Academic literature on the topic 'Washington University (Saint Louis, Mo.). Libraries'

Background: Accurate etiologic diagnoses are needed in patients with rapidly progressive dementia (RPD) to ensure access to symptomatic and disease-modifying therapies when available. Methods: Patients with RPD were prospectively enrolled and evaluated at Washington University (Saint Louis, MO; 2016-2019) and Mayo Clinic (Jacksonville, FL; 2020-2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of diagnostic tests; disagreements were resolved via blinded review by a third specialist. Results: 160 RPD patients were enrolled and followed. Average age-at-symptom onset was 60.0±15.9 years; 50% were female. Inter-rater reliability (91% agreement; Cohen’s κ=0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%), Creutzfeldt-Jakob disease (15%), and other causes (15%). Patients with potentially treatable causes of RPD were younger (54.5±18.2 than those with neurodegenerative causes (67.3±9.5; p<0.001), and more likely to present with altered levels of consciousness, seizures, or CSF pleocytosis (p<0.05). Conclusions: Etiologic diagnoses can be reliably established in RPD patients using available clinical data. The prevalence of autoimmune encephalitis in this series justifies routine screening for potentially treatment-responsive causes of RPD, particularly in younger patients.

Abstract Background: CDK4/6 inhibitors (CDK4/6i) paired with endocrine therapy (ET) are considered first-line (1L) therapy for patients (pts) with HR+ HER2- advanced breast cancer (aBC). A minority of pts will demonstrate primary resistance to CDK4/6i, as characterized by early progression. Thymidine kinase 1 (TK1) is a cell-cycle regulated enzyme downstream of CDK4/6 and involved in nucleotide metabolism during DNA synthesis. Prior studies have shown TK1 may serve as a biomarker of response to CDK4/6i, with early TK1 activity (TK1a) suppression after initiation of CDK 4/6i therapy associated with improved PFS. Lack of TK1a suppression may be associated with primary resistance to CDK4/6i. In this study, we aim to analyze response to subsequent lines of therapy and overall survival (OS) of pts with early progression on 1L CDK4/6i. Methods: Pts with HR+ HER2- aBC from a phase II trial of an alternative schedule of palbociclib (palbo alt dosing trial NCT 3007979) and from a retrospective palbociclib study were included in this analysis. Pts in the palbo alt dosing trial underwent baseline and C1D15 TK1a analysis after initiation on CDK4/6i. C1D15 TK1a suppression was defined at TK1a &lt; 30 Du/L. Pts in the retrospective palbociclib study included pts receiving palbo as part of their standard of care 1L therapy for HR+ HER2- aBC at Washington University in Saint Louis from 2016 to 2021. Clinical information, including treatment start and stop dates on each of the next-line therapies, were collected from the electronic medical record. PFS was estimated by the treatment duration on a specified treatment regimen. Early progression on CDK4/6i was defined as PFS &lt; 6 mo. Best response was defined as next line of therapy with the numerically longest PFS. OS was defined as time to death from the initiation of CDK4/6i. Results: Of the 54 pts enrolled on the palbo alt dosing trial, 51 pts were evaluable for clinical benefit and 46 pts were evaluable for TK1a suppression rate at C1D15. 7 pts (15.2%) were found without TK1a suppression at C1D15. This lack of TK1a suppression on palbo was associated with a significantly shorter PFS (median PFS=3.1 mo) compared to not reached in pts with TK1a suppression at C1D15. We conducted clinical analysis on N=26 pts who exhibited early progression on CDK4/6i which included 10 pts from the palbo alt dosing trial and 16 from the retrospective study. The average subsequent line of therapies in this cohort was 3, with the most common second line (2L) therapy being chemotherapy (N=17, 65.4%) and ET (N=8, 30.8%). The median PFS for pts receiving 2L chemotherapy and ET was 4.09 mo and 3.64 mo, respectively. 10 pts received both chemotherapy and ET with 7 (70.0%) achieving best response with chemotherapy compared to 3 pts (30.0%) who achieved best response with ET. The median OS for the cohort was 14.6 mo. Conclusions: Early progression on CDK4/6i is associated with a particularly poor prognosis. In our cohort, the median OS was far below the expected median OS for pts receiving 1L palbo as reported in the PALOMA-2 trial (14.6 mo vs 53.9 mo). Early progression on CDK4/6i is associated with more aggressive disease which may respond more favorably to chemotherapy, as demonstrated by best response to therapy. Further prospective studies are warranted to explore this treatment approach. Citation Format: Katherine K. Clifton, Shana N. Thomas, Jingqin Luo, Jing Xi, Nusayba A. Bagegni, Foluso O. Ademuyiwa, Rama Suresh, Ashley Frith, Andrew A. Davis, Ron Bose, Katherine Weilbaecher, Whitney L. Hensing, Timothy Pluard, Massimo Cristofanilli, Hyo S. Han, Adam M. Brufsky, Kevin Kalinsky, Shom Goel, Seth A. Wander, Lindsay L. Peterson, Cynthia Ma. PD13-09 Clinical outcomes of patients with HR+ HER2- advanced breast cancer with early progression on CDK4/6 inhibitors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD13-09.

Abstract Background: Identifying pathways that can be targeted to reduce breast density and breast cancer incidence is an unmet need, especially in premenopausal women. Receptor activator of nuclear factor-κB ligand (RANKL) signaling mediates the major proliferative response of mammary epithelium to progesterone and is positively associated with breast density but there are no clinical trial data on the impact of RANKL inhibition on breast tissue markers in women with dense breasts. We, therefore, determined the impact of RANKL inhibition on breast tissue gene expression in high-risk premenopausal women with dense breasts. Study design: Pilot phase I clinical trial of 9 healthy high-risk pre-menopausal women (≥35 years of age) with dense breasts performed at Washington University School of Medicine, St. Louis, MO from July 2018-December 2018. Fifty-five percent of participants had a positive family history of breast cancer in a first degree relative. Intervention: Participants were given a single dose of subcutaneous RANKL antibody, denosumab (60mg), at baseline (Day 1). On the same day, prior to the denosumab injection, participants had an ultrasound guided core needle biopsy and a blood draw. All study participants returned for repeat core needle biopsy and blood draw after 60 days (Day 60). Outcome Measures: Changes in breast tissue gene expression between Day 1 and Day 60 with a focus on immune/inflammatory and hormone markers. Gene expression was profiled using NanoString nCounter platform. We performed pathway enrichment analysis and used Cell Maker Enrichment library from EnrichR to identify differentially expressed genes. Genes with a p-value&lt;0.05 on differential expression analysis were considered statistically significant for utilization in pathway enrichment analysis. Libraries utilized for pathway enrichment using the EnrichR platform included the ChEA transcription factor library, GO Biological Process library, and Cellular Components library. Results: Macrophage markers, including CCR5, CD86, CD300A, and CD84 and targets downstream of IRF8: (p-value =4.73e-7), neutrophil degranulation/neutrophil activation in the immune response (p-value=6.0e-21), and the secretory granule membrane pathways (p-value=2.4e-14) were downregulated in breast tissues on Day 60. Pathways involved in progesterone metabolism (p-value=0.0003), estrogen response (p-value=0.0014) and fatty acid metabolism, (p-value=0.0001) were significantly upregulated on Day 60. Specifically, genes involved in steroid hormone metabolism such as DHRS2 (p-value=3.13e-05), and AKR1B15: p-value=4.12e-05) were upregulated on Day 60. Conclusions: A single 60 mg dose of subcutaneous denosumab injection was associated with alterations in pathways involved in hormone, immune and inflammatory signaling in the breast tissues of healthy premenopausal women with dense breasts. Citation Format: Michael Waters, Kay Jayachandran, Debbie Bennet, Jin Zhang, Katherine Weilbaecher, Ian S. Hagemann, Graham A. Colditz, Catherine M. Appleton, Adetunji T. Toriola. Pilot phase I clinical trial of RANKL inhibition and breast tissue gene expression in high-risk premenopausal women with dense breasts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2206.

