Digital Commons Network^™

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A Schultz, Eric Mcdade, Nicolas R Barthelemy, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D Chen, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Jason J Hassenstab, Celeste M Karch, John C Morris, Richard J Perrin, Chengjie Xiong, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Impact Of Donor Age And Relationship On Outcomes Of Peripheral Blood Haploidentical Hematopoietic Cell Transplantation, Aaron Pruitt, Feng Gao, Elisa De Togni, Hunter Cochran, Sonia Godbole, Michael Slade, Ramzi Abboud

2020-Current year OA Pubs

Here we describe a retrospective analysis of outcomes in 299 patients who underwent peripheral blood haplo-HCT with PTCy from July 2009 through May 2021 and their association with donor characteristics. Patients had mostly acute leukemias and high or very high DRI. Multivariate analyses were conducted examining OS, NRM, relapse, cytokine release syndrome, acute and chronic GVHD. Donor characteristics included age, sex, relationship, ABO status, CMV status, and HLA match grade. Our analysis revealed increasing donor age was associated with higher NRM (compared to age <30; age 30-44 HR, 1.65; P = 0.110, age >44 HR, 1.80; P = 0.056) but lower relapse risk (compared to age <30; age 30-44 HR, 0.61; P = 0.034, age > 44 HR, 0.71; …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

Impact Of Prior Therapies And Subsequent Transplantation On Outcomes In Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) …

Communication Of Patients’ And Family Members’ Ethical Concerns To Their Healthcare Providers, Mariam Noorulhuda, Christine Grady, Paul Wakim, Talia Bernhard, Hae Lin Cho, Marion Danis

Student Papers, Posters & Projects

BACKGROUND: Little is known about communication between patients, families, and healthcare providers regarding ethical concerns that patients and families experience in the course of illness and medical care. To address this gap in the literature, we surveyed patients and family members to learn about their ethical concerns and the extent to which they discussed them with their healthcare providers.

METHODS: We surveyed adult, English-speaking patients and family members receiving inpatient care in five hospitals in the Washington DC-Baltimore metropolitan area from July 2017 to March 2020. Descriptive statistics were used to determine the frequency, comfortableness, and helpfulness of discussions regarding …

Telehealth Diagnosis Of Autism Spectrum Disorder Through Clinical Cases, Emmanuela Ojukwu, Eunice Bawafaa, Sara Afsah, Shivangi Singh, Harsimran Grewal, Zainab Raja, Emily Mckay

Faculty, Staff and Student Publications

INTRODUCTION: African, Caribbean and Black (ACB) adolescents are disproportionately affected by teen pregnancy in North America. Teen pregnancy poses risks to the quality of life of adolescent boys and girls, including physical, psychosocial and socioeconomic risks. Our review aims to explore this public health concern for ACB adolescents within North America. We aim to identify and analyse available evidence on the incidence and prevalence of, associated factors of and interventions to curtail teen pregnancy involvement (TPI) among ACB adolescent boys and girls in North America. This review will explore TPI, rather than teen pregnancy, to ensure a review of men' …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

China Stroke Surveillance Report 2021, Wen-Jun Tu, Long-De Wang, Special Writing Group Of China Stroke Surveillance Report

Faculty, Staff and Student Publications

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6–18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3–3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2–2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4–12.5%) of stroke survivors were left disabled, as defined by a modified …

Proteomics Analysis Of Plasma From Middle-Aged Adults Identifies Protein Markers Of Dementia Risk In Later Life, Keenan A Walker, Jingsha Chen, Liu Shi, Yunju Yang, Myriam Fornage, Linda Zhou, Pascal Schlosser, Aditya Surapaneni, Morgan E Grams, Michael R Duggan, Zhongsheng Peng, Gabriela T Gomez, Adrienne Tin, Ron C Hoogeveen, Kevin J Sullivan, Peter Ganz, Joni V Lindbohm, Mika Kivimaki, Alejo J Nevado-Holgado, Noel Buckley, Rebecca F Gottesman, Thomas H Mosley, Eric Boerwinkle, Christie M Ballantyne, Josef Coresh

Faculty, Staff and Student Publications

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that …

Segmentation Of Human Functional Tissue Units In Support Of A Human Reference Atlas, Yashvardhan Jain, Leah L Godwin, Yingnan Ju, Naveksha Sood, Ellen M Quardokus, Andreas Bueckle, Teri Longacre, Aaron Horning, Yiing Lin, Edward D Esplin, John W Hickey, Michael P Snyder, Nathan Heath Patterson, Jeffrey M Spraggins, Katy Börner

2020-Current year OA Pubs

The Human BioMolecular Atlas Program (HuBMAP) aims to compile a Human Reference Atlas (HRA) for the healthy adult body at the cellular level. Functional tissue units (FTUs), relevant for HRA construction, are of pathobiological significance. Manual segmentation of FTUs does not scale; highly accurate and performant, open-source machine-learning algorithms are needed. We designed and hosted a Kaggle competition that focused on development of such algorithms and 1200 teams from 60 countries participated. We present the competition outcomes and an expanded analysis of the winning algorithms on additional kidney and colon tissue data, and conduct a pilot study to understand spatial …

Hypertension Education To Enhance Health Literacy, Kylee Westrip

Student Scholarly Projects

Practice Problem: The health of patients suffers greatly when their health literacy is not addressed through evidence-based education material.

PICOT: The PICOT question that guided this project was, in adult patients with hypertension (P), how does evidence-based education material (I) compared to the current state of verbal instructions provided (C) affect health literacy rates based on the high blood pressure health literacy scale (O) within 12-weeks (T)?

Evidence: The literature evidence revealed three strong themes, which included information on who is most at risk for low health literacy levels, education delivery methods, and specific education to be used.

Intervention: …

Back To Basics: Improving The Quality Of Blood Pressure Measurement, Heather Sailor

Student Scholarly Projects

Practice Problem: Hypertension is a leading cause of death and disability worldwide. Blood pressure measurement (BPM) is at the forefront of diagnosing and treating hypertension, however, it is often measured inaccurately.

PICOT: The PICOT question that guided this project was: In outpatient adult patients (P), what is the effect of implementing a standardized blood pressure measurement protocol (I) versus standard measurement (C), on the quality of blood pressure measurement (O) within 8 weeks (T)?

Evidence: Implementation of a blood pressure measurement protocol has been shown to improve the quality of blood pressure measurement.

Intervention: A blood pressure measurement protocol …

Temporal Trends And Geographic Variations In Mortality Rates From Tobacco And Firearms In The United States, Sarah A Palumbo, Robert S Levine, Janet D Robishaw, Charles H Hennekens

Faculty, Staff and Students Publications

We explored temporal trends and geographic variations in United States of America (US) mortality rates from smoking and firearms from 1999 to 2019. To do so, we used the publicly available Centers for Disease Control and Prevention (CDC) Wide Ranging Online Data for Epidemiologic Research (WONDER) with Multiple Cause of Death files from 1999 to 2019. Using age-specific rates and ArcGIS Pro Advanced software for Optimized Hot Spot Analyses from Esri, we generated maps of statistically significant spatial clusters with 90-99% confidence intervals with the Getis-Ord Gi* statistic for mortality from smoking-related causes and firearms. These data show temporal trends …

Long-Term Outcomes In Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Focus On Hypertension And Cardiovascular Toxicity, Max J Gordon, Jade E Jones, Binsah George, Christine Peterson, Jan A Burger, Nitin Jain, Michael Keating, William G Wierda, Jean-Bernard Durand, Alessandra Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities.

METHODS: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method.

