Digital Commons Network^™

Outcomes In Patients With Severe Covid-19 Disease Treated With Tocilizumab: A Case-Controlled Study, G. Rojas-Marte, M. Khalid, O. Mukhtar, A. T. Hashmi, M. A. Waheed, S. Ehrlich, A. Aslam, S. Siddiqui, C. Agarwal, J. Shani, +8 Additional Authors

Journal Articles

© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: [email protected]. BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated …

Extracellular Hmgb1: A Therapeutic Target In Severe Pulmonary Inflammation Including Covid-19?, U Andersson, W Ottestad, Kj Tracey

Journal Articles

No abstract provided.

Immunotherapies For Covid-19: Lessons Learned From Sepsis, Ke Remy, Sc Brakenridge, B Francois, T Daix, Cs Deutschman, G Monneret, R Jeannet, Pf Laterre, Rs Hotchkiss, Ll Moldawer

Journal Articles

No abstract provided.

Tissue Plasminogen Activator (Tpa) Treatment For Covid-19 Associated Acute Respiratory Distress Syndrome (Ards): A Case Series, J Wang, N Hajizadeh, Ee Moore, Rc Mcintyre, Pk Moore, La Veress, Mb Yaffe, Hb Moore, Cd Barrett

Journal Articles

No abstract provided.

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Nebraska Center for Virology: Faculty Publications

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid …

A Randomized Phase Ii Trial Of Epigenetic Priming With Guadecitabine And Carboplatin In Platinum-Resistant, Recurrent Ovarian Cancer, A. M. Oza, U. A. Matulonis, A. A. Secord, J. Nemunaitis, L. D. Roman, S. P. Blagden, S. Banerjee, W. P. Mcguire, B. Schwartz, D. Matei, +18 Additional Authors

Journal Articles

© 2020 American Association for Cancer Research Inc.. All rights reserved. Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (GþC) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. Patients and Methods: Patients received either GþC (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint …

Seizures Induce Obstructive Apnea In Dba/2j Audiogenic Seizure-Prone Mice: Lifesaving Impact Of Tracheal Implants, R. Irizarry, D. Sukato, R. Kollmar, S. Schild, J. Silverman, K. Sundaram, S. Stephenson, M. Stewart

Journal Articles

Wiley Periodicals, Inc. © 2020 International League Against Epilepsy The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure-induced laryngospasm and obstructive apnea lasting until respiratory arrest. We hypothesized that DBA/2J mice, which display lethal audiogenic seizures, would be protected from death by implanting a tracheal T-tube as a surrogate airway. In a 2 × 2 design, mice were implanted with either open or closed tracheal T-tubes and treated with either low-dose ketamine/xylazine to …

The Validity Of Infrared Coagulator, And Bioglue With Antibiotics To Assist Surgical Treatment Of Infective Endocarditis?, G. Pettersson, S. Unai, S. Gordon, S. T. Hussain, E. Eriksson

Journal Articles

No abstract provided.

Pneumatosis Intestinalis In Covid-19: Case Series., K. Wong, D. H. Kim, S. Khanijo, A. Melamud, G. Zaidi

Journal Articles

OBJECTIVE:To describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who developed pneumatosis intestinalis (PI). METHODS:This case series was conducted in intensive care units at two large tertiary care centers within the Northwell Health System, located in New York State. Patients were included if they were identified as having confirmed COVID-19 as well as pneumatosis intestinalis from March 16, 2020 to July 31, 2020. Patient demographics, clinical characteristics, vasopressor use, anticoagulation use, opiate use, paralytic use, COVID-19 treatment regimen, serum lactate, arterial pH, serum bicarbonate, subsequent intervention, and outcomes during hospitalization were collected. Results: A total …

Altered Monocyte And Langerhans Cell Innate Immunity In Patients With Recurrent Respiratory Papillomatosis (Rrp), M. Israr, J. A. Devoti, F. Lam, A. L. Abramson, B. M. Steinberg, V. R. Bonagura

Journal Articles

No abstract provided.

Demographics And Outcomes Of Patients With Eating Disorders Treated In Residential Care, M. Fisher, J. R. Henretty, S. A. Cox, R. Feinstein, V. Fornari, L. Moskowitz, M. Schneider, S. Levine, J. Malizio, J. Fishbein

Journal Articles

No abstract provided.

Management Of Pediatric Systemic Lupus Erythematosus: Focus On Belimumab, M. Guzman, J. S. Hui-Yuen

Journal Articles

No abstract provided.

The Course Of Sars-Cov2 Infection Was Not Severe In A Crohn's Patient Who Administered Maintenance Anti-Tnf Therapy Overlapping The Early Pre-Symptomatic Period Of Infection., F. Okeke, A. Mone, A. Swaminath

Journal Articles

The Inflammatory Bowel Disease (IBD) population, which may require treatment with immunosuppressive medications, may be uniquely vulnerable to COVID-19 infection. In fact, there is some evidence these medications may inhibit the cytokine storm that is theorized to cause a rapid decline seen in COVID-19. In addition, the digestive symptoms of COVID-19 can be difficult to distinguish from the activation of IBD. We present an interesting case of a Crohn's patient inadvertently administering anti-cytokine therapy during the pre-symptomatic period of COVID-19 infection. Immune suppression during early infection with SARS-COV2 risks a poor immune response to the virus and could theoretically result …

Predictors Of Bleeding In The Perioperative Anticoagulant Use For Surgery Evaluation Study, A. J. Tafur, N. P. Clark, A. C. Spyropoulos, N. Li, E. Kaplovitch, K. Macdougall, S. Schulman, J. A. Caprini, J. Douketis

Journal Articles

No abstract provided.

Evaluating Of Hpv-Dna Ish As An Adjunct To P16 Testing In Oropharyngeal Cancer, J. Chi, I. R. Preeshagul, S. Sheikh-Fayyaz, S. Teckie, N. Kohn, Y. Ziemba, A. Laser, D. Frank, M. Ghaly, D. Kamdar, D. Kraus, D. Paul, N. Seetharamu

Journal Articles

© 2020 Jeffrey Chi. Aim: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. Methods: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. Results: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between …

Deep Brain Stimulation For Refractory Obsessive-Compulsive Disorder (Ocd): Emerging Or Established Therapy?, H. Wu, M. Hariz, V. Visser-Vandewalle, L. Zrinzo, V. A. Coenen, S. A. Sheth, C. Bervoets, M. Naesstrom, M. Schulder, B. Nuttin, +45 Additional Authors

Journal Articles

No abstract provided.

Tdp-43 Is Elevated In Plasma Neuronal-Derived Exosomes Of Patients With Alzheimer’S Disease, N. Zhang, D. Gu, M. Meng, M. L. Gordon

Journal Articles

© Copyright © 2020 Zhang, Gu, Meng and Gordon. Background: Recently, TDP-43 has been recognized as a common proteinopathy in the “oldest old” and a neuropathological comorbidity in patients with Alzheimer’s disease (AD). However, since it has a low concentration in cerebrospinal fluid, the presence of TDP-43 in AD is rarely investigated in vivo. Methods: Twenty-four patients with amyloid PET confirmed AD and 15 healthy controls (HCs) were included in this study. TDP-43 level in plasma neuronal-derived exosomes (NDEs) was measured by enzyme-linked immunosorbent assay. Results: TDP-43 level was elevated in patients with AD compared with HCs (median 1.08 ng/ml, …

Association Of Anticoagulation Dose And Survival In Hospitalized Covid-19 Patients: A Retrospective Propensity Score-Weighted Analysis, F. Ionescu, I. Jaiyesimi, I. Petrescu, P. R. Lawler, E. Castillo, Y. Munoz-Maldonado, Z. Imam, M. Narasimhan, A. E. Abbas, G. B. Nair, +1 Additional Author

Journal Articles

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives: We evaluated the impact on survival of different AC doses in COVID-19 patients. Methods: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n …

Pathophysiology And Pathology Of Acute Kidney Injury In Patients With Covid-19, J. H. Ng, V. Bijol, M. A. Sparks, M. E. Sise, H. Izzedine, K. D. Jhaveri

Journal Articles

© 2020 National Kidney Foundation, Inc. Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to …

A Case Of Wernicke's Encephalopathy In A Pregnant Woman With A History Of Sleeve Gastrectomy., H. Kandlakunta, D. Gurala, J. Philipose, A. Polavarapu, J. R. Abergel

Journal Articles

Wernicke's encephalopathy (WE) is a neurological complication of thiamine deficiency characterized by a triad of acute confusion, ataxia, and ophthalmoplegia. Even though it is most common in chronic alcoholism, an increase in prevalence has been reported recently due to the increased popularity of bariatric surgeries. WE is a known neurological complication after gastric bypass surgery but rarely reported after sleeve gastrectomy. We present a unique case of WE in pregnant women four months after sleeve gastrectomy.

Surgical Gps Proof Of Concept For Scoliosis Surgery, Austin Tapp, Michel Audette

Computational Modeling & Simulation Engineering Faculty Publications

Scoliotic deformities may be addressed with either anterior or posterior approaches for scoliosis correction procedures. While typically quite invasive, the impact of these operations may be reduced through the use of computer-assisted surgery. A combination of physician-designated anatomical landmarks and surgical ontologies allows for real-time intraoperative guidance during computer-assisted surgical interventions. Predetermined landmarks are labeled on an identical patient model, which seeks to encompass vertebrae, intervertebral disks, ligaments, and other soft tissues. The inclusion of this anatomy permits the consideration of hypothetical forces that are previously not well characterized in a patient-specific manner. Updated ontologies then suggest procedural directions throughout …

The Effects Of Modifiable And Non-Modifiable Risk Factors On The Severity Of Gastroparesis-Like Symptoms, Jonathon B. Nelson

Honors Undergraduate Theses

Gastroparesis (GP) is a clinical disorder recognized by measured delayed gastric emptying without mechanical obstruction, in addition to symptoms such as nausea, vomiting, chronic abdominal pain, heartburn, early satiety upon eating a regular-sized meal, and exaggerated postprandial fullness. While GP is considered a clinically rare disorder, there is much suspicion that a much larger number of patients experience GP-like symptoms without an official diagnosis. Furthermore, little work has been done to identify the causes and exacerbations of this gastrointestinal (GI) distress in the young adult population. This study's primary goal was to establish a relationship between modifiable and non-modifiable risk …

Global Survey On Pancreatic Surgery During The Covid-19 Pandemic., A. Oba, T. F. Stoop, M. Löhr, T. Hackert, N. Zyromski, W. H. Nealon, M. Unno, R. D. Schulick, M. H. Al-Musawi, M. Del Chiaro, +6 Additional Authors

Journal Articles

OBJECTIVE:The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity. SUMMARY BACKGROUND DATA:The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS:An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery …

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …

Can The Fut 2 Gene Variant Have An Effect On The Body Weight Of Patients Undergoing Bariatric Surgery? - Preliminary, Exploratory Study, Natalia Komorniak, Alexandra Martynova-Van Kley, Armen Nalian, Wiktoria Wardziukiewicz, Karolina Skoniecznaa-Zydecka, Daniel Styburski, Joanna Palma, Bartosz Kowalewski, Krzysztof Kaseja, Ewa Stachowska

Faculty Publications

Background: The FUT2 gene (Se gene) encoding the enzyme α-1,2-L-fucosyltransferase 2 seems to have a significant effect on the number and type of bacteria colonizing the intestines. Methods: In a group of 19 patients after bariatric surgery, the polymorphism (rs601338) of FUT2 gene was analyzed in combination with body mass reduction, intestinal microbiome (16S RNA sequencing), and short chain fatty acids (SCFA) measurements in stools. Results: Among the secretors (Se/Se polymorphism of the FUT2 gene rs601338, carriers of GG variant), correlations between waist-hip ratio (WHR) and propionate content and an increase in Prevotella, Escherichia, Shigella, and Bacteroides were observed. On …

A Modular Framework For Early-Phase Seamless Oncology Trials, Philip S. Boonstra, Thomas M. Braun, Elizabeth C. Chase

The University of Michigan Department of Biostatistics Working Paper Series

Background: As our understanding of the etiology and mechanisms of cancer becomes more sophisticated and the number of therapeutic options increases, phase I oncology trials today have multiple primary objectives. Many such designs are now 'seamless', meaning that the trial estimates both the maximum tolerated dose and the efficacy at this dose level. Sponsors often proceed with further study only with this additional efficacy evidence. However, with this increasing complexity in trial design, it becomes challenging to articulate fundamental operating characteristics of these trials, such as (i) what is the probability that the design will identify an acceptable, i.e. safe …

The Role Of Rassf5 On Cell Growth And Hippo Signaling In Rhabdomyosarcoma, Megan Garver, Lee Helman, Md, Katrina Slemmons, Phd

Phase 1

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Dysregulation of the Hippo pathway, a signaling cascade that regulates many biological processes, is associated with many human cancers. The goal of my project was to delete RASSF5, a regulator of the Hippo pathway, in RMS cells utilizing CRISPR/Cas9 and then to evaluate how the absence of RASSF5 affects RMS cell growth and Hippo signaling, with and without DNMTi Tx.

Methods: A lipofectamine transfection was performed in two different RMS cell lines, Rh30 & RD, in which two different CRIPSR/Cas9 vectors with RASSF5 guide RNA were introduced. …

Stochastic Expression Of Sae-Dependent Virulence Genes During Staphylococcus Aureus Biofilm Development Is Dependent On Saes, Elizabeth A. Delmain, Derek E. Moormeier, Jennifer L. Endres, Rebecca E. Hodges, Marat R. Sadykov, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The intricate process of biofilm formation in the human pathogen Staphylococcus aureus involves distinct stages during which a complex mixture of matrix molecules is produced and modified throughout the developmental cycle. Early in biofilm development, a subpopulation of cells detaches from its substrate in an event termed “exodus” that is mediated by SaePQRS-dependent stochastic expression of a secreted staphylococcal nuclease, which degrades extracellular DNA within the matrix, causing the release of cells and subsequently allowing for the formation of metabolically heterogenous microcolonies. Since the SaePQRS regulatory system is involved in the transcriptional control of multiple S. aureus virulence factors, the …

Fluorescent Sensor Arrays Can Predict And Quantify The Composition Of Multicomponent Bacterial Samples, Denis Svechkarev, Marat Sadykov, Lucas J. Houser, Kenneth W. Bayles, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Fast and reliable identification of infectious disease agents is among the most important challenges for the healthcare system. The discrimination of individual components of mixed infections represents a particularly difficult task. In the current study we further expand the functionality of a ratiometric sensor array technology based on small-molecule environmentally-sensitive organic dyes, which can be successfully applied for the analysis of mixed bacterial samples. Using pattern recognition methods and data from pure bacterial species, we demonstrate that this approach can be used to quantify the composition of mixtures, as well as to predict their components with the accuracy of ~80% …

An Integrated Computational And Experimental Study To Investigate Staphylococcus Aureus Metabolism, Mohammad Mazharul Islam, Vinai Chittezham Thomas, Matthew Van Beek, Jong-Sam Ahn, Abdulelah A. Alqarzaee, Chunyi Zhou, Paul D. Fey, Kenneth W. Bayles, Rajib Saha

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and regulation information from biochemical databases and previous strain-specific models. Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic consistency. To further refine the model, growth assessment of 1920 nonessential mutants from the Nebraska Transposon Mutant Library …