Laboratory Medicine Commons^™

Limitations Of Available Blood Products For Massive Transfusion During Mass Casualty Events At Us Level 1 Trauma Centers, James Williams, Michael Gustafson, Yu Bai, Samuel Prater, Charles E Wade, Oscar D Guillamondegui, Mansoor Khan, Megan Brenner, Paula Ferrada, Derek Roberts, Tal Horer, David Kauvar, Andrew Kirkpatrick, Carlos Ordonez, Bruno Perreira, Artai Priouzram, Juan Duchesne, Bryan A Cotton

Faculty, Staff and Student Publications

INTRODUCTION: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs.

METHODS: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete …

A Selective Antibiotic For Lyme Disease, Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E Mccarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis

Faculty, Staff and Student Publications

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining …

Comparison Of Transcriptional Profiles Of Treponema Pallidum During Experimental Infection Of Rabbits And In Vitro Culture: Highly Similar, Yet Different, Bridget D De Lay, Todd A Cameron, Nicholas R De Lay, Steven J Norris, Diane G Edmondson

Faculty, Staff and Student Publications

Treponema pallidum ssp. pallidum, the causative agent of syphilis, can now be cultured continuously in vitro utilizing a tissue culture system, and the multiplication rates are similar to those obtained in experimental infection of rabbits. In this study, the RNA transcript profiles of the T. pallidum Nichols during in vitro culture and rabbit infection were compared to examine whether gene expression patterns differed in these two environments. To this end, RNA preparations were converted to cDNA and subjected to RNA-seq using high throughput Illumina sequencing; reverse transcriptase quantitative PCR was also performed on selected genes for validation of results. The …

Sars-Cov-2 Infects Human Engineered Heart Tissues And Models Covid-19 Myocarditis, Adam L Bailey, Oleksandr Dmytrenko, Lina Greenberg, Andrea L Bredemeyer, Pan Ma, Jing Liu, Vinay Penna, Emma S Winkler, Sanja Sviben, Erin Brooks, Ajith P Nair, Kent A Heck, Aniket S Rali, Leo Simpson, Mehrdad Saririan, Dan Hobohm, W Tom Stump, James A Fitzpatrick, Xuping Xie, Xianwen Zhang, Pei-Yong Shi, J Travis Hinson, Weng-Tein Gi, Constanze Schmidt, Florian Leuschner, Chieh-Yu Lin, Michael S Diamond, Michael J Greenberg, Kory J Lavine

Faculty, Staff and Student Publications

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology …

Parameters Affecting Continuous In Vitro Culture Of Treponema Pallidum Strains, Diane G Edmondson, Bridget D Delay, Lindsay E Kowis, Steven J Norris

Faculty, Staff and Student Publications

The bacterium that causes syphilis, Treponema pallidum subsp. pallidum, has now been cultured in vitro continuously for periods exceeding 3 years using a system consisting of coculture with Sf1Ep rabbit epithelial cells in TpCM-2 medium and a low-oxygen environment. In addition, long-term culture of several other syphilis isolates (SS14, Mexico A, UW231B, and UW249B) and the T. pallidum subsp. endemicum Bosnia A strain has been achieved. During in vitro passage, T. pallidum subsp. pallidum exhibited a typical bacterial growth curve with logarithmic and stationary phases. Sf1Ep cells are required for sustained growth and motility; however, high initial Sf1Ep cell …

Primary Effusion Lymphoma: A Clinicopathological Study Of 70 Cases, Zhihong Hu, Zenggang Pan, Weina Chen, Yang Shi, Wei Wang, Ji Yuan, Endi Wang, Shanxiang Zhang, Habibe Kurt, Brenda Mai, Xiaohui Zhang, Hui Liu, Adan A Rios, Hilary Y Ma, Nghia D Nguyen, L Jeffrey Medeiros, Shimin Hu

Faculty, Staff and Student Publications

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26–91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses …

Biomarkers In Acute Myeloid Leukemia: Leveraging Next Generation Sequencing Data For Optimal Therapeutic Strategies, Hanadi El Achi, Rashmi Kanagal-Shamanna

Faculty, Staff and Student Publications

Next generation sequencing (NGS) is routinely used for mutation profiling of acute myeloid leukemia. The extensive application of NGS in hematologic malignancies, and its significant association with the outcomes in multiple large cohorts constituted a proof of concept that AML phenotype is driven by underlying mutational signature and is amenable for targeted therapies. These findings urged incorporation of molecular results into the latest World Health Organization (WHO) sub-classification and integration into risk-stratification and treatment guidelines by the European Leukemia Net. NGS mutation profiling provides a large amount of information that guides diagnosis and management, dependent on the type and number …

Effects Of Image Quantity And Image Source Variation On Machine Learning Histology Differential Diagnosis Models, Elham Vali-Betts, Kevin J Krause, Alanna Dubrovsky, Kristin Olson, John Paul Graff, Anupam Mitra, Ananya Datta-Mitra, Kenneth Beck, Aristotelis Tsirigos, Cynthia Loomis, Antonio Galvao Neto, Esther Adler, Hooman H Rashidi

Faculty, Staff and Student Publications

Aims:

Histology, the microscopic study of normal tissues, is a crucial element of most medical curricula. Learning tools focused on histology are very important to learners who seek diagnostic competency within this important diagnostic arena. Recent developments in machine learning (ML) suggest that certain ML tools may be able to benefit this histology learning platform. Here, we aim to explore how one such tool based on a convolutional neural network, can be used to build a generalizable multi-classification model capable of classifying microscopic images of human tissue samples with the ultimate goal of providing a differential diagnosis (a list of …

The Bmal1/Hif2a Heterodimer Modulates Circadian Variations Of Myocardial Injury, Hui Li, Xinwei Kuang, Long Liang, Youqiong Ye, Yongchang Zhang, Jialu Li, Fangyu Ma, Juan Tao, Guang Lei, Shuang Zhao, Juan Su, Nong Yang, Cong Peng, Xiaowei Xu, Mien-Chie Hung, Leng Han, Hong Liu, Jing Liu, Xiang Chen

Faculty, Staff and Student Publications

Immune checkpoints blockades have shown promising clinical effects in various malignancies, but the overall response rate is low. Here, the immune features are comprehensively characterized in >10 000 cancer patients from The Cancer Genome Atlas and significantly positive correlations are observed between targets of Sunitinib and inhibitory immune checkpoints and suppressive immune cells. It is further confirmed that Sunitinib treatment increases the antitumor immunity in a phase III trial. Mechanistically, it is discovered that Sunitinib regulates the stability of tumor PD‐L1 via p62, that p62 can bind to PD‐L1 and specifically promote its translocation into autophagic lysosome for degradation. Preclinically, …