Digital Commons Network^™

Disparities In The Operative Experience Between Female And Male General Surgery Residents: A Multi-Institutional Study From The Us Rope Consortium, Leah K Winer, Sarah Kader, Jonathan S Abelson, Austin C Hammaker, Chukwuma N Eruchalu, James C Etheridge, Nancy L Cho, Darci C Foote, Felicia A Ivascu, Savannah Smith, Lauren M Postlewait, Kathriena Greenwell, Katherine M Meister, Kelsey B Montgomery, Polina Zmijewski, Samuel E Byrd, Mary K Kimbrough, Stephen J Stopenski, Jeffry T Nahmias, Jalen Harvey, Deborah Farr, Zachary M Callahan, Joshua A Marks, Christopher C Stahl, Motaz Al Yafi, Jeffrey M Sutton, Ali Elsaadi, Samuel J Campbell, Shah-Jahan M Dodwad, Sasha D Adams, Matthew R Woeste, Robert C G Martin, Purvi Patel, Michael J Anstadt, Bilal Waqar Nasim, Ross E Willis, Jitesh A Patel, Melisa R Newcomb, Brian C George, Ralph C Quillin, Alexander R Cortez

Faculty, Staff and Student Publications

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents.

BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level.

METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents.

RESULTS: There were 1343 graduates from …

High Extracellular Glucose Promotes Cell Motility By Modulating Cell Deformability And Contractility Via The Camp-Rhoa-Rock Axis In Human Breast Cancer Cells, Mijung Oh, Skylar Batty, Nayan Banerjee, Tae-Hyung Kim

Pathology Research and Scholarship

The mechanical properties, or mechanotypes, of cells are largely determined by their deformability and contractility. The ability of cancer cells to deform and generate contractile force is critical in multiple steps of metastasis. Identifying soluble cues that regulate cancer cell mechanotypes and understanding the underlying molecular mechanisms regulating these cellular mechanotypes could provide novel therapeutic targets to prevent metastasis. Although a strong correlation between high glucose level and cancer metastasis has been demonstrated, the causality has not been elucidated, and the underlying molecular mechanisms remain largely unknown. In this study, using novel high-throughput mechanotyping assays, we show that human breast …

Effect Of Longitudinal Variation In Tumor Volume Estimation For Mri-Guided Personalization Of Breast Cancer Neoadjuvant Treatment, Natsuko Onishi, Teffany Joy Bareng, Jessica Gibbs, Wen Li, Elissa R Price, Bonnie N Joe, John Kornak, Laura J Esserman, David C Newitt, Nola M Hylton, I-Spy 2 Investigator Network

Faculty, Staff and Student Publications

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen …

Histone Demethylase Kdm5d Upregulation Drives Sex Differences In Colon Cancer, Jiexi Li, Zhengdao Lan, Wenting Liao, James W Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A Labella, Chang-Jiun Wu, Kenneth Dunner, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J Spring, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP)2, revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

A Radiomics Model Based On Synthetic Mri Acquisition For Predicting Neoadjuvant Systemic Treatment Response In Triple-Negative Breast Cancer, Ken-Pin Hwang, Nabil A Elshafeey, Aikaterini Kotrotsou, Huiqin Chen, Jong Bum Son, Medine Boge, Rania M Mohamed, Abeer H Abdelhafez, Beatriz E Adrada, Bikash Panthi, Jia Sun, Benjamin C Musall, Shu Zhang, Rosalind P Candelaria, Jason B White, Elizabeth E Ravenberg, Debu Tripathy, Clinton Yam, Jennifer K Litton, Lei Huo, Alastair M Thompson, Peng Wei, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose

To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Materials and Methods

In this prospective study, 181 women diagnosed with stage I–III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting …

Pontocerebellar Hypoplasia Associated With Parg183trp Homozygous Variant In Exosc1 Gene: A Case Report, Nadirah S Damseh, Ali N Obeidat, Khondakar Sayef Ahammed, Motee Al-Ashhab, Motee Abu Awad, Ambro Van Hoof

Faculty, Staff and Student Publications

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Co-Operative Roles Of Il-4rα And Il-13rα1 In The Progression Of Ovarian Carcinomas And The Survival Of Ovarian Carcinoma Patients, Won Ku Choi, Usama Khamis Hussein, Asmaa Gamal Ahmed, Junyue Zhang, Kyoung Min Kim, Ae Ri Ahn, Ho Sung Park, See-Hyoung Park, Dong Hyu Cho, Kyu Yun Jang

