Medicine and Health Sciences Commons^™

Metabolic Effects Of Testosterone Added To Intensive Lifestyle Intervention In Older Men With Obesity And Hypogonadism, Adrian M Gonzalez-Gil, Yoann Barnouin, Alessandra Celli, Viola Viola, Marcos D Villarreal, Maria Liza Duremdes Nava, Adam Sciuk, Clifford Qualls, Reina Armamento-Villareal, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

Objective: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Design: Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Setting: Veterans Affairs Medical Center.

Participants: Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty.

Interventions: LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for …

Unveiling The Genetic Landscape Of Coronary Artery Disease Through Common And Rare Structural Variants, Kruthika R Iyer, Erica P Young, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. …

Next-Generation Sequencing-Based Msi Scoring Predicts Benefit In Mismatch Repair-Deficient Tumors Treated With Nivolumab: Follow-Up On Nci-Match Arm Z1d, Jonathan D Schoenfeld, Nilofer S Azad, Jacob Gross, Li Chen, Michael J Overman, Katrina Kao, Latifa Jackson, Donna Brunnquell, Xiangning Bu, Christina Coppola, Ping Guan, Jennifer Lee, David Sims, Rebecca Fuchs, Jason L Weirather, Kathleen L Pfaff, Lauren Gunasti, Srin Ranasinghe, Stanley R Hamilton, Victoria Wang, Peter J O'Dwyer, Catherine J Wu, Scott J Rodig, David R Patton, Lyndsay Harris

Faculty, Staff and Student Publications

Purpose: Mismatch repair-deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Patients and methods: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-Molecular Analysis for Therapy Choice arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with noncolorectal dMMR tumors. Genomic analyses were performed using next-generation sequencing (NGS), whole-exome sequencing, and RNA sequencing and supplemented by multiplex immunofluorescence performed on tissue samples.

Results: In this dMMR population, more extensive …

Perceived Hbv-Related Stigma Is Associated With Lower Antiviral Medication Adherence In Patients With Chronic Hepatitis B, Hee-Soon Juon, Daniel Yang, Cindy Xin Fang, Hie-Won Hann, Ho Bae, Mimi Chang, Ann C. Klassen

Department of Medical Oncology Faculty Papers

Medication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high-risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8-item Morisky Medication Adherence Scale (MMAS-8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS-8 scores. Of the …

Reassessing Estrogen Receptor Expression Thresholds For Breast Cancer Prognosis In Her2-Negative Patients Using Shape Restricted Modeling, Wenli Dong, Takeo Fujii, Jing Ning, Toshiaki Iwase, Jing Qin, Naoto T Ueno, Yu Shen

Faculty, Staff and Student Publications

We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our model treats ER as a continuous variable using a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. The study included 3055 patients with stage II/III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR …

Inadequate Intensification Of Ldl-Cholesterol Lowering Therapy After Coronary Revascularization: Insights From The Gould Registry, Benjamin E Peterson, Deepak L Bhatt, Christie M Ballantyne, James A De Lemos, Robert S Rosenson, Mikhail N Kosiborod, Christopher P Cannon

Faculty, Staff and Students Publications

Background: Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks.

Methods: This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study). Baseline- and 24-month follow-up characteristics-including LDL-C levels and strategies for lipid-lowering therapy (LLT)-were evaluated.

Results: Out of 5006 patients, 2195 (43.8%) had prior coronary revascularization. At baseline, these patients had lower LDL-C (99.2 mg/dL vs. 102.5 mg/dL; p < 0.001) and were more likely to be on intensive LLT (52.8% vs. 42.7%; p < 0.001). At 24 months, they had small reductions in LDL-C (-15.6% vs. -13.7%; p = 0.145) and were more likely to be on intensive LLT (61.9% vs. 51.5%; p < 0.001). Similar LDL-C reductions were observed in the PCSK9i group regardless of revascularization status.

