Medicine and Health Sciences Commons^™

Hydroxocobalamin For Vasoplegia In Cardiac Surgery: A Retrospective Cohort Analysis, Luai Zakaria, Karan Shah, Dongsheng Yang, Marta Kelava, Haytham Elgharably, Ashish K Khanna, Sanchit Ahuja, Benjamin Hohlfelder, Andrej Alfirevic, Andra E Duncan, Nikolaos J Skubas, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Vasoplegia during cardiac surgery is common and associated with perioperative mortality. Hydroxocobalamin is a catecholamine-sparing approach for treating vasoplegia. However, there is currently limited evidence to inform its use.

Methods: We conducted a single-centre retrospective propensity-matched cohort study of patients who developed vasoplegia after cardiopulmonary bypass. Our primary outcome was vasopressor requirement, expressed as norepinephrine equivalents (NEE), at 1, 4, 24, and 48 h after treatment. Our secondary outcome was a collapsed composite of in-hospital complications comprising stroke, sternal wound infection, mesenteric ischaemia, renal failure, and death.

Results: We identified 2727 (11%) patients with vasoplegia from 2018 to 2024. …

The Effect Of Chronic Azithromycin Use In Winter On Health Care Utilization For Children With Bronchopulmonary Dysplasia: A Double Blind Randomized Controlled Study (Rct), Ricardo A Mosquera, Aravind Yadav, Maria Del Mar Romero-Lopez, Ivan G Magana-Ceballos, S Shahrukh Hashmi, Wilfredo De Jesus Rojas, Maria E Tellez, Kaleigh Riggs-Harpur, Fatima M Boricha, Tina S Reddy, Janice L John, Tomika S Harris, Carlos E Rodriguez-Martinez, Jefferson Buendia, Katrina E Mcbeth, Cindy K Jon, James M Stark, Giuseppe N Colasurdo

Faculty, Staff and Student Publications

Background: Bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, often leads to acute respiratory exacerbations triggered by infections. Our previous mouse study suggested that azithromycin's anti-inflammatory properties may benefit virus-induced respiratory illnesses prophylactically.

Methods: In this single-center, double-blind RCT, 60 children (6 months to 6 years) with BPD received azithromycin (5 mg/kg three times weekly; n = 30) or placebo (n = 30) for one winter season (October to March). Primary outcome was the total number of days of unscheduled healthcare clinic visits, ER visits, and hospital days. Secondary outcomes comprised clinic visits, ER visits, hospital admissions, hospital …

Sexual Health Education For Behavior Change: Revisiting How Much Is Enough, Ross Shegog, Elizabeth R Baumler, Robert C Addy, Christine M Markham, Melissa F Peskin, Susan Tortolero Emery, Melanie A Thiel, Shehla Sadruddin, Dennis Reidy, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Successful implementation of school sexual health curricula relies on students receiving sufficient exposure to lesson content. This large replication study assesses the longitudinal association between exposure to sexual health lesson frequency and content domains and delayed sexual initiation of middle school students.

Methods: Post hoc data analysis was conducted using a large harmonized dataset from 3 randomized controlled trials evaluating It's Your Game curricula in the South Central United States. The sample comprised 1,022 sexually inexperienced middle school students (grades 7 and 8) who completed grade 9 follow-up after using either a 24-lesson hybrid (classroom and computer-based) (It's Your …

Sleep Eeg And Respiratory Biomarkers Of Sudden Unexpected Death In Epilepsy (Sudep): A Case-Control Study, Oman Magana-Tellez, Rama Maganti, Norma J Hupp, Xi Luo, Sandhya Rani, Johnson P Hampson, Manuela Ochoa-Urrea, Sudha S Tallavajhula, Rup K Sainju, Daniel Friedman, Maromi Nei, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the most common category of epilepsy-related mortality. Centrally mediated respiratory dysfunction has been observed to lead to death in the majority of cases of SUDEP. SUDEP also mainly occurs during nighttime sleep. This study seeks to identify sleep EEG and sleep-related respiratory biomarkers of SUDEP risk.

Methods: In this case-control study, we compared demographic, clinical, EEG, and respiratory data from people with epilepsy who later died of SUDEP (the SUDEP group) with data from age and sex-matched living people with epilepsy, classified as high risk of SUDEP (with ≥1 generalised tonic-clonic seizure …

Wire-In-Needle Versus Conventional Syringe-On-Needle Technique For Ultrasound-Guided Central Venous Catheter Insertion In The Internal Jugular Vein: The Win Randomized Trial, Kristen K Thomsen, Jovana Stekovic, Felix Köster, Alina Bergholz, Karim Kouz, Moritz Flick, Daniel I Sessler, Christian Zöllner, Bernd Saugel, Leonie Schulte-Uentrop

Faculty, Staff and Student Publications

Purpose: There are different techniques for ultrasound-guided central venous catheter (CVC) insertion. When using the conventional syringe-on-needle technique, the syringe needs to be removed from the needle after venous puncture to pass the guidewire through the needle into the vein. When, alternatively, using the wire-in-needle technique, the needle is preloaded with the guidewire, and the guidewire-after venous puncture-is advanced into the vein under real-time ultrasound guidance. We tested the hypothesis that the wire-in-needle technique reduces the time to successful guidewire insertion in the internal jugular vein compared with the syringe-on-needle technique in adults.

Methods: We randomized 250 patients to the …

Continuous Versus Bolus Norepinephrine Administration And Arterial Blood Pressure Stability During Induction Of General Anaesthesia In High-Risk Noncardiac Surgery Patients: A Randomised Trial, Christina Vokuhl, Karim Kouz, Moritz Flick, Linda Krause, Alina Kröker, Parisa Moll-Khosrawi, Christian Zöllner, Daniel I Sessler, Bernd Saugel, Kristen K Thomsen

Faculty, Staff and Student Publications

Background: Hypotension after induction of general anaesthesia is common in high-risk patients having noncardiac surgery. Anaesthesiologists often give manual boluses of vasopressors repeatedly to maintain blood pressure during induction of general anaesthesia, including the fast-acting vasopressor norepinephrine which has a short half-life. We tested the hypothesis that giving norepinephrine continuously during induction of general anaesthesia, compared with giving it as repeated manual boluses, improves blood pressure stability in high-risk noncardiac surgery patients.

Methods: In this single-centre trial, 72 participants undergoing noncardiac surgery were randomised to continuous norepinephrine infusion or manual bolus norepinephrine administration during induction of general anaesthesia. Blood pressure …

Mitochondrial Haplogroups, But Not Heteroplasmy, Are Associated With Midlife Cognitive Function, Nien Yeh Daphne Yu, Shea J Andrews, Lifang Hou, Myriam Fornage, Kristine Yaffe

Faculty, Staff and Student Publications

Introduction: Mitochondrial DNA (mtDNA) variation may influence cognitive performance, but prior findings are inconsistent.

Methods: We analyzed data from 2308 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, assessing heteroplasmy (mtHz) burden and haplogroups (mtHg) from blood-derived mtDNA at three timepoints and cognitive function across multiple domains. Multivariate linear regression models and multivariate linear mixed models adjusted for age, sex, education, and race.

Results: MtDNA heteroplasmy burden and count were not associated with cognitive performance. However, mtHgs in macro-mtHg L were linked to poorer cognitive outcomes, particularly in processing speed and global cognition in cross-sectional and …

Engaging And Empowering Future Female Surgeons: Development Of The Medical Student Section Of The Society Of Women In Urology, Allison G Booher, Sasha J Vereecken, Erin Kim, Neharika Penmatcha, Alexandra Aponte, Eman N Chaudhri, Meghana Noonavath, Ibukunoluwa Omole, Joanna Orzel, Leigh Martin, Gina Demeo, Tyler L Overholt, Akanksha Mehta

Faculty, Staff and Student Publications

Objective: To describe a replicable model for a large-scale, cross-institutional, and student-driven initiative to promote gender equity within surgical fields.

Methods: To address the lack of a national infrastructure to support female medical students pursuing careers in Urology, a historically male-dominated specialty, the society of women in urology (SWIU) established its medical student section, called SWIUdents, as a student-led initiative to offer mentorship, education, and networking resources for future female urologists. In 2022, SWIUdents convened its first medical student leadership board, comprised of two co-chairs and four subcommittees focused on membership, program implementation, mentorship, and community relations. SWIUdents membership was …

Changes In Antiviral Prescribing For Children With Influenza In Us Emergency Departments., Tess Stopczynski, Olla Hamdan, Justin Z. Amarin, James W. Antoon, Laura S. Stewart, Haya Hayek, James Chappell, Andrew J. Spieker, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, John V. Williams, Marian G. Michaels, Julie A. Boom, Leila C. Sahni, Mary Allen Staat, Elizabeth P. Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Ayzsa Tannis, Heidi L. Moline, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low.

OBJECTIVE: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control …

Natriuretic Peptide Cut Points For Heart Failure Classification In Individuals With And Without Obesity, Mandana Chitsazan, Juhi K Parekh, Leah B Kosyakovsky, Sophie M Nemeth, Emily S Lau, James L Januzzi, Thomas J Wang, Daniel Levy, Chiadi E Ndumele, Elizabeth Selvin, Christie M Ballantyne, Bruce M Psaty, John S Gottdiener, Jorge R Kizer, Christopher R Defilippi, Norrina B Allen, Rudolf A De Boer, Sanjiv J Shah, Jennifer E Ho

Faculty, Staff and Students Publications

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines introduced elevated natriuretic peptide (NP) levels as a criterion for defining stage B heart failure (HF), or pre-HF, to identify individuals at greatest risk for future HF. Given the known NP deficiency in obesity, we aimed to assess whether a single NP cut point would disproportionately up-classify individuals with versus without obesity to stage B HF.

Methods: Participants free of HF from 5 community-based cohorts were included. We examined the reclassification of individuals to stage B HF using the 2022 versus 2013 guidelines, stratified by obesity …

Feasibility And Usage Of A Virtual Assistant Device In Cognitively Impaired Homebound Older Adults, Matthew Nunez, Prisha Patel, Lindsey Ulin, Leslie Kian, Martin Cominsky, Jason Burnett, Jessica L Lee

Faculty, Staff and Student Publications

Social technology in older adults can improve self-rated health; however, there can also be difficulties using it. Our study aimed to evaluate the feasibility and acceptance of virtual assistant device (VAD) use in cognitively impaired homebound older adults. 52 newly referred Meals on Wheels clients aged 60 and older were recruited for a three-phase study: 6 weeks of meals alone (control), followed by 6 weeks of meals+Alexa Echo Show 8 (AES8) basic usage, and lastly 6 weeks of meals+AES8 advanced usage. Technology acceptance with the AES8 was significantly higher by the end of the study and participants anecdotally enjoyed playing …

Hypoperfusion Intensity Ratio Is Associated With Follow-Up Infarct Volume In Medium Vessel Occlusions: A Multicenter Multinational Study, Vivek Yedavalli, Hamza Adel Salim, Dhairya Lakhani, Basel Musmar, Nimer Adeeb, Davide Simonato, Yan-Lin Li, Orabi Hajjeh, Muhammed Amir Essibayi, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Leonard Ll Yeo, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Takahiro Ota, Ashkan Mowla, Kareem El Naamani, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Gaultier Marnat, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Tobias D Faizy, Illario Tancredi, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Maurizio Fuschi, Max Wintermark, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Medium vessel occlusion (MeVO) contributes significantly to acute ischemic stroke (AIS). The hypoperfusion intensity ratio (HIR), reflecting collateral circulation via the ratio of Tmax >10s to Tmax >6s volumes, predicts infarct progression in large-vessel occlusions but is unstudied in MeVOs. In this multicenter, multinational retrospective study, we evaluated consecutive patients with MeVO who underwent mechanical thrombectomy with or without intravenous thrombolysis. Inclusion required available follow-up imaging and pretreatment CT perfusion. Follow-up infarct volume (FIV) was measured on CT or MRI 12-36 h post-procedure. Univariable and multivariable linear regression models were used to identify predictors of FIV, with HIR as the …

