Medical Specialties Commons^™

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …

Disease-Specific And Overall Survival For Patients With Lacrimal Gland Adenoid Cystic Carcinoma In Recent Decades, Bita Esmaeli, Zhouxuan Li, Tracy J Lu, Hila Goldberg, Jing Ning, James Matthew Debnam, Steven Jay Frank, Renata Ferrarotto

Faculty, Staff and Student Publications

Purpose: To evaluate the presenting symptoms, and the overall survival (OS) and disease-specific survival (DSS) in patients with lacrimal gland adenoid cystic carcinoma (LGACC).

Methods: This retrospective single-centre cohort study included all consecutive patients with LGACC treated by the primary author from November 1998 through August 2024. Demographic data, presenting symptoms, the histological subtype of LGACC, type of surgical treatment, adjuvant radiotherapy or chemotherapy, T category at presentation and survival data were reviewed. Correlations between histological subtypes, T-category, type of surgery (eye sparing vs orbital exenteration), and DSS and OS were analysed.

Results: 52 patients had a median age of …

Genomics Define Malignant Transformation In Myeloma Precursor Conditions, Francesco Maura, P Leif Bergsagel, Bachisio Ziccheddu, Shaji Kumar, Kylee Maclachlan, Andriy Derkach, Juan-Jose Garces, Ross Firestone, Esteban Braggio, Yan Asmann, Michael Durante, Benjamin T Diamond, Marios Papadimitriou, Malin Hultcrantz, Alessio Marella, Giancarlo Castellano, Akihiro Maeda, Marta Lionetti, Antonio Matera, Stefania Pioggia, Matteo Claudio Da Vià, Claudio De Magistris, Daniel Leongamornlert, Danny Deavila, Praneeth Reddy Sudalagunta, Rafael Renatino Canevarolo, Erin M Siegel, Phaedra Agius, Jamie Teer, Andrew Mcpherson, Yusuke Yamashita, Ariosto S Silva, Patrick Blaney, Rachid Baz, Krina K Patel, Peter Campbell, Gareth Morgan, Rafael Fonseca, Ola Landgren, Robert Z Orlowski, Kenneth H Shain, Niccolo Bolli, Saad Usmani, S Vincent Rajkumar

Faculty, Staff and Student Publications

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify …

Epigenome-Wide Association Study Meta-Analysis Of Bmi In African Americans, Kendra Ferrier, Mariaelisa Graff, Iain R Konigsberg, Maggie Stanislawski, Heather M Highland, Laura M Raffield, April P Carson, Eric Boerwinkle, Jill M Norris, Chris R Gignoux, Audrey E Hendricks, Sridharan Raghavan, Kari E North, Kristin L Young, Anne E Justice, Matthew A Allison, Mathew J Budoff, Silva Kasela, François Aguet, Joshua J Joseph, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Ethan M Lange, Leslie A Lange

Faculty, Staff and Student Publications

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

Workflow Improvements From Automated Large Vessel Occlusion Detection Algorithms Are Dependent On Care Team Engagement, Emmanuel C Ebirim, Ngoc Mai Le, Joseph N Samaha, Hussain Azeem, Ananya Iyyangar, Anjan N Ballekere, Saagar Dhanjani, Luca Giancardo, Eunyoung Lee, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Automated machine learning (ML)-based large vessel occlusion (LVO) detection algorithms have been shown to improve in-hospital workflow metrics including door-to-groin time (DTG). The degree to which care team engagement and interaction are required for these benefits remains incompletely characterized.

Methods: This analysis was conducted as a pre-planned post-hoc analysis of a randomized prospective clinical trial. ML-based LVO detection software was implemented at four comprehensive stroke centers (CSCs) from January 1, 2021, to February 27, 2022. Patients were included if they underwent endovascular thrombectomy for LVO acute ischemic stroke. ML software utilization was quantified as the total number of active …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …

Clinical And Dosimetric Dataset Of Time-To-Event Normal Tissue Complication Probability For Osteoradionecrosis, Natalie A West, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Renjie He, Mohamed A Naser, Katherine A Hutcheson, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Laia Humbert-Vidan

Faculty, Staff and Student Publications

Osteoradionecrosis of the jaw (ORNJ) is a radiation-induced late toxicity that can dramatically decrease patients' quality of life. Recent increases in survival rates of head and neck cancers associated with human papillomavirus (HPV) infection have resulted in a higher frequency of radiation-induced toxicities, particularly ORNJ. Recent work with Normal Tissue Complication Probability (NTCP) models and a Weibull Accelerated Failure Time (WAFT) model have further developed our understanding of ORNJ clinical/dosimetric risk factors and longitudinal features, respectively. In this data descriptor, 1129 head and neck cancer (HNC) patients received curative intent radiotherapy (RT) at MD Anderson Cancer Center and were followed …

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

A Phase 1, First-In-Human, Dose Escalation Study Of Jnj-80038114, A Psmaxcd3 Bispecific Antibody, In Participants With Metastatic Castration-Resistant Prostate Cancer, Andrew Hudson, Anuradha Jayaram, Benjamin Garmezy, Nicholas Zorko, Kevin Zarrabi, Ligi Mathews, Brent Rupnow, Mengjie Li, Debopriya Ghosh, Karen Urtishak, Peter Francis, Sherry Wang, Edward Attiyeh, Johann De Bono

Department of Medical Oncology Faculty Papers

PURPOSE: Prostate-specific membrane antigen (PSMA) has been identified as a therapeutic target for metastatic castration-resistant prostate cancer (mCRPC). The recent success of radioligands targeting PSMA spurred development of new PSMA-targeting agents including immunotherapy. JNJ-80038114 is a bispecific antibody that binds PSMA on tumor cells and CD3 on T cells to induce anti-tumor activity.

METHODS: This was a phase 1, open-label, multicenter study of JNJ-80038114 in participants with mCRPC and ≥ 1 prior systemic therapy. JNJ-80038114 was administered subcutaneously every 3 weeks (Q3W), starting at 0.1 mg. The primary endpoint was safety. Secondary endpoints included pharmacokinetics (PK), immunogenicity, and prostate-specific antigen …

Music Therapy Versus Cognitive Behavioral Therapy Via Telehealth For Anxiety In Survivors Of Cancer: A Randomized Clinical Trial, Kevin T. Liou, Joke Bradt, M. Beatriz Currier, Raymond Baser, Katherine Panageas, Jodi Macleod, Desiree Walker, Susan Q. Li, Ana Maria Lopez, Kelly Mcconnell, Jun J. Mao

Department of Medical Oncology Faculty Papers

PURPOSE: Anxiety is prevalent, disruptive, and undertreated among survivors of cancer. Cognitive behavioral therapy (CBT) is the first-line treatment, but not all individuals have access, respond to treatment, or prefer this option because of stigma. Music therapy is effective for short-term anxiety reduction, but it is unknown whether it is noninferior to first-line CBT for long-term anxiety reduction.

METHODS: This comparative effectiveness trial randomly assigned English- or Spanish-speaking survivors of cancer to seven weekly telehealth sessions of music therapy or CBT. The coprimary end points were changes in the Hospital Anxiety and Depression Scale (HADS) anxiety score at weeks 8 …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H. B. Wu, Simon A. Mahler, Stacey L. House, Saeed A. Jortani, Michael H. Creer, Kristin L. Rising, Jason J. Bischof, Chad Crystal, Gary F. Headden, Fred S. Apple, Nicholas E. Harrison, Andrew C. Meltzer, Justin T. Baca, Brian Tiffany, Mark Sochor, Grace U. Pentecostes, Katrina P. Di Tullio, Manish S. Gupta, Adam J. Singer, James L. Januzzi

Department of Emergency Medicine Faculty Papers

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Deep-Learning Serial Ct Prediction Of Survival In Immunotherapy-Treated Non-Small Cell Lung Cancer., Chiharu Sako, Brenda F Kurland, Taly G Schmidt, Jing He, Marius De Groot, Arpan A Patel, Dwight H Owen, Arya Amini, Brendan D Curti, Ronan J Kelly, Ray D Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Stephane Sanchez, Jakob Weiss, An Liu, Olivier Gevaert, Alma Hart, George R Simon, Ravi B Parikh, Jasper Van Der Aart, Petr Jordan

Oncology Articles

IMPORTANCE: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.

OBJECTIVE: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Efficacy And Safety Of Epcoritamab In Relapsed Or Refractory Large B-Cell Lymphoma: 3-Year Update From The Epcore Nhl-1 Trial, Yasmin H. Karimi, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Umar Farooq, Tatyana Feldman, Herve Ghesquieres, Wojciech Jurczak, Kim M. Linton, Tycel Phillips, Julie M. Vose, Won Seog Kim, Pegah Jafarinasabian, Barbara D'Angelo Månsson, David Soong, Andrew J. Steele, Zhu Li, Christian W. Eskelund, Martin Hutchings, Catherine Thieblemont

Journal Articles: Oncology and Hematology

Epcoritamab, a CD3xCD20 bispecific antibody, resulted in deep, durable responses with a manageable safety profile in patients with relapsed/refractory large B-cell lymphoma (LBCL) in EPCORE^® NHL-1 (NCT03625037). We report results from a 3-year follow-up. Adults with relapsed/refractory LBCL received epcoritamab until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Median age was 64.0 years, 39% of patients received prior CAR T-cell treatment, and 75% were refractory to ≥ 2 consecutive lines of treatment. As of May 3, 2024 (median follow-up 37.1 months [range, 0.3-45.5]), ORR was 59% and complete response (CR) rate …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Hungarian Validation Of The Pelvic Floor Distress Inventory - 20 (Pfdi-20) Questionnaire And The Pelvic Floor Impact Questionnaire - 7 (Pfiq - 7), Barbara Kozma, Bence Kozma, Peter Takacs, Dávid Rátonyi, Nelli Farkas, Attila G. Sipos, Balint Farkas

Department of Obstetrics & Gynecology Faculty Publications

Introduction and Hypotheses

Pelvic floor disorders (PFDs) affect women's quality of life through physical, psychological, and social domains. The Pelvic Floor Distress Inventory-20 (PFDI-20) and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) are validated tools for assessing symptom severity and quality of life impact. The current study aim to investigate the reliability and validity of the Hungarian versions of these questionnaires in women with PFD symptoms.

Methods

This validation study was carried out at the University of Debrecen among women with clinically confirmed pelvic floor disorders. The PFDI-20 and PFIQ-7 questionnaires were translated into Hungarian using independent native English speaker in …

Tezepelumab's Effects On Patient-Reported Symptoms In Severe Asthma, Overall And With History Of Comorbid Chronic Rhinosinusitis With Nasal Polyps (Crswnp), Njira L. Lugogo, Joseph K. Han, Anju T. Peters, Stella E. Lee, Monica Kraft, Mary Kay Margolis, Sonia F. Shenoy, Nicole Martin, Shradha Chandarana, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) treatment resulted in reduced exacerbations and improved sino-nasal symptoms and health-related quality of life in patients with severe uncontrolled asthma (SUA) and chronic rhinosinusitis with nasal polyps (CRSwNP) in the NAVIGATOR study.

Objective

To evaluate the effect of tezepelumab versus placebo on sleep disturbances, activity levels, and physical exertion tolerance in NAVIGATOR patients with SUA overall and in those with past medical history of comorbid CRSwNP.

Methods

Patients (12-80 years old) with SUA were randomized to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Patient responses to …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes., Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M. Starke, Marios-Nikos Psychogios, Edgar A. Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A. Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G. Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S. Park, Michael R. Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J. Altschul, Alejandro M. Spiotta, Peter Kan

Department of Medicine Faculty Papers

INTRODUCTION: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

PATIENTS AND METHODS: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

Phase 1 Trial Of Withania Somnifera Leaf Extract (Rh324) In Advanced Non-Small Cell Lung Cancer Including [18f]Fdg Pet/Ct As A Short-Term Metabolic Biomarker To Assess Efficacy: A Novel Model For Assessment Of Complimentary Therapies In Early Phase Human Clinical Trials, Jin Uk Heo, Santosh Rao, Herbert B Newton, Afshin Dowlati, Raymond F Muzic, Arash Kardan

Faculty, Staff and Students Publications

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Rahim Abo Kasem, Ilko Maier, Ansaar Rai, Pascal Jabbour, Joon-Tae Kim, Brian Howard, Ali Alawieh, Stacey Quintero Wolfe, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Justin Dye, Ali Alaraj, Mohamad Ezzeldin, Shinichi Yoshimura, David Fiorella, Omar Tanweer, Daniele G Romano, Pedro Navia, Hugo Cuellar, Isabel Fragata, Adam Polifka, Joshua Osbun, Fazeel Siddiqui, Mark Moss, Kaustubh Limaye, Maxim Mokin, Charles Matouk, Min S Park, Waleed Brinjikji, Ergun Daglioglu, Richard Williamson, David J Altschul, Christopher S Ogilvy, Roberto Crosa, Michael R Levitt, Benjamin Gory, Alexandra Paul, Peter Kan, Walter Casagrande, Shakeel Chowdhry, Michael F Stiefel, Ramesh Grandhi, Alejandro Spiotta, Justin Mascitelli

Faculty, Staff and Students Publications

Background: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

Methods: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

Brain Death Versus Circulatory Death: How Functional Warm Ischemia And Cold Storage Impact Myocardial Membrane Repair In Human Donor Hearts, Shiyi Li, Rishav Bhattacharya, Abdussalam E Elsenousi, Katherine V Nordick, Adel M Hassan, Syed B Peer, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

This study compares myocardial injury responses in human donor hearts from donation after brain death (DBD) and donation after circulatory death (DCD), with a focus on myocardial membrane integrity, pyroptosis, and damage. Unlike DCD hearts, which are exposed to varying durations of functional warm ischemic time (fWIT), DBD hearts, which are never subjected to warm ischemia, served as controls. A total of 24 human hearts were procured, consisting of 6 from the DBD group and 18 from the DCD group. All procured hearts were placed in cold normal saline and stored for up to 6 h. Left ventricular biopsies were …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

Insulinemic And Inflammatory Dietary Patterns And Colorectal Cancer Risk: A Dietary Data Harmonization Study Of One Million Participants In The Consortium Of Metabolomics Studies (Comets), Ni Shi, Rachel Hoobler, Rhea Harewood, Amanda E Toland, Demetrius Albanes, Emmanouil Bouras, Marc J Gunter, Linda M Liao, Steven C Moore, Fulvio Ricceri, Jerome I Rotter, Rashmi Sinha, Rachael Stolzenberg-Solomon, Anne Tjønneland, Alexis C Wood, Danxia Yu, Mary C Playdon, Fred K Tabung

Children’s Nutrition Research Center Staff Publications

Background: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established.

Objectives: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk.

Methods: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and …