Digital Commons Network^™

Unique Molecular Identifier-Based High-Resolution Hla Typing And Transcript Quantitation Using Long-Read Sequencing, Caleb Cornaby, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

HLA typing provides essential results for stem cell and solid organ transplants, as well as providing diagnostic benefits for various rheumatology, gastroenterology, neurology, and infectious diseases. It is becoming increasingly clear that understanding the expression of patient HLA transcripts can provide additional benefits for many of these same patient groups. Our study cohort was evaluated using a long-read RNA sequencing methodology to provide rapid HLA genotyping results and normalized HLA transcript expression. Our assay used NGSEngine to determine the HLA genotyping result and normalized mRNA transcript expression using Athlon2. The assay demonstrated an excellent concordance rate of 99.7%. Similar to …

Experiences Using A Multidisciplinary Model For Treating Injection Drug Use Associated Infections: A Qualitative Study, Nathanial S Nolan, Emily Gleason, Laura R Marks, Tracey Habrock-Bach, Stephen Y Liang, Michael J Durkin

2020-Current year OA Pubs

Background: Over the past two decades, the United States has experienced a dramatic increase in the rate of injection drug use, injection associated infections, and overdose mortality. A hospital-based program for treating opioid use disorder in people who inject drugs presenting with invasive infections was initiated at an academic tertiary care center in 2020. The goal of this program was to improve care outcomes, enhance patient experiences, and facilitate transition from the hospital to longer term addiction care. The purpose of this study was to interview two cohorts of patients, those admitted before vs. after initiation of this program, to …

Efficient T Cell Migration And Activation Require L-Plastin, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T …

Coronavirus Disease 2019 (Covid-19) Vaccine Breakthrough Infections Among Healthcare Personnel, December 2020-April 2021, Katelin B Nickel, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19) vaccine effectiveness in the early months of vaccine availability was high among healthcare personnel (HCP) at 88.3% for 2-doses. Among those testing positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), those with breakthrough infection after vaccination were more likely to have had a non-work-related SARS-CoV-2 exposure compared to unvaccinated HCP.

Child Dietary Patterns In Homo Sapiens Evolution: A Systematic Review, Lora L Iannotti, Emmanuel A Gyimah, Miranda Reid, Melissa Chapnick, Mary Kate Cartmill, Chessa K Lutter, Charles Hilton, Theresa E Gildner, Elizabeth A Quinn

2020-Current year OA Pubs

Dietary patterns spanning millennia could inform contemporary public health nutrition. Children are largely absent from evidence describing diets throughout human evolution, despite prevalent malnutrition today signaling a potential genome-environment divergence. This systematic review aimed to identify dietary patterns of children ages 6 months to 10 years consumed before the widespread adoption of agriculture. Metrics of mention frequency (counts of food types reported) and food groups (globally standardized categories) were applied to: compare diets across subsistence modes [gatherer-hunter-fisher (GHF), early agriculture (EA) groups]; examine diet quality and diversity; and characterize differences by life course phase and environmental context defined using Köppen-Geiger …

Antibodies In Healthcare Personnel Following Severe Acute Respiratory Syndrome Coronavirus Virus 2 (Sars-Cov-2) Infection, Rachel E Bosserman, Christopher W Farnsworth, Caroline A O'Neil, Candice Cass, Daniel Park, Claire Ballman, Meghan A Wallace, Emily Struttmann, Henry Stewart, Olivia Arter, Kate Peacock, Victoria J Fraser, Philip J Budge, Margaret A Olsen, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters

2020-Current year OA Pubs

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Variation In Ampicillin Dosing For Lower Respiratory Tract Infections And Neonatal Bacterial Infections In Us Children's Hospitals, Elizabeth A Daniels, Christopher C Mcpherson, Jason G Newland, Brian R Lee

2020-Current year OA Pubs

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications.

DESIGN: Retrospective cohort study.

SETTING: The study included data from 32 children's hospitals in the United States.

METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, …

Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings

2020-Current year OA Pubs

Treatment of

Classical And Γδ T Cells Are Each Independently Sufficient To Establish Protection Against A Classical Strain Of Klebsiella Pneumoniae, Joseph J Mackel, Catherine Morffy Smith, Rachel K Wasbotten, Joy Twentyman, David A Rosen

2020-Current year OA Pubs

Infections with classical strains of the Gram-negative bacterium

Influenza: Toward Understanding The Immune Response In The Young, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

Annually influenza causes a global epidemic resulting in 290,000 to 650,000 deaths and extracts a massive toll on healthcare and the economy. Infants and children are more susceptible to infection and have more severe symptoms than adults likely mitigated by differences in their innate and adaptive immune responses. While it is unclear the exact mechanisms with which the young combat influenza, it is increasingly understood that their immune responses differ from adults. Specifically, underproduction of IFN-γ and IL-12 by the innate immune system likely hampers viral clearance while upregulation of IL-6 may create excessive damaging inflammation. The infant's adaptive immune …

A Role For An Htlv-1 Vaccine?, Lee Ratner

2020-Current year OA Pubs

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, …

Conceptual Tensions And Practical Trade-Offs In Tailoring Implementation Interventions, Sheena M Mchugh, Fiona Riordan, Geoff M Curran, Cara C Lewis, Luke Wolfenden, Justin Presseau, Rebecca Lengnick-Hall, Byron J Powell

2020-Current year OA Pubs

Tailored interventions have been shown to be effective and tailoring is a popular process with intuitive appeal for researchers and practitioners. However, the concept and process are ill-defined in implementation science. Descriptions of how tailoring has been applied in practice are often absent or insufficient in detail. This lack of transparency makes it difficult to synthesize and replicate efforts. It also hides the trade-offs for researchers and practitioners that are inherent in the process. In this article we juxtapose the growing prominence of tailoring with four key questions surrounding the process. Specifically, we ask: (1) what constitutes tailoring and when …

Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although new evidence-based practices are frequently implemented in clinical settings, many are not sustained, limiting the intended impact. Within implementation science, there is a gap in understanding sustainability. Pediatric healthcare settings have a robust history of quality improvement (QI), which includes a focus on continuation of change efforts. QI capability and sustainability capacity, therefore, serve as a useful concept for connecting the broader fields of QI and implementation science to provide insights on improving care. This study addresses these gaps in understanding of sustainability in pediatric settings and its relationship to QI.

METHODS: This is a cross-sectional observational study …

Challenges And Progress In Research, Diagnostics, And Therapeutics In Alzheimer's Disease And Related Dementias, Nikolay V Dokholyan, Richard C Mohs, Randall J Bateman

2020-Current year OA Pubs

The health, well-being, and financial security of Americans are greatly impacted by Alzheimer's disease. The forecast paints an upward trajectory with the number of Americans suffering from Alzheimer's disease and related dementia. To discuss the Alzheimer's crisis, The Senate Committee on Finance, Subcommittee on Health Care, held a hearing titled, "The Alzheimer's Crisis: Examining, Testing, and Treatment Pipelines and Fiscal Implications," on December 16, 2020. Here, we summarize and expand on the discussion of the panel and its review of recent progress, ongoing challenges associated with Alzheimer's disease, and potential initiatives that promise to speed progress in developing treatments and …

Washington University Magazine, April 2022

Washington University Magazine

No abstract provided.

Washington University Magazine, August 2022

Washington University Magazine

No abstract provided.

Washington University Magazine, December 2022

Washington University Magazine

No abstract provided.

Characteristics Of Antifungal Utilization For Hospitalized Children In The United States, Lourdes Eguiguren, Brian R Lee, Jason G Newland, Matthew P Kronman, Adam L Hersh, Jeffrey S Gerber, Grace M Lee, Hayden T Schwenk

2020-Current year OA Pubs

OBJECTIVE: To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States.

DESIGN: We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017.

