Medical Genetics Commons^™

From Mitochondria To Tumor Suppression: Acat1’S Crucial Role In Gastric Cancer, Wei He, Yanfang Li, Song-Bai Liu, Ying Chang, Shiyuan Han, Xingyu Han, Zixin Ma, Hesham M Amin, Yao-Hua Song, Jin Zhou

Faculty, Staff and Student Publications

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 …

Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer

Faculty, Staff and Student Publications

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of …

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 …

Mri-Guided High-Dose-Rate Gynecologic Brachytherapy Using An Mr-Linac As An Mr Simulator: A Single Institutional Experience, Whitney Massock, Yusung Kim, M Alex Dresner, Wenqing Sun, Joseph Caster, Quentin Adams, Jill Jespersen, Joel St-Aubin

Faculty, Staff and Student Publications

Purpose: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development.

Methods and materials: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New …

Stereotactic Body Radiation Therapy For Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review, Colton Ladbury, Mark H Sueyoshi, Nellie M Brovold, Ritesh Kumar, Therese Y Andraos, Emile Gogineni, Minsun Kim, Ann Klopp, Kevin Albuquerque, Charles Kunos, Eric Leung, Constantine Mantz, Tithi Biswas, Sushil Beriwal, William Small, Beth Erickson, David Gaffney, Simon S Lo, Akila N Viswanathan

Faculty, Staff and Student Publications

Purpose: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients.

Methods and materials: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a …

Public Perspectives On Investigative Genetic Genealogy: Findings From A National Focus Group Study, Jacklyn Dahlquist, Jill O Robinson, Amira Daoud, Whitney Bash-Brooks, Amy L Mcguire, Christi J Guerrini, Stephanie M Fullerton

Center for Medical Ethics and Health Policy Staff Publications

Background: Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes.

Methods: We conducted eight focus groups with members of the public (N = 72), sampled from four geographically diverse US regions, …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

RESULTS: One hundred ninety-two patients had a median follow-up of 82 …

Isolated Vaginal Recurrence In Women With Stage I Endometrial Cancer, Eric Rios-Doria, Han T Cun, Olga T Filippova, Jennifer J Mueller, Kaled M Alektiar, Lora H Ellenson, Vicky Makker, Yulia Lakhman, Mario M Leitao, Anuja Jhingran, Pamela T Soliman, Nadeem R Abu-Rustum

Faculty, Staff and Student Publications

Objective: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence.

Methods: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests.

Results: Of 2815 women identified, 278 (10%) experienced a …

Development And Validation Of Age-Specific Risk Prediction Models For Primary Ovarian Insufficiency In Long-Term Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study And St Jude Lifetime Cohort, Cindy Im, Zhe Lu, Sogol Mostoufi-Moab, Angela Delaney, Lin Yu, Jessica L Baedke, Yutong Han, Yadav Sapkota, Yutaka Yasui, Eric J Chow, Rebecca M Howell, Smita Bhatia, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Paul C Nathan, Yan Yuan

Faculty, Staff and Student Publications

BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer.

METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We …

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M Humphries, Kwangmi Ahn, Rachel L Kember, Fabiana L Lopes, Evelina Mocci, Juan M Peralta, John Blangero, David C Glahn, Fernando S Goes, Peter P Zandi, Peter Kochunov, Cristopher Van Hout, Alan R Shuldiner, Toni I Pollin, Braxton D Mitchell, Maja Bucan, L Elliot Hong, Francis J Mcmahon, Seth A Ament

Faculty, Staff and Student Publications

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network …

Skin Cancers In Medicare Beneficiaries With Actinic Keratoses, Cassandra Mohr, Yao Li, Lucy J Navsaria, Candice L Hinkston, Sanjay S Shete, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Importance: Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown.

Objective: To calculate the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs.

Design, setting, and participants: This retrospective cohort study was performed using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries from 2009 through 2018. Patients with treated AKs were …

The Risk Index As A Basis For Risk/Benefit Analyses And Protocol Optimization In Diagnostic Nuclear Imaging, Juan C Ocampo Ramos, Lukas M Carter, Justin L Brown, Harry Marquis, Carlos F Uribe, Pat B Zanzonico, Wesley E Bolch, Adam L Kesner

Faculty, Staff and Student Publications

Background: Potential risk associated with low-dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk-related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging-appropriate risks factors including patient-specific size, age, and sex.

Purpose: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure …

Evaluating Strength Of Recommendations For Commonly Administered Medications In Lactating Women, Yevgenia Y Fomina, John J Byrne, Catherine Y Spong

Faculty, Staff and Student Publications

Objective: To characterize the data on medications for lactating people in the LactMed database and evaluate the strength of the data for the most commonly administered medications in lactating women.

