Obstetrics and Gynecology Commons^™

Alternative Dosing Regimen Of Exemestane In A Randomized Presurgical Trial: The Role Of Obesity In Biomarker Modulation, Harriet Johansson, Aliana Guerrieri-Gonzaga, Sara Gandini, Bjørn-Erik Bertelsen, Debora Macis, Davide Serrano, Gunnar Mellgren, Matteo Lazzeroni, Parijatham S Thomas, Katherine D Crew, Nagi B Kumar, Irene Maria Briata, Viviana Galimberti, Giuseppe Viale, Lana A Vornik, Valentina Aristarco, Tania Buttiron Webber, Stefano Spinaci, Powel H Brown, Brandy M Heckman-Stoddard, Eva Szabo, Bernardo Bonanni, Andrea Decensi

Faculty, Staff and Student Publications

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4-6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass …

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 …

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 …

Activation Of Piezo1 Increases The Sensitivity Of Breast Cancer To Hyperthermia Therapy, Shao-Kang Wang, Xiao-Ting Zhang, Xuan-Yao Jiang, Bi-Jiang Geng, Tao-Lin Qing, Lei Li, Yun Chen, Jin-Feng Li, Xiao-Fang Zhang, Shuo-Gui Xu, Jiang-Bo Zhu, Yu-Ping Zhu, Mei-Tang Wang, Ji-Kuai Chen

Faculty, Staff and Student Publications

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress

Association Between Symptom Burden And Early Lymphatic Abnormalities After Regional Nodal Irradiation For Breast Cancer, Alison K Yoder, Tianlin Xu, Peter Youssef, Sarah Desnyder, Kathryn E Marqueen, Lynn Isales, Ruitao Lin, Benjamin D Smith, Wendy A Woodward, Michael C Stauder, Eric A Strom, Melissa B Aldrich, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRF-LI) signals preclinical lymphedema that precedes the development of volumetrically defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI).

METHODS AND MATERIALS: Patients with breast cancer planned for axillary dissection and RNI prospectively underwent perometry, NIRF-LI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey [LSIDS] and QuickDASH) at baseline, after surgery, and at 6, 12, and 18 months after radiation. Clinical lymphedema was defined as an arm volume increase ≥5% over baseline. Trends …

Pregnancy-Related Factors Responsible For Delivering Low Birth Weight Babies: An Institutional-Based Cross-Sectional Study, Jamnagar, Gujarat, Harsh K Patel, Jitesh P Mehta, Bela A Patel, Rohitkumar Ram, Dipesh V Parmar

Faculty, Staff and Student Publications

BACKGROUND: The WHO defines LBW as "Birth weight less than 2500 grams" regardless of gestational age. Being born with a low birth weight also incurs enormous economic costs, including higher medical expenditures and social service expenses, and decreased productivity in adulthood.

OBJECTIVE: To study distribution of newborns' according to pregnancy related factors and its association with newborns' birth weight.

METHODS: An institutional based cross-sectional study. New-borns delivered at study institute were considered as study participants. Estimated final sample size was 500. Guardians (mothers) were face-to-face interviewed and also recorded data were collected from the case file and Mother and Child …

Association Between Serum Vitamin D Status And Uterine Leiomyomas: A Case-Control Study, Chukwuemeka Chukwubuikem Okoro, Okechukwu Christian Ikpeze, George Uchenna Eleje, Gerald Okanandu Udigwe, Chukwuemeka Okwudili Ezeama, Joseph Odirichukwu Ugboaja, Chukwunonso Isaiah Enechukwu, Osita Samuel Umeononihu, Chukwudi Anthony Ogabido, Charlotte Blanche Oguejiofor, Tobechi Kingsley Njoku, Richard Obinwanne Egeonu, Chigozie Geoffrey Okafor, Hillary Ikechukwu Obiagwu, Chukwudubem Chinagorom Onyejiaka, Afam Ben Obidike, Christian Ejike Onah, Ifeanyi Uzukwu, Amarachukwu Doris Okoro, Evaristus Chino Ezema, Adaobi Maryann Ibekwe, Joseph Ifeanyichukwu Ikechebelu

Faculty, Staff and Student Publications

OBJECTIVE: Uterine leiomyoma is a common gynecological condition that negatively affects women's quality of life. Vitamin D plays an important role in tumor development and progression. However, clinical studies comparing serum vitamin D levels between women with and without uterine leiomyomas are limited and inconclusive. This study aimed to compare serum vitamin D levels in women with and without uterine leiomyomas.

