Medicine and Health Sciences Commons^™

Safety And Efficacy Outcomes Of Early Cessation Of Anti-Pd1 Therapy In Patients 80 Years Or Older: A Retrospective Cohort Study, Kylie Fletcher, Alessio Cortellini, Teja Ganta, Roma Kankaria, Haocan Song, Fei Ye, Rebecca Irlmeier, Neha Debnath, Anwaar Saeed, Maluki Radford, Asrar Alahmadi, Akiva Diamond, Christopher Hoimes, Carolyn J Presley, Dwight H Owen, Sarah Abou Alaiwi, Amin H Nassar, Giuseppe Lamberti, Fabiana Perrone, Sebastiano Buti, Raffaele Giusti, Marco Filetti, Vito Vanella, Domenico Mallardo, Tamara A Sussman, Domenico Galetta, Foteini Kalofonou, Ella Daniels, Paolo A Ascierto, David J Pinato, Caroline Nebhan, Stephanie Berg, Toni K Choueiri, Thomas U Marron, Yinghong Wang, Abdul Rafeh Naqash, Douglas B Johnson

Faculty, Staff and Students Publications

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (< 12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of < 12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility To Pulmonary Fibrosis, Kai Xu, Linke Ding, Wenwen Li, Yaxuan Wang, Shuaichen Ma, Hui Lian, Xiaoyue Pan, Ruyan Wan, Weiming Zhao, Juntang Yang, Ivan Rosas, Lan Wang, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by pulmonary fibroblast overactivation, resulting in the accumulation of abnormal extracellular matrix and lung parenchymal damage. Although the pathogenesis of IPF remains unclear, aging was proposed as the most prominent nongenetic risk factor. Propionate metabolism undergoes reprogramming in the aging population, leading to the accumulation of the by-product methylmalonic acid (MMA). This study aimed to explore alterations in propionate metabolism in IPF and the impact of the by-product MMA on pulmonary fibrosis. It revealed alterations in the expression of enzymes involved in propionate metabolism within IPF lung tissues, characterized …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Analytical Validation Of The Multitarget Stool Rna Test For Colorectal Cancer Screening, Erica K Barnell, Jack Land, Kimberly Kruse, Maya C Scott, Ben Wedeking, Catherine Morrison, Clayton Grass, Ann Zuniga, Elizabeth M Wurtzler, Eric J Duncavage

2020-Current year OA Pubs

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of < 0.6, < 0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and < 20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non-colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.

Population Pharmacokinetic Modelling And Simulation Of Tranexamic Acid In Adult Trauma Patients, Gideon Stitt, Philip C Spinella, Grant V Bochicchio, Ian Roberts, Kevin J Downes, Athena F Zuppa

2020-Current year OA Pubs

AIMS: The aim of this study is to describe the disposition of tranexamic acid (TXA) in adult trauma patients and derive a dosing regimen that optimizes exposure based on a predefined exposure target.

METHODS: We performed a population pharmacokinetic (popPK) analysis of participants enrolled in the Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial (≥18 years with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room) who were randomized to a single dose of either 2 or 4 g of TXA ≤2 h from time of injury. PopPK analysis was conducted using nonlinear …

Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock

2020-Current year OA Pubs

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as …

Overall Survival In Patients With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel In The Randomized Engot-En6/Gog-3031/Ruby Trial, M A Powell, C Mccourt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis.

PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were …

Predicting Post-Surgical Functional Status In High-Grade Glioma With Resting State Fmri And Machine Learning, Patrick H Luckett, Michael O Olufawo, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.

METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of …

Medicare Utilization And Cost Trends For Car T Cell Therapies Across Settings Of Care In The Treatment Of Diffuse Large B-Cell Lymphoma, James Wu, Armin Ghobadi, Richard Maziarz, Krish Patel, Hil Hsu, Zihao Liu, Caitlin Sheetz, Peter Kardel, Christine Fu

2020-Current year OA Pubs

INTRODUCTION: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways.

METHODS: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products-lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)-which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of …

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …

Lisocabtagene Maraleucel In Follicular Lymphoma: The Phase 2 Transcend Fl Study, Franck Morschhauser, Brad Kahl, Et Al.

2020-Current year OA Pubs

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. …

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .

Posttraumatic Stress Disorder And Type 2 Diabetes Outcomes In Veterans, Jeffrey F Scherrer, Joanne Salas, Wenjin Wang, Kenneth E Freedland, Patrick J Lustman, Paula P Schnurr, Beth E Cohen, Allan S Jaffe, Matthew J Friedman

2020-Current year OA Pubs

IMPORTANCE: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown.

OBJECTIVE: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to …

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

Association Of Surgical Approaches And Outcomes In Total Mesorectal Excision And Margin Status For Rectal Cancer, Muhammad Bilal Mirza, Adriana C Gamboa, Rebecca Irlmeier, Benjamin Hopkins, Scott E Regenbogen, Katherine A Hrebinko, Jennifer Holder-Murray, Jason T Wiseman, Aslam Ejaz, Paul E Wise, Fei Ye, Kamran Idrees, Alexander T Hawkins, Glen C Balch, Aimal Khan

2020-Current year OA Pubs

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer.

METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected …

Comparing Balance Using The Bestest In Alzheimer, Huntington And Parkinson Disease, Lauren E Tueth, Ryan P Duncan, Beth E Crowner, Gammon M Earhart

2020-Current year OA Pubs

No abstract provided.

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Diestro, Rachel Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann Lay, Adrien Guenego, Leonardo Renieri, Nicole Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin Vranic, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Jay Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad Hafeez, Joshua Catapano, Muhammad Waqas, Vincent Tutino, Mohamed Ibrahim, Marwa Mohammed, M. Ozgur Ozates, Giyas Ayberk, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Stéphanie Elens, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian Jankowitz, Jan-Karl Burkhardt, Ricardo Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Essibayi, Sunil Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo Cuellar-Saenz, Pascal Jabbour, Vitor Pereira, Aman Patel, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Adel Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Danilo Bengzon Diestro, Rachel M Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Nicole M Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin E Vranic, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Jay A Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Vincent M Tutino, Mohamed K Ibrahim, Marwa A Mohammed, M Ozgur Ozates, Giyas Ayberk, James D Rabinov, Yifan Ren, Clemens M Schirmer, Mariangela Piano, Anna L Kühn, Caterina Michelozzi, Stéphanie Elens, Robert M Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian T Jankowitz, Jan-Karl Burkhardt, Ricardo A Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Amir Essibayi, Sunil A Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit S Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew F Ducruet, Felipe C Albuquerque, Robert W Regenhardt, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula I Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo H Cuellar-Saenz, Pascal M Jabbour, Vitor Mendes Pereira, Aman B Patel, Adam A Dmytriw

Faculty, Staff and Student Publications

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …

Iatrogenic Atrial Septal Defect After Mitraclip Transcatheter Edge-To-Edge Repair: To Close Or Not To Close??, Mariem Abdelsalam, Raghad Younus, Lamis F Abdalla, Abdelkader Almanfi

The Texas Heart Institute Journal

The evolution of percutaneous procedures that use transseptal puncture to treat left-sided structural heart disease has led to the emergence of iatrogenic atrial septal defects as a potential complication. These defects can result in hemodynamic decompensation and worsening clinical outcomes. Some iatrogenic atrial septal defects require immediate closure, others do not. This case report presents 2 patients who underwent transcatheter edge-to-edge mitral valve repair with transseptal puncture and required iatrogenic atrial septal defect closure (1 immediate and 1 delayed). The goal of this report is to highlight iatrogenic atrial septal defect assessment and the possible need for closure after transseptal …

Potential S1 Nerve Root Blocks Associated With Sacroiliac Joint Injections, Andrew Ng, Jesse Lou, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Sacroiliac (SI) joint dysfunction is a common cause of lower back pain. The diagnosis of SI joint pain remains challenging. Sacroiliac joint injection remains the gold standard of diagnosis of SI joint pain as well as providing therapeutic effect. One complication related to SI joint injection is temporary numbness and weakness of the leg.