RESULTS: Three hundred patients …

Effectiveness Of Individualized Counseling On The Duration Of Exclusive Breastfeeding: Study Protocol For A Multicenter, Randomized, Parallel, And Open Clinical Trial., Mariana Torreglosa Ruiz, Elisa Da Conceição Rodrigues, Karine Emanuelle Peixoto Oliveira Da Silva, Cynthya Viana De Resende, Michele Curcino Cavalcanti, Luciano Marques Dos Santos, Monika Wernet, Ana Letícia Monteiro Gomes, Marialda Moreira Christoffel, Maria Beatriz Guimarães Raponi, Jéssica Aparecida Da Silva, Jacqueline Faria De Oliveira, Divanice Contim, Ana Linares

Nursing Faculty Publications

BACKGROUND: Despite the benefits of breastfeeding, early weaning is a reality, so less than 50% of children worldwide and in Brazil are on exclusive breastfeeding in the sixth month of life. A strategy to counteract this scenario is breastfeeding counseling. This study aims to verify the effectiveness of individualized counseling by nurses trained in breastfeeding counseling, on the duration of exclusive breastfeeding, compared to standard care.

METHODS: Multicenter, randomized, parallel, and open clinical trial, with primiparous women aged over 18 years, hospitalized in rooming-in wards at participating centers and hemodynamically stable, aware, and oriented, who had a single-fetus pregnancy and …

Associations Between Age, Sex, Apoe Genotype, And Regional Vascular Physiology In Typically Aging Adults, Nikou L Damestani, John Jacoby, Shrikanth M Yadav, Allison E Lovely, Aurea Michael, Melissa Terpstra, Marziye Eshghi, Barnaly Rashid, Carlos Cruchaga, David H Salat, Meher R Juttukonda

2020-Current year OA Pubs

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood …

Attention-Deficit Hyperactivity Disorder: Improving Outcomes Through Early Identification, Tina Lusk

Dissertations

Problem: Failure to identify and treat attention-deficit hyperactivity disorder (ADHD) is associated with academic underachievement, social difficulties, negative physical and mental health effects. Evidence suggests approximately 3% of a broad-based population sample and roughly 13% of an at-risk population are undiagnosed despite significant symptomology (Downey & Zun, 2018; Madsen et al., 2018; Okumura et al., 2019). The United States (U.S.) has no structured screening system for ADHD. Consequently, children receive no referral for diagnosis or treatment to mitigate its effects.

Methods: The Institute for Healthcare Improvement (IHI) Model for Evidence-Based Practice using the Plan Do Study Act (PDSA) cycle guided …

Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 …

Brentuximab Vedotin After Autologous Transplantation In Pediatric Patients With Relapsed/Refractory Hodgkin Lymphoma, Christopher J Forlenza, Jaclyn Rosenzweig, Audrey Mauguen, Ilia Buhtoiarov, Branko Cuglievan, Hema Dave, Rebecca J Deyell, Jamie E Flerlage, Anna K Franklin, Jennifer Krajewski, Kasey J Leger, Lianna J Marks, Robin E Norris, Martha Pacheco, Faye Willen, Adam Paul Yan, Paul D Harker-Murray, Lisa Giulino-Roth

Faculty, Staff and Student Publications

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with ∼50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplantation (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after ASCT for the treatment of relapsed/refractory HL to …

A Multicenter Analysis Of The Outcomes With Venetoclax In Patients With Relapsed Mantle Cell Lymphoma, Yazeed Sawalha, Scott Goldsmith, Brad S Kahl, Et Al.

2020-Current year OA Pubs

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n = 50, 62%) or in combination with a Bruton tyrosine kinase inhibitor (BTKi) (n = 16, 20%), an anti-CD20 monoclonal antibody (n = 11, 14%), or other active agents at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTKis in 91%. Venetoclax alone or in combination resulted in an overall response rate …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Mitophagy Promotes Resistance To Bh3 Mimetics In Acute Myeloid Leukemia, Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis

Faculty, Staff and Student Publications

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 …

Feasibility And Safety Of Personalized, Multi-Target, Adoptive Cell Therapy (Ima101): First-In-Human Clinical Trial In Patients With Advanced Metastatic Cancer, Apostolia M Tsimberidou, Kerstin Guenther, Borje S Andersson, Regina Mendrzyk, Amir Alpert, Claudia Wagner, Anna Nowak, Katrin Aslan, Arun Satelli, Fabian Richter, Sabrina Kuttruff-Coqui, Oliver Schoor, Jens Fritsche, Zoe Coughlin, Ali S Mohamed, Kerry Sieger, Becky Norris, Rita Ort, Jennifer Beck, Henry Hiep Vo, Franziska Hoffgaard, Manuel Ruh, Linus Backert, Ignacio I Wistuba, David Fuhrmann, Nuhad K Ibrahim, Van Karlyle Morris, Bryan K Kee, Daniel M Halperin, Graciela M Nogueras-Gonzalez, Partow Kebriaei, Elizabeth J Shpall, David Vining, Patrick Hwu, Harpreet Singh, Carsten Reinhardt, Cedrik M Britten, Norbert Hilf, Toni Weinschenk, Dominik Maurer, Steffen Walter

Faculty, Staff and Student Publications

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with …

Phenotype And Genotype Heterogeneity Of Pla2g6-Associated Neurodegeneration In A Cohort Of Pediatric And Adult Patients, Ali Zare Dehnavi, Maryam Bemanalizadeh, Seyyed Mohammad Kahani, Mahmoud Reza Ashrafi, Mohammad Rohani, Mehran Beiraghi Toosi, Morteza Heidari, Sareh Hosseinpour, Behnam Amini, Shaghayegh Zokaei, Zahra Rezaei, Hajar Aryan, Man Amanat, Hassan Vahidnezhad, Pouria Mohammadi, Masoud Garshasbi, Ali Reza Tavasoli

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6.

METHODS: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In …

Tissue Mass Spectrometry: How Solid Is Our Future?, Daisy Unsihuay, William S Phipps, Amanda G Paulovich, Jessica R Chapman, Axel Ducret, Livia S Eberlin, Jeffrey M Spraggins, Richard J A Goodwin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality In People With Human Immunodeficiency Virus In High-Income Countries: An International Collaborative Cohort Study, Suzanne M Ingle, Elvin Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings.

METHODS: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 …

Comparison Of Patient Exit Interviews With Unannounced Standardised Patients For Assessing Hiv Service Delivery In Zambia: A Study Nested Within A Cluster Randomised Trial, Kombatende Sikombe, Aaloke Mody, Ingrid Eshun-Wilson, Elvin Geng, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias.

SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART).

PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021.

INTERVENTION: Systematic sample (every n

OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to …

Conditional Metastasis Of Uveal Melanoma In 8091 Patients Over Half-Century (51 Years) By Age Group: Assessing The Entire Population And The Extremes Of Age, Carol L. Shields, Annika Samuelson, Glenn Oh, Joseph D. Desimone, Zaynab Sajjadi, Zeynep Bas, Nicholas E Kalafatis, Sara E. Lally, Jerry A. Shields, Philip W. Dockery

Wills Eye Hospital Papers

PURPOSE: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age).

METHODS: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific …

Reasons Patients Cite To Their Health-Care Professional For Not Initiating Or Completing Human Papillomavirus Vaccination, Onyema Greg Chido-Amajuoyi, Ikponmwosa Osaghae, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Vaccination against human papillomavirus (HPV) is critical to the prevention of HPV-associated cancers. This study aimed to describe the reasons patients cited for not initiating or completing the HPV vaccination series, as reported by health-care professionals.

METHODS: Study data were obtained from a University of Texas MD Anderson Cancer Center population-based cross-sectional survey of health-care professionals practicing in Texas. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated by patient population (parents of children and adult patients).

RESULTS: The study included 973 primary care clinicians, of whom 45.53% were physicians and 54.47% were midlevel …