Conclusions: Despite slightly better baseline …

Rideshare Services For Transportation Assistance In Gynecologic Oncology: A Quality Improvement Study, Anna Jo Smith, Sam Pancoe, Mary Pat Lynch, Megan Wachlin, Kristina Powell, Stefanie N. Hinkle, Nathanael C. Koelper, Meredith Doherty, Justin E. Bekelman, Fiona Simpkins, Emily M. Ko

SKMC Student Presentations and Publications

OBJECTIVE: Transportation barriers can lead to delays in care and suboptimal treatment. Our objective was to assess the utilization of a novel transportation pilot intervention in gynecologic oncology.

METHODS: Since May 2022, we have provided donor-funded transportation to patients receiving gynecologic cancer treatment at 5 University of Pennsylvania practices. Patients are screened for transportation barriers at first visit and re-screened during care. Patients who screen positive are referred to the intervention, a HIPAA-compliant ride-sharing service. There are no income or insurance restrictions; distance was limited to 25 miles. We report descriptive statistics on ride completion, distance traveled, and cost.

RESULTS: …

Treatment Of Small Intracranial Aneurysms Using The Smallss Scoring System: A Novel System For Decision Making, Mira Salih, Michael Young, Thomas B. Fodor, Alexander Andreev, Samuel D. Pettersson, Joanna M. Roy, Basel Musmar, Max Shutran, Phillip Taussky, Christopher S. Ogilvy

Department of Neurosurgery Faculty Papers

BACKGROUND: Treatment of unruptured intracranial aneurysms (UIA) less than 7 mm is controversial. We created a scoring system to guide decision making and validated the system utilizing over 700 cases treated with microsurgery or endovascular procedures.

METHODS: The scoring system SMALLSS included Size, (4-7 mm: 1 point, < 3.9 mm: 0 point), Multiple aneurysms (yes: 1, no: 0), Anatomic location (posterior: 1, anterior: 0), Lineage- family history of aneurysm (yes:1, no: 0), Lifetime risk (age < 65: 1, age > 65: 0), Smoking history (yes: 1, no: 0 ), Shape (irregular:1, smooth:0 ). Validation of this system was performed through retrospective review of prospectively maintained data for UIA patients treated between 2014 and 2021. We then performed an external validation of a cohort of 200 small aneurysms < 7 mm treated at a high volume cerebrovascular center.

RESULTS: A total of 1152 cases …

Successful Posthospitalisation Oncology Workflow Implementing Lace+ Score To Stratify And Reduce Readmissions Within A Safety-Net Hospital, Cindy M Pabon, Janine Wong, Marcela Perez, Jessica Jimenez-Abarca, Lianchun Xiao, Lymesia Jackson, Anne Park, Anjali Lankford, Vinita Akula, Saumil Datar, Taylor Hopper, Yaser Alkhatib, Terri Earles, Tejal Patel

Faculty, Staff and Student Publications

Background: Patients with advanced cancers visit the emergency room and get hospitalised frequently, with potentially half of these visits being avoidable. Our institution provides comprehensive, low-cost cancer treatment to a safety-net population in Texas. We performed a retrospective review of hospital readmission patterns amongst our oncology patients and developed a posthospitalisation workflow to reduce readmissions.

Method: Following discharge, oncology patients were risk stratified based on their Length of stay, Acuity of admission, Charlson comorbidity index score and Emergency department visits+index in the past 6 months. The higher the score, the quicker the outpatient oncology follow-up. In addition to addressing acute …

Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu

Faculty, Staff and Students Publications

Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.

Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …

Phase 3 Trial Of Cabozantinib To Treat Advanced Neuroendocrine Tumors, Jennifer A Chan, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

METHODS: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points …

Long-Term 3-Year Follow-Up Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma After ≥2 Prior Therapies, Laurie H Sehn, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Mosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 …

Efficacy And Safety Of Nivolumab Plus Ipilimumab In Patients With Metastatic Variant Histology (Non-Clear Cell) Renal Cell Carcinoma, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Kiran L Malikayil, Devaki Shilpa Surasi, Tharakeswara K Bathala, Yiyun Lin, Priya Rao, Pheroze Tamboli, Kanishka Sircar, Helen Ajufo, Khaled M Elsayes, Amishi Shah, Andrew C Johns, Sangeeta Goswami, Elshad Hasanov, Eric Jonasch, Pavlos Msaouel, Matthew T Campbell, Omar Alhalabi, Nizar M Tannir

Faculty, Staff and Student Publications

Background: Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC.

Methods: Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed …

Assessment Of Environmental, Sociocultural, And Physiological Influences On Women's Toileting Decisions And Behaviors Using "Where I Go": Pilot Study Of A Mobile App, Abigail R Smith, Elizabeth R Mueller, Cora E Lewis, Alayne Markland, Caroline Smerdon, Ariana L Smith, Siobhan Sutcliffe, Jean F Wyman, Lisa Kane Low, Janis M Miller

2020-Current year OA Pubs

BACKGROUND: Little is known about women's decisions around toileting for urination and how those decisions influence moment-to-moment behaviors to manage bladder needs. The new smartphone app "Where I Go" captures such nuanced and granular data in real-world environments.

OBJECTIVE: This study aims to describe participant engagement with "Where I Go", variation in novel parameters collected, and readiness for the data collection tool's use in population-based studies.

METHODS: "Where I Go" has three components: (1) real-time data, (2) short look-back periods (3-4 h), and (3) event location (GPS recorded at each interaction). The sample size was 44 women. Recording of real-time …

Dna Immunotherapy For Recurrent Respiratory Papillomatosis (Rrp): Phase 1/2 Study Assessing Efficacy, Safety, And Immunogenicity Of Ino-3107, Matthew P Morrow, Randal C Paniello, Et Al.

2020-Current year OA Pubs

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity …

Designing Patient-Centered Interventions For Emergency Care: Participatory Design Study, Woosuk Seo, Shruti Jain, Vivian Le, Jiaqi Li, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan, Sun Young Park

Faculty, Staff and Students Publications

Background: Emergency departments (EDs) are high-pressure environments where clinicians diagnose patients under significant constraints, including limited medical histories, severe time pressures, and frequent interruptions. Current ED care practices often inadequately support meaningful patient participation. Most interventions prioritize clinical workflow and health care provider communication, inadvertently overlooking patients' needs. Additionally, patient-facing technologies in EDs are typically developed without meaningful patient input, leading to solutions that may not effectively address patients' specific challenges. To enhance both patient-centered care practices and the diagnosis process in EDs, patient involvement in technology design is essential to ensure their needs during emergency care are understood and …

Intensive Lifestyle Intervention, Cardiac Biomarkers, And Cardiovascular Outcomes In Diabetes: Look Ahead Cardiac Biomarker Ancillary Study, Kershaw V Patel, Zainali Chunawala, Subodh Verma, Matthew W Segar, Katelyn R Garcia, Chiadi E Ndumele, Thomas J Wang, James L Januzzi, Antoni Bayes-Genis, Javed Butler, Carolyn S P Lam, Christie M Ballantyne, James A De Lemos, Alain G Bertoni, Mark Espeland, Ambarish Pandey

Faculty, Staff and Students Publications

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular outcomes and are recommended for measurement in type 2 diabetes (T2D). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers and the prognostic association of changes in these biomarkers with risk of adverse cardiovascular outcomes in T2D are not well-established.

Objectives: This study sought to evaluate the effects of an ILI on cardiac biomarkers and the association of changes in cardiac biomarkers with risk of cardiovascular outcomes in T2D.