Methods: A retrospective analysis of all medications in the LactMed database in 12/2020 was performed. Each medication was classified into one of three categories: absent data, minimal-moderate data, strong data pertaining to safety in lactation. No data was defined as no available research studies associated with the medication. Minimal-moderate data was defined as absent research studies in one or more of the four LactMed categories: maternal drug levels, infant drug …

Outcomes Of Autologous Stem Cell Transplantation In Patients With Ultra-High-Risk Multiple Myeloma, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Adeel Masood, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM). This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT). We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by …

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy In Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial, Yongwoo David Seo, Hailing Lu, Graeme Black, Kimberly Smythe, Yuexin Yu, Cynthia Hsu, Juliana Ng, Pedro Hermida De Viveiros, E Houston Warren, Brett A Schroeder, Ryan B O'Malley, Lee D Cranmer, Elizabeth T Loggers, Michael J Wagner, Lynn Bonham, Venu G Pillarisetty, Gabrielle Kane, Peter Berglund, Frank J Hsu, Xinlei Mi, Borislav A Alexiev, Robert H Pierce, Stanley R Riddell, Robin L Jones, Jan Ter Meulen, Edward Y Kim, Seth M Pollack

Faculty, Staff and Student Publications

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts.

Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions.

Design, setting, and participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis …

Prediagnostic Selenium Status, Selenoprotein Gene Variants And Association With Breast Cancer Risk In A European Cohort Study, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Veronika Fedirko, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst, Guri Skeie, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Sandra M Colorado Yohar, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Alicia K Heath, Laure Dossus

Faculty, Staff and Student Publications

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional …

Circulating Metabolites May Illustrate Relationship Of Alcohol Consumption With Cardiovascular Disease, Yi Li, Mengyao Wang, Xue Liu, Jian Rong, Patricia Emogene Miller, Roby Joehanes, Tianxiao Huan, Xiuqing Guo, Jerome I Rotter, Jennifer A Smith, Bing Yu, Matthew Nayor, Daniel Levy, Chunyu Liu, Jiantao Ma

Faculty, Staff and Student Publications

BACKGROUND: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.

METHODS: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Characteristics And Clinical Outcomes Of Patients With Myeloid Malignancies And Ddx41 Variants, Alex Bataller, Sanam Loghavi, Yoheved Gerstein, Alexandre Bazinet, Koji Sasaki, Kelly S Chien, Danielle Hammond, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas Short, Ghayas C Issa, Tapan M Kadia, Naval Daver, Guilin Tang, Andres Quesada, Keyur P Patel, Farhad Ravandi, Warren Fiskus, Cristopher P Mill, Hagop M Kantarjian, Kapil Bhalla, Guillermo Garcia-Manero, Betul Oran, Courtney D Dinardo

Faculty, Staff and Student Publications

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides …

Patient-Reported Quality Of Life After Breast-Conserving Surgery With Radiotherapy Versus Mastectomy And Reconstruction, Kevin Diao, Xiudong Lei, Weiguo He, Reshma Jagsi, Sharon H Giordano, Grace L Smith, Abigail Caudle, Yu Shen, Susan K Peterson, Benjamin D Smith

Faculty, Staff and Student Publications

Objective: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors.

Background: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood.

Methods: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. …

Remotely Delivered Cancer Genetic Testing In The Making Genetic Testing Accessible (Magenta) Trial: A Randomized Clinical Trial, Elizabeth M Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Barbara M Norquist, Tara Coffin, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie N Bakkum-Gamez, Stephanie V Blank, Mark F Munsell, Denise Nebgen, Gini F Fleming, Olufunmilayo I Olopade, Sherman Law, Alicia Zhou, Douglas A Levine, Alan D'Andrea, Karen H Lu

Faculty, Staff and Student Publications

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, setting, and participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US …

Clinical Outcome And Therapeutic Impact On Neuroendocrine Neoplasms Of The Breast: A National Cancer Database Study, Libo Yang, Heather Lin, Yu Shen, Madhuchhanda Roy, Constance Albarracin, Qingqing Ding, Lei Huo, Hui Chen, Bing Wei, Hong Bu, Isabelle Bedrosian, Yun Wu

Faculty, Staff and Student Publications

Purpose: Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast.

Methods: Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. …

Care After Premenopausal Risk-Reducing Salpingo-Oophorectomy In High-Risk Women: Scoping Review And International Consensus Recommendations, Denise R Nebgen, Susan M Domchek, Joanne Kotsopoulos, Joanne A De Hullu, Emma J Crosbie, Vincent Singh Paramanandam, Monique M A Brood-Van Zanten, Barbara M Norquist, Theresa Guise, Serge Rozenberg, Allison W Kurian, Holly J Pederson, Nese Yuksel, Rachel Michaelson-Cohen, Sharon L Bober, Agnaldo Lopes Da Silva Filho, Nora Johansen, F Guidozzi, D Gareth Evans, Usha Menon, Sheryl A Kingsberg, C Bethan Powell, Giovanni Grandi, Claudia Marchetti, Michelle Jacobson, Donal J Brennan, Martha Hickey

Faculty, Staff and Student Publications

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Opioid-Free Discharge After Pancreatic Resection Through A Learning Health System Paradigm, Artem Boyev, Anish J Jain, Timothy E Newhook, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Elsa M Arvide, Whitney L Dewhurst, Michael P Kim, Jessica E Maxwell, Naruhiko Ikoma, Rebecca A Snyder, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume.

Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes.

Design, setting, and participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = …

Supportive Care For Dual Caregivers Who Care For Their Partner With Cancer And Their Young Children, Sujin Ann-Yi, Kathrin Milbury, Morgan Jones, Victoria Necroto, Meagan Whisenant, Yisheng Li, Eduardo Bruera

Faculty, Staff and Student Publications

Purpose: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program.

Methods: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological …

Mmp-2 Associates With Incident Heart Failure And Atrial Fibrillation: The Aric Study, Leo F Buckley, Ali M Agha, Pranav Dorbala, Brian L Claggett, Bing Yu, Aliza Hussain, Vijay Nambi, Lin Yee Chen, Kunihiro Matsushita, Ron C Hoogeveen, Christie M Ballantyne, Amil M Shah

Faculty, Staff and Student Publications

BACKGROUND: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease.

METHODS: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (

RESULTS: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident …

Texas Youth Depression And Suicide Research Network (Tx-Ydsrn) Research Registry And Learning Healthcare Network: Rationale, Design, And Baseline Characteristics, Madhukar H Trivedi, Abu Minhajuddin, Holli Slater, Regina Baronia, Joseph C Blader, Jamon Blood, Ryan Brown, Cynthia Claassen, Melissa Defilippis, David Farmer, Cynthia Garza, Jennifer L Hughes, Beth D Kennard, Israel Liberzon, Sarah Martin, Taryn L Mayes, Jair C Soares, Cesar A Soutullo, Eric A Storch, Sarah M Wakefield

Faculty, Staff and Student Publications

Background: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants.

Methods: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality …

Re-Stratification Of Patients With Copy-Number Low Endometrial Cancer By Clinicopathological Characteristics, Li Liwei, Li He, Dai Yibo, Zhao Luyang, Shen Zhihui, Kang Nan, Shen Danhua, Wang Junzhu, Wang Zhiqi, Wang Jianliu

Faculty, Staff and Student Publications

Objective: To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics.

Methods: EC patients who underwent surgery between June 2018 and June 2022 at Peking University People's Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases …

Project Inclusive Genetics: Protecting Reproductive Autonomy From Bias Via Prenatal Patient-Centered Counseling, Apolline Jungels, Lindsay Demers, Eric Ford, Blair K Stevens, Maya Sabatello, Shoumita Dasgupta

Faculty, Staff and Student Publications

Clinician bias negatively impacts the healthcare received by marginalized communities. In this study, we explored factors that influence clinician and trainee bias against individuals with intellectual disabilities and its impact on clinical judgment in prenatal genetic testing settings. Specifically, we examined bias toward a fetus with a higher chance of developing a disability. We compared genetics specialists with their non-expert counterparts. This web-based study included clinical vignettes, implicit association tests (IATs), and an educational module. 595 participants were recruited via their institution or professional society. We conducted statistical analyses, including regression models controlling for key demographic characteristics, to analyze recommendation …

Endocrine Therapy Synergizes With Smac Mimetics To Potentiate Antigen Presentation And Tumor Regression In Hormone Receptor-Positive Breast Cancer, Francisco Hermida-Prado, Yingtian Xie, Shira Sherman, Zsuzsanna Nagy, Douglas Russo, Tara Akhshi, Zhengtao Chu, Avery Feit, Marco Campisi, Minyue Chen, Agostina Nardone, Cristina Guarducci, Klothilda Lim, Alba Font-Tello, Irene Lee, Juana García-Pedrero, Israel Cañadas, Judith Agudo, Ying Huang, Tal Sella, Qingchun Jin, Nabihah Tayob, Elizabeth A Mittendorf, Sara M Tolaney, Xintao Qiu, Henry Long, William F Symmans, Jia-Ren Lin, Sandro Santagata, Isabelle Bedrosian, Denise A Yardley, Ingrid A Mayer, Edward T Richardson, Giacomo Oliveira, Catherine J Wu, Eugene F Schuster, Mitch Dowsett, Alana L Welm, David Barbie, Otto Metzger, Rinath Jeselsohn

Faculty, Staff and Student Publications

Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated β2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of …