Chair Elliott Antman, MD, FAHA Brigham and Women's Hospital Boston, MA Vice-Chair Robert A. Harrington, MD, FACC, FAHA Stanford University Stanford, CA Incoming Vice Chair/At Large Ken Bloch, MD, FAHA Massachusetts General Hospital Boston, MA President Donna Arnett, PhD, FAHA University of Alabama at Birmingham Birmingham, AL 3CPR, Council Program Chair Ben Abella, MD, MPhil, FACEP University of Pennsylvania Philadelphia, PA 3CPR Francois Haddad, MD Stanford University Palo Alto, CA 3CPR Fumito Ichinose, MD, PhD, FAHA Massachusetts General Hospital Boston, MA 3CPR Graham Nichol, MD, MPH, FRCP(C) University of Washington Seattle, WA At Large Lisa de las Fuentes, MD, MS, FASE Washington University School of Medicine Saint Louis, MO At Large Angel Leon, MD, FACC Emory University Hospital Midtown Atlanta, Georgia At Large Jorge Saucedo, MD, FACC, MBA University of Oklahoma Health Sciences Center Oklahoma City, OK At Large Kevin Sneed, PharmD USF College of Medicine Tampa, FL ATVB, Council Program Chair William M. Chilian, PhD, FAHA Northeastern Ohio University College of Medicine Rootstown, OH ATVB Yabing Chen, PhD, FAHA University of Alabama Birmingham, AL ATVB Gregory S. Shelness, PhD, FAHA Wake Forest University Winston-Salem, NC BCVS, Council Program Chair Yibin Wang, PhD, FAHA UCLA Los Angeles, CA BCVS Gerald W. Dorn, II, MD, FAHA Washington University School of Medicine St. Louis, MO BCVS Bjorn Knollman, MD, PhD, FAHA Vanderbilt University School of Medicine Nashville, TN BCVS Hong Wang, MD, PhD, EMBA Temple University School of Medicine Philadelphia, PA BCVS Joseph C. Wu, MD, PhD Stanford University School of Medicine Stanford, CA BCVS Jianyi (Jay) Zhang, MD, PhD, FAHA University of Minnesota Medical School Minneapolis, MN Clinical Cardiology, Council Program Chair Eric R Bates, MD, FAHA, FACC University of Michigan Medical Center Ann Arbor, MI Clinical Cardiology Monica Colvin-Adams, MD, MS University of Minnesota Minneapolis, MN Clinical Cardiology Patrick Ellinor, MD, PhD, FAHA Massachusetts General Hospital Boston, MA Clinical Cardiology Navin K. Kapur, MD Tufts Medical Center Hanover, MA Clinical Cardiology Mark S. Link, MD Tufts University School of Medicine Boston, MA Clinical Cardiology J. V. (Ian) Nixon, MD, FACC VCU Health System Richmond, VA Clinical Cardiology Manesh R. Patel, MD Duke University Durham, NC CVDY, Council Program Chair Wolfgang A. Radtke, MD, FAHA AI Dupont Hospital for Children Wilmington, DE CVDY David Dunbar Ivy, MD University of Colorado Denver School of Medicine Children's Hospital Colorado Aurora, CO CVDY Ariane Marelli, MD, MPH McGill University Health Center Montreal, Quebec, Canada CVN, Council Program Chair Nancy T. Artinian, PhD, RN, FAHA, FPCNA, FAAN Wayne State University Detroit, MI CVN Bunny J. Pozehl, RN, PhD, CRNP, FAHA UNMC College of Nursing Lincoln, NE CVN Sue Sendelbach, PhD, RN, CCNS, FAHA Abbott Northwestern Hospital Minneapolis, MN CVN Kathy Wood, RN, PhD Duke University School of Nursing Durham, NC CVRI, Council Program Chair Constantino Peña, MD Baptist Cardiac & Vascular Institute Miami, FL CVRI Sanjay Misra, MD Mayo Clinic Rochester, MN CVSA, Council Program Chair Y. Joseph Woo, MD, FAHA University of Pennsylvania