Digital Commons Network^™

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

On The Number Of Monochromatic Cliques In A Graph, Deepak Bal, Jonathan Cutler, Luke Pebody

Department of Mathematics Faculty Scholarship and Creative Works

Nordhaus and Gaddum proved sharp upper and lower bounds on the sum and product of the chromatic number of a graph and its complement. Over the years, similar inequalities have been shown for a plenitude of different graph invariants. In this paper, we consider such inequalities for the number of cliques (complete subgraphs) in a graph G, denoted k(G). We note that some such inequalities have been well-studied, e.g., lower bounds on k(G) + k(G) = k(G) + i(G), where i(G) is the number of independent subsets of G, has been come to be known as the study of Ramsey …

Clinical Trials For Wolfram Syndrome Neurodegeneration: Novel Design, Endpoints, And Analysis Models, Guoqiao Wang, Zhaolong Adrian Li, Ling Chen, Heather Lugar, Tamara Hershey

2020-Current year OA Pubs

OBJECTIVE: Wolfram syndrome, an ultra-rare condition, currently lacks effective treatment options. The rarity of this disease presents significant challenges in conducting clinical trials, particularly in achieving sufficient statistical power (e.g., 80%). The objective of this study is to propose a novel clinical trial design based on real-world data to reduce the sample size required for conducting clinical trials for Wolfram syndrome.

METHODS: We propose a novel clinical trial design with three key features aimed at reducing sample size and improve efficiency: (i) Pooling historical/external controls from a longitudinal observational study conducted by the Washington University Wolfram Research Clinic. (ii) Utilizing …

Examining And Classifying Reasons For Missing Viral Loads Among Adults Living With Hiv: An Extended Outcome Investigation And Ascertainment Approach In Western Kenya, Harriet Fridah Adhiambo, Jayne Lewis-Kulzer, Edwin Nyagesoa, Sarah Gimbel, Eliud Akama, Dorothy Mangale, Lina Montonya, Ingrid Eshun-Wilson, Sarah Iguna, Everlyne Nyandieka, Elizabeth Bukusi, Lisa Abuogi, Thomas Odeny, Maya L. Petersen, Elvin H. Geng

2020-Current year OA Pubs

Gaps in HIV RNA monitoring persist globally impeding the ability to determine clinical progress and outcomes. This study systematically evaluated provider (e.g., guideline non-adherence), system (e.g., laboratory error) and participant-level (e.g., refusal) drivers of missed viral load (VL) monitoring measurements among people with HIV in Kenya. Adults aged 18-65 years were followed across five health facilities in Kenya as part of a clinical trial (NCT#02338739) where HIV RNA monitoring was done routinely. Instances of missed VL despite being indicated per Kenyan guidelines were identified. An algorithm for assessing root causes of missing HIV RNA was developed and generalized linear models …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …

Revisiting Abdominal Wall "Morbidity" Of The Extensile Anterolateral Approach To The Thoracolumbar Spine, Alekos A Theologis, Andrew P Collins, Kanwar Parhar, Munish C Gupta

2020-Current year OA Pubs

PURPOSE: To assess patients' perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires.

METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ).

RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 …

Costs Of Non-Metastatic Prostate Cancer Treatment Among Privately Insured Men In The United States, Ashley J. Housten, Su-Hsin Chang, Hannah E. Rice, Allison J. L'Hotta, Eric H. Kim, Bettina F. Drake, Joanna L. Buss, Mary C. Politi

2020-Current year OA Pubs

BACKGROUND: Our objective was to quantify the cumulative total and out-of-pocket (OOP) costs for 3 non-metastatic prostate cancer treatment modalities: radiation, surgery, and conservative management at intervals of 1-, 3-, and 5-years post-diagnosis. We predicted these cumulative costs for a typical patient to improve cost transparency, facilitate conversations about potential costs, and to help advance non-metastatic prostate cancer cost evaluation.

METHODS: We used Merative™ MarketScan® Commercial Database data from 2007-2020. The cumulative total costs evaluated from the healthcare sector perspective were patient, clinician, and system/facility costs. We used descriptive statistics to summarize the sociodemographic characteristics of the cohort and a …

First Successful Ovarian Cortex Allotransplant To A Turner Syndrome Patient Requiring Immunosuppression: Wide Implications, Sherman J Silber, Sierra Goldsmith, Benjamin Rubinoff, Eduardo Kelly, Rowena Delos Santos, Anibal Melo, Daniel Brennan

2020-Current year OA Pubs

OBJECTIVE: To determine whether we can safely and successfully transplant an ovary tissue allograft from a nonidentical donor to her Turner syndrome sister.

DESIGN: Transplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However, there have not yet been any ovary transplants between nonidentical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available.

PATIENT(S): A 20-year-old amenorrheic woman with nonmosaic 45-XO Turner syndrome requested ovary tissue transplantation from her …

A Holistic Ecosystem Model To Diversify The Physician Workforce And Enhance Health, Erik J Porfeli, Sunny Nakae, Leila Amiri, Leila E Harrison, Will Ross

2020-Current year OA Pubs

IMPORTANCE: The U.S. medical education system attracts and trains the next generation of physicians to advance the health care needs of a growing and increasingly diverse nation. This system can be credited for supplying a physician workforce achieving remarkable growth and innovation, yielding one of the world's most technologically advanced health care systems on the planet. This system, unfortunately, also contributes to educational, workforce, and health disparities.

OBSERVATIONS: The successes and challenges of the medical education and health care system align with broader economic, health, and educational patterns in the United States. An ecological model can be employed to unite …

Baseline Clinical Characterization Of Participants In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

METHODS: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity …

Sample Ascertainment And Recruitment Sources In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

METHODS: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various …

Dfcp1 Is A Regulator Of Starvation-Driven Atgl-Mediated Lipid Droplet Lipolysis, Victoria A Ismail, Meg Schuetz, Zak N Baker, Jean A Castillo-Badillo, Teri V Naismith, David J Pagliarini, David J Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and therefore play a central role in cellular metabolism. Double FYVE Domain Containing Protein 1 (DFCP1/ZFYVE1) has emerged as a key regulator of LD metabolism, where the nucleotide-dependent accumulation of DFCP1 on LDs influences their size, number, and dynamics. Here we show that DFCP1 regulates lipid metabolism by directly modulating the activity of Adipose Triglyceride Lipase (ATGL/PNPLA2), the rate-limiting lipase driving the catabolism of LDs. We show through pharmacological inhibition of key enzymes associated with LD metabolism that …

Multisensory Naturalistic Decoding With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Zachary E Markow, Morgan Fogarty, Mariel L Schroeder, Alexa M Svoboda, Adam T Eggebrecht, Bradley L Schlaggar, Jason W Trobaugh, Joseph P Culver

2020-Current year OA Pubs

SIGNIFICANCE: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

AIM: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications. Although early visual decoding studies with HD-DOT have been promising, decoding of naturalistic auditory and multisensory stimulus information from HD-DOT data …

Zika Virus Encephalitis Causes Transient Reduction Of Functional Cortical Connectivity, Shannon C Agner, Lindsey M Brier, Jeremy D Hill, Ethan Y Liu, Annie Bice, Rachel M Rahn, Shengxuan Chen, Joseph P Culver, Robyn S Klein

2020-Current year OA Pubs

SIGNIFICANCE: Determining the long-term cognitive impact of infections is clinically challenging. Using functional cortical connectivity, we demonstrate that interhemispheric cortical connectivity is decreased in individuals with acute Zika virus (ZIKV) encephalitis. This correlates with decreased presynaptic terminals in the somatosensory cortex. During recovery from ZIKV infection, presynaptic terminals recover, which is associated with recovered interhemispheric connectivity. This supports the contribution of synapses in the cortex to functional networks in the brain, which can be detected by widefield optical imaging. Although myeloid cell and astrocyte numbers are still increased during recovery, RNA transcription of multiple proinflammatory cytokines that increase during acute …

Structural Diversity Of Axonemes Across Mammalian Motile Cilia, Miguel Ricardo Leung, Chen Sun, Jianwei Zeng, Jacob R Anderson, Qingwei Niu, Wei Huang, Willem E M Noteborn, Alan Brown, Tzviya Zeev-Ben-Mordehai, Rui Zhang

2020-Current year OA Pubs

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii

Slc35a2 Gene Product Modulates Paramyxovirus Fusion Events During Infection, Yanling Yang, Yuchen Wang, Danielle E. Campbell, Heng-Wei Lee, Wandy Beatty, Leran Wang, Megan Baldridge, Carolina B. López

2020-Current year OA Pubs

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed …

Enhancing Engagement In Hiv Care Among Adolescents And Young Adults: A Focus On Phone-Based Navigation And Relationship Building To Address Barriers In Hiv Care, Harriet Fridah Adhiambo, Dorothy Imbuka Mangale, Elvin Geng, Et Al.

2020-Current year OA Pubs

Structural, psychological, and clinical barriers to HIV care engagement among adolescents and young adults living with HIV (AYAH) persist globally despite gains in HIV epidemic control. Phone-based peer navigation may provide critical peer support, increase delivery flexibility, and require fewer resources. Prior studies show that phone-based navigation and automated text messaging interventions improve HIV care engagement, adherence, and retention among AYAH. However, little is known about AYAH experiences utilizing electronic phone-based peer navigation and automated text messaging (E-NAV). We assessed the experiences of AYAH receiving phone-based peer navigation to address barriers to HIV care engagement and viral suppression. We purposefully …

Patient Stratification By Genetic Risk In Alzheimer's Disease Is Only Effective In The Presence Of Phenotypic Heterogeneity, Jack Euesden, Muhammad Ali, Chloe Robins, Praveen Surendran, Padhraig Gormley, Alzheimer’S Disease Neuroimaging Initiative, David Pulford, Carlos Cruchaga

2020-Current year OA Pubs

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving …

What Is The Optimal Management Of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate Or Not To Operate?, William Chu Kwan, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Systematic review.

OBJECTIVE: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

METHODS: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery. Dates of publication were between 2013-22. Patients …

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A. Rosa, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …

Overview Of Molecular Prognostication For Common Solid Tumor Histologies - What The Surgeon Should Know, C Rory Goodwin, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Literature review.

OBJECTIVE: To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting.

METHODS: A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language. Relevant articles were reviewed for commonly described molecular mutations or targeted therapeutics, as well as associated clinical outcomes, and surgery-related …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …

Menin Inhibition With Revumenib For Kmt2a-Rearranged Relapsed Or Refractory Acute Leukemia (Augment-101), Ghayas C Issa, John Dipersio, Et Al.

2020-Current year OA Pubs

PURPOSE: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with

METHODS: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R

RESULTS: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), …

Sentence Determination As A Function Of Sex Offender Gender, Kyle Gamache, Matt Zaitchik, Judith Platania, Willem Pontbriand

Arts & Sciences Faculty Publications

The current study examines perceptions of dangerousness and sentencing recommendations for female sex offenders (FSOs) compared to male sex offenders (MSOs). Participants (N = 82) were randomly assigned to read one of three vignettes depicting a sexual offense committed by a male, female, or male-female co defendant pair. Key individual difference variables—Need for Cognition (NFC) and Gender Role Beliefs (GRB)—were assessed to examine their influence on sentencing and attributional judgments. NFC emerged as a significant moderator: participants with low NFC assigned longer sentences to FSOs, whereas high NFC participants gave longer sentences to MSOs. Participants endorsing traditional gender role beliefs …

Diversifying Ecology Education For Everyone Through More Inclusive, Interdisciplinary, And Accessible Teaching, Loren B. Byrne, Emily S. J. Rauschert, Vikki L. Rodgers, Gillian Bowser, Et Al.

Arts & Sciences Faculty Publications

Educating more students about ecology and its beneficial applications to societal issues is urgent yet challenging. To address this challenge, diversifying ecology education is a key way to make ecology more inclusive, accessible, and interdisciplinary for more people than ever. Advancing this goal requires ecology educators to develop a more expansive view of (1) how to engage more diverse undergraduate students in ecology courses, especially those from historically underrepresented groups and non-majors, (2) the interdisciplinarity of content in those courses, and (3) the learner-centered pedagogies used to engage students. We suggest ways that ecologists can advance “ecology education for everyone” …

Burkitt's Lymphoma Presenting As Multiple Nerve Sheath Tumors Of The Cauda Equina., Jason Milton, Punit Pandya, Sergio Ulloa, Vijay Kudithipudi, Shakir Sarwar, Victor Awuor

Oncology Articles

BACKGROUND: Primary central nervous system lymphomas comprise 0.8% of all lymphomas. Burkitt's lymphoma is a B-cell lymphoma with highly aggressive features that rapidly progress and have early hematogenous spread. Sporadic Burkitt's lymphoma accounts for 1-2% of adult lymphomas worldwide. Extranodal sites are involved in approximately 40% of cases of B-cell lymphomas. Central nervous system disease is found in < 15% of sporadic cases. Less than 5% of cases of all non-Hodgkin's lymphomas present with radiculopathy, with the thoracic spinal region being most commonly affected.

CASE DESCRIPTION: In this report, we discuss the case of a patient with extranodal Burkitt's lymphoma within the nerve roots of the cauda equina who underwent surgical intervention due to the presence of lumbar radiculopathy and weakness. This patient also exhibited hematogenous …

Methylome Analysis Of Ftld Patients With Tdp-43 Pathology Identifies Epigenetic Signatures Specific To Pathological Subtypes, Cristina T. Vicente, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

No abstract provided.

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer's Disease, Farid Rajabli, Bruno A. Bonitez, Nigel J. Cairns, John C. Morriswashington University School Of Medicine In St. Louis, Carlos Cruchaga, Oscar Harari, Laura Ibanez, Et Al.

2020-Current year OA Pubs

No abstract provided.

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …