Digital Commons Network^™

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and …

Impact Of An Adapted Diabetes Prevention Program In A Spanish Primary Care Setting: Protocol For A Type Ii Hybrid Effectiveness-Implementation Cluster-Randomized Trial (Aladim), Miquel Bennasar-Veny, Manuela Abbate, Miquel Colom-Rosselló, Laura Capitán-Moyano, Ivonne C Hernández-Bermúdez, Ignacio Ricci-Cabello, Aina M Yañez, Maria E Fernandez

Faculty, Staff and Student Publications

Background: Type 2 diabetes (T2D) is a global health concern affecting 10.5% of the adult population and is projected to rise significantly in the coming decades. Lifestyle modification programs, such as the Diabetes Prevention Program (DPP), can effectively reduce T2D risk among individuals with prediabetes. However, their implementation in real-world healthcare settings remains poor, particularly in Spain, where T2D prevalence is the highest in Europe. The ALADIM study aims to evaluate the effectiveness and implementation of an adapted DPP in Spanish Primary Care Centers (PCCs). The primary effectiveness outcome is weight, the co-primary implementation outcome is implementation fidelity. We will …

Longitudinal Outcomes Of The Covid-19 Pandemic On Youth Physical Fitness, Andjelka Pavlovic, David Leonard, Timothy J Walker, Derek W Craig, Jizyah Injil, Laura F Defina

Faculty, Staff and Student Publications

Importance: The COVID-19 pandemic led to a decline in physical activity levels among youths, which could have a negative impact on their fitness.

Objective: To examine longitudinal changes in cardiorespiratory fitness (CRF) and musculoskeletal fitness (MSF) among students at schools participating in a school-based physical activity program during fall 2019 through spring 2023.

Design, setting, and participants: This longitudinal cohort study included US schools reporting CRF and MSF data at least once during the pandemic (fall 2020 to fall 2021) and at least 1 additional time before or after. In a subset of schools for which learning modality data was …

Suppression Of Brca1 Facilitates Kidney Regeneration, Kaira A Church, Xunian Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Maladaptive repair following kidney injury leads to the development of kidney disease. In this issue of JEM, Ajay et al. (https://doi.org/10.1084/jem.20231107) uncover the role of breast cancer susceptibility gene 1 (BRCA1) in cell cycle arrest, DNA damage, and cell senescence, preventing maladaptive repair.

Drosha: A New Tumor Suppressor In Pineoblastoma, Zhixuan Huang, Xueli Ren, Jian Hu

Faculty, Staff and Student Publications

In this Outlook, Huang et al. discuss a study in this issue of Genes & Development by Fraire et al. that shows that a deficiency in miRNA processors Drosha and Dicer and consequent cell cycle gene derepression promote pineoblastoma development. The authors highlight the heterogeneity of pineoblastoma's pathogenic mechanisms and its implications for therapeutic interventions in the clinic.

Switching On The Evolutionary Potential Of Pancreatic Cancer: The Tumor Suppressor Functions Of Pbrm1, Luigi Perelli, Giannicola Genovese

Faculty, Staff and Student Publications

Cell plasticity is a hallmark of cancer, enabling tumor cells to acquire multiple phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this issue of the JCI, Kawai and colleagues leveraged genetically engineered mouse models (GEMM) of pancreatic ductal adenocarcinoma (PDAC) to demonstrate that loss of Pbrm1, a member of the SWI/SNF complex, drives dedifferentiation and aggressive tumor features. Pbrm1 loss activated a program of epithelial-to-mesenchymal transition (EMT) and allowed the emergence of poorly differentiated histologies that are commonly associated with high recurrence rate and dismal prognosis. These findings reveal the role of the SWI/SNF complex during PDAC evolution …

Hyaluronan Network Remodeling By Zeb1 And Itih2 Enhances The Motility And Invasiveness Of Cancer Cells, Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Younseo Lee, Sungsoo Park, Keunsoo Kang, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn

Faculty, Staff and Student Publications

Hyaluronan (HA) in the extracellular matrix promotes epithelial-mesenchymal transition (EMT) and metastasis; however, the mechanism by which the HA network constructed by cancer cells regulates cancer progression and metastasis in the tumor microenvironment (TME) remains largely unknown. In this study, inter-α-trypsin inhibitor heavy chain 2 (ITIH2), an HA-binding protein, was confirmed to be secreted from mesenchymal-like lung cancer cells when cocultured with cancer-associated fibroblasts. ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1, along with HA synthase 2 (HAS2), which positively correlates with ZEB1 expression. Depletion of ITIH2 and HAS2 reduced HA matrix formation and the migration and …

