Women's Health Commons^™

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 …

Serum Exosomal Microrna Pathway Activation In Placenta Accreta Spectrum: Pathophysiology And Detection, Jessian L Munoz, Brett D Einerson, Robert M Silver, Sureshkumar Mulampurath, Lauren S Sherman, Pranela Rameshwar, Egle Bytautiene Prewit, Patrick S Ramsey

Faculty, Staff and Students Publications

BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues.

OBJECTIVE: We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection.

STUDY DESIGN: This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with …

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 …

Invisible Hand Of Socioeconomic Factors In Rising Trend Of Maternal Mortality Rates In The U.S., Disha Kanada

Dissertations, Theses, and Capstone Projects

Maternal death is a tragedy with devastating effect on families and serves as an important indicator of the quality of a health system. Worldwide, the maternal mortality rate has fallen; however, the maternal mortality rate is increasing in the United States in comparison to other wealthy developed countries. The United States spends a lot of resources on healthcare funds and therefore, the increasing maternal mortality rate is alarming. Apart from this, the birth rates are decreasing, so, it is hard to understand the relationship between declining birth rates (and fertility rates) and inclining mortality rates – logically, this does not …

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 …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Faculty, Staff and Student Publications

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

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 …

Anatomy Of The Female Reproductive Tract Organs Of The Brown Anole (Anolis Sagrei), Bonnie K Kircher, Edward L Stanley, Richard R Behringer

Faculty, Staff and Student Publications

Female reproduction in squamate reptiles (lizards and snakes) is highly diverse and mode of reproduction, clutch size, and reproductive tract morphology all vary widely across this group of ~11,000 species. Recently, CRISPR genome editing techniques that require manipulation of the female reproductive anatomy have been developed in this group, making a more complete understanding of this anatomy essential. We describe the adult female reproductive anatomy of the model reptile the brown anole (Anolis sagrei). We show that the brown anole female reproductive tract has three distinct anterior-to-posterior regions, the infundibulum, the glandular uterus, and the nonglandular uterus. The infundibulum has …

Tetravalent Sars-Cov-2 S1 Subunit Protein Vaccination Elicits Robust Humoral And Cellular Immune Responses In Siv-Infected Rhesus Macaque Controllers, Rachel C Vanderkruik, Craig Ferguson, Lauren A Kobylski, Joseph J Locascio, Gabriella E Hamlett, Parker C Killenberg, Robert Lewis, Noah Jones, Ella T Rossa, Hannah Dineen, Rosalind Picard, Lee S Cohen

Faculty, Staff and Student Publications

BACKGROUND: Depression during pregnancy is increasingly recognized as a worldwide public health problem. If untreated, there can be detrimental outcomes for the mother and child. Anxiety is also often comorbid with depression. Although effective treatments exist, most women do not receive treatment. Technology is a mechanism to increase access to and engagement in mental health services.

OBJECTIVE: The Guardians is a mobile app, grounded in behavioral activation principles, which seeks to leverage mobile game mechanics and in-game rewards to encourage user engagement. This study seeks to assess app satisfaction and engagement and to explore changes in clinical symptoms of depression …

Epha2- And Hdac-Targeted Combination Therapy In Endometrial Cancer, Robiya Joseph, Santosh K Dasari, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mark Seungwook Kim, Sara Corvigno, Katherine Foster, Pahul Hanjra, Thanh Chung Vu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing

Faculty, Staff and Student Publications

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell …

Analysis Of Breast Cancer Mortality In The Us-1975 To 2019, Jennifer L Caswell-Jin, Liyang P Sun, Diego Munoz, Ying Lu, Yisheng Li, Hui Huang, John M Hampton, Juhee Song, Jinani Jayasekera, Clyde Schechter, Oguzhan Alagoz, Natasha K Stout, Amy Trentham-Dietz, Sandra J Lee, Xuelin Huang, Jeanne S Mandelblatt, Donald A Berry, Allison W Kurian, Sylvia K Plevritis

Faculty, Staff and Student Publications

IMPORTANCE: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.

OBJECTIVE: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.

DESIGN, SETTING, AND PARTICIPANTS: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by …

A Life-Threatening Emergency Exacerbated By Untreated Mental Illness In A Low-Barrier Health Center, Brendan J. Prast, Byron Marshall

Journal of Maine Medical Center

Introduction: We report on a patient with untreated severe mental illness who presented with a life-threatening emergency: retained products of conception and hemorrhage.

Clinical Findings: A female patient experiencing homelessness developed life-threatening hemorrhage. Her mental illness impaired effective communication and treatment.

Clinical Course: The patient presented with fatigue, vaginal bleeding, and known retained products of conception. Her active mental illness complicated the situation as it limited effective communication and treatment due to delusions. She requested only treatment for an infectious cause of her symptoms. She refused most interventions and had a self-directed discharge from the hospital. Throughout this process, we …

Editorial: Care During Pregnancy And Early Childhood For Growth And Development In Low- And Middle- Income Countries, Ranadip Chowdhury, Ravi Prakash Upadhyay, Bireshwar Sinha, Nita Bhandari, Sunita Taneja, Jai K. Das

Centre of Excellence in Women and Child Health

No abstract provided.

Mastitis And Mammary Abscess Management Audit (Mamma) In The Uk And Ireland, Alona Courtney, Jonathon Clymo, Ruth Parks, Alexander Wilkins, Ruth Brown, Rachel O'Connell, Rajiv Dave, Marianne Dillon, Hiba Fatayer, Rachel Gallimore, Ashu Gandhi, Matthew Gardiner, Victoria Harmer, Lyndsey Hookway, Gareth Irwin, Charlotte Ives, Helen Mathers, Juliette Murray, D Peter O'Leary, Neill Patani, Sophie Paterson, Shelley Potter, Ruth Prichard, Giovanni Satta, T G Teoh, Paul Ziprin, Stuart Mcintosh, Michael R Boland, Daniel Richard Leff, Mamma Research Collaborative

Faculty, Staff and Student Publications

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention.

METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical).

RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage …

Cell State Of Origin Impacts Development Of Distinct Endometriosis-Related Ovarian Carcinoma Histotypes, Ian Beddows, Huihui Fan, Karolin Heinze, Benjamin K Johnson, Anna Leonova, Janine Senz, Svetlana Djirackor, Kathleen R Cho, Celeste Leigh Pearce, David G Huntsman, Michael S Anglesio, Hui Shen

Faculty, Staff and Student Publications

Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of …

Research Action Brief: Healthcare Experiences And Perceptions As Drivers Of Gaps In Mammography, Core (Center For Outcomes Research & Education)

Reports

No abstract provided.