METHODS: Inpatients aged <18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics.

RESULTS: Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the …

Exploring The Role Of Low-Density Neutrophils During Mycobacterium Tuberculosis Infection, Ananda N Rankin, Skyler V Hendrix, Sumanta K Naik, Christina L Stallings

2020-Current year OA Pubs

Tuberculosis (TB) is caused by infection with the bacterium

Medication For Opioid Use Disorder At Hospital Discharge Is Not Associated With Intravenous Antibiotic Completion In Post-Acute Care Facilities, Edward C Traver, Patrick R Ching, Shivakumar Narayanan

Open Access Publications

Background: People with opioid use disorder and severe infections may complete their prolonged courses of outpatient parenteral antimicrobial therapy at a post-acute care facility due to adherence and safety concerns. We hypothesized that treatment with medications for opioid use disorder, such as methadone and buprenorphine, would increase antibiotic completion in these facilities.

Methods: We performed a retrospective cohort study of people with opioid use disorder and severe infections who were discharged from the University of Maryland Medical Center to a post-acute care facility to complete intravenous antibiotic therapy. The primary outcome was completion of outpatient parenteral antimicrobial therapy. We compared …

Multicenter, Prospective Validation Of A Phenotypic Algorithm To Guide Carbapenemase Testing In Carbapenem-Resistant Pseudomonas Aeruginosa Using The Erace-Pa Global Surveillance Program, Christian M. Gill, Carey-Ann D. Burnham, Et Al

Open Access Publications

Background: Carbapenemase-producing, carbapenem-resistant

Methods: CRPA isolates were collected during the Enhancing Rational Antimicrobials for

Results: A total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%.

Conclusions: Application of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) …

Patients With Serious Injection Drug Use-Related Infections Who Experience Patient-Directed Discharges On Oral Antibiotics Have High Rates Of Antibiotic Adherence But Require Multidisciplinary Outpatient Support For Retention In Care, Sophia Lewis, Stephen Y. Liang, Evan S. Schwarz, David B. Liss, Rachel P. Winograd, Nathanial S. Nolan, Michael J. Durkin, Laura R. Marks

Open Access Publications

Background: Persons who inject drugs (PWID) are frequently admitted for serious injection-related infections (SIRIs). Outcomes and adherence to oral antibiotics for PWID with patient-directed discharge (PDD) remain understudied.

Methods: We conducted a prospective multicenter bundled quality improvement project of PWID with SIRI at 3 hospitals in Missouri. All PWID with SIRI were offered multidisciplinary care while inpatient, including the option of addiction medicine consultation and medications for opioid use disorder (MOUD). All patients were offered oral antibiotics in the event of a PDD either at discharge or immediately after discharge through an infectious diseases telemedicine clinic. Additional support services included …

Serologic And Cytokine Signatures In Children With Multisystem Inflammatory Syndrome And Coronavirus Disease 2019, Stacey A. Lapp, Carol M. Kao, David A. Hunstad, Et Al

Open Access Publications

Background: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.

Methods: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and …

Dysregulation Of The Leukocyte Signaling Landscape During Acute Covid-19, Isaiah R. Turnbull, Anja Fuchs, Kenneth E. Remy, Michael P. Kelly, Elfaridah P. Frazier, Sarbani Ghosh, Shin-Wen Chang, Monty B. Mazer, Annie Hess, Jennifer M. Leonard, Mark H. Hoofnagle, Marco Colonna, Richard S. Hotchkiss

Open Access Publications

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation …

Salaries, Degrees, And Babies: Trends In Fertility By Income And Education Among Japanese Men And Women Born 1943-1975-Analysis Of National Surveys, Cyrus Ghaznavi, Haruka Sakamoto, Lisa Yamasaki, Shuhei Nomura, Daisuke Yoneoka, Kenji Shibuya, Peter Ueda

Open Access Publications

BACKGROUND: While fertility rates have decreased during the second half of the 20th century in Japan, little is known regarding trends in the number of children that men and women have across birth cohorts and whether these differ by education and income.

METHODS: We used data from four rounds of the National Fertility Survey (1992, 2005, 2010 and 2015) and included men and women aged 40-49 years (16728 men and 17628 women). By 5-year birth cohorts, we assessed the distribution of number of children (0, 1, 2 and 3 or more) and total fertility (the mean number of children) at …

Understanding Contributors To Racial And Ethnic Inequities In Covid-19 Incidence And Mortality Rates, Karen E. Joynt Maddox, Mat Reidhead, Joshua Grotzinger, Timothy Mcbride, Aaloke Mody, Elna Nagasako, Will Ross, Joseph T. Steensma, Abigail R. Barker

Open Access Publications

BACKGROUND: Racial inequities in Coronavirus 2019 (COVID-19) have been reported over the course of the pandemic, with Black, Hispanic/Latinx, and Native American individuals suffering higher case rates and more fatalities than their White counterparts.

METHODS: We used a unique statewide dataset of confirmed COVID-19 cases across Missouri, linked with historical statewide hospital data. We examined differences by race and ethnicity in raw population-based case and mortality rates. We used patient-level regression analyses to calculate the odds of mortality based on race and ethnicity, controlling for comorbidities and other risk factors.

RESULTS: As of September 10, 2020 there were 73,635 confirmed …

Isolation Of Sars-Cov-2 In Viral Cell Culture In Immunocompromised Patients With Persistently Positive Rt-Pcr Results, Abby Sung, Adam L Bailey, Henry B Stewart, David Mcdonald, Meghan A Wallace, Kate Peacock, Candace Miller, Kimberly A Reske, Caroline A O'Neil, Victoria J Fraser, Michael S Diamond, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon

Open Access Publications

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2

It's Getting Complicated-A Fresh Look At P53-Mdm2-Arf Triangle In Tumorigenesis And Cancer Therapy, Che-Pei Kung, Jason D Weber

Open Access Publications

Anti-tumorigenic mechanisms mediated by the tumor suppressor p53, upon oncogenic stresses, are our bodies' greatest weapons to battle against cancer onset and development. Consequently, factors that possess significant p53-regulating activities have been subjects of serious interest from the cancer research community. Among them, MDM2 and ARF are considered the most influential p53 regulators due to their abilities to inhibit and activate p53 functions, respectively. MDM2 inhibits p53 by promoting ubiquitination and proteasome-mediated degradation of p53, while ARF activates p53 by physically interacting with MDM2 to block its access to p53. This conventional understanding of p53-MDM2-ARF functional triangle have guided the …

Perceptions Of Telemedicine And Costs Incurred By A Visit To A General Infectious Diseases Clinic: A Survey, Emily C. Evers, Stephanie A. Fritz, Graham A. Colditz, Jason P. Burnham

Open Access Publications

Background: The costs of attending in-person general infectious diseases clinics and preferences for visit type (telemedicine vs in-person) are not well known. We aimed to measure the time-related, monetary, social, and societal costs associated with travel to an in-person clinic visit and to assess patients' preferences, questions, and concerns regarding telemedicine.

Methods: Patients (≥18 years, living ≥25 miles from clinic at time of clinic visit) were recruited for this survey study from the general infectious diseases (ID) clinic at Washington University from June 2019 to February 2020. We calculated time and money potentially saved by telemedicine, as well as carbon …

Simulated Cost-Effectiveness And Long-Term Clinical Outcomes Of Addiction Care And Antibiotic Therapy Strategies For Patients With Injection Drug Use-Associated Infective Endocarditis, Joëlla W. Adams, Alexandra Savinkina, James C. Hudspeth, Mam Jarra Gai, Raagini Jawa, Laura R. Marks, Benjamin P. Linas, Alison Hill, Jason Flood, Simeon Kimmel, Joshua A. Barocas

Open Access Publications

Importance: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown.

Objective: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE.

Design, Setting, and Participants: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included …