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …

Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, Steve Parrish, David Fuentes

Faculty, Staff and Student Publications

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very …

Impact Of Extracellular Matrix Scaffold On Driveline Infection Rate In Patients With Left Ventricular Assist Devices, Mehmet H Akay, Mateja K Jezovnik, Rajko Radovancevic, Ismael A Salas De Armas, Maria Patarroyo Aponte, Marwan Jumean, Manish K Patel, Jayeshkumar Patel, Biswajit Kar, Igor D Gregoric

Faculty, Staff and Student Publications

Objective: Left ventricular assist device (LVAD) implantation is a life-saving procedure for patients with advanced heart failure. However, postimplantation complications such as driveline infections (DLIs) can significantly affect patient outcomes. We assessed whether placing an extracellular matrix (ECM) scaffold around the driveline during LVAD implantation reduces the incidence of DLIs in patients with LVADs.

Methods: This retrospective observational study included 196 consecutive patients with LVADs between January 2018 and June 2022. We compared the data of patients who received ECM implantation during LVAD implantation (ECM group, n = 69) with those who did not (control group, n = 127).

Results: …

Colorectal Adenosquamous Carcinoma: Clinicopathologic Analysis Of Two Large Cohorts And Literature Review Confirm Poor Prognosis And Reveal Prognostic Aspects, Raul S Gonzalez, Rachel K Horton, Xuchen Zhang, Rondell P Graham, Teri A Longacre, Anupamjit Mehrotra, Daniela S Allende, Kelsey E Mchugh, Jinru Shia, Maria Westerhoff, Amitabh Srivastava, Wei Chen, Jennifer Vazzano, Paul E Swanson, Deyali Chatterjee, Hassam Cheema, Changqing Ma, Rifat Mannan, Runjan Chetty, Klaudia M Nowak, Stefano Serra, Diana Agostini-Vulaj, Rossana Kazemimood, Patrick Henn, Sanjay Kakar, Won-Tak Choi, Oyedele Adeyi, Sarah M Jenkins, Iris D Nagtegaal

Faculty, Staff and Student Publications

Aims: We compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta-analysis of cohorts and individual case series.

Methods and results: We identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome. ASC comprised 0.02% of colorectal cancers in the Dutch database. The median cohort patient ages at resection were 65 and 69 years (North American and Dutch cohorts, respectively), with a …

Baseline Predictors Of Responders To Auricular Point Acupressure In Chronic Low Back Pain, Nada Lukkahatai, Wanqi Chen, Jennifer Kawi, Hulin Wu, Claudia M Campbell, Johannes Thrul, Xinran Huang, Paul Christo, Constance M Johnson

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a major cause of disability, with varied patient responses to treatments. Auricular point acupressure (APA) has shown potential as a non-pharmacological intervention, but individual responses may differ significantly.

Objective: This study aimed to determine the predictability of baseline characteristics, including functional disability, symptom severity, and treatment expectancy, on clinically significant responses to APA in reducing pain and improving function.

Methods: A secondary analysis was performed using data from a randomized controlled trial with 263 cLBP patients. Participants were randomly assigned to targeted APA (T-APA), non-targeted APA (NT-APA), or to a control group. APA …

Computerized Diagnostic Decision Support Systems-Isabel Pro Versus Chatgpt-4 Part Ii, Joe M Bridges, Xiaoqian Jiang, Michael Ige, Oluwatoniloba Toyobo

Faculty, Staff and Student Publications

Objective: Does a Tree-of-Thought prompt and reconsideration of Isabel Pro's differential improve ChatGPT-4's accuracy; does increasing expert panel size improve ChatGPT-4's accuracy; does ChatGPT-4 produce consistent outputs in sequential requests; what is the frequency of fabricated references?

Materials and methods: Isabel Pro, a computerized diagnostic decision support system, and ChatGPT-4, a large language model. Using 201 cases from the New England Journal of Medicine, each system produced a differential diagnosis ranked by likelihood. Statistics were Mean Reciprocal Rank, Recall at Rank, Average Rank, Number of Correct Diagnoses, and Rank Improvement. For reproducibility, the study compared the initial expert panel run …

Derivation And Internal-External Validation Of Clinical Prediction Model For Postoperative Clinically Important Hypotension In Patients Undergoing Noncardiac Surgery: An International Prospective Cohort Study, Stephen Su Yang, German Malaga, Maria Lazo-Porras, Patricia Busta-Flores, Aida Del Carmen Rotta-Rotta, Pavel S Roshanov, Daniel I Sessler, Amal Bessissow, Thomas Schricker, Vicky Tagalakis, Diane Heels-Ansdell, Shirley Pettit, P J Devereaux

Faculty, Staff and Student Publications

Background: Intraoperative and postoperative hypotension are associated with myocardial injury/infarction, stroke, acute kidney injury, and death. Because of its prolonged duration, postoperative hypotension contributes more to the risk of organ injury compared with intraoperative hypotension. A prediction model for clinically important postoperative hypotension after noncardiac surgery is needed to guide clinicians.

Methods: We performed a secondary analysis of the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study. Patients aged ≥45 yr who had inpatient noncardiac surgery across 28 centres in 14 countries were included. In 14 of the centres selected at random (derivation cohort), we evaluated 49 variables …

A Bundle To Prevent Postinduction Hypotension In High-Risk Noncardiac Surgery Patients: The Zero-Hypotension Single-Arm Interventional Proof-Of-Concept Study, Kristen K Thomsen, Alina Kröker, Linda Krause, Karim Kouz, Christian Zöllner, Daniel I Sessler, Bernd Saugel, Moritz Flick

Faculty, Staff and Student Publications

Background: Postinduction hypotension is common and associated with organ injury but might be largely preventable by careful anaesthetic management. We thus aimed to quantify the severity and duration of postinduction hypotension in high-risk noncardiac surgery patients treated with a hypotension prevention bundle.

Methods: In this prospective single-arm interventional proof-of-concept study, 107 high-risk noncardiac surgery patients were treated with a hypotension prevention bundle. The bundle included continuous intra-arterial blood pressure monitoring, a hypotension alarm set at a mean arterial pressure (MAP) of 75 mm Hg, careful administration of anaesthetic drugs, and continuous administration of norepinephrine when MAP decreased below 75 mm …

Large-Scale Plasma Proteomic Profiling Unveils Diagnostic Biomarkers And Pathways For Alzheimer’S Disease, Gyujin Heo, Ying Xu, Erming Wang, Muhammad Ali, Hamilton Se-Hwee Oh, Patricia Moran-Losada, Federica Anastasi, Armand González Escalante, Raquel Puerta, Soomin Song, Jigyasha Timsina, Menghan Liu, Daniel Western, Katherine Gong, Yike Chen, Pat Kohlfeld, Allison Flynn, Alvin G Thomas, Joseph Lowery, John C Morris, David M Holtzman, Joel S Perlmutter, Suzanne E Schindler, Natalia Vilor-Tejedor, Marc Suárez-Calvet, Pablo García-González, Marta Marquié, Maria Victoria Fernández, Mercè Boada, Amanda Cano, Agustín Ruiz, Bin Zhang, David A Bennett, Tammie Benzinger, Tony Wyss-Coray, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer's disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to identify new proteins, pathways and predictive models for AD. We identified 416 proteins (294 new) associated with clinical AD status and validated the findings in two external datasets representing more than 7,000 samples. AD-related proteins reflected blood-brain barrier disruption and other processes implicated in AD, such as lipid dysregulation or immune responses. A machine learning model was used to identify a set …

Longitudinal Trends In Pediatric Survival By Congenital Heart Defect In Texas, 1999 To 2017, Sara B Stephens, Shaine A Morris, Renata H Benjamin, Mark A Canfield, Charles J Shumate, Ruosha Li, Cecilia Cazaban-Ganduglia, A J Agopian

Faculty, Staff and Student Publications

Background: Despite previously improved survival among children with congenital heart defects (CHDs), U.S. population-level evaluations of survival within recent years are scarce.

Objectives: The purpose of this study was to describe the survival landscape among children with CHDs in a large population-based birth defects registry overall and by CHD lesion.

Methods: This population-based cohort study evaluated 1999 to 2017 live births with ≥1 major CHD in the statewide Texas Birth Defects Registry. Variables included CHD lesion, demographics, gestational age at birth (term/preterm), low birthweight (< 2,500 g at birth), among others. Kaplan-Meier analyses were used to describe survival to 7 days, 28 days, 1 year, 5 years, and 10 years of life. Kaplan-Meier survival estimates were generated for 1-year survival for CHDs overall by lesion, using log-rank tests assessing differences by exposure.

Results: Of 61,656 children with CHDs, survival was 98.1% and 90.7% at 7 days and …

Early Life Exposure To Fine Particulate Matter And Fine Motor Function, Attentional Function, And Working Memory Among Spanish School-Aged Children, Kristina W Whitworth, Aitana Lertxundi, Mingze Yuan, Alison Rector-Houze, Wei-Jen Chen, Mònica Guxens, Jordi Julvez, Michael Swartz, Elaine Symanski, Antonia Valentin, Carmen Iniguez, Llúcia L González-Safont, Jesús Ibarluzea

Faculty, Staff and Student Publications

Background: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.

Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had …

The Association Of Vision And Hearing Impairment On Cognitive Function And Loneliness: Evidence From The Mexican Health And Aging Study, Kimberly Hreha, Rafael Samper-Ternent, Heather E Whitson, L P Downer, Jessica S West, Brian Downer

Faculty, Staff and Student Publications

Objectives: We investigated whether self-reported vision and hearing were associated with cognitive function and loneliness among Mexican adults aged 50 and older.

Methods: Mexican Health and Aging Study data. Vision/hearing status was self-reported (excellent-very good, good, fair-poor). Cognition was measured using nine tasks. Loneliness was measured using the UCLA Loneliness Scale. Analyses controlled for demographic and health characteristics.

Results: Among 12,353 participants (mean age = 67, 58% female), poor vision, but not hearing, was associated with lower global cognition (β = -0.03, p < .05). Poor vision (OR = 1.57, 95% CI = 1.30-1.91) and hearing (OR = 1.35, 95% CI = 1.14-1.61) were associated with higher odds of being lonely after adjusting for demographics and comorbidities, but not when adjusting for limitations in daily activities and depressive symptoms.

Discussion: Poor vision is a potentially modifiable risk factor for lower cognition and loneliness among Mexican adults. …

Understanding Utilization And Prevention Measures Associated With A Caries Risk Assessment In Oral Health Transformation, Melody Mcgee, Ryan Brandon, Muhammad Walji, Joel White, Kristen Moses, Eric P Tranby, Lisa J Heaton, Kristen Simmons

Faculty, Staff and Student Publications

Objectives: Dental decay is endemic in the United States, underscoring the need to measure the utilization of caries risk management tools to elucidate the effect of prevention interventions in reducing the dental decay rates of individuals. An academic institution partnered with a third-party institute to call attention to the utilization and prevention measures associated with caries risk assessment (CRA) used with children 0-18 years. This environmental scan examined claims across the United States to evaluate the proportion of dental examinations, CRAs, and caries prevention procedures within a calendar year.

Methods: A 12-month deidentified participant list categorized by age, race, sex, …

The Macrophage Sterol Transport Protein Orp2 Promotes Cholesterol Efflux And Prevents Foam Cell Formation And Atherosclerosis, Xiaowei Wang, Kenan Peng, Yudi Zhao, Liwen Qiu, Chenxi Liang, Yaqian Dou, Qianqian Dong, Xiaoting Ma, Jinye Tang, Yidan Ma, Lin Liu, Mingqi Zheng, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2MOE) mice were generated and crossed with atherosclerotic-prone ApoE−/− mice and then fed a high-fat diet (HFD) to induce atherosclerosis. Our results showed that myeloid-specific hORP2 overexpression significantly reduced the atherosclerotic …

Endovascular Repair Of Type A Dissection Using Thoracic Stent Graft With Innominate Artery Flaring To Correct For Length Mismatch, Aidin Baghbani-Oskouei, Lucas Ruiter Kanamori, Safa Savadi, Steven Maximus, Thanila A Macedo, Anthony Estrera, Salman A Arain, Gustavo S Oderich

Faculty, Staff and Student Publications

Type A aortic dissection is the most common aortic catastrophe posing challenges for endovascular repair owing to the fragile aortic wall, proximity to the aortic valve, coronaries, and supra-aortic trunks. While open surgical repair remains the gold standard, endovascular repair is considered in select high-risk patients who meet anatomical criteria, including more than 10 mm length between sinotubular junction to primary tear, aortic diameter of less than 40 mm, and suitable length between sinotubular junction and innominate artery. This illustrated video and case presentation address a modified technique using stent graft flaring of the innominate artery to adjust for length …

Psychometrics Of Inflammatory Back Pain Criteria In The Us Population, Mark C Hwang, Seokhun Kim, Shervin Assassi, Alexis Ogdie, Michael H Weisman, John Reveille, Charles Green

Faculty, Staff and Student Publications

Objectives: Evaluation of axial spondyloarthritis relies on capturing various inflammatory back pain (IBP) features represented in different criteria. These criteria are likely to be interpreted differently across demographic subpopulations. We examined IBP criteria dimensionality and differential item functioning (DIF) among different age, gender, and race groups using a nationally representative sample.

Methods: We utilised the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset, a US nationally representative data collection with demographic weighting. The Arthritis Questionnaire (ARQ) within NHANES included questions from published Calin, European Spondyloarthropathy Study Group, and Berlin criteria (8a and 7b). Confirmatory factor analysis (CFA) was performed …

Design Of Conquest, A Novel, Randomized, Placebo-Controlled, Phase 2b Platform Clinical Trial To Investigate New Treatments For Patients With Early Active Systemic Sclerosis With Interstitial Lung Disease, Dinesh Khanna, Luke B Evnin, Shervin Assassi, Wade W Benton, Gregory Gordon, Karina Maslova, Juergen Steffgen, Toby M Maher

Faculty, Staff and Student Publications

Objective: Safe, effective therapies are urgently needed for patients with systemic sclerosis. However, clinical trial recruitment is challenging given the limited number of people with systemic sclerosis and further restrictions imposed by eligibility criteria. Innovative approaches are needed to accelerate development of new therapies. This article describes the rationale and trial design for CONQUEST (NCT06195072), a novel platform clinical trial sponsored by the Scleroderma Research Foundation, a not-for-profit organization.

Methods: CONQUEST is a multicentre, double-blind, randomized, placebo-controlled, Phase 2b platform trial evaluating the efficacy, safety and pharmacodynamics of multiple investigational products to treat early active systemic sclerosis with …

Perceptions Of The Intensity Of Heart Failure Medications Among Hospitalized Older Adults: A Pilot Qualitative Study, Nuzha A Amjad, Saeed Shoar, Catherine Bryant, Meghan Hunt, Min Ji Kwak

Faculty, Staff and Student Publications

Background: Guidelines for heart failure (HF) management recommend high target doses for medications. These targets are based on standardized dosing regimens that rarely consider the complex challenges faced by older patients. However, little is known about such challenges perceived by older adults. We assessed older adults' perceived challenges with HF medication utilization, which may guide a more patient-centered definition of the target intensity for HF medications.

Methods: We conducted a pilot qualitative study using one-on-one, semi-structured interviews with older adults. We included patients over the age of 65 years admitted to the acute cardiac care units (cardiac intensive care unit …

Cardio-Oncology Outcomes In Ultrasound-Assisted Versus Standard Catheter-Directed Thrombolysis For Acute Pulmonary Embolus, Dominique J Monlezun, Dinu Balanescu, Teodora Donisan, Arashk Motiei, Brenden S Ingraham, Keir Mackay, Hyeon-Ju Ali, Kevin Honan, Abdelrahman Ali, Salman Arain, Konstantinos Charitakis, Mehmet Cilingiroglu, Konstantinos Dean Boudoulas, Jaime Caballero, Konstantinos Marmagkiolis, Cezar Iliescu

Faculty, Staff and Student Publications

No abstract provided.

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques, Jumah G Ahmad, Alexander J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

Placenta Accreta Spectrum, Present And Future: The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Workshop Summary, Christina M Duzyj, Brett D Einerson, Yalda Afshar, Karin A Fox, Antonio F Saad, Daniela A Carusi, Christina L Herrera, Deirdre J Lyell, Alfred Z Abuhamad, Michaela K Farber, Anne C Roberts, Sebastian R Hobson, Loic Sentilhes, Baha M Sibai, Koji Matsuo, Kristen Terlizzi, Scott A Shainker, Robert M Silver, Helena C Bartels, Thomas D Shipp, Marilyn Huang, Alison G Cahill, Jason D Wright, George R Saade, Monica Longo

Faculty, Staff and Student Publications

Placenta accreta spectrum (PAS) disorder poses significant risks to maternal health, given the complexities of screening, diagnosis, and management. To address these challenges, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) hosted a workshop on June 10-11, 2024, bringing together expert health care professionals, researchers, stakeholders, and patient advocates to identify knowledge gaps, with an overarching goal of informing future research and best practices for PAS. Key discussions revolved around the resources and infrastructure needed to advance screening, diagnosis, and clinical management of PAS, alongside ways to enhance collaboration across disciplines. Participants considered strategies to …