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Eliminating Breast Surgery For Invasive Cancer With Exceptional Response To Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint, Helen M Johnson, Vicente Valero, Wei T Yang, Benjamin D Smith, Savitri Krishnamurthy, Yu Shen, Heather Lin, Anthony Lucci, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

Background: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

Study design: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with < 2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

Results: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were …

Carboplatin Dosing In The Treatment Of Ovarian Cancer: An Nrg Oncology Group Study, Aaron M Praiss, Austin Miller, Judith Smith, Stuart M Lichtman, Michael Bookman, Carol Aghajanian, Paul Sabbatini, Floor Backes, David E Cohn, Peter Argenta, Michael Friedlander, Michael J Goodheart, David G Mutch, David M Gershenson, Krishnansu S Tewari, Robert M Wenham, Andrea E Wahner Hendrickson, Roger B Lee, Heidi Gray, Angeles Alvarez Secord, Linda Van Le, Roisin E O'Cearbhaill

Faculty, Staff and Student Publications

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity …

Association Of Second-Generation Antiandrogens With Cognitive And Functional Toxic Effects In Randomized Clinical Trials: A Systematic Review And Meta-Analysis, Malgorzata K Nowakowska, Rachel M Ortega, Mackenzie R Wehner, Kevin T Nead

Faculty, Staff and Student Publications

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.

Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

Data sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022).

Study selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, …

A Cre Driver Line For Genetic Targeting Of Kappa Opioid Receptor Expressing Cells, Franciely Paliarin, Chelsea Duplantis, Andrea F Jones, Jessica Cucinello-Ragland, Samhita Basavanhalli, Emily Blaze, Evan Doré, Anna Isabella Neel, Haiguo Sun, Rong Chen, Scott Edwards, Nicholas W Gilpin, Robert O Messing, Rajani Maiya

Faculty, Staff and Student Publications

Here we describe the generation and characterization of a Cre knock-in mouse line that harbors a Cre insertion in the 3′UTR of the κ opioid receptor gene (Oprk1) locus and provides genetic access to populations of κ opioid receptor (KOR)-expressing neurons throughout the brain. Using a combination of techniques including RNA in situ hybridization and immunohistochemistry, we report that Cre is expressed with high fidelity in KOR-expressing cells throughout the brain in this mouse line. We also provide evidence that Cre insertion does not alter basal KOR function. Baseline anxiety-like behaviors and nociceptive thresholds are unaltered in Oprk1-Cre …

Route Of Delivery Does Not Impact Postnatal Surgical Morbidity In Pregnancies Affected By Fetal Achondroplasia, Bobby K Brar, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Lorena Dujmusic, Mary E Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Janet M Legare, Julie E Hoover-Fong

Faculty, Staff and Student Publications

Purpose: Pregnancies affected by maternal or fetal achondroplasia present unique challenges. The optimal route of delivery in fetuses with achondroplasia has not been established. Our objective was to determine whether the route of delivery affects postnatal achondroplasia-related surgical burden.

Methods: We conducted a secondary analysis of Achondroplasia Natural History Study (CLARITY), which is a multicenter natural history cohort study of patients with achondroplasia. Achondroplasia-related surgical morbidity, which we defined as the need for one or more postnatal achondroplasia-related surgeries, was assessed in relation to the route of delivery and whether the mother also had achondroplasia. Rate of each individual surgery …

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline, Anthony Patrizz, Ahmad El Hamamy, Michael Maniskas, Yashasvee Munshi, Louise Atadja, Hilda Ahnstedt, Matthew Howe, Fan Bu, Daniel K Mulkey, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS: Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were …

Prognostic Factors For Pediatric, Adolescent, And Young Adult Patients With Non-Dipg Grade 4 Gliomas: A Contemporary Pooled Institutional Experience, Jennifer K Matsui, Pamela K Allen, Haley K Perlow, Jason M Johnson, Arnold C Paulino, Mary Frances Mcaleer, Maryam Fouladi, David R Grosshans, Amol J Ghia, Jing Li, Wafik T Zaky, Murali M Chintagumpala, Joshua D Palmer, Susan L Mcgovern

Faculty, Staff and Student Publications

Purpose: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population.

Methods: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis.

Results: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival.

Conclusion: Age is a significant prognostic factor in WHO grade …

Genome-Wide Association Study Of Thoracic Aortic Aneurysm And Dissection In The Million Veteran Program, Derek Klarin, Poornima Devineni, Anoop K Sendamarai, Anthony R Angueira, Sarah E Graham, Ying H Shen, Michael G Levin, James P Pirruccello, Ida Surakka, Purushotham R Karnam, Tanmoy Roychowdhury, Yanming Li, Minxian Wang, Krishna G Aragam, Kaavya Paruchuri, Verena Zuber, Gabrielle E Shakt, Noah L Tsao, Renae L Judy, Ha My T Vy, Shefali S Verma, Daniel J Rader, Ron Do, Joseph E Bavaria, Girish N Nadkarni, Marylyn D Ritchie, Stephen Burgess, Dong-Chuan Guo, Patrick T Ellinor, Scott A Lemaire, Dianna M Milewicz, Cristen J Willer, Pradeep Natarajan, Philip S Tsao, Saiju Pyarajan, Scott M Damrauer

Faculty, Staff and Student Publications

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and …

View-Vlu Observational Study Of The Effect Of Varithena On Wound Healing In The Treatment Of Venous Leg Ulcers., Michael Y Shao, Stuart Harlin, Beverly Chan, Kathylee Santangelo, Eri Fukaya, Julianne Stoughton, Raghu Kolluri

Heart and Vascular Articles

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates.

METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included …

Stress Responses And Ammonia Nitrogen Removal Efficiency Of Oocystis Lacustris In Saline Ammonium-Contaminated Wastewater Treatment, Linda Ewing-Cobbs, Christina V Danna, Tammy D Tolar, Douglas Granger, Charles S Cox, Mary R Prasad

Faculty, Staff and Student Publications

Traumatic injury is linked increasingly to alterations in both stress response systems and psychological health. We investigated reactivity of salivary analytes of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (salivary alpha amylase, sAA) during a psychosocial stress procedure in relation to psychological health outcomes. In a prospective cohort design, stress reactivity of children ages 8 to 15 years hospitalized for traumatic brain injury (TBI; n = 74) or extracranial injury (EI; n = 35) was compared with healthy controls (n = 51) 7 months after injury. Area under the curve increase (AUCinc) assessed pre-stressor to post-stressor cortisol and …

The Effects Of Obesity And Metabolic Abnormalities On Severe Covid-19-Related Outcomes After Vaccination: A Population-Based Study, Rebeca Kelly, Diego Aviles, Catriona Krisulevicz, Krystal Hunter, Lauren Krill, David Warshal, Olga Ostrovsky

Faculty, Staff and Student Publications

High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in …

Endovascular Versus Medical Management Of Posterior Cerebral Artery Occlusion Stroke: The Plato Study, Thanh N Nguyen, Muhammad M Qureshi, Davide Strambo, Daniel Strbian, Silja Räty, Christian Herweh, Mohamad Abdalkader, Marta Olive-Gadea, Marc Ribo, Marios Psychogios, Urs Fischer, Anh Nguyen, Joji B Kuramatsu, David Haupenthal, Martin Köhrmann, Cornelius Deuschl, Jordi Kühne Escola, Shadi Yaghi, Liqi Shu, Volker Puetz, Daniel P O Kaiser, Johannes Kaesmacher, Adnan Mujanovic, Dominique Cornelius Marterstock, Tobias Engelhorn, Piers Klein, Diogo C Haussen, Mahmoud H Mohammaden, Hend Abdelhamid, Lorena Souza Viana, Bruno Cunha, Isabel Fragata, Michele Romoli, Francesco Diana, Pekka Virtanen, Kimmo Lappalainen, Judith Clark, Stavros Matsoukas, Johanna T Fifi, Sunil A Sheth, Sergio Salazar-Marioni, João Pedro Marto, João Nuno Ramos, Milena Miszczuk, Christoph Riegler, Ashutosh P Jadhav, Shashvat M Desai, Volker Maus, Maximilian Kaeder, Adnan H Siddiqui, Andre Monteiro, Hesham E Masoud, Neil Suryadevara, Maxim Mokin, Shail Thanki, James E Siegler, Jane Khalife, Italo Linfante, Guilherme Dabus, Negar Asdaghi, Vasu Saini, Christian H Nolte, Eberhard Siebert, Thomas R Meinel, Stefanos Finitsis, Markus A Möhlenbruch, Peter A Ringleb, Anne Berberich, Raul G Nogueira, Uta Hanning, Lukas Meyer, Patrik Michel, Simon Nagel

Faculty, Staff and Student Publications

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion.

Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift …

Functional Assessment Of The Dural Lymphatic Vessels Using Dynamic Contrast Mri In Multiple Sclerosis, Refaat E Gabr, John A Lincoln, Khader M Hasan, Larry A Kramer

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance.

METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T …

Real-World Outcomes Associated With Poly(Adp-Ribose) Polymerase Inhibitor Monotherapy Maintenance In Patients With Primary Advanced Ovarian Cancer, John K Chan, Jinan Liu, Jinlin Song, Cheryl Xiang, Eric Wu, Linda Kalilani, Jean A. Hurteau, Premal H. Thaker

2020-Current year OA Pubs

OBJECTIVE: This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC).

METHODS: Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses.

RESULTS: Of 705 patients who completed …

Cisplatin Decreases Voluntary Wheel-Running Activity But Does Not Impair Food-Motivated Behavior In Mice, Kiersten S Scott, Brandon Chelette, Chinenye Chidomere, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less …

Addressing The Global Expertise Gap In Radiation Oncology: The Radiation Planning Assistant, Laurence Court, Ajay Aggarwal, Hester Burger, Carlos Cardenas, Christine Chung, Raphael Douglas, Monique Du Toit, David Jaffray, Anuja Jhingran, Michael Mejia, Raymond Mumme, Sikudhani Muya, Komeela Naidoo, Jerry Ndumbalo, Kelly Nealon, Tucker Netherton, Callistus Nguyen, Niki Olanrewaju, Jeannette Parkes, Willie Shaw, Christoph Trauernicht, Melody Xu, Jinzhong Yang, Lifei Zhang, Hannah Simonds, Beth M Beadle

Faculty, Staff and Student Publications

PURPOSE: Automation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).

DESIGN: In this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and …

Plasma Proteomic Patterns Show Sex Differences In Early Concentric Left Ventricular Remodeling, Anne-Mar Van Ommen, Ernest Diez Benavente, N. Charlotte Onland-Moret, Gideon B. Valstar, Maarten J. Cramer, Frans H. Rutten, Arco J. Teske, Roxana Menken, Leonard Hofstra, Igor I. Tulevski, Nancy Sweitzer, G. Aernout Somsen, Hester M. Den Ruijter

2020-Current year OA Pubs

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women.

METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM.

RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, …

Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan

2020-Current year OA Pubs

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition …

Proteogenomic Approaches For The Identification Of Nf1/Neurofibromin-Depleted Estrogen Receptor-Positive Breast Cancers For Targeted Treatment, Beom-Jun Kim, Ze-Yi Zheng, Jonathan T Lei, Matthew V Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, María Del Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella B Hanker, Nada Mohamed, Susan G Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew J Ellis, Eric C Chang

Faculty, Staff and Student Publications

NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking both pathways by fulvestrant (F), a selective ER degrader, together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models. We aimed to establish approaches to determine how NF1 protein levels impact B+F treatment response to improve our ability to identify B+F sensitive tumors. We examined a panel of ER+ patient-derived xenograft (PDX) models by DNA and mRNA sequencing and found that more than half of these models carried an NF1 shallow deletion and generally have low mRNA …

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections, Sidra Zafar, Annette Walder, Salim Virani, Kristin Biggerstaff, Silvia Orengo-Nania, Jonathan Chang, Roomasa Channa

Faculty, Staff and Students Publications

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups.

OBJECTIVE: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and …

Sex-Based Differences In The Presentation And Outcomes Of Acute Pulmonary Embolism: A Systematic Review And Meta-Analysis, Yu Zhang, Yu Qiu, Jinming Luo, Jian Zhang, Qingqing Yan

The Texas Heart Institute Journal

BACKGROUND: The study aimed to review differences in the presentation and outcomes of acute pulmonary embolism (PE) between men and women.

METHODS: PubMed, CENTRAL, Web of Science, and Embase were searched for studies comparing clinical features or outcomes of PE between men and women. Baseline comorbidities, risk factors, clinical features, and mortality rates were also compared between men and women.

RESULTS: Fourteen studies were included. It was noted that men presented with PE at a statistically significantly younger age than women (P < .001). Smoking history (P < .001), lung disease (P = .004), malignancy (P = .02), and unprovoked PE (P = .004) were significantly more frequent among men than among women. There was no difference between the sexes for hypertension, diabetes, and a history of recent immobilization. A significantly higher proportion of men presented with chest pain (P = .02) and hemoptysis (P < .001), whereas syncope (P = .005) was more frequent in women. Compared with men, women had a higher proportion of high-risk PE (P = .003). There was no difference in the use of thrombolytic therapy or inferior vena cava filter. Neither crude nor adjusted mortality rates were significantly different between men and women.

CONCLUSION: This review found that the age at presentation, comorbidities, and symptoms of PE differed between men and …