Philadelphia, PA CVSA Marc Ruel, MD, MPH, FRCSC, FAHA University of Ottawa Heart Institute Ottawa, Ontario, Canada EPI, Council Program Chair Donald M. Lloyd-Jones, MD, ScM, FACC Northwestern University Feinberg School of Medicine Chicago, IL EPI Jarett D. Berry, MD UT Southwestern Medical School Dallas, TX FGTB, Council Program Chair Christopher Newton-Cheh, MD, MPH, FAHA Harvard Medical School Massachusetts General Hospital Broad Institute of Harvard and MIT Boston, MA FGTB Roberta A. Gottlieb, MD, FAHA San Diego State University San Diego, CA FGTB Jennifer L. Hall, PhD, FAHA University of Minnesota Minneapolis, MN FGTB Peipei Ping, PhD, FISHR, FAHA UCLA School of Medicine Los Angeles, CA HBPR, Council Program Chair Kenneth Baker, MD, FAHA Texas A Health Science Center, College of Medicine Temple, TX HBPR Patrice Delafontaine, MD, FAHA Tulane University School of Medicine New Orleans, LA HBPR Michael Ryan, MD, PhD, FAHA University of Mississippi Medical Center Jackson, MS KCVD, Council Program Chair Christine Maric, PhD, FAHA University of Mississippi Medical Center Jackson, MS NPAM, Council Program Chair Eliot A. Brinton, MD, FAHA University of Utah Salt Lake City, UT NPAM Caroline Fox, MD, MPH National Heart, Lung and Blood Institute Framingham, MA NPAM Paul Poirier, MD, PhD, FRCPC, FACC, FAHA Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec, Québec, Canada PVD, Council Program Chair Alan T. Hirsch, MD University of Minnesota Medical School Minneapolis, MN PVD James B. Froehlich, MD, MPH University of Michigan Medical School Ann Arbor, MI PVD Christopher Kramer, MD, FAHA University of Virginia Health System Charlottesville, VA QCOR, Council Program Chair Mikhail Kosiborod, MD Saint Luke's Hospital Mid-America Heart Institute Kansas City, MO QCOR Adrian Hernandez, MD, MHS Duke Clinical Research Institute Durham, NC QCOR Henry Ting, MD, MBA, FAHA Mayo Clinic Rochester, MN Stroke, Council Program Chair Cathy A. Sila, MD, FAHA Case Medical Center Cleveland, OH Stroke, Council Michael A. De Georgia, MD, FACP, FAHA, FCCM Case Western Reserve University School of Medicine Cleveland, OH International Congress Subcommittee Eric R. Bates, MD, FAHA, FACC, Chair Robert O. Bonow, MD, Vice Chair Helene Eltchaninoff, MD Kathy E. Magliato, MD, MBA, FACS Audrey Marshall, MD Kathy Hoercher, RN International Subcommittee Robert Harrington, MD, FACC, FAHA, Chair Conville Brown, MD, MBBS, FACC, FESC Anthony J. Dalby, MB, ChB, FCP, FACC, FESC Basil Lewis, MD, FRCP Akira Matsumori, MD, PhD, FAHA, FACC, FAPSC, FESC John McMurray, BSc, MB, ChB, MD, FRCP, FESC, FACC, FAHA, FRSE Eduardo F. Mele, MD, FACC, FESC Ali Oto, MD, MD, FESC, FACC, FHRS Daniel Piniero, MD Dong Zhao, MD, PhD Inteventional Cardiology Subcommittee Manesh R. Patel, MD, Chair Duane S. Pinto, MD, MPH, Vice Chair J. Dawn Abbott, MD Deepak L. Bhatt, MD, MPH, FAHA Mauricio G. Cohen MD, FSCAI Douglas E. Drachman, MD C. Michael Gibson, MS, MD Allen Jeremias, MD, MSc W. Schuyler Jones MD David E. Kandzari, MD, FSCAI Navin K. Kapur, MD, FAHA Raj R. Makkar, MD Laura Mauri, MD, MSc Julie M. Miller, MD Seung-Jung Park, MD, PhD, Sunil V. Rao, MD Horst Sievert, MD Paul Sorajja, MD Thomas T. Tsai, MD, MSc Christopher J. White, MD, FSCAI, FAHA, FESC