OBJECTIVES: To evaluate the anatomy of the SI joint and the flow of the contrast in the sacroiliac joint and to understand how local anesthetic can affect the nerve roots and cause temporary weakness and numbness of the leg.

METHODS: Patients who underwent SI joint …

Developing A Fair And Interpretable Representation Of The Clock Drawing Test For Mitigating Low Education And Racial Bias., Jiaqing Zhang, Sabyasachi Bandyopadhyay, Faith Kimmet, Jack Wittmayer, Kia Khezeli, David J. Libon, Catherine C Price, Parisa Rashidi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The clock drawing test (CDT) is a neuropsychological assessment tool to screen an individual's cognitive ability. In this study, we developed a Fair and Interpretable Representation of Clock drawing test (FaIRClocks) to evaluate and mitigate classification bias against people with less than 8 years of education, while screening their cognitive function using an array of neuropsychological measures. In this study, we represented clock drawings by a priorly published 10-dimensional deep learning feature set trained on publicly available data from the National Health and Aging Trends Study (NHATS). These embeddings were further fine-tuned with clocks from a preoperative cognitive screening program …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Adrenocortical Carcinoma Cohort, Sandip P Patel, Megan Othus, Young Kwang Chae, Tridu Huynh, Benjamin Tan, Timothy Kuzel, Christine Mcleod, Gabby Lopez, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles Blanke, Razelle Kurzrock

2020-Current year OA Pubs

OBJECTIVES: Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.

DESIGN/SETTING: A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites.

PARTICIPANTS: 21 eligible patients were registered. Median age was 53 years (range 26-69); 16 (76%) were women.

INTERVENTIONS: Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously …

Blinatumomab For Mrd-Negative Acute Lymphoblastic Leukemia In Adults, Mark R Litzow, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

METHODS: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with

RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full …

Patients' Perceptions Of Using Technology For Self-Reporting Cancer Medication Safety Events From Home, Katie Gahn, Misun Hwang, Youmin Cho, Heidi Mason, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Frequent transitions of care among patients with cancer increase their risks for medication safety events (MSEs). Patients and families need to become "vigilant partners" in MSE self-reporting when transitioning back home. However, limited evidence is available to guide patient and family engagement in preventing and managing MSEs. This study explored patients' perceptions of using technology for MSE self-reporting by interviewing 41 patients with breast, prostate, lung, or colorectal cancer. The findings revealed that patients with cancer perceived technology as convenient and easy to use to address urgent MSE concerns. However, the lack of access to technology and being unconfident in …

Impact Of Patient Demographics And Neighborhood Socioeconomic Variables On Clinical Trial Participation Patterns For Nhl, Chijioke Nze, Clark R Andersen, Amy A Ayers, Jason Westin, Michael Wang, Swaminathan Iyer, Sairah Ahmed, Chelsea Pinnix, Francisco Vega, Lynne Nguyen, Lorna Mcneill, Loretta J Nastoupil, Kehe Zhang, Cici X Bauer, Christopher R Flowers

Faculty, Staff and Student Publications

Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive …

A Scaled Proteomic Discovery Study For Prostate Cancer Diagnostic Markers Using Proteograph, Matthew E K Chang, Jane Lange, Jessie May Cartier, Travis W Moore, Sophia M Soriano, Brenna Albracht, Michael Krawitzky, Harendra Guturu, Amir Alavi, Alexey Stukalov, Xiaoyuan Zhou, Eltaher M Elgierari, Jessica Chu, Ryan Benz, Juan C Cuevas, Shadi Ferdosi, Daniel Hornburg, Omid Farokhzad, Asim Siddiqui, Serafim Batzoglou, Robin J Leach, Michael A Liss, Ryan P Kopp, Mark R Flory