Methods: Participants of the Look AHEAD (Action for Health …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

A Targeted Gene Expression Biomarker Predicts Clinic Low-Risk Meningioma Recurrence, Minh P Nguyen, Ramin A Morshed, Mark W Youngblood, Haley K Perlow, Calixto-Hope G Lucas, Akash J Patel, Joshua D Palmer, Craig M Horbinski, Stephen T Magill, William C Chen, David R Raleigh

Duncan NRI Faculty and Staff Publications

Background: Despite reassuring clinical and histological features, low-grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.

Methods: This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression …

Tigit Inhibitor M6223 As Monotherapy Or In Combination With Bintrafusp Alfa In Patients With Advanced Solid Tumors: A First-In-Human, Phase 1, Dose-Escalation Trial, Aung Naing, Meredith Mckean, Anthony Tolcher, Anja Victor, Ping Hu, Wei Gao, Marco A F Nogueira Filho, Thomas Kitzing, Stephan Gleicher, Daniel Holland, Emilia Richter, Keyvan Tadjalli-Mehr, Lillian L Siu

Faculty, Staff and Student Publications

Background: M6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.

Methods: This first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10-2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300-1600 mg with BA 1200 mg; both every 2 weeks, intravenous). Primary objectives were safety, tolerability, …

Sex And Outcomes Of Patients With Microsatellite Instability-High And Braf V600e Mutated Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Vincenzo Nasca, Joseph Zhao, Javier Ros, Sara Lonardi, Koen Zwart, Romain Cohen, Marwan Fakih, Priya Jayachandran, Jeanine M L Roodhart, Jeroen Derksen, Rossana Intini, Francesca Bergamo, Giacomo Mazzoli, Filippo Ghelardi, Marta Ligero, Jitendra Jonnagaddala, Nicholas Hawkins, Robyn L Ward, Durgesh Wankhede, Hermann Brenner, Michael Hoffmeister, Marco Vitellaro, Lisa Salvatore, Claire Gallois, Pierre Laurent-Puig, Chiara Cremolini, Michael J Overman, Julien Taieb, David Tougeron, Thierry Andre, Jakob Nikolas Kather, Raghav Sundar, Javier Carmona, Elena Elez, Miriam Koopman, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A significant proportion of patients show resistance, making the identification of determinants of response crucial. Growing evidence supports the role of sex in determining susceptibility to anticancer therapies, but data is lacking for patients with MSI-H CRC.

Methods: In this real-world cohort comprising 624 patients with MSI-H mCRC receiving ICIs, we investigated the impact of sex on patients' outcomes, overall and according to RAS-BRAF mutational status or type of treatment (anti-PD-(L)1 with or without anti-CTLA-4 agents). We …

Contrast-Enhanced Magnetic Resonance Imaging Based Calf Muscle Perfusion And Machine Learning In Peripheral Artery Disease, Bijen Khagi, Tatiana Belousova, Christina M Short, Addison A Taylor, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) remains underdiagnosed and undertreated and is associated with an increased risk for adverse cardiovascular outcomes. Imaging provides an approach to identifying patients with PAD. However, the role of integrating imaging with machine learning to identify PAD patients and potentially assess disease severity remains understudied. A total of 56 participants, including 36 PAD patients with intermittent claudication and 20 matched controls, underwent contrast-enhanced magnetic resonance imaging (CE-MRI) calf muscle perfusion scanning. CE-MRI-derived dynamic muscle perfusion maps were developed to quantify alterations of the microvascular circulation in the calf muscles based on voxel contrast enhancement. These dynamic muscle …

Swog S1815: A Phase Iii Randomized Trial Of Gemcitabine, Cisplatin, And Nab-Paclitaxel Versus Gemcitabine And Cisplatin In Newly Diagnosed, Advanced Biliary Tract Cancers, Rachna T Shroff, Benjamin Tan, Et Al.