Isoform-Level Analyses Of 6 Cancers Uncover Extensive Genetic Risk Mechanisms Undetected At The Gene-Level, Yung-Han Chang, Sean T Bresnahan, S Taylor Head, Tabitha A Harrison, Yao Yu, Chad D Huff, Bogdan Pasaniuc, Sara Lindström, Arjun Bhattacharya

Faculty, Staff and Student Publications

Background: Integrating genome-wide association study (GWAS) and transcriptomic datasets can identify mediators for genetic risk of cancer. Traditional methods often are insufficient as they rely on total gene expression measures and overlook alternative splicing, which generates different transcript-isoforms with potentially distinct effects.

Methods: We integrate multi-tissue isoform expression data from the Genotype Tissue-Expression Project with GWAS summary statistics (all N > ~20,000 cases) to identify isoform- and gene-level associations with six cancers (breast, endometrial, colorectal, lung, ovarian, prostate) and six related cancer subtype classifications (N = 12 total).

Results: Directly modeling isoforms using transcriptome-wide association studies (isoTWAS) significantly improves discovery of …

Ideate-Lung02: A Phase 3 Study Of Second-Line Ifinatamab Deruxtecan In Patients With Relapsed Small Cell Lung Cancer, Taofeek K Owonikoko, Lauren Byers, Ying Cheng, Hidetoshi Hayashi, Luis Paz-Ares, Maurice Pérol, Haichuan Hu, Meng Qian, Cecilio Roi Garcia, Juliette Godard, Mei Tang, Charles M Rudin

Faculty, Staff and Student Publications

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated …

Evaluating Dimensionality Reduction For Patient-Reported Outcome-Based Survival Modeling In Patients With Head And Neck Cancer, Eric Ababio Anyimadu, Yaohua Wang, Amy C Moreno, Clifton David Fuller, Xinhua Zhang, G Elisabeta Marai, Guadalupe M Canahuate

Faculty, Staff and Student Publications

Purpose: This study aims to improve survival modeling in head and neck cancer (HNC) by integrating patient-reported outcomes (PROs) using dimensionality reduction techniques. PROs capture symptom severity across the treatment timeline and offer key insights for personalized care. However, their high dimensionality poses challenges such as overfitting and computational complexity. This work focuses on transforming and incorporating PRO data to enhance model performance in HNC.

Materials and methods: We analyzed retrospective data of 923 patients with HNC treated at the University of Texas MD Anderson Cancer Center between 2010 and 2021. Baseline clinical data including demographic, treatment, and disease characteristics …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Herthena-Pantumor01: A Phase Ii Study Of Patritumab Deruxtecan (Her3-Dxd) In Previously Treated Advanced Solid Tumors, Thomas Powles, Aarti Bhatia, Barbara Burtness, Takahiro Kogawa, Tomohiro Nishina, Izuma Nakayama, Christos Fountzilas, Dani R Castillo, Meredith Mckean, Funda Meric-Bernstam, Nicoletta Colombo, James W Smithy, Jérome Fayette, Sunandana Chandra, David W Sternberg, Fan Jin, Kendall Sullivan, Sue Yueh, Graham Clinthorne, Ariel E Aguilo, Ragini Kudchadkar, Hidetoshi Hayashi

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is expressed in numerous solid tumors. Higher levels of HER3 expression in multiple tumor types are associated with adverse clinical outcomes, such as reduced survival. However, there is currently no HER3-directed antibody-drug conjugate approved for the treatment of any cancer. Improved treatment options are needed, in particular for patients who progress on standard therapies. HER3-DXd is an investigational HER3-directed antibody-drug conjugate composed of an anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In previous clinical trials, HER3-DXd demonstrated a …

Factors Associated With Medication Adherence Among Patients With Attention-Deficit/Hyperactivity Disorder (Adhd), Linh Nguyen, Yen-Chi L Le, Hannah Reygaerts, Todd R Johnson, Cesar A Soutullo

Faculty, Staff and Student Publications

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common behavioral health condition that impacts 5% to 8% of children and 2.5% of adults worldwide. The symptoms of ADHD are effectively managed with medication, yet patients with ADHD may inconsistently take their medication. We assessed medication adherence among patients with ADHD and identified factors associated with medication adherence that may be utilized to optimize adherence.

Method: This is a retrospective, observational study among patients aged 4 years and older with a diagnosis of ADHD at primary care and multispecialty outpatient clinics during May 2021 to May 2023. We assessed sociodemographic characteristics, stratified by …

Transfer Learning Via Distributed Brain Recordings Enables Reliable Speech Decoding, Aditya Singh, Tessy Thomas, Jinlong Li, Greg Hickok, Xaq Pitkow, Nitin Tandon

Faculty, Staff and Student Publications

Speech brain-computer interfaces (BCIs) combine neural recordings with large language models to achieve real-time intelligible speech. However, these decoders rely on dense, intact cortical coverage and are challenging to scale across individuals with heterogeneous brain organization. To derive scalable transfer learning strategies for neural speech decoding, we used minimally invasive stereo-electroencephalography recordings in a large cohort performing a demanding speech motor task. A sequence-to-sequence model enabled decoding of variable-length phonemic sequences prior to and during articulation. This enabled development of a cross-subject transfer learning framework to isolate shared latent manifolds while enabling individual model initialization. The group-derived decoder significantly outperformed …

Performance Characteristics For Physiological Measures Of Progressive Pulmonary Fibrosis, Chad A Newton, Ashwatha Thenappan, Gabrielle Y Liu, Leda Yazbeck, Cathryn T Lee, Janelle Vu Pugashetti, Jennifer M Wang, Ethan White, Kevin R Flaherty, Elizabeth A Belloli, Jamie S Sheth, Nisha Mohan, Nazanin Nazemi, Andrew R Yu, Sahand Ghodrati, Kerri A Johannson, Veronica Marcoux, Jolene H Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Julie Morisset, Christine Kim Garcia, Felix Chua, Mary E Strek, Yet H Khor, Ayodeji Adegunsoye, Christopher J Ryerson, Philip L Molyneaux, Justin M Oldham

Faculty, Staff and Student Publications

Rationale: Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear.

Objectives: To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes.

Methods: A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of FVC and DlCO decline, together with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ⩾5% or DlCO ⩾15%, or radiological progression) for discriminating 2-year death or lung transplant among patients fibrotic interstitial lung disease from the United States, United …

Family History Of Substance Use And Stressful Life Events Impact Adolescent Maturation Of Cerebral White Matter, Yizhou Ma, Ashley Acheson, Corneliu Bolbocean, Mustafa N Mithaiwala, Si Gao, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Xiaoming Du, A Ankeeta, Alia Warner, Antonio F Pagán, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Family history (FH) of substance use disorders (SUDs) and stressful life events (SLEs) are known risk factors for SUDs in adolescents and young adults. Cross‐sectional studies suggest that FH and SLEs affect adolescent white matter (WM) development and form abnormal WM patterns. Here, we examined the effects of FH, SLEs and their interaction on WM integrity in youths in the Adolescent Cognitive Brain Development (ABCD) study at baseline and 2‐ and 4‐year follow‐ups. ABCD youths (N = 8939, age ± SD = 9.9 ± 0.6 years, 4302 female) completed baseline diffusion tensor imaging, of which 5661 repeated the scan …

Community Firearm Violence And Dental Care Use In Middle Adulthood, Alexander Testa, Luis Mijares, Daniel Semenza, Richard Stansfield, Ian Silver, Dylan B Jackson, Ana Neumann, Jeff R Temple, Rahma Mungia

Faculty, Staff and Student Publications

Prior research links violence inside the home to reduced dental care utilization, yet little is known about how community firearm violence affects dental care behaviors. The current study used data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), linked to census tract-level fatal and nonfatal shooting data from the American Violence Project for the 100 largest cities in the United States. The analytic sample included 1925 respondents aged 33-42. The primary outcome was self-reported dental care use in the past year. Firearm violence exposure was categorized as 0, 1, or 2 + …

Tirzepatide For The Maintenance Of Body Weight Reduction: Rationale, Design, And Baseline Characteristics Of Surmount-Maintain, Deborah B Horn, Louis J Aronne, Sean Wharton, Harold E Bays, Elisa Gomez-Valderas, Avigdor D Arad, Palash Sharma, Julia P Dunn, Cagri Senyucel, Clare J Lee

Faculty, Staff and Student Publications

Objective: SURMOUNT-MAINTAIN aims to evaluate the efficacy and safety of reducing the tirzepatide dose and/or continuing the maximum tolerated dose (MTD) versus placebo in maintaining body weight (BW) reduction achieved with tirzepatide MTD.

Methods: This Phase 3b, multicenter, randomized, parallel-arm, double-blinded, placebo-controlled, 52-week clinical trial is in progress comparing treatment with once weekly tirzepatide (5 mg and/or MTD of 15 mg or 10 mg) versus placebo in achieving BW reduction maintenance from the initial 60-week open-label weight-loss period on tirzepatide MTD, in adults with obesity (BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with ≥ 1 obesity-related comorbidity, excluding type …

A Comparative Study Of Clinically Used Fast Monte Carlo Dose Engines For Proton Therapy, Sherif M Gadoue, Narayan Sahoo

Faculty, Staff and Student Publications

Background: Several fast Monte Carlo (MC) codes have been implemented and used to simulate proton transport and calculate patient doses in proton therapy. The resulting dose is typically compared to full MC codes, rather than other fast MC codes.

Purpose: The primary goal of this study was to compare the gamma pass rates (GPRs) of dose calculation from different fast MC codes to evaluate the accuracy of the computation and modeling among these codes.

Methods: Two GPU codes and one CPU MC code were commissioned to model our clinical proton beamline at University of Texas MD Anderson Cancer Center. The …

Precemtabart Tocentecan, An Anti-Ceacam5 Antibody-Drug Conjugate, In Metastatic Colorectal Cancer: A Phase 1 Trial, Scott Kopetz, Valentina Boni, Ken Kato, Kanwal P S Raghav, Maria Vieito, Athanasios Pallis, Christina Habermehl, Abdul Siddiqui, Perrine Courlet, Willem Sloot, Sabine Raab-Westphal, Felix Hart, Ildefonso Rodriguez-Rivera

Faculty, Staff and Student Publications

CEACAM5, a cell surface protein, is overexpressed in colorectal cancer (CRC). Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as payload. Precem-TcT demonstrated strong antitumor activity and potent bystander activity in preclinical models. Its toxicity profile in cynomolgus monkeys was consistent with that of exatecan. In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6–3.2 mg kg−1). Primary endpoints were dose-limiting toxicities (DLTs), adverse events and preliminary clinical activity to establish …

Updated Estimates Of Patients With Oropharyngeal Cancer In The Us, Caineng Cao, Anna Lee, Jung Julie Kang, Irini Yacoub, Kaveh Zakeri, Edward Christopher Dee, Nadeem Riaz, Achraf Shamseddine, Yao Yu, Jennifer Ma, Teeradon Treechairusame, Marc A Cohen, Jennifer R Cracchiolo, Richard J Wong, Winston Wong, Lara A Dunn, Eric J Sherman, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Updated estimates of oropharyngeal cancer (OPC) in the US are needed.

Objective: To calculate the most recent epidemiologic estimates of OPC in the US and provide projections for future trends up to 2040.

Design, setting, and participants: This cross-sectional epidemiological analysis used data from the recent National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The SEER-22 (excluding Illinois and Massachusetts) database provided data for incidence, prevalence, survival, and initial treatment by OPC stage. Patients with OPC diagnosed according to International Classification of Diseases for Oncology, Third Edition morphology codes were included. The analysis was conducted from September …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …