Medicine and Health Sciences Commons^™

Detecting Cognitive Impairment And Dementia In The Emergency Department: A Scoping Review, Armin Nowroozpoor, Jeff Dussetschleger, William Perry, Mary Sano, Amy Aloysi, Michael Belleville, Alexandria Brackett, Jon Mark Hirshon, William Hung, Joan Michelle Moccia, Ugochi Ohuabunwa, Manish N Shah, Ula Hwang

Faculty, Staff and Student Publications

OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).

DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.

SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients.

METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and …

Association Of Changes In Antithrombin Activity Over Time With Responsiveness To Enoxaparin Prophylaxis And Risk Of Trauma-Related Venous Thromboembolism, Laura E Vincent, Michael M Talanker, Dakota D Butler, Xu Zhang, Jeanette M Podbielski, Yao-Wei W Wang, Amber Chen-Goodspeed, Selina L Hernandez Gonzalez, Erin E Fox, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity < 80%).

Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis.

Design, setting, and participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January …

Venetoclax Combined With Flag-Ida Induction And Consolidation In Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Curtis A Lachowiez, Koichi Takahashi, Sanam Loghavi, Tapan Kadia, Naval Daver, Lianchun Xiao, Maria Adeoti, Nicholas J Short, Koji Sasaki, Sa A Wang, Gautam Borthakur, Ghayas Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Multi-agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single-center phase Ib/II study evaluating fludarabine, cytarabine, G-CSF, and idarubicin combined with venetoclax (FLAG-IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of …

Insulin Resistance In Depression: A Large Meta-Analysis Of Metabolic Parameters And Variation, Brisa S Fernandes, Estela Salagre, Nitesh Enduru, Iria Grande, Eduard Vieta, Zhongming Zhao

Faculty, Staff and Student Publications

Increased insulin resistance is recognized in psychiatric disorders, such as schizophrenia and bipolar disorder, but its occurrence in depression is less clear. Our aims were to verify if insulin resistance is altered in depression, to test the metabolic subgroup hypothesis of depression and if there are changes with antidepressants. Inclusion criteria were studies including adult subjects with depression and either a control group or follow-up after treatment with antidepressants, and assessing fasting insulin or glucose levels or the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Seventy studies with 240,704 participants were included. Both insulin levels and the HOMA-IR index …

Phase Ii Study Of Durvalumab (Anti-Pd-L1) And Trametinib (Meki) In Microsatellite Stable (Mss) Metastatic Colorectal Cancer (Mcrc), Benny Johnson, Cara L Haymaker, Edwin R Parra, Luisa Maren Solis Soto, Xuemei Wang, Jane V Thomas, Arvind Dasari, Van K Morris, Kanwal Raghav, Eduardo Vilar, Bryan K Kee, Cathy Eng, Christine M Parseghian, Robert A Wolff, Younghee Lee, Daniele Lorenzini, Caddie Laberiano-Fernandez, Anuj Verma, Wenhua Lang, Ignacio I Wistuba, Andrew Futreal, Scott Kopetz, Michael J Overman

Faculty, Staff and Student Publications

Background: Monotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells.

Methods: Open-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L Phan, Jacob H Elnaggar, Brianna Resendiz, Andrea Y Delgado Medrano, Erica J Lynn, Nicholas D Nguyen, Sonal S Noticewala, Geena G Mathew, Emma B Holliday, Bruce D Minsky, Prajnan Das, Van K Morris, Cathy Eng, Melissa P Mezzari, Joseph F Petrosino, Nadim J Ajami, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert

Faculty, Staff and Student Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Patient Preferences For Strategies To Improve Tuberculosis Diagnostic Services In Zambia, Andrew D Kerkhoff, Lophina Chilukutu, Sarah Nyangu, Mary Kagujje, Kondwelani Mateyo, Nsala Sanjase, Ingrid Eshun-Wilson, Elvin H Geng, Diane V Havlir, Monde Muyoyeta

2020-Current year OA Pubs

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.

Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.

Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was …

Nivolumab Plus Rucaparib For Metastatic Castration-Resistant Prostate Cancer: Results From The Phase 2 Checkmate 9kd Trial, Karim Fizazi, Margitta Retz, Daniel P Petrylak, Jeffrey C Goh, Jose Perez-Gracia, Louis Lacombe, Stefanie Zschäbitz, Mauricio Burotto, Hakim Mahammedi, Gwenaelle Gravis, Diogo Assed Bastos, Steven L Mccune, Juan Carlos Vázquez Limón, Edmond M Kwan, Daniel Castellano, Aude Fléchon, Fred Saad, Marc-Oliver Grimm, David R Shaffer, Andrew J Armstrong, Prabhu Bhagavatheeswaran, Neha P Amin, Keziban Ünsal-Kaçmaz, Xuya Wang, Jun Li, Andrea Loehr, Russell K Pachynski

2020-Current year OA Pubs

BACKGROUND: CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib.

METHODS: CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 …

Household Transmission Of Group A Streptococcus Necrotizing Fasciitis., Michael Markowitz, Stephanie Kwan, Jonas Matzon

Department of Orthopaedic Surgery Faculty Papers

A healthy 40-year-old woman was diagnosed with necrotizing fasciitis 2 days after her husband's death from the same infectious process. Prompt identification and immediate surgical intervention prevented a similar result in this patient. Additional investigation into both patients' medical records found the inciting organism to be group A streptococcus. Although the exact mechanism of inoculation is unknown, the spread of this infection within a household prompts the question of whether antibiotic prophylaxis should be given among close contacts in future cases of necrotizing fasciitis.

Resting-State Functional Connectivity Identifies Individuals And Predicts Age In 8-To-26-Month-Olds, Omid Kardan, Sydney Kaplan, Muriah D. Wheelock, Dominique Meyer, Adam T. Eggebrecht, Christopher D. Smyser, Et Al.

2020-Current year OA Pubs

Resting-state functional connectivity (rsFC) measured with fMRI has been used to characterize functional brain maturation in typically and atypically developing children and adults. However, its reliability and utility for predicting development in infants and toddlers is less well understood. Here, we use fMRI data from the Baby Connectome Project study to measure the reliability and uniqueness of rsFC in infants and toddlers and predict age in this sample (8-to-26 months old; n = 170). We observed medium reliability for within-session infant rsFC in our sample, and found that individual infant and toddler's connectomes were sufficiently distinct for successful functional connectome …

Detection Of Brain Tau Pathology In Down Syndrome Using Plasma Biomarkers, Shorena Janelidze, Bradley T Christian, Julie Price, Charles Laymon, Nicole Schupf, William E Klunk, Ira Lott, Wayne Silverman, H Diana Rosas, Shahid Zaman, Mark Mapstone, Florence Lai, Beau M Ances, Benjamin L Handen, Oskar Hansson

2020-Current year OA Pubs

IMPORTANCE: Novel plasma biomarkers, especially phosphorylated tau (p-tau), can detect brain tau aggregates in Alzheimer disease.

OBJECTIVE: To determine which plasma biomarker combinations can accurately detect tau pathological brain changes in Down syndrome (DS).

DESIGN, SETTING, AND PARTICIPANTS: The cross-sectional, multicenter Alzheimer's Biomarker Consortium-Down Syndrome study included adults with DS and a control group of siblings without DS. All participants with plasma, positron emission tomography (PET), and cognitive measures available by the time of data freeze 1.0 were included. Participants were enrolled between 2016 and 2019, and data were analyzed from August 2021 to April 2022.

EXPOSURES: Plasma p-tau217, glial …

Predicting Brain Age From Functional Connectivity In Symptomatic And Preclinical Alzheimer Disease, Peter R. Millar, Patrick H. Luckett, Brian A. Gordon, Tammie L. S. Benzinger, Suzanne E. Schindler, Anne M. Fagan, Carlos Cruchaga, Randall J. Bateman, Ricardo Allegri, Mathias Jucker, Jae-Hong Lee, Hiroshi Mori, Stephen P. Salloway, Igor Yakushev, John C. Morris, Beau M. Ances, Dominantly Inherited Alzheimer Network

2020-Current year OA Pubs

"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and …

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression For Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series, Momodou L Jammeh, Alexander Yang, Ahmmad A Abuirqeba, J Westley Ohman, Robert W Thompson

2020-Current year OA Pubs

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge.

OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS.

METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively.

RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 …

The University Of Pennsylvania Glioblastoma (Upenn-Gbm) Cohort: Advanced Mri, Clinical, Genomics, & Radiomics, Spyridon Bakas, Aristeidis Sotiras, Sung Min Ha, Et Al

2020-Current year OA Pubs

Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the "University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics" (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during …

Stem Cell Transplantation For Systemic Sclerosis, Sebastian Bruera, Harish Sidanmat, Donald A Molony, Maureen D Mayes, Maria E Suarez-Almazor, Kate Krause, Maria Angeles Lopez-Olivo

Faculty, Staff and Students Publications

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.

OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).

SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February …

Ketamine For Acute Pain After Trauma: The Kapt Randomized Controlled Trial, Thaddeus J Puzio, James Klugh, Michael W Wandling, Charles Green, Julius Balogh, Samuel J Prater, Christopher T Stephens, Paulina B Sergot, Charles E Wade, Lillian S Kao, John A Harvin

Faculty, Staff and Student Publications

BACKGROUND: Evidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain.

METHODS: This is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

Reducing Falls Related To Toileting, Brian Locastro

Student Scholarly Projects

Practice Problem: The practice problem for the medical-surgical unit is a high rate of falls associated with toileting activities, despite universal fall precautions for all patients. The current fall rate is an average rate of 4 falls per 1,000 patient days.

PICOT: The PICOT question that guided this project was: Among adult patients in the inpatient medical-surgical unit (P), what is the effect of adding a toileting care plan (I) to the current practice of universal fall precautions (C) to reduce the severity and incidence of falls (O) within an 8-week period (T)?

Evidence: Nine high-quality articles supported a toileting …

Graded Variation In T1w/T2w Ratio During Adolescence: Measurement, Caveats, And Implications For Development Of Cortical Myelin, Graham L Baum, John C Flournoy, Matthew F Glasser, Michael P Harms, Patrick Mair, Ashley F P Sanders, Deanna M Barch, Randy L Buckner, Susan Bookheimer, Mirella Dapretto, Stephen Smith, Kathleen M Thomas, Essa Yacoub, David C Van Essen, Leah H Somerville

2020-Current year OA Pubs

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D;

Describing Characteristics Of Adults With And Without Congenital Heart Defects Hospitalized With Covid-19, Perla Diaz, Will Coughlin, Wilson Lam, Peter Ermis, David Aguilar, Cecilia M Ganduglia Cazaban, A J Agopian

Faculty, Staff and Student Publications

BACKGROUND: We sought to describe patient characteristics in adults with and without congenital heart defects (CHDs) during hospitalization for COVID-19.

METHODS: We analyzed data collected by Optum®, a nationally representative database of electronic medical records, for 369 adults with CHDs and 41,578 without CHDs hospitalized for COVID-19 between January 1, 2020, and December 10, 2020. We used Poisson regression to describe and compare epidemiologic characteristics, heart-related conditions, and severe outcomes between these two groups.

RESULTS: The distributions of many epidemiologic characteristics were similar between the two groups, but patients with CHDs were significantly more likely to be current or former …

Factors Affecting Pathways To Care For Children And Adolescents With Complex Vascular Malformations: Parental Perspectives, Bryan A Sisk, Anna Kerr, Katherine A King

2020-Current year OA Pubs

BACKGROUND: Complex vascular malformations (VMs) are rare disorders that can cause pain, coagulopathy, disfigurement, asymmetric growth, and disability. Patients with complex VMs experience misdiagnosis, delayed diagnosis, delayed or inappropriate treatments, and worsened health. Given the potential consequences of delaying expert care, we must identify the factors that impede or facilitate this access to care.

RESULTS: We performed semi-structured interviews with 24 parents (21 mothers; 3 fathers; median age = 42.5 years) of children with complex VMs and overgrowth disorders living in the US, recruited through two patient advocacy groups - CLOVES Syndrome Community, and Klippel-Trenaunay Support Group. We performed thematic …

Echocardiographic Predictors Of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: A Systematic Review And Meta-Analysis, Muhammad Umer Siddiqui, Youssef Yaacoub, Heidi-Anne Hanson, Joey Junarta, Ahmed K Pasha, Mahek Shah

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy.

OBJECTIVE: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy.

METHODS: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures …

Triplet Therapy, Transplantation, And Maintenance Until Progression In Myeloma, Paul G Richardson, Susanna J Jacobus, Edie A Weller, Hani Hassoun, Sagar Lonial, Noopur S Raje, Eva Medvedova, Philip L Mccarthy, Edward N Libby, Peter M Voorhees, Robert Z Orlowski, Larry D Anderson, Jeffrey A Zonder, Carter P Milner, Cristina Gasparetto, Mounzer E Agha, Abdullah M Khan, David D Hurd, Krisstina Gowin, Rammurti T Kamble, Sundar Jagannath, Nitya Nathwani, Melissa Alsina, R Frank Cornell, Hamza Hashmi, Erica L Campagnaro, Astrid C Andreescu, Teresa Gentile, Michaela Liedtke, Kelly N Godby, Adam D Cohen, Thomas H Openshaw, Marcelo C Pasquini, Sergio A Giralt, Jonathan L Kaufman, Andrew J Yee, Emma Scott, Pallawi Torka, Amy Foley, Mariateresa Fulciniti, Kyle Hebert, Mehmet K Samur, Kelly Masone, Michelle E Maglio, Andrea A Zeytoonjian, Omar Nadeem, Robert L Schlossman, Jacob P Laubach, Claudia Paba-Prada, Irene M Ghobrial, Aurore Perrot, Philippe Moreau, Hervé Avet-Loiseau, Michel Attal, Kenneth C Anderson, Nikhil C Munshi, Determination Investigators

Faculty, Staff and Students Publications

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.

METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received …

Association Of Cardiovascular Health Through Young Adulthood With Genome-Wide Dna Methylation Patterns In Midlife: The Cardia Study, Yinan Zheng, Brian T Joyce, Shih-Jen Hwang, Jiantao Ma, Lei Liu, Norrina B Allen, Amy E Krefman, Jun Wang, Tao Gao, Drew R Nannini, Haixiang Zhang, David R Jacobs, Myron D Gross, Myriam Fornage, Cora E Lewis, Pamela J Schreiner, Stephen Sidney, Dongquan Chen, Philip Greenland, Daniel Levy, Lifang Hou, Donald M Lloyd-Jones

Faculty, Staff and Student Publications

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.

Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was …

High-Sensitivity Next-Generation Sequencing Mrd Assessment In All Identifies Patients At Very Low Risk Of Relapse, Nicholas J Short, Hagop Kantarjian, Farhad Ravandi, Marina Konopleva, Nitin Jain, Rashmi Kanagal-Shamanna, Keyur P Patel, Walid Macaron, Tapan M Kadia, Sa Wang, Jeffrey L Jorgensen, Joseph D Khoury, Musa Yilmaz, Partow Kebriaei, Koichi Takahashi, Guillermo Garcia-Manero, Naval Daver, Sean M Post, Xuelin Huang, Steven M Kornblau, Sara Pelletier, Wilmer Flores, Jairo Matthews, Rebecca Garris, Elias Jabbour

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is highly prognostic for relapse and overall survival (OS) in acute lymphoblastic leukemia (ALL), although many patients with apparent "MRD negativity" by standard assays still relapse. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay in 74 adults with ALL undergoing frontline therapy. Among remission samples that were MRD negative by multiparameter flow cytometry (MFC), 46% were MRD+ by the NGS assay. After 1 cycle of induction chemotherapy, MRD negativity by MFC at a sensitivity of 1 × 10-4 and NGS at a sensitivity of 1 × 10-6 was achieved in …

Disparities In Adult Critical Care Resources Across Pakistan: Findings From A National Survey And Assessment Using A Novel Scoring System, Mustafa Ali Khan, Hamna Shahbaz, Ali Aahil Noorali, Anam Noor Ehsan, Mareeha Zaki, Fahham Asghar, Mohammed Moizul Hassan, Haroon Muhammad Arshad, Muhammad Sohaib, Adil H. Haider

Medical College Documents

Background: In response to the COVID-19 pandemic, concerted efforts were made by provincial and federal governments to invest in critical care infrastructure and medical equipment to bridge the gap of resource-limitation in intensive care units (ICUs) across Pakistan. An initial step in creating a plan toward strengthening Pakistan's baseline critical care capacity was to carry out a needs-assessment within the country to assess gaps and devise strategies for improving the quality of critical care facilities.
Methods: To assess the baseline critical care capacity of Pakistan, we conducted a series of cross-sectional surveys of hospitals providing COVID-19 care across the country. …

Dissecting The Treatment-Naive Ecosystem Of Human Melanoma Brain Metastasis, Jana Biermann, Johannes C Melms, Amit Dipak Amin, Yiping Wang, Lindsay A Caprio, Alcida Karz, Somnath Tagore, Irving Barrera, Miguel A Ibarra-Arellano, Massimo Andreatta, Benjamin T Fullerton, Kristjan H Gretarsson, Varun Sahu, Vaibhav S Mangipudy, Trang T T Nguyen, Ajay Nair, Meri Rogava, Patricia Ho, Peter D Koch, Matei Banu, Nelson Humala, Aayushi Mahajan, Zachary H Walsh, Shivem B Shah, Daniel H Vaccaro, Blake Caldwell, Michael Mu, Florian Wünnemann, Margot Chazotte, Simon Berhe, Adrienne M Luoma, Joseph Driver, Matthew Ingham, Shaheer A Khan, Suthee Rapisuwon, Craig L Slingluff, Thomas Eigentler, Martin Röcken, Richard Carvajal, Michael B Atkins, Michael A Davies, Albert Agustinus, Samuel F Bakhoum, Elham Azizi, Markus Siegelin, Chao Lu, Santiago J Carmona, Hanina Hibshoosh, Antoni Ribas, Peter Canoll, Jeffrey N Bruce, Wenya Linda Bi, Praveen Agrawal, Denis Schapiro, Eva Hernando, Evan Z Macosko, Fei Chen, Gary K Schwartz, Benjamin Izar

Faculty, Staff and Student Publications

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant …

Long-Term Follow-Up For The Development Of Subsequent Malignancies In Patients Treated With Genetically Modified Iecs, David H M Steffin, Ibrahim N Muhsen, Laquisa C Hill, Carlos A Ramos, Nabil Ahmed, Meenakshi Hegde, Tao Wang, Mengfen Wu, Stephen Gottschalk, Sarah B Whittle, Premal D Lulla, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Andras Heczey, Leonid S Metelitsa, Bambi J Grilley, Catherine Robertson, Virginia Torrano, Natalia Lapteva, Adrian P Gee, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop

Faculty, Staff and Students Publications

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, …

Etiology Of Persistent Microalbuminuria In Nigeria (P_Micro Study): Protocol And Study Design, C William Wester, Philip J Budge, Et Al.

2020-Current year OA Pubs

BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and …

Antibody Responses To Sars-Cov-2 After Infection Or Vaccination In Children And Young Adults With Inflammatory Bowel Disease., Joelynn Dailey, Lina Kozhaya, Mikail Dogan, Dena Hopkins, Blaine Lapin, Katherine Herbst, Michael Brimacombe, Kristen Grandonico, Fatih Karabacak, John Schreiber, Bruce Tsan-Liang Liang, Juan C Salazar, Derya Unutmaz, Jeffrey S Hyams

Faculty Research 2022

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and …