2020-Current year OA Pubs

PURPOSE: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

METHODS: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m

RESULTS: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC. There was no significant difference in overall survival (OS) between GAP versus GC. Median …

Efficacy Of Zenocutuzumab In Nrg1 Fusion-Positive Cancer, Alison M Schram, Koichi Goto, Dong-Wan Kim, Teresa Macarulla, Antoine Hollebecque, Eileen M O'Reilly, Sai-Hong Ignatius Ou, Jordi Rodon, Sun Young Rha, Kazumi Nishino, Michaël Duruisseaux, Joon Oh Park, Cindy Neuzillet, Stephen V Liu, Benjamin A Weinberg, James M Cleary, Emiliano Calvo, Kumiko Umemoto, Misako Nagasaka, Christoph Springfeld, Tanios Bekaii-Saab, Grainne M O'Kane, Frans Opdam, Kim A Reiss, Andrew K Joe, Ernesto Wasserman, Viktoriya Stalbovskaya, Jim Ford, Shola Adeyemi, Lokesh Jain, Shekeab Jauhari, Alexander Drilon, Enrgy Investigators

Faculty, Staff and Student Publications

Background: Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with NRG1 fusion-positive solid tumors are unclear.

Methods: In this registrational, phase 2 clinical study, we assigned patients with advanced NRG1 fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall …

Differentiating Between Renal Medullary And Clear Cell Renal Carcinoma With A Machine Learning Radiomics Approach, Rahim Jiwani, Koustav Pal, Iwan Paolucci, Bruno Odisio, Kristy Brock, Nizar M Tannir, Daniel D Shapiro, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Background: The objective of this study was to develop and validate a radiomics-based machine learning (ML) model to differentiate between renal medullary carcinoma (RMC) and clear cell renal carcinoma (ccRCC).

Methods: This retrospective Institutional Review Board -approved study analyzed CT images and clinical data from patients with RMC (n = 87) and ccRCC (n = 93). Patients without contrast-enhanced CT scans obtained before nephrectomy were excluded. A standard volumetric software package (MIM 7.1.4, MIM Software Inc.) was used for contouring, after which 949 radiomics features were extracted with PyRadiomics 3.1.0. Radiomics analysis was then performed with RadAR for differential radiomics …

Heterogeneous Clinical Phenotypes Of Sporadic Early-Onset Alzheimer's Disease: A Neuropsychological Data-Driven Approach, Deepti Putcha, Erik Musiek, Kyle Womack, Et Al.

2020-Current year OA Pubs

BACKGROUND: The clinical presentations of early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) described EOAD as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the phenotypic range of EOAD presentation, we applied a neuropsychological data-driven method to subtype the LEADS cohort.

METHODS: Neuropsychological test performance from 169 amyloid-positive EOAD participants were analyzed. Education-corrected normative comparisons were made using a sample of 98 cognitively normal participants. Comparing the relative levels of …

Punch Cd3-Ols: A Phase 3 Prospective Observational Cohort Study To Evaluate The Safety And Efficacy Of Fecal Microbiota, Live-Jslm (Rebyota) In Adults With Recurrent Clostridioides Difficile Infection, Paul Feuerstadt, Teena Chopra, Whitfield Knapple, Nicholas W Van Hise, Erik R Dubberke, Brian Baggott, Beth Guthmueller, Lindy Bancke, Michael Gamborg, Theodore S Steiner, Daniel Van Handel, Sahil Khanna

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.

METHODS: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam Jaber, Carin Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal Gandhi, Keith Pereira, Jay Giri, Sameer Khandhar, Khawaja Afzal Ammar, David Lasorda, Brian Stegman, Lucas Busch, David Dexter, Ezana Azene, Nikhil Daga, Fakhir Elmasri, Chandra Kunavarapu, Mark Rea, Joseph Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason Smith, Thomas Tamlyn, Gabriel Hernandez, Parth Rali, Torrey Schmidt, Jeffrey Bruckel, Juan Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian Bergmark, Bhavraj Khalsa, David Zlotnick, Jordan Castle, David O'Connor, C. Michael Gibson

Department of Radiology Faculty Papers

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson, Peerless Committees And Investigators

Faculty, Staff and Student Publications

Background: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

Methods: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …