Digital Commons Network^™

Cytokine Release By Microglia Exposed To Neurologic Injury Is Amplified By Lipopolysaccharide, Michael C Scott, Olivia Leblanc, Harper Day, Candice Haase, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Introduction: Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury.

Methods: Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were …

Combined Ion Beam Irradiation Platform And 3d Fluorescence Microscope For Cellular Cancer Research, Andrew D Harken, Naresh T Deoli, Citlali Perez Campos, Brian Ponnaiya, Guy Garty, Grace S Lee, Malte J Casper, Shikhar Dhingra, Wenze Li, Gary W Johnson, Sally A Amundson, Peter W Grabham, Elizabeth M C Hillman, David J Brenner

Faculty, Staff and Student Publications

To improve particle radiotherapy, we need a better understanding of the biology of radiation effects, particularly in heavy ion radiation therapy, where global responses are observed despite energy deposition in only a subset of cells. Here, we integrated a high-speed swept confocally-aligned planar excitation (SCAPE) microscope into a focused ion beam irradiation platform to allow real-time 3D structural and functional imaging of living biological samples during and after irradiation. We demonstrate dynamic imaging of the acute effects of irradiation on 3D cultures of U87 human glioblastoma cells, revealing characteristic changes in cellular movement and intracellular calcium signaling following ionizing irradiation.

Recurrent Nontraumatic Subgaleal Hematomas In A Pediatric Patient With Sickle Cell Disease, Irtiza N Sheikh, Olayinka Okeleji, Rabya Afzal, Eliana Bonfante, Monica Kodakandla, Neethu M Menon

Faculty, Staff and Student Publications

Spontaneous subgaleal hematoma in pediatric patients with sickle cell disease (SCD) is a rare occurrence that can present with symptoms mimicking ischemic stroke, a known complication of SCD. However, unlike ischemic stroke, subgaleal hematoma is nonlethal and can be managed conservatively without major sequelae. Here, we present the case of an adolescent with SCD who presented with 2 episodes of subgaleal and epidural hematomas, 2 years apart. The latter episode occurred while on crizanlizumab, an anti-P-selectin antibody, approved for use in SCD in 2019 to reduce the number of acute pain crises. We demonstrate the diagnosis of subgaleal hematoma and …

Blockade Of Rho-Associated Kinase Prevents Inhibition Of Axon Regeneration Of Peripheral Nerves Induced By Anti-Ganglioside Antibodies, Andrés Berardo, Cristian R Bacaglio, Bárbara B Báez, Rubén Sambuelli, Kazim A Sheikh, Pablo H H Lopez

Faculty, Staff and Student Publications

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon …

Activation Of Cerebral Ras-Related C3 Botulinum Toxin Substrate (Rac) 1 Promotes Post-Ischemic Stroke Functional Recovery In Aged Mice, Fan Bu, Jia-Wei Min, Md Abdur Razzaque, Ahmad El Hamamy, Anthony Patrizz, Li Qi, Akihiko Urayama, Jun Li

Faculty, Staff and Student Publications

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term …

Efficacy And Safety Results After >35 Years Of Treatment With The Bruton’S Tyrosine Kinase Inhibitor Evobrutinib In Relapsing Multiple Sclerosis: Long-Term Follow-Up Of A Phase Ii Randomised Clinical Trial With A Cerebrospinal Fluid Sub-Study, Xavier Montalban, Karolina Piasecka-Stryczynska, Jens Kuhle, Pascal Benkert, Douglas L Arnold, Martin S Weber, Andrea Seitzinger, Hans Guehring, Jamie Shaw, Davorka Tomic, Yann Hyvert, Danielle E Harlow, Martin Dyroff, Jerry S Wolinsky

Faculty, Staff and Student Publications

BACKGROUND: Evobrutinib - an oral, central nervous system (CNS)-penetrant, and highly selective Bruton's tyrosine kinase inhibitor - has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS.

OBJECTIVE: Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal fluid (CSF) sub-study.

METHODS: In the 48-week double-blind period (DBP), patients received evobrutinib 25 mg once-daily, 75 mg once-daily, 75 mg twice-daily or placebo (switched to evobrutinib 25 mg once-daily after week 24). Patients could then enter the OLE, receiving evobrutinib 75 mg once-daily (mean (± standard deviation (SD)) …

Minimally Invasive Anterior Cervical Foraminotomy For Unilateral Radiculopathy, Duncan J Trimble, Dallas L Sheinberg, Joseph A Cochran

Faculty, Staff and Student Publications

Anterior cervical foraminotomy (ACF) is an alternative surgical option for the treatment of refractory unilateral radiculopathy due to disc herniation or spondylosis. The efficacy and adverse event rate in experienced practitioners are comparable to those of anterior cervical discectomy and fusion, total disc arthroplasty, and posterior foraminotomy. However, this technique has not been widely adopted, likely because of the proximity of the working zone and the vertebral artery. The authors present a detailed operative video of a patient successfully treated with an ACF. They also present a review of the ACF literature.

The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23196

Identifying Age-Specific Risk Factors For Poor Outcomes After Trauma With Machine Learning, Heather R Kregel, Gabrielle E Hatton, John A Harvin, Thaddeus J Puzio, Charles E Wade, Lillian S Kao

Faculty, Staff and Student Publications

Introduction: Risk stratification for poor outcomes is not currently age-specific. Risk stratification of older patients based on observational cohorts primarily composed of young patients may result in suboptimal clinical care and inaccurate quality benchmarking. We assessed two hypotheses. First, we hypothesized that risk factors for poor outcomes after trauma are age-dependent and, second, that the relative importance of various risk factors are also age-dependent.

Methods: A cohort study of severely injured adult trauma patients admitted to the intensive care unit 2014-2018 was performed using trauma registry data. Random forest algorithms predicting poor outcomes (death or complication) were built and validated …

Diffuse Alveolar Haemorrhage Due To Atypical Hemolytic Uremic Syndrome (Ahus) Associated With Covid-19, Atif Siddiqui, Amanda Tchakarov

Faculty, Staff and Student Publications

Delayed presentation of atypical HUS after COVID‐19 with diffuse alveolar haemorrhage is uncommon and can be life threatening.

How Territoriality And Sociality Influence The Habitat Selection And Movements Of A Large Carnivore, K Whitney Hansen, Nathan Ranc, John Morgan, Neil R Jordan, J Weldon Mcnutt, Alan Wilson, Christopher C Wilmers

Faculty, Staff and Student Publications

While territoriality is one of the key mechanisms influencing carnivore space use, most studies quantify resource selection and movement in the absence of conspecific influence or territorial structure. Our analysis incorporated social information in a resource selection framework to investigate mechanisms of territoriality and intra‐specific competition on the habitat selection of a large, social carnivore. We fit integrated step selection functions to 3‐h GPS data from 12 collared African wild dog packs in the Okavango Delta and estimated selection coefficients using a conditional Poisson likelihood with random effects. Packs selected for their neighbors' 30‐day boundary (defined as their 95% kernel …

Presentation Acuity And Surgical Outcomes For Patients With Health Insurance Living In Highly Deprived Neighborhoods, Susanne Schmidt, Michael A Jacobs, Jeongsoo Kim, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Importance: Insurance coverage expansion has been proposed as a solution to improving health disparities, but insurance expansion alone may be insufficient to alleviate care access barriers.

Objective: To assess the association of Area Deprivation Index (ADI) with postsurgical textbook outcomes (TO) and presentation acuity for individuals with private insurance or Medicare.

Design, setting, and participants: This cohort study used data from the National Surgical Quality Improvement Program (2013-2019) merged with electronic health record data from 3 academic health care systems. Data were analyzed from June 2022 to August 2023.

Exposure: Living in a neighborhood with an ADI greater than 85. …

Ems Treatment Guidelines In Major Traumatic Brain Injury With Positive Pressure Ventilation, Joshua B Gaither, Daniel W Spaite, Bentley J Bobrow, Bruce Barnhart, Vatsal Chikani, Kurt R Denninghoff, Gail H Bradley, Amber D Rice, Jeffrey T Howard, Samuel M Keim, Chengcheng Hu

Faculty, Staff and Student Publications

Importance: The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown.

Objective: To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV.

Design, setting, and participants: The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and …

Readiness Of Nociceptor Cell Bodies To Generate Spontaneous Activity Results From Background Activity Of Diverse Ion Channels And High Input Resistance, Jinbin Tian, Alexis G Bavencoffe, Michael X Zhu, Edgar T Walters

Faculty, Staff and Student Publications

Nociceptor cell bodies generate "spontaneous" discharge that can promote ongoing pain in persistent pain conditions. Little is known about the underlying mechanisms. Recordings from nociceptor cell bodies (somata) dissociated from rodent and human dorsal root ganglia have shown that previous pain in vivo is associated with low-frequency discharge controlled by irregular depolarizing spontaneous fluctuations of membrane potential (DSFs), likely produced by transient inward currents across the somal input resistance. Using mouse nociceptors, we show that DSFs are associated with high somal input resistance over a wide range of membrane potentials, including depolarized levels where DSFs approach action potential (AP) threshold. …

Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution …

4r-Cembranoid Suppresses Glial Cells Inflammatory Phenotypes And Prevents Hippocampal Neuronal Loss In Lps-Treated Mice, Luis A Rojas-Colón, John B Redell, Pramod K Dash, Pedro E Vegas, Wanda Vélez-Torres

Faculty, Staff and Student Publications

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for …

Impact Of Age-Related Change In Caval Flow Ratio On Hepatic Flow Distribution In The Fontan Circulation, Vijay Govindarajan, Lauren Marshall, Akshita Sahni, Maria A Cetatoiu, Emily E Eickhoff, Jocelyn Davee, Nicole St Clair, Noah E Schulz, David M Hoganson, Peter E Hammer, Sunil J Ghelani, Ashwin Prakash, Pedro J Del Nido, Rahul H Rathod

Faculty, Staff and Student Publications

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling.

Methods: SVC and …

Druggable Site Near The Upper Vestibule Determines The High Affinity And P2x3 Homotrimer Selectivity Of Sivopixant/S-600918 And Its Analogue Ddtpa, Dong-Ping Wang, Meng Zhang, Ming Li, Xiao-Na Yang, Changzhu Li, Peng Cao, Michael X Zhu, Yun Tian, Ye Yu, Yun-Tao Lei

Faculty, Staff and Student Publications

Background and purpose: The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF-219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S-600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3-(4-([3-chloro-4-isopropoxyphenyl]amino)-3-(4-methylbenzyl)-2,6-dioxo-3,6-dihydro-1,3,5-triazin-1(2H)-yl)propanoic acid (DDTPA), exhibit both high affinity …

Survey Of Neonatal Management After Amnioinfusion For Anhydramnios, Ellen M Bendel-Stenzel, Amaris M Keiser, Kristin J Mckenna, Valerie Y Chock, Suzanne Lopez, Jena L Miller, Meredith A Atkinson

Faculty, Staff and Student Publications

No abstract provided.

Open Repair With Latissimus Muscle Flap Coverage For Treatment Of Infected Thoracic Endovascular Aneurysm Repair, Lucas Ribé Bernal, Rana O Afifi, Anthony L Estrera

Faculty, Staff and Student Publications

A male patient, 70 years of age, was evaluated for an infected thoracic endovascular aneurysm repair (TEVAR). After presenting with persistent fever, a positron emission tomography scan found an infected aortic stent graft. The patient underwent open repair with explantation of the infected TEVAR, extensive periaortic debridement, graft replacement with a Dacron graft, and complete coverage with a latissimus dorsi muscle flap. Tissue culture revealed

Congenital Disseminated Malignant Rhabdoid Tumor Mimicking A Vascular Lesion, Scott K Wang, Prabhath Mannam, Katerina Dukleska, Fabiola Balarezo

Faculty, Staff and Student Publications

A congenital disseminated malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive pediatric cancer marked by the presence of malignant rhabdoid cells in various organs, including the brain, kidneys, and soft tissues, at birth. It is often detected prenatally or shortly post-birth. The malignancy's aggressiveness results in a bleak prognosis, offering limited treatment options and low survival rates. Early diagnosis and comprehensive medical intervention are crucial, but managing this condition is complicated by its rarity. We herein presented a case of a 37 and 1/7 week gestation male infant with a rapidly growing arm soft tissue mass within two …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

A Meta-Analysis On The Diagnostic Utility Of Ultrasound In Pediatric Distal Forearm Fractures, Amir Hassankhani, Melika Amoukhteh, Payam Jannatdoust, Parya Valizadeh, Delaram J Ghadimi, Pauravi S Vasavada, Jennifer H Johnston, Ali Gholamrezanezhad

Faculty, Staff and Student Publications

Pediatric distal forearm fractures, comprising 30% of musculoskeletal injuries in children, are conventionally diagnosed using radiography. Ultrasound has emerged as a safer diagnostic tool, eliminating ionizing radiation, enabling bedside examinations with real-time imaging, and proving effective in non-hospital settings. The objective of this study is to evaluate the diagnostic efficacy of ultrasound for detecting distal forearm fractures in the pediatric population. A systematic review and meta-analysis were conducted through a comprehensive literature search in PubMed, Scopus, Web of Science, and Embase databases until October 1, 2023, following established guidelines. Eligible studies, reporting diagnostic accuracy measures of ultrasound in pediatric patients …

Cytoplasmic Redox Imbalance In The Thioredoxin System Activates Hsf1 And Results In Hyperaccumulation Of The Sequestrase Hsp42 With Misfolded Proteins, Davi Goncalves, Duong Long Duy, Sara Peffer, Kevin A Morano

Faculty, Staff and Student Publications

Cells employ multiple systems to maintain homeostasis when experiencing environmental stress. For example, the folding of nascent polypeptides is exquisitely sensitive to proteotoxic stressors including heat, pH, and oxidative stress, and is safeguarded by a network of protein chaperones that concentrate potentially toxic misfolded proteins into transient assemblies to promote folding or degradation. The redox environment itself is buffered by both cytosolic and organellar thioredoxin and glutathione pathways. How these systems are linked is poorly understood. Here, we determine that specific disruption of the cytosolic thioredoxin system resulted in constitutive activation of the heat shock response in Saccharomyces cerevisiae and …

Tavr In Older Adults, Abdulla A Damluji, Gwen Bernacki, Jonathan Afilalo, Radmila Lyubarova, Ariela R Orkaby, Min Ji Kwak, Scott Hummel, James N Kirkpatrick, Mathew S Maurer, Nanette Wenger, Michael W Rich, Dae Hyun Kim, Roberta Y Wang, Daniel E Forman, Ashok Krishnaswami

Faculty, Staff and Student Publications

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. …

Definition Of Polypharmacy In Heart Failure: A Scoping Review Of The Literature, Keshav Patel, Jorge A Irizarry-Caro, Adil Khan, Travis Holder, Darrell Salako, Parag Goyal, Min Ji Kwak

Faculty, Staff and Student Publications

Patients with heart failure (HF) have a high prevalence of polypharmacy, which can lead to drug interactions, cognitive impairment, and medication non-compliance. However, the definition of polypharmacy in these patients is still inconsistent. The aim of this scoping review was to find the most common definition of polypharmacy in HF patients. We conducted a scoping review searching Medline, Embase, CINAHL, and Cochrane using terms including polypharmacy, HF and deprescribing, which resulted in 7,949 articles. Articles without a definition of polypharmacy in HF patients and articles which included patients < 18 years of age were excluded; only 59 articles were included. Of the 59 articles, 49% (n = 29) were retrospective, 20% (n = 12) were prospective, 10% (n = 6) were cross-sectional, and 27% (n = 16) were review articles. Twenty percent (n = 12) of the articles focused on HF with reduced ejection fraction, 10% (n = 6) focused on HF with preserved ejection fraction and 69% (n = 41) articles either focused on both diagnoses or did not clarify the specific type of HF. The most common cutoff for polypharmacy in HF was five medications (59%, n = 35). There was no consensus regarding the inclusion or exclusion of over-the-counter medications, supplements, or vitamins. Some newer studies used a cutoff of 10 medications (14%, n = 8), and this may be a more practical and meaningful definition for HF patients.

Performance Characteristics Of The 5-Ring Ge Discovery Mi Pet/Ct Scanner Using Aapm Tg-126 Report, Refaat Y Almazrou, Shadei F Alanazi, Mohammed H Alzaid, Razan S Al-Fakhranee, Shanli Ding, Osama R Mawlawi

Faculty, Staff and Student Publications

AIM: To report on the performance characteristics of the 5-ring GE Discovery MI PET/CT systems using the AAPM TG-126 report and compare these results to NEMA NU 2-2012 where applicable.

MATERIALS AND METHODS: TG-126 testing was performed on two GE 5-Rings Discovery MI scanners. Tests performed included spatial resolution, PET/CT image-registration accuracy, sensitivity, count rate performance, accuracy of corrections, image contrast, scatter/attenuation correction, and image uniformity. All acquired data were analyzed using scanner console or free software tools as described by TG-126 and the results were then compared to published NEMA NU 2-2012 values.

RESULTS: Both scanners gave similar resolution …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Normal Risk Ovarian Screening Study: 21-Year Update, Chae Young Han, Karen H Lu, Gwen Corrigan, Alexandra Perez, Sharlene D Kohring, Joseph Celestino, Deepak Bedi, Enrique Bedia, Therese Bevers, David Boruta, Matthew Carlson, Laura Holman, Leroy Leeds, Cara Mathews, Georgia Mccann, Richard G Moore, Matthew Schlumbrecht, Brian Slomovitz, Dan Tobias, Yvette Williams-Brown, Michael W Bevers, Jinsong Liu, Terrie G Gornet, Beverly C Handy, Zhen Lu, Jacob S Bedia, Steven J Skates, Robert C Bast

Faculty, Staff and Student Publications

Purpose: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

Methods: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and < 1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

Results: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 …

Disease Progression, Survival, And Molecular Disparities In Black And White Patients With Endometrioid Endometrial Carcinoma In Real-World Registries And Gog/Nrg Oncology Randomized Phase Iii Clinical Trials, Zachary A Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T Phippen, Christopher M Tarney, Erica R Hope, Stuart S Winkler, Suzanne Jokajtys, Calen W Kucera, John K Chan, Michael T Richardson, Daniel S Kapp, Chad A Hamilton, Charles A Leath, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Angeles Alvarez Secord, Casey M Cosgrove, Matthew A Powell, Ann Klopp, Joan L Walker, Gini F Fleming, Nicholas W Bateman, Thomas P Conrads, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …