

Introduction: Kenya reported its first COVID-19 case on 13 March 2020. Pandemic-driven health system changes followed and unforeseen societal, economic and health effects reported. This protocol aims to describe the methods used to identify the gender equality and health equity gaps and possible disproportional health and socioeconomic impacts experienced by paid and unpaid (community health volunteer) female healthcare providers in Kilifi and Mombasa Counties, Kenya during the COVID-19 pandemic.

Methods and analysis: Participatory mixed methods framed by gender analysis and human-centred design will be used. Research implementation will follow four of the five phases of the human-centred design approach. Community …

Challenges And Opportunities For Improving Access To Adolescent And Youth Sexual And Reproductive Health Services And Information In The Coastal Counties Of Kenya: A Qualitative Study., Evaline Chepchirchir Langat, Abdu Mohiddin, Flaura Kidere, Anisa Omar, Job Akuno, Violet Naanyu, Marleen Temmerman

Centre of Excellence in Women and Child Health

Background: Globally, adolescents and youth experience high unmet need for sexual and reproductive health (SRH) information and services. In Kenya, evidence shows that more than half of teenage pregnancies are unintended and that half of all new HIV infections occur in people ages 15-24-year-olds, with the majority of those being female. The coastal counties in Kenya record a relatively high adolescent pregnancy rate and higher rates of unmet need for contraception for all women of reproductive age compared to the national average. This study focused on gaining a deeper understanding of the existing challenges to and opportunities for accessing SRH …

Limited Independent Follow-Up With Germline Testing Of Variants Detected In Brca1 And Brca2 By Tumor-Only Sequencing, Carol J Nowlen, Molly Daniels, Burak Uzunparmak, Ecaterina E Ileana Dumbrava, Ying Yuan, Keyur P Patel, Nadine Rayes, Jacqueline Harkenrider, Chetna Wathoo, Jennifer Veazie, Krystle A Luna, Wanlin Wang, Chacha Horombe, Milind Javle, Jordi Rodon Ahnert, Timothy A Yap, Banu Arun, Karen H Lu, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Introduction

Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients.

Methods

A retrospective chart review was performed …

Facilitators To Cervical Cancer Screening In A Minority, Urban, Underserved Population, Noel Higgason, Linh Nguyen, Yen-Chi Le, Ogochukwu Juliet Ezeigwe, Tong Han Chung, Natalia Williams, Xochitl K Olguin, Abigail S Zamorano

Faculty, Staff and Student Publications

OBJECTIVES: Cervical cancer has markedly declined due to widespread use of screening, but Hispanic women continue to bear a disproportionate amount of the cervical cancer burden due to under-screening. Previous studies have explored barriers to screening but have failed to identify targetable facilitators in this group. We aimed to assess facilitators to cervical cancer screening among a predominantly urban, Hispanic population who presented to a no-cost, community-based clinic.

METHODS: Patients completed demographic and health information, a validated social determinants of health (SDOH) screen, and a self-reported facilitators survey on factors which enabled them to present to clinic. Descriptive statistics were …

Knowledge And Attitudes On Contraception And Reproductive Health In Women With Hiv, Anna Henricks, Samantha Singal, Dana Hughes, Sean Kelly, Jessica L Castilho, Jamison Norwood

Faculty, Staff and Student Publications

BACKGROUND: For reasons not fully explained to date, contraception usage among women with HIV remains low. The aim of our study was to understand attitudes toward and lifetime use of contraception among women with HIV.

METHODS: We administered an anonymous, community-informed, voluntary survey to cisgender, English-speaking women with HIV (≥18 years of age) at a Southern urban HIV clinic. It included multiple choice and Likert-scale questions on reproductive health. Participants reported contraception use, recollection of provider conversations about contraception, and perceived empowerment and knowledge regarding reproductive health. We used chi-square and Fisher exact tests to compare attitudes and prior conversations …