Medical Specialties Commons^™

Temporal Recording Of Mammalian Development And Precancer, Mirazul Islam, Yilin Yang, Alan J Simmons, Vishal M Shah, Krushna Pavan Musale, Yanwen Xu, Naila Tasneem, Zhengyi Chen, Linh T Trinh, Paola Molina, Marisol A Ramirez-Solano, Iannish D Sadien, Jinzhuang Dou, Andrea Rolong, Ken Chen, Mark A Magnuson, Jeffrey C Rathmell, Ian G Macara, Douglas J Winton, Qi Liu, Hamim Zafar, Reza Kalhor, George M Church, Martha J Shrubsole, Robert J Coffey, Ken S Lau

Faculty, Staff and Student Publications

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3–5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell …

Neoadjuvant And Adjuvant Treatments For Early Stage Resectable Nsclc: Consensus Recommendations From The International Association For The Study Of Lung Cancer, Jonathan D Spicer, Tina Cascone, Murry W Wynes, Myung-Ju Ahn, Sanja Dacic, Enriqueta Felip, Patrick M Forde, Kristin A Higgins, Mark G Kris, Tetsuya Mitsudomi, Mariano Provencio, Suresh Senan, Benjamin J Solomon, Ming Sound Tsao, Masahiro Tsuboi, Heather A Wakelee, Yi-Long Wu, James Chih-Hsin Yang, Caicun Zhou, David H Harpole, Karen L Kelly

Faculty, Staff and Student Publications

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer …

Multi-Modal Segmentation With Missing Image Data For Automatic Delineation Of Gross Tumor Volumes In Head And Neck Cancers, Yao Zhao, Xin Wang, Jack Phan, Xinru Chen, Anna Lee, Cenji Yu, Kai Huang, Laurence E Court, Tinsu Pan, He Wang, Kareem Abdul Wahid, Abdalah S R Mohamed, Mohamed Naser, Clifton D Fuller, Jinzhong Yang

Faculty, Staff and Student Publications

Background: Head and neck (HN) gross tumor volume (GTV) auto-segmentation is challenging due to the morphological complexity and low image contrast of targets. Multi-modality images, including computed tomography (CT) and positron emission tomography (PET), are used in the routine clinic to assist radiation oncologists for accurate GTV delineation. However, the availability of PET imaging may not always be guaranteed.

Purpose: To develop a deep learning segmentation framework for automated GTV delineation of HN cancers using a combination of PET/CT images, while addressing the challenge of missing PET data.

Methods: Two datasets were included for this study: Dataset I: 524 (training) …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, Lingzhi Hong, Sonia Patel, Leylah M Drusbosky, Yuanyuan Xiong, Rongrong Chen, Ruixuan Geng, Simon Heeke, Monique Nilsson, Jia Wu, John V Heymach, Yingyi Wang, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

A Simulation And Small-Group Pediatric Emergency Medicine Course For Generalist Healthcare Providers: Gastrointestinal And Nutrition Emergencies, Adeola Adekunbi Kosoko, Alicia E Genisca, Nicholas A Peoples, Connor Tompkins, Ryan Sorensen, Joy Mackey

Faculty, Staff and Student Publications

Audience and type of curriculum: This is a review curriculum utilizing multiple methods of education to enhance the skills of generalist healthcare providers in low- and middle-income countries (LMICs) in the identification and stabilization of pediatric respiratory emergencies. Our audience of implementation was Belizean generalist providers (nurses and physicians).

Length of curriculum: 8-10 hours.

Introduction: Early recognition and stabilization of critical pediatric patients can improve outcomes. Compared with resource-rich systems, many low-resource settings (i.e., LMICs) rely on generalists to provide most pediatric acute care. We created a curriculum for general practitioners comprising multiple educational modules focused on identifying and stabilizing …

Interest In And Willingness To Use Prep: A Cross-Sectional Study Of Individuals With Problematic Substance Use Residing In A High Hiv Prevalence Jurisdiction, Angela M Heads, Constanza De Dios, Kaixuan An, Jin H Yoon, Robert Suchting, Adrienne Gilmore-Thomas, Joy M Schmitz

Faculty, Staff and Student Publications

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting …

A Protein Expression Atlas On Tissue Samples And Cell Lines From Cancer Patients Provides Insights Into Tumor Heterogeneity And Dependencies, Jun Li, Wei Liu, Kamalika Mojumdar, Hong Kim, Zhicheng Zhou, Zhenlin Ju, Shwetha V Kumar, Patrick Kwok-Shing Ng, Han Chen, Michael A Davies, Yiling Lu, Rehan Akbani, Gordon B Mills, Han Liang

Faculty, Staff and Student Publications

The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our previous work to generate high-quality protein expression data for approximately 8,000 TCGA patient samples and around 900 CCLE cell line samples, covering 447 clinically relevant proteins, using reverse-phase protein arrays. These protein expression profiles offer profound insights into intertumor heterogeneity and cancer dependency and serve as sensitive functional readouts for somatic alterations. We develop a systematic protein-centered strategy …

Tools And Recommendations For Commissioning And Quality Assurance Of Deformable Image Registration In Radiotherapy, Lando S Bosma, Mohammad Hussein, Michael G Jameson, Soban Asghar, Kristy K Brock, Jamie R Mcclelland, Sara Poeta, Johnson Yuen, Cornel Zachiu, Adam U Yeo

Faculty, Staff and Student Publications

Multiple tools are available for commissioning and quality assurance of deformable image registration (DIR), each with their own advantages and disadvantages in the context of radiotherapy. The selection of appropriate tools should depend on the DIR application with its corresponding available input, desired output, and time requirement. Discussions were hosted by the ESTRO Physics Workshop 2021 on Commissioning and Quality Assurance for DIR in Radiotherapy. A consensus was reached on what requirements are needed for commissioning and quality assurance for different applications, and what combination of tools is associated with this. For commissioning, we recommend the target registration error of …

Autonomic Dysfunction Among Adult Survivors Of Childhood Cancer In The St Jude Lifetime Cohort Study, John D Groarke, Kirsten K Ness, Rikeenkumar Dhaduk, Juan C Plana, Jean Bernard Durand, Russell V Luepker, Vijaya M Joshi, Matthew Ehrhardt, Daniel A Mulrooney, Stephanie B Dixon, Anju Nohria, Daniel M Green, Rebecca M Howell, Deo Kumar Srivastava, John L Jefferies, Leslie L Robison, Melissa M Hudson, Gregory T Armstrong

Faculty, Staff and Student Publications

Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown.

Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors.

Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression …

Development Of An Engineered Extracellular Vesicles-Based Vaccine Platform For Combined Delivery Of Mrna And Protein To Induce Functional Immunity, Xin Luo, Kathleen M Mcandrews, Kent A Arian, Sami J Morse, Viktoria Boeker, Shreyasee V Kumbhar, Yingying Hu, Krishnan K Mahadevan, Kaira A Church, Sriram Chitta, Nicolas T Ryujin, Janine Hensel, Jianli Dai, Dara P Dowlatshahi, Hikaru Sugimoto, Michelle L Kirtley, Valerie S Lebleu, Shabnam Shalapour, Joe H Simmons, Raghu Kalluri

Faculty, Staff and Student Publications

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice …

High Throughput And Rapid Isolation Of Extracellular Vesicles And Exosomes With Purity Using Size Exclusion Liquid Chromatography, Kshipra S Kapoor, Kristen Harris, Kent A Arian, Lihua Ma, Beatriz Schueng Zancanela, Kaira A Church, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (< 20 min) EV isolation method termed size exclusion - fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …

Feasibility Of Quantitative Relaxometry For Prostate Target Localization And Response Assessment In Magnetic Resonance-Guided Online Adaptive Stereotactic Body Radiotherapy, Ergys Subashi, Eve Locastro, Sarah Burleson, Aditya Apte, Michael Zelefsky, Neelam Tyagi

Faculty, Staff and Student Publications

Purpose: Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL).

Methods: Fifty patients with intermediate-risk prostate cancer were included in the study. The clinical target volume (CTV) was defined as the prostate gland plus 1 cm of seminal vesicles. The gross tumor volume (GTV) was defined as the DIL identified on multiparametric MRI. Online adaptive radiotherapy was …

Small-Molecule Ccr4 Antagonists In Cutaneous T-Cell Lymphoma, José S Enriquez, Xiaohong Wang, Loka Reddy Velatooru, Wei Han, Pedram Bijani, Xiao Ni

Faculty, Staff and Student Publications

Mycosis fungoides (MF) and Sézary syndrome (SS) are two most common types of cutaneous T-cell lymphoma (CTCL). Despite advances in understanding the pathogenesis of MF and SS, effective treatments remain limited. CC chemokine receptor-4 (CCR4) is highly expressed on CTCL cells and serves as a great therapeutic target. Mogamulizumab, an FDA-approved anti-CCR4 antibody, has shown efficacy in treating MF/SS; however, its side effects have raised concerns, underscoring the need for more effective and less toxic CCR4-targeted therapies. Although small-molecule CCR4 antagonists have been studied in other diseases involving CCR4⁺ Th2 cells and regulatory T cells, their effects in CTCL …

Evaluating Dynamic And Predictive Discrimination For Recurrent Event Models: Use Of A Time-Dependent C-Index, Jian Wang, Xinyang Jiang, Jing Ning

Faculty, Staff and Student Publications

Interest in analyzing recurrent event data has increased over the past few decades. One essential aspect of a risk prediction model for recurrent event data is to accurately distinguish individuals with different risks of developing a recurrent event. Although the concordance index (C-index) effectively evaluates the overall discriminative ability of a regression model for recurrent event data, a local measure is also desirable to capture dynamic performance of the regression model over time. Therefore, in this study, we propose a time-dependent C-index measure for inferring the model's discriminative ability locally. We formulated the C-index as a function of time using …

Mhc Hammer Reveals Genetic And Non-Genetic Hla Disruption In Cancer Evolution, Clare Puttick, Thomas P Jones, Michelle M Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K Dijkstra, James R M Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A Quezada, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% …

Biomarker Trajectory For Earlier Detection Of Lung Cancer, Ehsan Irajizad, Johannes F Fahrmann, Iakovos Toumazis, Jody Vykoukal, Jennifer B Dennison, Yu Shen, Kim-Anh Do, Edwin J Ostrin, Ziding Feng, Samir Hanash

Faculty, Staff and Student Publications

Background: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement.

Methods: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which …

Meta-Analysis Of Censored Adverse Events, Xinyue Qi, Shouhao Zhou, Christine B Peterson, Yucai Wang, Xinying Fang, Michael L Wang, Chan Shen

Faculty, Staff and Student Publications

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete reporting of adverse events (AEs) in published clinical studies is frequently encountered, especially if the observed number of AEs is below a pre-specified study-dependent threshold. Ignoring the censored AE information, often found in lower frequency, can significantly bias the estimated incidence rate of AEs. Despite its importance, this prevalent issue in meta-analysis has received little statistical or analytic attention in the literature. To address this challenge, we propose a Bayesian …

Evaluation Of Vancomycin Dose Needed To Achieve 24-Hour Area Under The Concentration-Time Curve To Minimum Inhibitory Concentration Ratio Greater Than Or Equal To 400 Using Pharmacometric Approaches In Pediatric Intensive Care Patients, Dawoon Jung, Omayma A Kishk, Adnan T Bhutta, Ginny E Cummings, Hana M El Sahly, Manpreet K Virk, Brady S Moffett, Jennifer L Morris Daniel, Amy Watanabe, Nicholas Fishbane, Karen L Kotloff, Kenan Gu, Varduhi Ghazaryan, Jogarao V S Gobburu, Ayse Akcan-Arikan, James D Campbell

Faculty, Staff and Students Publications

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

DESIGN: Prospective population pharmacokinetic study of vancomycin.

SETTING: Critically ill patients in quaternary care PICUs.

PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the …

Demystifying Hispanic Versus Latino/A Versus Latinx: Which Do Emergency Department Patients Prefer?, Melanie F Molina, Anita N Chary, Karen Reyes, James S Ford, Brian Chinnock, Robert M Rodriguez

Faculty, Staff and Students Publications

No abstract provided.

Impact Of Functional Recovery On Patients Having Heart Surgery., Richard J Snow, Lauren Mckown, Geoffrey Blossom, Karen Vogel, Amy Creighton, Jason Shriver, Linda Will, Katie Lentz, Elizabeth Snow, Teresa Caulin-Glaser

Heart and Vascular Articles

OBJECTIVE: To describe the results of a program developed to manage institutional postacute care (IPAC) (postacute skilled nursing, inpatient rehabilitation facility, and long-term acute care) in a CMS Bundled Payments for Care Improvement (BPCI) project for coronary artery bypass graft (CABG) surgery.

STUDY DESIGN: We compared pre- and postutilization patterns during a 3-year period by evaluating risk-adjusted national, state, and other BPCI participant comparisons using a difference-in-differences (DID) analysis in a large urban community tertiary center with a CABG surgery program. Included in the analysis were all Medicare patients receiving CABG surgery at the institution (n = 504), across the …

Precision Imaging For Prostate Cancer Localization: How Multiparametric Ultrasound Stands Against Multiparametric Mri, Amr Mohammed, Priscilla Machado, Tania Siu Xiao, Aylin Tahmasebi, Mostafa Alnoury, Edouard Trabulsi, Ethan J. Halpern, John R. Eisenbrey, Flemming Forsberg

Department of Radiology Faculty Papers

Multiparametric MRI (mpMRI) is currently the standard imaging modality for the diagnosis of prostate cancer; however, studies have reported that targeted biopsy based on mpMRI may miss approximately 30% of clinically significant cases. Recent advances in ultrasound imaging have improved its accuracy for detection of prostate cancer. Newer techniques such as MicroUS, elastography, contrast-enhanced ultrasound (CEUS), and contrast ultrasound dispersion imaging (CUDI) have enabled a comprehensive, real-time, and relatively inexpensive approach to evaluate the prostate gland. Multiparametric ultrasound (mpUS) integrates multiple parameters from these techniques to generate multiparametric maps akin to those produced by mpMRI, to localize prostate cancer. This …

Evaluation Of Liver Fibrosis On Grayscale Ultrasound In A Pediatric Population Using A Cloud-Based Transfer Learning Artificial Intelligence Platform, Amr Mohammed, Aylin Tahmasebi, Sooji Kim, Mostafa Alnoury, Corinne E. Wessner, Tania Siu Xiao, Sharon W. Gould, Lauren A. May, Heidi Kecskemethy, David T. Saul, John R. Eisenbrey

Department of Radiology Faculty Papers

Objectives: The incidence of chronic liver diseases in children is increasing worldwide due to congenital, metabolic, autoimmune and viral diseases. Currently, liver biopsy for fibrosis assessment is considered the gold standard. However, this procedure is invasive, may result in unavoidable complications and is prone to sampling errors. These limitations have led to an increasing demand for noninvasive methods for fibrosis screening. Artificial intelligence integration in ultrasound diagnosis of liver fibrosis has gained interest in clinical research. In the current study we used a cloud-based artificial intelligence platform utilizing transfer learning to evaluate the accuracy of B-mode ultrasound based AI model …

A Guideline For Open-Source Tools To Make Medical Imaging Data Ready For Artificial Intelligence Applications: A Society Of Imaging Informatics In Medicine (Siim) Survey, Sanaz Vahdati, Bardia Khosravi, Elham Mahmoudi, Kuan Zhang, Pouria Rouzrokh, Shahriar Faghani, Mana Moassefi, Aylin Tahmasebi, Katherine Andriole, Peter Chang, Keyvan Farahani, Mona Flores, Les Folio, Sina Houshmand, Maryellen Giger, Judy Gichoya, Bradley Erickson

Department of Radiology Faculty Papers

In recent years, the role of Artificial Intelligence (AI) in medical imaging has become increasingly prominent, with the majority of AI applications approved by the FDA being in imaging and radiology in 2023. The surge in AI model development to tackle clinical challenges underscores the necessity for preparing high-quality medical imaging data. Proper data preparation is crucial as it fosters the creation of standardized and reproducible AI models while minimizing biases. Data curation transforms raw data into a valuable, organized, and dependable resource and is a fundamental process to the success of machine learning and analytical projects. Considering the plethora …

Response To Letter To The Editor Concerning The Article "The Clinical And Economic Impact Of Extended Battery Longevity Of A Substernal Extravascular Implantable Cardioverter Defibrillator"., Bradley P Knight, Nicolas Clémenty, Anish Amin, Ulrika Maria Birgersdotter-Green, Henri Roukoz, Reece Holbrook, Jaimie Manlucu

Heart and Vascular Articles

No abstract provided.