METHODS: This hospital-based case-control study included 150 women who visited a gynecological clinic. The cases included 75 women with uterine leiomyoma, whereas the controls included 75 age-and parity-matched participants without uterine leiomyoma. Serum vitamin D levels were measured in …

Mesenchymal Stem Cells Suppress Inflammatory Cytokines In Lipopolysaccharide Exposed Preterm And Term Human Pregnant Myometrial Cells, Arunmani Mani, John Hotra, Sean C Blackwell, Laura Goetzl, Jerrie S Refuerzo

Faculty, Staff and Student Publications

Objective  The objective of this study was to determine the cytokine response in human pregnant preterm and term myometrial cells exposed to lipopolysaccharide (LPS) and cocultured with mesenchymal stem cells (MSCs).

Study Design  Myometrium was obtained at cesarean delivery in term and preterm patients. Human myometrial cells were exposed to 5 μg/mL LPS for 4 hours followed by 1 μg/mL LPS for 24 hours and were cocultured with MSCs for 24 hours. Culture supernatants were collected at 24 hours and expression of cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and IL-10, was quantified …

Gut Pathobiont Enrichment Observed In A Population Predisposed To Dementia, Type 2 Diabetics Of Mexican Descent Living In South Texas, Lisa M Matz, Nisarg S Shah, Laura Porterfield, Olivia M Stuyck, Michael D Jochum, Rakez Kayed, Giulio Taglialatela, Randall J Urban, Shelly A Buffington

Faculty, Staff and Students Publications

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and accompanying dementia, including Alzheimer's Disease (AD), yet the mechanisms underlying this comorbidity remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the APOE-ε4 risk variant among the population and an absence of a similar predisposition among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. We therefore sought to test if differences in gut community structure could be observed in this population prior to any AD …

Thinking Twice About The Cervical Mass: A Case Report Of Primary Vaginal Leiomyosarcoma And Review Of The Literature, Caroline C Davitt, Yingao Zhang, Anthony B Costales

Faculty, Staff and Students Publications

Primary vaginal leiomyosarcoma (LMS) is an unusual cause of aggressive gynecologic cancer which requires prompt surgical treatment for favorable outcomes. Definitive diagnosis and treatment render unique challenges to clinicians based on vague presentation and limited evidence for management. Here, we describe a case of vaginal LMS in a middle-aged woman with a history of cervical dysplasia found to have a proximal vaginal mass after presenting with vaginal discharge and cramping pain. The patient was diagnosed on pathologic surgical specimen and subsequently underwent definitive surgical treatment. She remains with no evidence of disease 20 months later. In our report, we emphasize …

Comparison Of Four Protocols For In Vitro Differentiation Of Human Embryonic Stem Cells Into Trophoblast Lineages By Bmp4 And Dual Inhibition Of Activin/Nodal And Fgf2 Signaling, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

Human embryonic stem cells (hESCs) cultured in media containing bone morphogenic protein 4 (BMP4; B) differentiate into trophoblast-like cells. Supplementing media with inhibitors of activin/nodal signaling (A83-01) and of fibroblast growth factor 2 (PD173074) suppresses mesoderm and endoderm formation and improves specification of trophoblast-like lineages, but with variable effectiveness. We compared differentiation in four BMP4-containing media: mTeSR1-BMP4 only, mTeSR1-BAP, basal medium with BAP (basal-BAP), and a newly defined medium, E7-BAP. These media variably drive early differentiation towards trophoblast-like lineages with upregulation of early trophoblast markers CDX2 and KRT7 and downregulation of pluripotency markers (OCT4 and NANOG). As expected, based on …

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Gambian Mothers Lack Obstetric Danger Sign Knowledge, But Educational Intervention Shows Promise, Kara Shannon, Jocelyn Burridge, Brodus Franklin, Sheena Bhushan, Susan Hilsenbeck, Elena V Petrova, James N'Dow, Ibezimako Iwuh, Sharmila Anandasabapathy, Jeffrey P Wilkinson

Faculty, Staff and Students Publications

BACKGROUND: The Gambia has the 12th highest maternal mortality rate in the world, with 80% of deaths resulting from avoidable causes. Unawareness of pregnancy danger signs (DS) has been shown to be a barrier to seeking obstetric care, while app-based education intervention has shown promise.

OBJECTIVE: We aim to assess patient awareness of DS, identify barriers to awareness, and evaluate potential for implementing smartphone-based technologies for education.

METHODS: A cross-sectional semi-structured survey was administered to Gambian women (n = 100) across five hospitals/health centers. Data and informed consent were collected via an online survey portal. Analysis included bivariate analysis and …

Obesity Is Associated With Improved Progression-Free Survival In Microsatellite-Instability-High Endometrial Cancer Treated With Pembrolizumab, Laurence Bernard, Jeffrey A How, Shrina Patel, Melinda S Yates, Amir Jazaeri

Faculty, Staff and Student Publications

Objectives: To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas.

Methods: A retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body …

Systemic Treatment Of Patients With Metastatic Breast Cancer: Asco Resource-Stratified Guideline Q And A, Sana Al Sukhun, Bogda Koczwara, Sarah Temin, Banu K Arun

Faculty, Staff and Student Publications

The Systemic Treatment of Patients with Metastatic Breast Cancer: @ASCO Resource-Stratified Guideline Q and A presents takeways, rationale, and key recommendations based on #JCOGO full guideline for patients by menopausal and marker status.

Breast Multiparametric Mri For Prediction Of Neoadjuvant Chemotherapy Response In Breast Cancer: The Bmmr2 Challenge, Wen Li, Savannah C Partridge, David C Newitt, Jon Steingrimsson, Helga S Marques, Patrick J Bolan, Michael Hirano, Benjamin Aaron Bearce, Jayashree Kalpathy-Cramer, Michael A Boss, Xinzhi Teng, Jiang Zhang, Jing Cai, Despina Kontos, Eric A Cohen, Walter C Mankowski, Michael Liu, Richard Ha, Oscar J Pellicer-Valero, Klaus Maier-Hein, Simona Rabinovici-Cohen, Tal Tlusty, Michal Ozery-Flato, Vishwa S Parekh, Michael A Jacobs, Ran Yan, Kyunghyun Sung, Anum S Kazerouni, Julie C Dicarlo, Thomas E Yankeelov, Thomas L Chenevert, Nola M Hylton

Faculty, Staff and Student Publications

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging …

Mesenchymal Stem Cells Suppress Inflammatory Cytokines In Lipopolysaccharide Exposed Preterm And Term Human Pregnant Myometrial Cells, Arunmani Mani, John Hotra, Sean C Blackwell, Laura Goetzl, Jerrie S Refuerzo

Faculty, Staff and Student Publications

Objective  The objective of this study was to determine the cytokine response in human pregnant preterm and term myometrial cells exposed to lipopolysaccharide (LPS) and cocultured with mesenchymal stem cells (MSCs).

Study Design  Myometrium was obtained at cesarean delivery in term and preterm patients. Human myometrial cells were exposed to 5 μg/mL LPS for 4 hours followed by 1 μg/mL LPS for 24 hours and were cocultured with MSCs for 24 hours. Culture supernatants were collected at 24 hours and expression of cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and IL-10, was quantified …

Rural Racial Disparities And Barriers In Mammography Utilization Among Medicare Beneficiaries In Texas: A Longitudinal Study, Zhaoli Liu, Yong Shan, Yong-Fang Kuo, Sharon H Giordano

Faculty, Staff and Student Publications

This study examined rural racial/ethnic disparities in long-term mammography screening practices among Medicare beneficiaries. A retrospective longitudinal study was conducted using 100% Texas Medicare data for women aged 65-74 who enrolled in Medicare between 2010-2013. Of the 114,939 eligible women, 21.2% of Hispanics, 33.3% of non-Hispanic Blacks (NHB), and 38.4% non-Hispanic Whites (NHW) in rural areas were regular users of mammography, compared to 33.5%, 44.9%, and 45.3% of their counterparts in urban areas, respectively. Stratification analyses showed rural Hispanics and NHB were 33% (95% CI, 25% - 40%) and 22% (95% CI, 6% - 36%) less likely to be regular …

A Comprehensive Program To Improve Treatment Of Precancerous Cervical Lesions In The Rio Grande Valley Of Texas, Melissa Varon, Mila Pontremoli Salcedo, Bryan Fellman, Catherine Troisi, Rose Gowen, Maria Daheri, Ana M Rodriguez, Paul Toscano, Laura Guerra, Monica Gasca, Blanca Cavazos, Elena Marin, Susan Fisher-Hoch, Maria E Fernandez, Belinda Reininger, Li Ruosha, Ellen Baker, Kathleen Schmeler

Faculty, Staff and Student Publications

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment.

DESIGN: Retrospective cohort study.

INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO.

MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline …

Engineered Adoptive T-Cell Therapies For Breast Cancer: Current Progress, Challenges, And Potential, Diego F Chamorro, Lauren K Somes, Valentina Hoyos

Faculty, Staff and Students Publications

Breast cancer remains a significant health challenge, and novel treatment approaches are critically needed. This review presents an in-depth analysis of engineered adoptive T-cell therapies (E-ACTs), an innovative frontier in cancer immunotherapy, focusing on their application in breast cancer. We explore the evolving landscape of chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, highlighting their potential and challenges in targeting breast cancer. The review addresses key obstacles such as target antigen selection, the complex breast cancer tumor microenvironment, and the persistence of engineered T-cells. We discuss the advances in overcoming these barriers, including strategies to enhance T-cell efficacy. …

Biomarkers Of Affective Dysregulation Associated With In Utero Exposure To Etoh, Nune Darbinian, Nana Merabova, Gabriel Tatevosian, Mary Morrison, Armine Darbinyan, Huaqing Zhao, Laura Goetzl, Michael Edgar Selzer

Faculty, Staff and Student Publications

INTRODUCTION: Children with fetal alcohol spectrum disorders (FASD) exhibit behavioral and affective dysregulation, including hyperactivity and depression. The mechanisms are not known, but they could conceivably be due to postnatal social or environmental factors. However, we postulate that, more likely, the affective dysregulation is associated with the effects of EtOH exposure on the development of fetal serotonergic (5-HT) and/or dopaminergic (DA) pathways, i.e., pathways that in postnatal life are believed to regulate mood. Many women who use alcohol (ethanol, EtOH) during pregnancy suffer from depression and take selective serotonin reuptake inhibitors (SSRIs), which might influence these monoaminergic pathways in the …

Targeting Eif4a Triggers An Interferon Response To Synergize With Chemotherapy And Suppress Triple-Negative Breast Cancer, Na Zhao, Elena B Kabotyanski, Alexander B Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C Reineke, Nadia Lieu, Yang Gao, Diego A Pedroza, Sebastian J Calderon, Alex J Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M Solis, Susan G Hilsenbeck, Cheng Fan, Charles M Perou, Jeffrey M Rosen

Faculty, Staff and Students Publications

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 …

Metformin Plus Insulin For Preexisting Diabetes Or Gestational Diabetes In Early Pregnancy: The Mompod Randomized Clinical Trial, Kim A Boggess, Arielle Valint, Jerrie S Refuerzo, Noelia Zork, Ashley N Battarbee, Kacey Eichelberger, Gladys A Ramos, Gayle Olson, Celeste Durnwald, Mark B Landon, Kjersti M Aagaard, Kedra Wallace, Christina Scifres, Todd Rosen, Wadia Mulla, Amy Valent, Sherri Longo, Laura Young, M Alison Marquis, Sonia Thomas, Ashley Britt, Diane Berry

Faculty, Staff and Student Publications

IMPORTANCE: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes.

OBJECTIVE: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and …

Neonatal Survival After Serial Amnioinfusions For Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial, Jena L Miller, Ahmet A Baschat, Mara Rosner, Yair J Blumenfeld, Julie S Moldenhauer, Anthony Johnson, Mauro H Schenone, Michael V Zaretsky, Ramen H Chmait, Juan M Gonzalez, Russell S Miller, Anita J Moon-Grady, Ellen Bendel-Stenzel, Amaris M Keiser, Radhika Avadhani, Angie C Jelin, Jonathan M Davis, Daniel S Warren, Daniel F Hanley, Joslynn A Watkins, Joshua Samuels, Jeremy Sugarman, Meredith A Atkinson

Faculty, Staff and Student Publications

IMPORTANCE: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.

OBJECTIVE: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia.

DESIGN, SETTING, AND PARTICIPANTS: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.

EXPOSURE: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid …

Physical Activity, Anthropometric Measurements, Quality Of Life And Menopausal Symptoms Among South-Indian Women, Lavanya N, Sathyaprabha B

Faculty, Staff and Student Publications

INTRODUCTION: Menopause is the period when the reproductive capacity ceases in women's life. A wide range of symptoms occur as a consequence of estrogen decrease during menopause. Evidence suggests that physically active women have a better quality of life (QoL) and fewer menopausal symptoms. The aim of the study was to analyze the relationship between physical activity (PA), anthropometric measurements, QoL and menopausal symptoms.

MATERIAL AND METHOD: A cross-sectional study was conducted online through WhatsApp and Facebook and via email among menopausal women (April 2021 - June 2021). In total 168 responses were received; 153 responses were included in the …

Gene Transcription Regulation By Er At The Single Cell And Allele Level, Fabio Stossi, Alejandra Rivera Tostado, Hannah L Johnson, Ragini M Mistry, Maureen G Mancini, Michael A Mancini

Faculty, Staff and Students Publications

In this short review we discuss the current view of how the estrogen receptor (ER), a pivotal member of the nuclear receptor superfamily of transcription factors, regulates gene transcription at the single cell and allele level, focusing on in vitro cell line models. We discuss central topics and new trends in molecular biology including phenotypic heterogeneity, single cell sequencing, nuclear phase separated condensates, single cell imaging, and image analysis methods, with particular focus on the methodologies and results that have been reported in the last few years using microscopy-based techniques. These observations augment the results from biochemical assays that lead …

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enables Murine Embryo Implantation, Vineet K Maurya, Maria M Szwarc, David M Lonard, Ramakrishna Kommagani, San Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2’s role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2 ^d/d) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2 …

Big Advocacy, Little Recognition: The Hidden Work Of Black Patients In Precision Medicine, Lynette Hammond Gerido, Kenneth Resnicow, Elena M Stoffel, Tiah Tomlin, Robert Cook-Deegan, Melissa Cline, Amy Coffin, Jill Holdren, Mary Anderlik Majumder, Zhe He

Center for Medical Ethics and Health Policy Staff Publications

As cost-effective next-generation genome sequencing rapidly develops, calls for greater inclusion of Black people in genomic research, policy, and practice are necessary for effective translation of genomic science into precision population health and medicine. Employing a community-based participatory mixed methods research design, we developed a semi-structured survey that was disseminated to three cancer advocacy organizations. Of the 81 survey respondents 49 (60%) self-identified as Black, and 26 (32%) indicated a prior breast cancer diagnosis. Black participants' expressed concerns about genetic testing were evenly distributed between concerns that could be addressed through genetic counseling (24%) and concerns about subsequent use of …

Posterior-Scleritis: Case Report Of An Uncommon Immune-Related Adverse Event In The Treatment Of Advanced Endometrial Cancer, Brandon I Ing, Derek Kuhl, Deanna Glassman, Cynae A Johnson, Shrina Patel, Amir A Jazaeri

Faculty, Staff and Student Publications

As Immune checkpoint inhibitors are being expanded for use in gynecologic malignancies, rare immune-related adverse events are more frequently being reported. Here we describe a 63-year-old with Stage IIIB mismatch repair deficient uterine adenocarcinoma who underwent six cycles of carboplatin and paclitaxel with partial response but persistent disease. She was then started on single agent pembrolizumab. After six cycles of pembrolizumab, she developed bilateral vision changes and was diagnosed with posterior scleritis. Pembrolizumab was held and she was treated with oral prednisone, with rapid resolution of symptoms. One month after completion of prednisone, vision changes were again reported and she …