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Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Faculty, Staff and Student Publications

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The …

A High-Resolution 3d Atlas Of The Spectrum Of Tuberculous Andcovid-19 Lung Lesions, Gordon Wells, Joel N Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Leon Y Perumal, Malcolm Matthew, Robert L Hunter, Hayden Pacl, Jacelyn E Peabody Lever, Denise D Stanford, Satinder P Singh, Prachi Bajpai, Upender Manne, Paul V Benson, Steven M Rowe, Stephan Le Roux, Alex Sigal, Muofhe Tshibalanganda, Carlyn Wells, Anton Du Plessis, Mpumelelo Msimang, Threnesan Naidoo, Adrie J C Steyn

Faculty, Staff and Student Publications

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of …

Antibiotic Exposure Does Not Impact Immune Checkpoint Blockade Response In Msi-H/Dmmr Metastatic Colorectal Cancer: A Single-Center Experience, Victoria Serpas Higbie, Jane Rogers, Hyunsoo Hwang, Wei Qiao, Lianchun Xiao, Arvind Dasari, Kerri Mola-Rudd, Van K Morris, Robert A Wolff, Kanwal Raghav, Ryan Huey, Christine Parseghian, Jason Willis, Scott Kopetz, Michael J Overman, Benny Johnson

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has improved outcomes for patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors. However, not all MSI-H/dMMR patients will exhibit the same ICB efficacy. Previous studies suggest that concomitant antibiotic use while receiving ICB may result in poorer outcomes. We aimed to evaluate this association in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC).

MATERIALS AND METHODS: A single-site, retrospective review of 57 patients with MSI-H/dMMR mCRC that received ICB was completed. Data collected included patient demographics, ICB information, and antibiotic use. Antibiotic exposure was considered from 90 days prior to ICB through 6 weeks …

Evaluation Of Mrna-1273 Vaccine In Children 6 Months To 5 Years Of Age, Evan J Anderson, C Buddy Creech, Vladimir Berthaud, Arin Piramzadian, Kimball A Johnson, Marcus Zervos, Fredric Garner, Carl Griffin, Khozema Palanpurwala, Mark Turner, Jeffrey Gerber, Richard L Bennett, Kashif Ali, Madhavi Ampajwala, Gary Berman, Jennifer Nayak, Carey Chronis, Barbara Rizzardi, William J Muller, Christopher A Smith, George Fuchs, Daniel Hsia, Joanne E Tomassini, Dianne Delucia, Caroline Reuter, Barbara Kuter, Xiaoping Zhao, Weiping Deng, Honghong Zhou, Daniela Ramirez Schrempp, Kelly Hautzinger, Bethany Girard, Karen Slobod, Roderick Mcphee, Rolando Pajon, Anne Aunins, Rituparna Das, Jacqueline M Miller, Sabine Schnyder Ghamloush, Kidcove Study Group

Faculty, Staff and Student Publications

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown.

METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these …

Neoadjuvant Relatlimab And Nivolumab In Resectable Melanoma, Rodabe N Amaria, Michael Postow, Elizabeth M Burton, Michael T Tetzlaff, Merrick I Ross, Carlos Torres-Cabala, Isabella C Glitza, Fei Duan, Denái R Milton, Klaus Busam, Lauren Simpson, Jennifer L Mcquade, Michael K Wong, Jeffrey E Gershenwald, Jeffrey E Lee, Ryan P Goepfert, Emily Z Keung, Sarah B Fisher, Allison Betof-Warner, Alexander N Shoushtari, Margaret Callahan, Daniel Coit, Edmund K Bartlett, Danielle Bello, Parisa Momtaz, Courtney Nicholas, Aidi Gu, Xuejun Zhang, Brinda Rao Korivi, Madhavi Patnana, Sapna P Patel, Adi Diab, Anthony Lucci, Victor G Prieto, Michael A Davies, James P Allison, Padmanee Sharma, Jennifer A Wargo, Charlotte Ariyan, Hussein A Tawbi

Faculty, Staff and Student Publications

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid …

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …

Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik

Faculty, Staff and Student Publications

Background

Immune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8⁺ T cells and whether they have prognostic relevance.

METHODS

We analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Results

We show that senescent-like bone marrow CD8⁺ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival …

The Association Between Egocentric Sexual Networks And Sexual Meeting Venues With Prep Conversation And Encouragement For Use Among Latinx Men Who Have Sex With Men, Mariano Kanamori, Cho-Hee Shrader, Juan Flores-Arroyo, Ariana Johnson, Edda Rodriguez, Stephen Fallon, John Skvoretz, Victor Gonzalez, Susanne Doblecki-Lewis, Adam Carrico, Kayo Fujimoto, Mark Williams, Steven Safren

Faculty, Staff and Student Publications

Despite the increasing availability of pre-exposure prophylaxis (PrEP), Latinx men who have sex with men (LMSM) are not receiving PrEP-related information. To understand the influence of LMSM sexual networks on PrEP-related conversations and encouragement to use PrEP, this cross-sectional egocentric network study characterized the PrEP-related communication of 130 LMSM egos with 507 sexual partners (alters). Participants were recruited using respondent-driven sampling methods from a Miami-Dade County community-health organization. Egocentric-level data were collected from 2018-2019 and analyzed using multilevel modeling. Of egos, 30% reported using PrEP. Closeness between participants and sexual partners played a role in PrEP conversation and encouragement. Participants …

Clinical Impact Of Ceftriaxone Resistance In Escherichia Coli Bloodstream Infections: A Multicenter Prospective Cohort Study, Pranita D Tamma, Lauren Komarow, Lizhao Ge, Julia Garcia-Diaz, Erica S Herc, Yohei Doi, Cesar A Arias, Owen Albin, Elie Saade, Loren G Miller, Jesse T Jacob, Michael J Satlin, Martin Krsak, W Charles Huskins, Sorabh Dhar, Samuel A Shelburne, Carol Hill, Keri R Baum, Minal Bhojani, Kerryl E Greenwood-Quaintance, Suzannah M Schmidt-Malan, Robin Patel, Scott R Evans, Henry F Chambers, Vance G Fowler, David Van Duin, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Background

Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common.

Methods

This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding.

Results

Notable differences between patients infected with CRO-R and CRO-S …

Evaluation Of The Effectiveness Of Uv-C Dose For Photoinactivation Of Sars-Cov-2 In Contaminated N95 Respirator, Surgical And Cotton Fabric Masks, Patrícia Metolina, Lilian Gomes De Oliveira, Bruno Ramos, Yan De Souza Angelo, Paola Minoprio, Antonio Carlos Silva Costa Teixeira

Faculty, Staff and Student Publications

As part of efforts to combat the Covid-19 pandemic and decrease the high transmissibility of the new coronavirus, SARS-CoV-2, effective inactivation strategies, such as UV-C decontamination technologies, can be reliably disseminated and well-studied. The present study investigated the susceptibility of a high viral load of SARS-CoV-2 in filtering facepiece respirators (FFR) N95, surgical mask, cotton fabric mask and N95 straps under three different doses of UV-C, applying both real-time PCR (qPCR) and plaque formation assays to quantify viral load reduction and virus infectivity, respectively. The results show that more than 95% of the amount of SARS-CoV-2 RNA could be reduced …

T Cells Specific For Α-Myosin Drive Immunotherapy-Related Myocarditis, Margaret L Axelrod, Wouter C Meijers, Elles M Screever, Juan Qin, Mary Grace Carroll, Xiaopeng Sun, Elie Tannous, Yueli Zhang, Ayaka Sugiura, Brandie C Taylor, Ann Hanna, Shaoyi Zhang, Kaushik Amancherla, Warren Tai, Jordan J Wright, Spencer C Wei, Susan R Opalenik, Abigail L Toren, Jeffrey C Rathmell, P Brent Ferrell, Elizabeth J Phillips, Simon Mallal, Douglas B Johnson, James P Allison, Javid J Moslehi, Justin M Balko

Faculty, Staff and Student Publications

Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy1. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration2. Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1-/-Ctla4+/- mice, we identify clonal effector CD8+ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients, …

Systematic Analysis Of Mobile Genetic Elements Mediating Β-Lactamase Gene Amplification In Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections, W C Shropshire, A Konovalova, P Mcdaneld, M Gohel, B Strope, P Sahasrabhojane, C N Tran, D Greenberg, J Kim, X Zhan, S Aitken, M Bhatti, T C Savidge, T J Treangen, B M Hanson, C A Arias, S A Shelburne

Faculty, Staff and Student Publications

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were …

A Comprehensive Update On Cido: The Community-Based Coronavirus Infectious Disease Ontology, Yongqun He, Hong Yu, Anthony Huffman, Asiyah Yu Lin, Darren A Natale, John Beverley, Ling Zheng, Yehoshua Perl, Zhigang Wang, Yingtong Liu, Edison Ong, Yang Wang, Philip Huang, Long Tran, Jinyang Du, Zalan Shah, Easheta Shah, Roshan Desai, Hsin-Hui Huang, Yujia Tian, Eric Merrell, William D Duncan, Sivaram Arabandi, Lynn M Schriml, Jie Zheng, Anna Maria Masci, Liwei Wang, Hongfang Liu, Fatima Zohra Smaili, Robert Hoehndorf, Zoë May Pendlington, Paola Roncaglia, Xianwei Ye, Jiangan Xie, Yi-Wei Tang, Xiaolin Yang, Suyuan Peng, Luxia Zhang, Luonan Chen, Junguk Hur, Gilbert S Omenn, Brian Athey, Barry Smith

Faculty, Staff and Student Publications

BACKGROUND: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020.

RESULTS: As an Open Biomedical Ontology …

Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner

Faculty, Staff and Student Publications

IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.

OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 …

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

Structural And Functional Diversity Of Type Iv Secretion Systems, Melissa R Cruz, Shane Cristy, Shantanu Guha, Giuseppe Buda De Cesare, Elena Evdokimova, Hiram Sanchez, Dominika Borek, Pedro Miramón, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …

The Temporal Impulse Response Function In Infantile Nystagmus, Gal Avital, Felicia Kuperwaser, Andrew W Pountain, Keenan A Lacey, Erin E Zwack, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Itai Yanai

Faculty, Staff and Student Publications

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at …

Cue-Induced Cocaine Craving Enhances Psychosocial Stress And Vice Versa In Chronic Cocaine Users, Ann-Kathrin Kexel, Bruno Kluwe-Schiavon, Markus R Baumgartner, Etna J E Engeli, Monika Visentini, Clemens Kirschbaum, Erich Seifritz, Beate Ditzen, Leila M Soravia, Boris B Quednow

Faculty, Staff and Student Publications

Stress and craving, it has been found, contribute to the development and maintenance of and relapse in cocaine use disorder. Chronic cocaine users (CU), previous research has shown, display altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues. However, how psychosocial stress and cue-induced craving interact in relation to the CU's physiological responses remains largely unknown. We thus investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. In a crossed and balanced design, the participants were randomly exposed to a video-based cocaine-cue paradigm and the Trier Social Stress Test …

Dissection Of A Sensorimotor Circuit Underlying Pathogen Aversion In C Elegans, Adam Filipowicz, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

BACKGROUND: Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown.

RESULTS: Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops …

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021, Ariana Perez, Joana Y Lively, Aaron Curns, Geoffrey A Weinberg, Natasha B Halasa, Mary Allen Staat, Peter G Szilagyi, Laura S Stewart, Monica M Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A Englund, Eileen J Klein, Rangaraj Selvarangan, Christopher J Harrison, Julie A Boom, Leila C Sahni, Marian G Michaels, John V Williams, Gayle E Langley, Susan I Gerber, Angela Campbell, Aron J Hall, Brian Rha, Meredith Mcmorrow

Faculty, Staff and Student Publications

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …

Case Growth Analysis To Inform Local Response To Covid-19 Epidemic In A Diverse Us Community, Marcia C De Oliveira Otto, Frances A Brito, Ji Yun Tark, Eric Bakota, Jose-Miguel Yamal, Dritana Marko, Shreela V Sharma, Michael R Brown, Savitri N Appana, Alison M Rector, Stephen H Linder, Jennifer Kiger, Karen C Tseng, Alanna C Morrison, Eric Boerwinkle

Faculty, Staff and Student Publications

Early detection of new outbreak waves is critical for effective and sustained response to the COVID-19 pandemic. We conducted a growth rate analysis using local community and inpatient records from seven hospital systems to characterize distinct phases in SARS-CoV-2 outbreak waves in the Greater Houston area. We determined the transition times from rapid spread of infection in the community to surge in the number of inpatients in local hospitals. We identified 193,237 residents who tested positive for SARS-CoV-2 via molecular testing from April 8, 2020 to June 30, 2021, and 30,031 residents admitted within local healthcare institutions with a positive …

Low-Dose Immune Tolerance Induction In Children With Severe Hemophilia A With High-Titer Inhibitors: Type Of Factor 8 Mutation And Outcomes, Jie Sun, Zekun Li, Gang Li, Kun Huang, Di Ai, Guoqing Liu, Wanru Yao, Xingjuan Xie, Hao Gu, Yingzi Zhen, Zhenping Chen, Runhui Wu

Faculty, Staff and Student Publications

BACKGROUND: No studies evaluated the role of

OBJECTIVES: To explore the association between

METHODS: Children SHA with high-titer inhibitors who received low-dose ITI therapy at least for 1 year were included in this study. Based on the risk of inhibitor development,

RESULTS: Of 104 children included, 101 had

CONCLUSIONS: Types of

Surge In Incidence And Coronavirus Disease 2019 Hospital Risk Of Death, United States, September 2020 To March 2021, Bela Patel, Robert E Murphy, Siddharth Karanth, Salsawit Shiffaraw, Richard M Peters, Samuel F Hohmann, Raymond S Greenberg

Faculty, Staff and Student Publications

BACKGROUND: Studies of the early months of the coronavirus disease 2019 (COVID-19) pandemic indicate that patient outcomes may be adversely affected by surges. However, the impact on in-hospital mortality during the largest surge to date, September 2020-March 2021, has not been studied. This study aimed to determine whether in-hospital mortality was impacted by the community surge of COVID-19.

METHODS: This is a retrospective cohort study of 416 962 adult COVID-19 patients admitted immediately before or during the surge at 229 US academic and 432 community hospitals in the Vizient Clinical Database. The odds ratios (ORs) of death among hospitalized patients …

Development Of The Invasive Candidiasis Discharge [I Can Discharge] Model: A Mixed Methods Analysis, Jinhee Jo, Truc T Tran, Nicholas D Beyda, Debora Simmons, Joshua A Hendrickson, Masaad Saeed Almutairi, Faris S Alnezary, Anne J Gonzales-Luna, Edward J Septimus, Kevin W Garey

Faculty, Staff and Student Publications

Patients with invasive candidiasis (IC) have complex medical and infectious disease problems that often require continued care after discharge. This study aimed to assess echinocandin use at hospital discharge and develop a transition of care (TOC) model to facilitate discharge for patients with IC. This was a mixed method study design that used epidemiologic assessment to better understand echinocandin use at hospital discharge TOC. Using grounded theory methodology focused on patients given echinocandins during their last day of hospitalization, a TOC model for patients with IC, the invasive candidiasis [I Can] discharge model was developed to better understand discharge barriers. …

Investigation Of A Prolonged And Large Outbreak Of Healthcare-Associated Mucormycosis Cases In An Acute Care Hospital-Arkansas, June 2019-May 2021, Alexander Jordan, Allison E James, Jeremy A W Gold, Karen Wu, Janet Glowicz, Frankie Wolfe, Keyur Vyas, Anastasia Litvintseva, Lalitha Gade, Hazel Liverett, Mary Alverson, Mary Burgess, Amy Wilson, Ruoran Li, Isaac Benowitz, Trent Gulley, Naveen Patil, Rohan Chakravorty, Winston Chu, Atul Kothari, Brendan R Jackson, Kelley Garner, Mitsuru Toda

Faculty, Staff and Student Publications

BACKGROUND: Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak.

METHODS: We collected data on patients at Hospital A who had invasive mucormycosis during January 2017-June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection.

RESULTS: During the outbreak period (June 2019-June 2021), 16 patients had HCM; clinical …

Efficacy And Safety Of A Single Dose Of Casirivimab And Imdevimab For The Prevention Of Covid-19 Over An 8-Month Period: A Randomised, Double-Blind, Placebo-Controlled Trial, Gary A Herman, Meagan P O'Brien, Eduardo Forleo-Neto, Neena Sarkar, Flonza Isa, Peijie Hou, Kuo-Chen Chan, Katharine J Bar, Ruanne V Barnabas, Dan H Barouch, Myron S Cohen, Christopher B Hurt, Dale R Burwen, Mary A Marovich, Bret J Musser, John D Davis, Kenneth C Turner, Adnan Mahmood, Andrea T Hooper, Jennifer D Hamilton, Janie Parrino, Danise Subramaniam, Alina Baum, Christos A Kyratsous, A Thomas Dicioccio, Neil Stahl, Ned Braunstein, George D Yancopoulos, David M Weinreich, Covid-19 Phase 3 Prevention Trial Team

Faculty, Staff and Student Publications

BACKGROUND: There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2-8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings.

METHODS: This was a randomised, …

First-In-Human Study Of An Ox40 (Ivuxolimab) And 4-1bb (Utomilumab) Agonistic Antibody Combination In Patients With Advanced Solid Tumors, Omid Hamid, Alberto A Chiappori, John A Thompson, Toshihiko Doi, Siwen Hu-Lieskovan, Ferry A L M Eskens, Willeke Ros, Adi Diab, Jean-Philippe Spano, Naiyer A Rizvi, Jeffrey S Wasser, Eric Angevin, Patrick A Ott, Alison Forgie, Wenjing Yang, Cen Guo, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.

Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every …