Faculty, Staff and Student Publications

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate …

Global Burden Of Cardiovascular Disease Attributable To Smoking, 1990–2019: An Analysis Of The 2019 Global Burden Of Disease Study, Abdul Mannan Khan Minhas, Ramy Sedhom, Estelle D Jean, Michael D Shapiro, Julio A Panza, Mahboob Alam, Salim S Virani, Christie M Ballantyne, Dmitry Abramov

Faculty, Staff and Students Publications

Aims: This study aims to investigate the trends in the global cardiovascular disease (CVD) burden attributable to smoking from 1990 to 2019.

Methods and results: Global Burden of Disease Study 2019 was used to analyse the burden of CVD attributable to smoking (i.e. ischaemic heart disease, peripheral artery disease, stroke, atrial fibrillation and flutter, and aortic aneurysm). Age-standardized mortality rates (ASMRs) per 100 000 and age-standardized disability-adjusted life year rates (ASDRs) per 100 000, as well as an estimated annual percentage change (EAPC) in ASMR and ASDR, were determined by age, sex, year, socio-demographic index (SDI), regions, and countries or …

First-In-Human Dose Escalation Trial To Evaluate The Clinical Safety And Efficacy Of An Anti-Magea1 Autologous Tcr-Transgenic T Cell Therapy In Relapsed And Refractory Solid Tumors, Martin Wermke, Tobias A W Holderried, Jason John Luke, Van K Morris, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Ignacio I Wistuba, Edwin R Parra, Mohammad B Hossain, Sandra Grund-Gröschke, Katrin Aslan, Arun Satelli, Anantha Marisetty, Swapna Satam, Mamta Kalra, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Linus Backert, Melissa Baumeister, Sebastian Bunk, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Andrea Mayer-Mokler, Norbert Hilf, Delfi Krishna, Steffen Walter, Apostolia M Tsimberidou, Cedrik M Britten

Faculty, Staff and Student Publications

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of …

Association Between Diabetes Mellitus And Total Hip Arthroplasty Outcomes: An Observational Study Using The Us National Inpatient Sample, Sumanth Chandrupatla, Kranti Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

OBJECTIVES: To investigate the association of diabetes with postoperative outcomes in patients undergoing primary total hip arthroplasty (THA).

DESIGN: Retrospective cohort study using data from the US National Inpatient Sample (NIS).

SETTING: Study cohort was hospitalisations for primary THA in the USA, identified from the 2016-2020 NIS.

PARTICIPANTS: We identified 2 467 215 adults in the 2016-2020 NIS who underwent primary THA using International Classification of Diseases, 10th Revision codes. Primary THA hospitlizations were analysed as the overall group and also stratified by the underlying primary diagnosis for THA.

OUTCOME MEASURES: Outcome measures of interest were the length of hospital …

Transcatheter Heart Valve Explant With Infective Endocarditis-Associated Prosthesis Failure And Outcomes: The Explant-Tavr International Registry, Mateo Marin-Cuartas, Gilbert H L Tang, Philipp Kiefer, Shinichi Fukuhara, Rudiger Lange, Katherine B Harrington, Shekhar Saha, Christian Hagl, Neal S Kleiman, Sachin S Goel, Joerg Kempfert, Paul Werner, George A Petrossian, Arnar Geirsson, Nimesh D Desai, Michael W A Chu, Oliver D Bhadra, Christian Shults, Andrea Garatti, Flavien Vincent, Kendra J Grubb, Joshua B Goldberg, Michael J Mack, Thomas Modine, Paolo Denti, Tsuyoshi Kaneko, Vinayak N Bapat, Michael J Reardon, Michael A Borger, Syed Zaid

Faculty, Staff and Students Publications

Background and aims: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE.

Methods: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD).

Results: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant …