Digital Commons Network^™

Long-Term Outcomes Of A Drug-Eluting Resorbable Scaffold Vs Angioplasty In Infrapopliteal Chronic Limb-Threatening Ischemia: 3-Year Results From The Life-Btk Trial., Sahil A Parikh, Brian G Derubertis, Marc P Bonaca, Prakash Krishnan, Richard H Pin, Jen-Kuang Lee, David C Metzger, Raghu Kolluri, Mehdi H Shishehbor, Andrew H Holden, Osamu Iida, Ehrin Armstrong, Steven W C Kum, David J O'Connor, Danielle R Bajakian, Lawrence A Garcia, Shih-Wa Ying, Jin Wang, Karine Ruster, Brad J Martinsen, Zsuzsanna Igyarto, Ramon L Varcoe

Surgery Articles

Background: Chronic limb-threatening ischemia (CLTI) caused by infrapopliteal disease is a major therapeutic challenge, with percutaneous transluminal angioplasty (PTA) associated with high rates of restenosis and reintervention. The LIFE-BTK trial previously demonstrated superior efficacy of the Esprit (Abbott Vascular) BTK drug-eluting resorbable scaffold (DRS) over PTA at 1 year, with sustained benefits at 2 years, with comparable safety at both time points. This report presents the 3-year outcomes.

Objectives: We aimed to compare the 3-year safety and efficacy of DRS vs PTA in patients with CLTI and infrapopliteal artery disease.

Methods: In this randomized trial, 261 patients with CLTI were …

Trends In Lung Cancer Survival: Superior Outcomes In Us Veterans Compared With The General Population, Nikki E Rossetti, Brendan T Heiden, Steven Tohmasi, Nahom Seyoum, Theodore Thomas, Whitney S Brandt, Sara Malone, Yan Yan, Ana Baumann, Su-Hsin Chang, Daniel Kreisel, Ruben Nava, Bryan Meyers, Benjamin Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States, but survival outcomes are shifting with evolving therapies and screening. Recent findings suggest that survival improvements vary across health-care systems, with favorable trends observed in the Veterans Health Administration (VHA). We sought to compare NSCLC survival trends across US health systems.

METHODS: We conducted a retrospective cohort study of patients with NSCLC (2007-2019) using data from the VHA and the National Cancer Database (NCDB), representing the non-VHA US general population. The primary exposure was health system (VHA vs non-VHA), and the primary outcome …

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high

Longitudinal Genomic Surveillance Of Sars-Cov-2 In A University Microcosm Reflects Global Evolutionary Trends, Sankar Prasad Chaki, Melissa M Kahl-Mcdonagh, Benjamin W Neuman, Loni A Taylor, Rebecca S B Fischer, Blake M Hanson, Marlisa S Hardy, Jo Ann Culpepper, Eric Boerwinkle, Kurt A Zuelke

Faculty, Staff and Student Publications

SARS-CoV-2 transmission has declined, yet ongoing viral evolution continues to pose public health challenges. This study conducted long-term (2020-2024) genomic surveillance within a large and globally diverse university community. Viral genomes obtained from clinical (n = 1,786) and surveillance (n = 888) testing samples were classified under clade, lineage, and variant systems, and compared with global genomic data sets. Local patterns broadly paralleled global evolutionary trends, including the phased emergence of major variants, episodic introductions of new lineages, and shifts in dominant clades. Lineage diversity peaked during fall semesters and was highest among undergraduate-aged individuals, with similar distributions …

Biophysical Insights Into A Cryptic Ligand Site In The Hydrophobic Core Of Human Pcna, Alexis N. Dispensa, Sharon N, Greenwood, Jason Yang, Daniel E. Logatto, James Fusco, E. Railey White, Roderic G. Eckenhoff, Zhiwei Liu, Brian P. Weiser

Department of Anesthesiology Faculty Papers

Proteins contain small pockets that form due to imperfections in residue packing or the rotational and conformational movement of amino acids. In this work, we used the fluorescent probe 1-aminoanthracene (AMA) to detect a small ligand pocket in the hydrophobic core of human proliferating cell nuclear antigen (PCNA), which is a critical protein for DNA replication and repair. Fluorescence measurements of AMA reported that the core of PCNA had a dielectric constant (ε) of 4, which was very apolar and similar to cyclohexane (ε = 2). Protein mutagenesis, photoaffinity labeling, and molecular dynamics simulations localized the binding site for AMA …

Prenatal Predictors Of Fetal And Neonatal Death In Truncus Arteriosus: A Fetal Heart Society Research Collaborative Study., Kelly Cox, Nazia Husain, Deidra Ansah, Tiffany Knight, Alexandra Channing, Bettina Cuneo, Preeta Dhanantwari, Mary Donofrio, Miwa Geiger, Lisa Howley, Lisa K. Hornberger, Simone Javeri, Edward G. Jones, Michelle Kaplinski, Ann Kavanaugh-Mchugh, Maria Kiaffas, Katherine Kosiv, Christina Laternser, Olivia Low, Anita J. Moon-Grady, Shabnam Peyvandi, Nelangi Pinto, Avaliese Porlier, Aaron Prosnitz, Rashmi Rao, David Schidlow, Elena Sinkovskaya, Ranjini Srinivasan, Corey Stiver, Emilio Quezada, Bhawna Arya, Sheetal Patel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fetal and neonatal outcomes and factors increasing mortality risk in fetal truncus arteriosus are not well characterized. We aimed to examine the prenatally encountered cardiac spectrum, define extracardiac and genetic associations, explore clinical outcomes and identify prenatal factors associated with worse outcomes in a contemporary large cohort.

METHODS: A multicenter retrospective cohort study was conducted via the Fetal Heart Society Research Collaborative including fetal truncus arteriosus cases encountered between January 1, 2010, and September 1, 2021, within 22 North American cardiac centers. Demographic, clinical, anatomic, and functional fetal echocardiographic variables were analyzed for associations with presurgical death (fetal death/neonatal …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation, Liset Olarte, Jennifer E Schuster, Ibrahim Ahmed, Kristina G Hulten

Faculty, Staff and Students Publications

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Tau Pathology In Epilepsy: Emerging Mechanisms And Translational Opportunities, Arjune Sen, Xin You Tai, Aristea Galanopoulou, Maria Thom, Eleonora Aronica, Lucy Vivash, Martin Hardmeier, Action Amos, Stephan Rueegg, Matthias Koepp, Yaroslav Winter, Christoph Helmstaedter, Jeffrey L Noebels, Hilal A Lashuel, Terence J O'Brien

Faculty, Staff and Students Publications

The onset of epilepsy in adulthood occurs most commonly after 55 years of age. Given the ageing global population, this disorder represents an increasing burden on healthcare and society. The bidirectional link between epilepsy and dementia is a focus of intense research with underlying tau pathology highlighted as a potential mechanistic link. In this review, we examine the evidence for tau-related neurodegenerative processes in epilepsy beginning with how changes in biochemical and structural properties of the tau protein can lead to abnormal phosphorylation and pathological aggregation. We consider the role of tau in seizure occurrence and cognitive difficulties in experimental …

Association Between Trainee Involvement During Pediatric And Congenital Cardiac Catheterization And Procedural Outcomes., Natalie Jayaram, John A. Spertus, Kevin F. Kennedy, Andrew C. Glatz

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Participation in the cardiac catheterization laboratory is a requirement of cardiology fellowship training. We sought to determine whether trainee presence is associated with outcomes during pediatric and congenital cardiac catheterization.

METHODS: We identified catheterizations between January 2011 and September 2020 within the IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry. Multivariable multilevel regression was used to determine the association between trainee presence and procedural outcomes.

RESULTS: Of 122 760 catheterizations at 107 academic hospitals, a trainee was present in 71 651 (58.4%) cases. Rates of major adverse events were similar between trainee and nontrainee cases (9.0% versus 8.0%). Contrast …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation., Liset Olarte, Jennifer E. Schuster, Ibrahim Ahmed, Kristina G. Hulten

Manuscripts, Articles, Book Chapters and Other Papers

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Feasibility Evaluation Of Tumor Treating Fields For Brainstem Gliomas, Anthony Chen, Ryan Shah, William Shi, Noa Urman, Nadav Shapira, Nicholas Avgeropoulos, Patrick Conlon, Neil Mookerjee, Wenyin Shi

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor treating fields (TTFields) are FDA-approved for supratentorial glioblastoma, but feasibility in infratentorial tumors remains poorly defined. This simulation study evaluated TTFields dose in brainstem gliomas using patient-specific modeling with scalp-only transducer arrays.

METHODS: MRI and CT imaging from seven patients with brainstem gliomas were used for TTFields planning with MAXPOINT® (Novocure, Switzerland). Clinical target volume (CTV) was defined as enhancing tumor on T1 post-contrast MRI (Gross tumor volume, GTV) plus a 3 mm peritumoral expansion. The platform optimized scalp-only array layouts, and finite element calculations generated maps of local minimum field intensity (LMiFI, V/cm) and local minimum power …

Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle

2020-Current year OA Pubs

A-isoforms of cytosolic growth factor homologous factors (FGF11-14) mediate long-term inactivation (LTI) of voltage-dependent sodium (NaV) channels. LTI is a rapid onset process that is competitive with the fast inactivation (IF) intrinsic to NaV channels, with little or no interconversion between inactivated states. Since recovery from LTI is orders of magnitude slower than recovery from IF, repetitive depolarizations lead to use-dependent accumulation of NaV channels in slow recovery states, thereby limiting NaV availability during trains of action potentials. Of the two or more N-terminal splice variants of the various FGF homologues, LTI specifically arises only from the A-isoform of each …

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Krisha Shah, Rubén Herzog, Alan C Swann, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Tranexamic Acid In High-Risk Shoulder Arthroplasty Patients: Safety Across Thromboembolic, Cardiac, Renal, And Neurologic Risk Profiles, Tarishi Parmar, Akin Adio, Asim Handy, Mohammad Daher, Alec Kellish, Adam Khan, Joseph A. Abboud

Rothman Institute Papers

INTRODUCTION: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements in shoulder arthroplasty. However, concerns regarding thromboembolic, neurologic, cardiac, and renal complications have limited its use in medically high-risk patients. This study evaluated temporal trends and the safety of TXA in high-risk patients undergoing total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study was conducted using TriNetX, identifying patients who underwent shoulder arthroplasty (2012-2025). Patients were stratified by preexisting high-risk conditions, including prior thromboembolism, renal failure, atrial fibrillation, seizure disorders, and visual disturbances. Within each subgroup, patients receiving TXA were propensity score-matched to those who did not. Perioperative TXA …

Advancing Bioinformatics With Language Models: Components, Applications, And Perspectives, Jiajia Liu, Mengyuan Yang, Yankai Yu, Haixia Xu, Tiangang Wang, Kang Li, Xiaobo Zhou

Faculty, Staff and Student Publications

Large language models (LLMs) are deep learning-based artificial intelligence models that have achieved remarkable success in natural language processing. Typically composed of neural networks with billions of parameters, they are trained on massive unlabeled datasets using self-supervised or semi-supervised learning. Beyond language, LLMs hold immense potential for addressing complex bioinformatics challenges. This review provides a comprehensive overview of transformer-based model applications in genomics, transcriptomics, proteomics, drug discovery, and single-cell analysis. We discuss critical components, including tokenization strategies for diverse biological data, transformer architectures, attention mechanisms, and pretraining approaches. We also survey currently available foundation models and their downstream applications across …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

Molecular Classification And Association With Survival Outcomes In High-Intermediate And High-Risk Early-Stage Endometrial Cancers: Ancillary Analysis Of Gog-0249., Lindsay M Kuroki, Danielle M Enserro, Heather A Lankes, Kyle C Strickland, Rebecca Previs, Aine Clements, Matthew A Powell, Ann Klopp, Elena Ratner, Paul Disilvestro, Casey Cosgrove, Guilherme Henrique Cantuaria, Nicola M Spirtos, Michael Carney, Mitchell Edelson, Gottfried Konecny, Penny Anderson, Christopher Tarney, Britt K Erickson, Meredith Newton, Krishnansu S Tewari, Premal H Thaker, David Warshal, Amy Armstrong, Xun Clare Zhou, Angeles Alvarez Secord

Women’s Health Articles

OBJECTIVE: Determine whether mismatch repair (MMR) and p53 expression predict recurrence-free survival (RFS) and overall survival (OS) in early-stage endometrial cancer (EC) patients treated with vaginal cuff brachytherapy plus chemotherapy (VCB/C) versus pelvic radiation therapy (RT).

METHODS: In the GOG-0249 trial, 601 patients with high-intermediate risk (HIR) early-stage EC were randomized to VCB/C (carboplatin/paclitaxel for 3 cycles) or pelvic RT. Molecular subgroups, deficient MMR (dMMR), p53 wildtype (p53wt), p53 abnormal (p53abn), were determined by immunohistochemistry. Five-year RFS and OS were analyzed using Kaplan-Meier curves and Cox proportional hazards models, adjusting for lymphadenectomy, planned VCB, and treatment group.

RESULTS: Among 315 …

Pearson Syndrome: Expanding The Clinical Spectrum Of A Mitochondrial Cytopathy-A Case Report, Alizah Faisal, Hooria Waqas, Hania Masood, Armeen Butt, Saad Rahman, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Ali Iqbal, Muhammad Usama Naveed

Department of Medicine Faculty Papers

BACKGROUND: Pearson syndrome (PS) is a rare multisystem mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions (SLSMDs). It typically presents in infancy with refractory sideroblastic anemia, exocrine pancreatic insufficiency, and failure to thrive. Due to its heterogeneous manifestations and resemblance to other hematological conditions, early diagnosis remains a clinical challenge.

CASE PRESENTATION: A south asian male infant presented with persistent pancytopenia, severe anemia unresponsive to intravenous and oral iron and multivitamin supplements, exocrine pancreatic insufficiency, failure to thrive, and metabolic acidosis. Born to consanguineous parents, the child had a significant family history of early infant deaths and hematological abnormalities. …

Extending The Fundamental Theorem Of Biomedical Informatics For The Ai Era, Philip R O Payne, Jonathan H Chen, Christopher A Longhurst

2020-Current year OA Pubs

BACKGROUND: Charles Friedman's Fundamental Theorem of Biomedical Informatics holds that a person working in partnership with an information resource outperforms that same person unassisted. Since its publication, advances in artificial intelligence (AI), adaptive learning systems, and large-scale data infrastructures have transformed the biomedical ecosystem, extending informatics beyond clinical care into domains such as public health, consumer health, translational science, and the broader life sciences. Such expansion has further underscored the importance of the Fundamental Theorem while also elucidating ways it can be expanded to meet current needs.

OBJECTIVE: To reassess and extend the Fundamental Theorem for the AI era in …

In Vivo Evidence Of Blood Flow Slippage: Failure Of The No-Slip Boundary Condition Assumption, Alena Jarolímová, Jaroslav Hron, Karel Tůma, Radomír Chabiniok, Josef Málek, Keshava Rajagopal

Division of Cardiology Faculty Papers

The assumption that blood adheres to vessel walls with zero tangential velocity component, the so-called "no-slip" boundary condition, is a foundational premise of cardiovascular fluid dynamics. Whether the no-slip condition holds in vivo, however, remains unknown. Seven healthy adult volunteers underwent cardiovascular magnetic resonance imaging. With four-dimensional flow magnetic resonance imaging of the descending thoracic aorta and modeling blood as a Navier-Stokes fluid, near-wall blood velocities were quantified, and wall shear stress was calculated based on the measured velocity fields. Within the Navier-Stokes data assimilation framework, tangential wall velocities of ∼30-80% of the mean luminal velocity were consistently obtained. These …

Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Inferior petrosal sinus sampling (IPSS) is important for confirming Cushing's Disease (CD). Due to lack of corticotropin releasing hormone (CRH) availability, desmopressin/DDAVP is being used as the alternative stimulating agent but has limited data regarding testing cutoffs.

DESIGN: We compared the stimulation profiles of desmopressin and CRH in patients with CD.

METHODS: Data from the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID) was evaluated. 93 patients with CD confirmed by pathology or biochemical remission that underwent IPSS testing prior to surgical resection (desmopressin [n = 57], CRH [n = 36] or both [n = 1]). …

Not Just A Pediatric Condition: Down Syndrome Across The Lifespan., Emily Haury, Jacqueline Kitchen, Brenda Rogers

Manuscripts, Articles, Book Chapters and Other Papers

With increasing life expectancy for individuals with Down Syndrome (DS), there are growing numbers of adult DS patients needing care from primary care physicians who are knowledgeable regarding their health needs and risks. The Global Down Syndrome Foundation (GDSF) Medical Care Guidelines for Adults with Down Syndrome identify important areas of focus: mental health, dementia, diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, hypothyroidism and celiac disease. Additionally, there are unique considerations regarding cancer risk and screenings, as well as vaccination. Young adults with DS should have a structured transition from pediatric to adult care like any patient with chronic illness …

Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Increasing reliance on and complexity of laboratory testing necessitates laboratory stewardship initiatives to ensure appropriate test ordering, especially as reference testing costs continue to rise. Prospective manual review processes, although demanding of resources, have been shown to be cost-effective, but literature addressing the value of such a process is lacking.

METHODS: The pathology trainee-driven manual review process of 444 chemistry and microbiology tests on approval at a large academic center was reviewed. Data were extracted from an internal-use call-log and analyzed for test volumes, cancellation rates, and cost savings. A hypergeometric distribution was used to model random variation in …

Modern Molecular Profiling Recontextualizes The Nrg/Rtog 0539 Trial And Reveals Hidden High-Risk And Radiotherapy-Resistant Meningiomas, Leeor S Yefet, Clifford Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Meningiomas exhibit clinical heterogeneity. Radiotherapy (RT) remains the only adjuvant therapy, but tumor-control is variable, and biomarkers are limited. NRG/RTOG-0539 is the first prospective phase 2 trial to stratify meningioma patients for adjuvant RT based on clinical risk. Here, we apply modern molecular tools to this cohort and identify correlates of RT response.

METHODS: Tumor tissue from 100 RTOG-0539 patients was profiled using DNA methylation arrays, RNA sequencing, and whole-exome sequencing. Recurrence scores, Molecular Groups, gene expression, and copy number alterations were compared across clinical groups and between RT responders and non-responders; non-response was defined as progression or death …

Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).

METHODS: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were …

Improving Infant Health Equity: What Have We Learned, What Do We Do, Dewayne M Pursley, F Sessions Cole

2020-Current year OA Pubs

The United States neonatal and infant mortality rates have declined substantially over the last six decades. Despite these reductions, significant racial disparities in mortality and other important outcomes have persisted. While increased risk of preterm birth is a major contributor to these differences, racial inequities in risk-adjusted outcomes such as gestational age-specific and major congenital anomaly-associated mortality remain. Race-specific differences in inter- and intra-neonatal intensive care unit (NICU) practices associated with worse outcomes for infants of color suggest opportunities for reducing these disparate health outcomes during and after NICU hospitalization. Identifying NICU-based contributing factors and implementing factor-specific improvement strategies can …

Cardiorespiratory Signatures Of Necrotizing Enterocolitis: A 4-Nicu Study Of Very Low Birth Weight Infants, Sherry L Kausch, Zachary A Vesoulis, Colm P Travers, Carie Taveras, Rachel Benz, Amanda Duncan, Angela K S Gummadi, Katy N Krahn, Rakesh Sahni, Joseph Isler, Namasivayam Ambalavanan, J Randall Moorman, Douglas E Lake, Karen D Fairchild, Brynne A Sullivan

2020-Current year OA Pubs

BACKGROUND: Necrotizing enterocolitis (NEC) is a disorder in very low birth weight (VLBW, < 1500 g) infants, associated with significant morbidity and mortality. Earlier detection of NEC may improve outcomes. We hypothesized that NEC's physiological signature resembles that of sepsis and that our model developed for sepsis, the Pulse Oximetry Warning System (POWS), would also predict NEC.

OBJECTIVES: Assess relationships between continuous heart rate (HR) and oxygen saturation (SpO

METHODS: In a retrospective multicenter analysis, we studied VLBW infants at four level IV NICUs, identifying cases of late-onset sepsis (LOS) and NEC (Bell stages 2 or 3). Using HR and SpO

RESULTS: Among 3914 infants evaluated, 5% had NEC and 13% had LOS. Cardiorespiratory data analysis showed that HR/SpO

CONCLUSION: NEC shares a cardiorespiratory signature with LOS. POWS predicted NEC with a dynamic rise before clinical diagnosis.

IMPACT: A cardiorespiratory early warning score analyzing …

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …

Prescribed Short-Acting Hormonal Contraceptive Use Among Premenopausal Females, Israel Bacha, Suleepon Uttamapinan, Hannah Harsanyi, Abigail Liberty, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Hormonal contraceptive use has important implications for both reproductive and general health. However, the patterns and trends of short-acting hormonal contraceptive use among US premenopausal females remain insufficiently characterized.

OBJECTIVE: To evaluate trends in and factors associated with prescribed short-acting hormonal contraceptive use among US premenopausal females.

DESIGN, SETTING, AND PARTICIPANTS: Serial, cross-sectional analyses were conducted using US nationally representative data from the National Health and Nutrition Examination Survey (NHANES), including 10 survey cycles between 1999 to 2000 and 2017 to 2020 (before the COVID-19 pandemic). Participants included noninstitutionalized premenopausal females aged 15 years to younger than 60 years …

Brain Volumes In Fetuses With Congenital Heart Disease And Placental Vascular Abnormalities, Erin A O'Brien, Kaylin Taylor, Joshua S Shimony, Cynthia M Ortinau, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Investigate the association between placental vascular abnormalities and regional brain volumes in congenital heart disease (CHD) fetuses with and without genetic abnormalities.

STUDY DESIGN: Secondary analysis of brain magnetic resonance imaging (MRI) and placental pathology data from 121 CHD fetuses enrolled in prospective neuroimaging studies at two centers.

RESULTS: Placental vascular abnormality was present in 46% of fetuses, and genetic abnormality was present in 19%, including 12% with both abnormalities. Fetuses with the combination of placental and genetic abnormalities had smaller brain volumes compared to fetuses without either abnormality for total brain, subcortical gray matter, brainstem, and cerebellum, with …