Medical Specialties Commons^™

Backfilling Patients In Phase I Dose-Escalation Trials Using Bayesian Optimal Interval Design (Boin), Yixuan Zhao, Ying Yuan, Edward L Korn, Boris Freidlin

Faculty, Staff and Student Publications

In recent years, there has been increased interest in incorporation of backfilling into dose-escalation clinical trials, which involves concurrently assigning patients to doses that have been previously cleared for safety by the dose-escalation design. Backfilling generates additional information on safety, tolerability, and preliminary activity on a range of doses below the maximum tolerated dose (MTD), which is relevant for selection of the recommended phase II dose and dose optimization. However, in practice, backfilling may not be rigorously defined in trial protocols and implemented consistently. Furthermore, backfilling designs require careful planning to minimize the probability of treating additional patients with potentially …

Neoadjuvant Trebananib Plus Paclitaxel-Based Chemotherapy For Stage Ii/Iii Breast Cancer In The Adaptively Randomized I-Spy2 Trial-Efficacy And Biomarker Discovery, Kathy S Albain, Christina Yau, Emanuel F Petricoin, Denise M Wolf, Julie E Lang, A Jo Chien, Tufia Haddad, Andres Forero-Torres, Anne M Wallace, Henry Kaplan, Lajos Pusztai, David Euhus, Rita Nanda, Anthony D Elias, Amy S Clark, Constantine Godellas, Judy C Boughey, Claudine Isaacs, Debu Tripathy, Janice Lu, Rachel L Yung, Rosa I Gallagher, Julia D Wulfkuhle, Lamorna Brown-Swigart, Gregor Krings, Yunn Yi Chen, David A Potter, Erica Stringer-Reasor, Sarah Blair, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Adam L Asare, Jeffrey B Matthews, Angela M Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van't Veer, Douglas Yee, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial.

Patients and methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Duncan NRI Faculty and Staff Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Circulating Microrna Panel For Prediction Of Recurrence And Survival In Early-Stage Lung Adenocarcinoma, Mei-Chee Tai, Leonidas E Bantis, Gargy Parhy, Taketo Kato, Ichidai Tanaka, Chi-Wan Chow, Junya Fujimoto, Carmen Behrens, Tetsunari Hase, Koji Kawaguchi, Johannes F Fahrmann, Edwin J Ostrin, Kohei Yokoi, Toyofumi F Chen-Yoshikawa, Yoshinori Hasegawa, Samir M Hanash, Ignacio I Wistuba, Ayumu Taguchi

Faculty, Staff and Student Publications

Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and …

Development Of A Practical Nomogram For Personalized Anemia Management In Patients Treated With Ataxia Telangiectasia And Rad3-Related Inhibitor Camonsertib, Ezra Rosen, Timothy A Yap, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Ruth Plummer, Adrian J Fretland, Danielle Ulanet, Yi Xu, Robin Mcdougall, Maria Koehler, Elisa Fontana

Faculty, Staff and Student Publications

PURPOSE: Camonsertib is a highly selective and potent inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Dose-dependent anemia is a class-related on-target adverse event often requiring dose modifications. Individual patient risk factors for the development of significant anemia complicate the selection of a "one-size-fits-all" ATR inhibitor (ATRi) dose and schedule, possibly leading to suboptimal therapeutic doses in patients at low risk of anemia. We evaluated whether early predictors of anemia could be identified to ultimately inform a personalized dose-modification approach.

PATIENTS AND METHODS: On the basis of preclinical observations and a mechanistic understanding of ATRi-related anemia, we identified several potential …

Serum Biomarker Signature Is Predictive Of The Risk Of Hepatocellular Cancer In Patients With Cirrhosis, Hashem El-Serag, Fasiha Kanwal, Jing Ning, Hannah Powell, Saira Khaderi, Amit G Singal, Sumeet Asrani, Jorge A Marrero, Christopher I Amos, Aaron P Thrift, Michelle Luster, Abeer Alsarraj, Luis Olivares, Darlene Skapura, Jenny Deng, Emad Salem, Omar Najjar, Xian Yu, Hao Duong, Michael E Scheurer, Christie M Ballantyne, Salma Kaochar

Faculty, Staff and Student Publications

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study.

METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Virtual Facilitation Best Practices And Research Priorities: A Scoping Review, Asya Agulnik, Derrecka Boykin, Denalee M O'Malley, Julia Price, Mia Yang, Mark Mckone, Geoffrey Curran, Mona J Ritchie

Faculty, Staff and Students Publications

Background: Facilitation is an implementation strategy that supports the uptake of evidence-based practices. Recently, use of virtual facilitation (VF), or the application of facilitation using primarily video-based conferencing technologies, has become more common, especially since the COVID-19 pandemic. Thorough assessment of the literature on VF, however, is lacking. This scoping review aimed to identify and describe conceptual definitions of VF, evaluate the consistency of terminology, and recommend "best" practices for its use as an implementation strategy.

Methods: We conducted a scoping review to identify literature on VF following the PRISMA-ScR guidance. A search of PubMed, Embase, Web of Science, and …

Author Correction: The Cerebellum Contributes To Generalized Seizures By Altering Activity In The Ventral Posteromedial Nucleus, Jaclyn Beckinghausen, Joshua Ortiz-Guzman, Tao Lin, Benjamin Bachman, Luis E Salazar Leon, Yu Liu, Detlef H Heck, Benjamin R Arenkiel, Roy V Sillitoe

Faculty, Staff and Students Publications

No abstract provided.

Virtual Facilitation Best Practices And Research Priorities: A Scoping Review, Asya Agulnik, Derrecka Boykin, Denalee M O'Malley, Julia Price, Mia Yang, Mark Mckone, Geoffrey Curran, Mona J Ritchie

Department of Pediatrics Faculty Papers

BACKGROUND: Facilitation is an implementation strategy that supports the uptake of evidence-based practices. Recently, use of virtual facilitation (VF), or the application of facilitation using primarily video-based conferencing technologies, has become more common, especially since the COVID-19 pandemic. Thorough assessment of the literature on VF, however, is lacking. This scoping review aimed to identify and describe conceptual definitions of VF, evaluate the consistency of terminology, and recommend "best" practices for its use as an implementation strategy.

METHODS: We conducted a scoping review to identify literature on VF following the PRISMA-ScR guidance. A search of PubMed, Embase, Web of Science, and …

" Does Educational Level Affect The Outcome Of Myocardial Infarction? ", Ahmed Magdy Ahmed Elsayed

Theses and Dissertations

Background: Heath awareness plays a major role in determining the outcomes of serious medical conditions specially when response time is crucial. STEMI patients are prone to serious compilations if they didn’t receive the appropriate treatment on time. Raising the health awareness of the community would result in seeking medical help at earlier stage of the disease. Earlier presentation to the medical center would result in better health outcomes. Certain factors form the health awareness of the community. This includes educational level, previous exposure to similar situations, and exposure to health awareness materials.

Methods: This is a cohort study in …

Development Of A Curriculum For Osteoporosis Education In Rural Populations, Serin Baker, Hannah Berhow, Rebekah Hans, Emily Schwartz, Hunter Stutz, Mehruba Alam, Alizon Pachas, Darell Schmick, David Sant Phd, Erika Noonan Md

Annual Research Symposium

Osteoporosis contributes to annual costs exceeding $10 billion in the U.S. due to hip fractures and is the primary cause of hospitalization among older women. Historically, geriatric populations have received inadequate education in navigating the U.S. medical system, emphasizing the importance of targeted education among the elderly. The study’s objective is to improve health literacy among the geriatric population in rural Utah by expanding their understanding of osteoporosis.

Ligaplant: Recreating Natural From Artificial, Disha Kamavisdar

Annual Research Symposium

Missing teeth can be substituted by the use of the dental implants. The most widely used implants in the current scenario are the osseointegrated implants with various shortcomings and the most prominent one is the lack of the periodontal ligament. To overcome this, implants with periodontal ligaments can be procured and this can be possible by the application of the tissue engineering concept along with suitable implant material.

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …

Application Of In-Silico Computational Biology Strategies To Demonstrate Mechanism Of Oral Cancer Cell Death By Natural Peptide, Dr Dominic Augustine

Annual Research Symposium

This research work is designed to identify biomolecules from Earthworm Coelomic Fluid (ECF) of Eudrilus Eugeniae (EE) that can inhibit oral cancer cells from proliferating. The study aims to construct a homology model of the 18 kDa protein from ECF of EE (18-ECFP) with molecular dynamics simulation (MDS) to enable its molecular docking with pro-apoptotic caspase receptors with determination of binding energy scores. The study also evaluates the anti-cancer potential of 18-ECFP on SCC-9 cells in vitro by wet lab techniques.

Distinguishing Leukemic Cells Using Fractal Chromatin Patterns And Machine Learning, Abigail Gordhamer, Paul Young, Ryan Cordner

Annual Research Symposium

One of the most important tests in the clinical laboratory is the Complete Blood Count, which involves identifying the white blood cells in a patient’s blood. The respective counts of the different white blood cell types correlate with various states of health and disease, and are critical to diagnosing diseases such as leukemia. Leukemic cells are considered especially difficult to distinguish, and it is of the upmost importance that these cells are identified correctly. To aid in the process of leukemic cell identification, we quantified fractal patterns in the chromatin of white blood cells and used the data to identify …

Pathogenic Implications Of Candidal Species In Both Oral Cancer And Oral Potentially Malignant Disorders - A Review, Dr Dominic Augustine, Sowmya Sv, Kuntala Mondal

Annual Research Symposium

Oral squamous cell carcinoma (OSCC) is the 6th most common cancer in worldwide. Cigarette smoking, alcohol consumption, and betel quid chewing are its major risk factors other factors that can lead to OSCC include excessive sun exposure, viral or fungal infection, poor nutrition, and poor oral hygiene. The carcinogenesis of OSCC occurs gradually and oral epithelial dysplasia is considered a potential histologic precursor of OSCC. Most OSCC cases are preceded by clinically evident oral potentially malignant disorders (OPMDs). The aim of this review is to correlate the association between Candida species and oral potentially malignant disorders and its possible mechanisms …

Immunohistochemical Expression Of Cyclin D1 In Dentigerous Cyst, Odontogenic Keratocyst And Unicystic Ameloblastoma- An In-Vitro Study, Kuntala Mondal, Sv Sowmya, Dominic Augustine

Annual Research Symposium

Cyclin D1, a G1 cyclin member, regulates the transition of the cell cycle from the G1 phase to the S phase. The uncontrolled and elevated expression of cyclin D1 has been associated with rapid growth, heightened proliferative activity and increased histologic aggressiveness. Unicystic ameloblastoma pertains to cystic lesions that present clinical, radiographic, or gross features akin to jaw cysts. Nevertheless, upon histological scrutiny, these lesions display a distinctive ameloblastomatous epithelium lining the cystic cavity, with or without luminal or mural proliferation. This cystic variant of tumor bears substantial resemblances to dentigerous cysts, and occasionally, both entities can become indistinguishable upon …

An Immunohistochemical Panel For The Accurate Differentiation Between Mucoepidermoid Carcinoma And Pleomorphic Adenoma, Kuntala Mondal, Sv Sowmya, Dominic Augustine

Annual Research Symposium

Salivary Gland Tumors (SGTs) are a diverse group of neoplasms, with a wide range of histological subtypes, some of which can exhibit overlapping features. Amongst this group of tumors, Pleomorphic Adenoma (PA) and Mucoepidermoid Carcinoma (MEC) stand out as prevalent entities originating from the salivary glands. The accurate differentiation between these two entities is crucial for treatment planning, as it influences decisions regarding the extent of surgical resection. Because of the overlapping histopathological features, it is difficult to differentiate these two lesions with the help of conventional Hematoxylin & Eosin (H& E). The evaluation of Immunohistochemical (IHC) markers holds pivotal …

Cheiloscopic Characteristics Detection And Pattern Classification By Machine Learning Technique, Dr Dominic Augustine, Sowmya Sv

Annual Research Symposium

Machine Learning (ML) is a field enhancing the rapid growth of technology. Though use of digital softwares for cheiloscopic investigations have been attempted with limited success, the use of ML based techniques are scarce and seldom have been employed in forensic odontology. The present study aimed to identify cheiloscopic patterns through machine learning based methods and to correlate the segmented patterns with age and gender of individuals.

Association Between Abo Blood Grouping And Odontometry: An Unexplored Evidence In Forensics, Dr Dominic Augustine, Sowmya Sv

Annual Research Symposium

Recent research has exhibited a strong association between ABO blood groups and susceptibility to diseases. Extraoral and intraoral hard tissue landmarks provide a stable and reliable record for odontological and anthropological analysis, forensic investigations and identification. The association between anthropometric indices and ABO blood grouping have been reported in the past, however, the association between ABO blood groups and odontometric indices is yet to be comprehensively explored. This study aimed to establish the correlation of ABO blood groups with odontometric indices and extraoral hard tissue landmarks for personnel identification.

Advanced Techniques For Tooth Pulp Rna Extraction In Forensic Investigations-A Systematic Review, Kuntala Mondal, Sv Sowmya, Dominic Augustine

Annual Research Symposium

Teeth are fundamental structures in a forensic context due to their high strength and specificity. It is challenging to obtain high quality RNA from pulpal tissues. It has been described that pulp RNA degradation could be an indicator of post-mortem interval. Researchers have been in the quest to develop optimal techniques for tooth RNA extraction. The systematic review aimed to determine the most reliable method of RNA extraction from dental tooth pulp for forensic investigations.

Assessment Of Micrometastasis In Lymph Nodes Of Oral Squamous Cell Carcinoma –Attaining Excellence Through Immunohistochemistry, Dr Dominic Augustine, Sowmya Sv, Kuntala Mondal

Annual Research Symposium

Cervical lymph node metastasis is the most important prognostic factor in Squamous Cell Carcinoma of Head and Neck (SCCHN). Lymph node prognostic determinants hold immense significance in influencing both patient’s survival outcomes and the propensity for recurrence. The current study aimed to evaluate the diagnostic accuracy of Cyclin D1 and Pan-CK for the detection of lymph node micrometastasis in oral squamous cell carcinoma tissue sections and re-evaluate the tumor staging.

Harm Reduction Measures In Substance Use Disorder (Sud), Kent Wood

Annual Research Symposium

This literature review aims to comprehensively analyze harm reduction strategies employed in addressing Substance Use Disorder (SUD). Focusing on key interventions such as fentanyl testing strips, naloxone distribution, syringe exchange programs, and methadone/buprenorphine clinics, the study seeks to evaluate the effectiveness of these approaches in reducing the associated harms of substance misuse.

Substance Use Disorder –The Role Of The Pharmacist, Mackenzie Cruzan

Annual Research Symposium

The study illuminates the pivotal role of community pharmacists as accessible healthcare providers, offering medication management, patient education, and preventive care services. Simultaneously, it explores the intricate responsibilities of inpatient pharmacists, emphasizing their involvement in therapeutic monitoring and collaboration with healthcare teams.

Once Upon A Lime: A Tale Of Pediatric Phytophotodermatitis, Kyanna Orr

Annual Research Symposium

Phytophotodermatitis is a blistering skin condition caused by photoactivation of furocoumarins in certain plants including limes, carrots, and parsnips. High clinical suspicion based on the presentation and distribution of a patient’s findings, followed by thorough history-taking and identification of an exposure, were enough to diagnose this condition in an otherwise healthy child.

Phenolic Acids Prevent Sex-Steroid Deficiency-Induced Bone Loss And Bone Marrow Adipogenesis In Mice, Perry C. Caviness, Oxana P. Lazarenko, Michael L. Blackburn, Jennifer F. Chen, Christopher E. Randolph, Jovanny Zabaleta, Fenghuang Zhan, Jin Ran Chen

School of Medicine Faculty Publications

Phenolic acids, such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA), can be produced from microbiome digestion of polyphenols. Previously it was found that HA and 3-3-PPA facilitate bone formation and suppress bone resorption. However, the mechanism of action by which HA and 3-3-PPA protect bone from degeneration is currently unknown. In this report, we present that HA and 3-3-PPA suppression of bone resorption is able to ameliorate bone loss in an ovariectomy (OVX) osteopenic mouse model though not to the extent of Zoledronic acid (ZA). HA and 3-3-PPA treatments were shown to significantly decrease bone marrow adipocyte-like cell …

Cyp2a6 Activity And Cigarette Consumption Interact In Smoking-Related Lung Cancer Susceptibility, Mulong Du, Junyi Xin, Rui Zheng, Qianyu Yuan, Zhihui Wang, Hongliang Liu, Hanting Liu, Guoshuai Cai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gad Rennert, Susanne Arnold, Paul Brennan, John K Field, Sanjay S Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Matthew B Schabath, Melinda C Aldrich, Meilin Wang, Hongbing Shen, Feng Chen, Zhengdong Zhang, Rayjean J Hung, Christopher I Amos, Qingyi Wei, Philip Lazarus, David C Christiani

Faculty, Staff and Student Publications

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns …

Risk Of Chronic Health Conditions In Lesbian, Gay, And Bisexual Survivors Of Adolescent And Young Adult Cancers, Amy M Berkman, Eunju Choi, Christabel K Cheung, John M Salsman, Susan K Peterson, Clark R Andersen, Qian Lu, J Andrew Livingston, Michelle A T Hildebrandt, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

BACKGROUND: In the general population, individuals with minoritized sexual orientation and gender identity have a higher burden of chronic health conditions than heterosexual individuals. However, the extent to which sexual orientation is associated with excess burden of chronic conditions in adolescent and young adult cancer survivors (AYACS) is unknown.

METHODS: Lesbian, gay, and bisexual (LGB) AYACSs, LGB individuals without a history of cancer, and heterosexual AYACSs were identified by self-reported data from the cross-sectional National Health Interview Survey (2013-2020). Socioeconomic factors and the prevalence of chronic health conditions were compared between groups using χ

RESULTS: One hundred seventy LGB cancer …

Acute Neutrophilic Vasculitis (Leukocytoclasia) In 36 Covid-19 Autopsy Brains, Roy H. Rhodes, Gordon L. Love, Fernanda Da Silva Lameira, Maryam Sadough Shahmirzadi, Sharon E. Fox, Richard S. Vander Heide

School of Medicine Faculty Publications

Background: Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. Methods: Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons …