Medicine and Health Sciences Commons^™

Surgical Repair Of An Atypical Midsubstance Distal Biceps Tendon Partial Tear: A Case Report, Michael M. Valenzuela, Genoveffa R. Morway, Christopher M. Jones

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

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, …

A Neuronal Code For Object Representation And Memory In The Human Amygdala And Hippocampus, Runnan Cao, Peter Brunner, Puneeth N Chakravarthula, Krista L Wahlstrom, Cory Inman, Elliot H Smith, Xin Li, Adam N Mamelak, Nicholas J Brandmeir, Ueli Rutishauser, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

How the brain encodes, recognizes, and memorizes general visual objects is a fundamental question in neuroscience. Here, we investigated the neural processes underlying visual object perception and memory by recording from 3173 single neurons in the human amygdala and hippocampus across four experiments. We employed both passive-viewing and recognition memory tasks involving a diverse range of naturalistic object stimuli. Our findings reveal a region-based feature code for general objects, where neurons exhibit receptive fields in the high-level visual feature space. This code can be validated by independent new stimuli and replicated across all experiments, including fixation-based analyses with large natural …

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 …

Motor Pool Selectivity Of Neuromuscular Degeneration In Type I Spinal Muscular Atrophy Is Conserved Between Human And Mouse, Justin C Lee, Wendy K Chung, David J Pisapia, Christopher E Henderson

Faculty, Staff and Students Publications

Spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein. Even though SMN is ubiquitously expressed, the disease selectively affects motor neurons, leading to progressive muscle weakness. Even among motor neurons, certain motor units appear more clinically resistant to SMA. To quantitatively survey selective resistance, we studied extensive neuromuscular autopsies of Type I SMA patients and age-matched controls. We found highly divergent degrees of degeneration of neighboring motor units, even within individual cranial nerves or a single anatomical area such as the neck. Examination of a Type I SMA patient maintained on life support …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

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 …

Snap Participation As A Moderator Of Food And Nutrition Security And Combined Cardiometabolic Conditions: A Mixed Regression Approach, Maha Almohamad, Ruosha Li, Natalia I Heredia, Jayna M Dave, Eric E Calloway, Anjail Sharrief, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: To examine the relationships between food security, nutrition security, Supplemental Nutrition Assistance Program (SNAP) participation, and cardiometabolic outcomes, including hypertension, hyperlipidemia, or diabetes, among low-income U.S. individuals.

Methods: A cross-sectional survey of 486 participants (April–June 2021) assessed food and nutrition security and cardiometabolic outcomes. Mixed-effects logistic regression models adjusted for covariates and included a random effect for state of residence. Moderation analyses evaluated SNAP participation’s impact.

Results: Very low food security was associated with higher odds of having at least one cardiometabolic condition, such as hypertension, hyperlipidemia, or diabetes (AOR = 1.96; 95% CI: 1.04–3.69; p = 0.04). SNAP …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

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 …

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 …

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

Heart and Vascular Articles

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 …

Metabolites And Lipid Species Mediate The Associations Of Adiposity In Childhood And Early Adulthood With Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Lili Liu, Lei Liu, Haixiang Zhang, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women.

METHODS: This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Kenneth E. Remy, Jane Blood, Andrew H. Walton, Teresa Blood, Richard Hotchkiss, Et Al.

2020-Current year OA Pubs

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 …

Sleep Trajectories And All-Cause Mortality Among Low-Income Adults, Kelsie M Full, Hui Shi, Loren Lipworth, Lawrence T Dauer, Michael T Mumma, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Short and long sleep durations are adversely associated with cardiovascular disease (CVD), type 2 diabetes, and mortality. It remains unclear how sleep duration trajectories over time are associated with mortality and whether these associations vary by well-documented sex, race, and socioeconomic sleep disparities.

OBJECTIVE: To investigate the association of 5-year sleep duration trajectories with all-cause and cause-specific mortality among US adults, predominantly those in low-income groups.

DESIGN, SETTING, AND PARTICIPANTS: The Southern Community Cohort Study included participants aged 40 to 79 years recruited and enrolled (from March 2002 to September 2009) from community health centers by using random sampling …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

Short Duration Of Antenatal Corticosteroid Exposure And Outcomes In Extremely Preterm Infants, Sanjay Chawla, Myra H Wyckoff, Satyan Lakshminrusimha, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Abhik Das, Rachel G Greenberg, Girija Natarajan, Seetha Shankaran, Edward F Bell, Namasivayam Ambalavanan, Noelle E Younge, Abbot R Laptook, Leeann R Pavlek, Carl H Backes, Krisa P Van Meurs, Erika F Werner, Waldemar A Carlo, National Institute Of Child Health And Human Development (Nichd) Neonatal Research Network (Nrn)

Faculty, Staff and Student Publications

Importance: When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

Objective: To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

Design, setting, and participants: This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks' gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive …

Combined Clinical, Structural And Cellular Studies Discriminate Pathogenic And Benign Trpv4 Variants, Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A Mccray

Faculty, Staff and Students Publications

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 …

A Comprehensive Head-To-Head Comparison Of Key Plasma Phosphorylated Tau 217 Biomarker Tests, Noëlle Warmenhoven, Nicolas R Barthélemy, Suzanne E Schindler, Andrew J Aschenbrenner, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Laura Ibanez, Jigyasha Timsina, Carlos Cruchaga, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests. Samples from 998 individuals [mean (range) age 68.5 (20.0-92.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and …

Racial Differences In Ctdna Profiles, Targeted Therapy Use, And Outcomes In Metastatic Breast Cancer, Emily L Podany, Katherine Clifton, Shaili Tapiavala, Foluso O Ademuyiwa, Cynthia X Ma, Andrew A Davis, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment.

OBJECTIVES: To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included.

EXPOSURES: Targeted treatment …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

PURPOSE: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

PATIENTS AND METHODS: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

RESULTS: More than 2,500 patients were …

Intersection Of Race And Rurality With Health Care-Associated Infections And Subsequent Outcomes, Katelin B Nickel, Hannah Kinzer, Anne M Butler, Karen E Joynt Maddox, Victoria J Fraser, Jason P Burnham, Jennie H Kwon

2020-Current year OA Pubs

IMPORTANCE: Health care-associated infections (HAIs) are a major cause of morbidity and mortality, but little is known about whether structural factors impacting race and rurality are associated with HAI and subsequent outcomes.

OBJECTIVE: To evaluate the association of race and rurality, which are proxies for structural disadvantage, with HAI and subsequent outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at 3 US urban and suburban hospitals. Participants were adults aged 18 years or older admitted for 48 hours or longer from January 1, 2017, to August 31, 2020. Statistical analysis was performed from November 2022 to April 2024. …