Medicine and Health Sciences Commons^™

Skeletal Dysplasia-Causing Trpv4 Mutations Suppress The Hypertrophic Differentiation Of Human Ipsc-Derived Chondrocytes, Amanda R Dicks, Grigory I Maksaev, Zainab Harissa, Alireza Savadipour, Ruhang Tang, Nancy Steward, Wolfgang Liedtke, Colin G Nichols, Chia-Lung Wu, Farshid Guilak

2020-Current year OA Pubs

Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human-induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype (WT). There were no differences in …

Creating Research-Ready Partnerships: The Initial Development Of Seven Implementation Laboratories To Advance Cancer Control, Gina R Kruse, Erica Hale, Justin E Bekelman, Jennifer E Devoe, Rachel Gold, Peggy A Hannon, Thomas K Houston, Aimee S James, Ashley Johnson, Lisa M Klesges, Andrea L Nederveld

2020-Current year OA Pubs

BACKGROUND: In 2019-2020, with National Cancer Institute funding, seven implementation laboratory (I-Lab) partnerships between scientists and stakeholders in 'real-world' settings working to implement evidence-based interventions were developed within the Implementation Science Centers in Cancer Control (ISC3) consortium. This paper describes and compares approaches to the initial development of seven I-Labs in order to gain an understanding of the development of research partnerships representing various implementation science designs.

METHODS: In April-June 2021, members of the ISC3 Implementation Laboratories workgroup interviewed research teams involved in I-Lab development in each center. This cross-sectional study used semi-structured interviews and case-study-based methods to collect and …

Predicting Later Categories Of Upper Limb Activity From Earlier Clinical Assessments Following Stroke: An Exploratory Analysis, Jessica Barth, Keith R Lohse, Marghuretta D Bland, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Accelerometers allow for direct measurement of upper limb (UL) activity. Recently, multi-dimensional categories of UL performance have been formed to provide a more complete measure of UL use in daily life. Prediction of motor outcomes after stroke have tremendous clinical utility and a next step is to explore what factors might predict someone's subsequent UL performance category.

PURPOSE: To explore how different machine learning techniques can be used to understand how clinical measures and participant demographics captured early after stroke are associated with the subsequent UL performance categories.

METHODS: This study analyzed data from two time points from a …

Ccl17 Protects Against Viral Myocarditis By Suppressing The Recruitment Of Regulatory T Cells, Guoshuai Feng, Cuige Zhu, Chieh-Yu Lin, Andrea Bredemeyer, Irmgard Förster, Daniel Kreisel, Kory J Lavine

2020-Current year OA Pubs

Background Viral myocarditis is characterized by leukocyte infiltration of the heart and cardiomyocyte death. We recently identified C-C chemokine ligand (CCL) 17 as a proinflammatory effector of C-C chemokine receptor 2-positive macrophages and dendritic cells that are recruited to the heart and contribute to adverse left ventricular remodeling following myocardial infarction and pressure overload. Methods and Results Mouse encephalomyocarditis virus was used to investigate the function of CCL17 in a viral myocarditis model.

The Status Of Digital Pathology And Associated Infrastructure Within Alzheimer's Disease Centers, Rebeca Scalco, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Digital pathology (DP) has transformative potential, especially for Alzheimer disease and related disorders. However, infrastructure barriers may limit adoption. To provide benchmarks and insights into implementation barriers, a survey was conducted in 2019 within National Institutes of Health's Alzheimer's Disease Centers (ADCs). Questions covered infrastructure, funding sources, and data management related to digital pathology. Of the 35 ADCs to which the survey was sent, 33 responded. Most respondents (81%) stated that their ADC had digital slide scanner access, with the most frequent brand being Aperio/Leica (62.9%). Approximately a third of respondents stated there were fees to utilize the scanner. For …

Efficacy And Safety Of Non-Steroidal Anti-Inflammatory Drugs (Nsaids) For The Treatment Of Acute Pain After Orthopedic Trauma: A Practice Management Guideline From The Eastern Association For The Surgery Of Trauma And The Orthopedic Trauma Association, Patrick B. Murphy, Anna Miller, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Fracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established.

METHODS: Clinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) …

Hydrogel Encapsulation Of Genome-Engineered Stem Cells For Long-Term Self-Regulating Anti-Cytokine Therapy, Kelsey H Collins, Lara Pferdehirt, Leila S Saleh, Alireza Savadipour, Luke E Springer, Kristin L Lenz, Dominic M Thompson, Sara J Oswald, Christine T N Pham, Farshid Guilak

2020-Current year OA Pubs

Biologic therapies have revolutionized treatment options for rheumatoid arthritis (RA) but their continuous administration at high doses may lead to adverse events. Thus, the development of improved drug delivery systems that can sense and respond commensurately to disease flares represents an unmet medical need. Toward this end, we generated induced pluripotent stem cells (iPSCs) that express interleukin-1 receptor antagonist (IL-1Ra, an inhibitor of IL-1) in a feedback-controlled manner driven by the macrophage chemoattractant protein-1 (Ccl2) promoter. Cells were seeded in agarose hydrogel constructs made from 3D printed molds that can be injected subcutaneously via a blunt needle, thus simplifying implantation …

Tcr-Engineered Adoptive Cell Therapy Effectively Treats Intracranial Murine Glioblastoma, Maximilian O. Schaettler, Rupen Desai, Anthony Z. Wang, Alexandra J. Livingstone, Dale K. Kobayashi, Andrew T. Coxon, Jay A. Bowman-Kirigin, Connor J. Liu, Mao Li, Diane E. Bender, Michael J. White, David M. Kranz, Tanner M. Johanns, Gavin P. Dunn

2020-Current year OA Pubs

BACKGROUND: Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. As an alternative, T cell receptor (TCR)-engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma.

METHODS: We employed single-cell PCR to isolate a TCR specific for the Imp3

RESULTS: We isolated and characterized the 3×1.1C TCR that displayed a high affinity for mImp3 but no wild-type cross-reactivity. To provide a …

The Gut Microbiota Of People With Asthma Influences Lung Inflammation In Gnotobiotic Mice, Naomi G Wilson, Ariel Hernandez-Leyva, Anne L Rosen, Natalia Jaeger, Ryan T Mcdonough, Jesus Santiago-Borges, Michael A Lint, Thomas R Rosen, Christopher P Tomera, Leonard B Bacharier, S Joshua Swamidass, Andrew L Kau

2020-Current year OA Pubs

The gut microbiota in early childhood is linked to asthma risk, but may continue to affect older patients with asthma. Here, we profile the gut microbiota of 38 children (19 asthma, median age 8) and 57 adults (17 asthma, median age 28) by 16S rRNA sequencing and find individuals with asthma harbored compositional differences from healthy controls in both adults and children. We develop a model to aid the design of mechanistic experiments in gnotobiotic mice and show enterotoxigenic

Hallmarks Of Neurodegenerative Diseases, David M Wilson 3rd, Mark R Cookson, Ludo Van Den Bosch, Henrik Zetterberg, David M Holtzman, Ilse Dewachter

2020-Current year OA Pubs

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks of NDD: pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. We describe the hallmarks, their biomarkers, and their interactions as a framework to study NDDs using a holistic approach. The framework can serve as a basis for defining pathogenic mechanisms, categorizing different NDDs based on their primary hallmarks, stratifying patients within a specific NDD, and designing multi-targeted, personalized therapies to effectively …

Benchmarking The Generalizability Of Brain Age Models: Challenges Posed By Scanner Variance And Prediction Bias, Robert J Jirsaraie, Tobias Kaufmann, Vishnu Bashyam, Guray Erus, Joan L Luby, Lars T Westlye, Christos Davatzikos, Deanna M Barch, Aristeidis Sotiras

2020-Current year OA Pubs

Machine learning has been increasingly applied to neuroimaging data to predict age, deriving a personalized biomarker with potential clinical applications. The scientific and clinical value of these models depends on their applicability to independently acquired scans from diverse sources. Accordingly, we evaluated the generalizability of two brain age models that were trained across the lifespan by applying them to three distinct early-life samples with participants aged 8-22 years. These models were chosen based on the size and diversity of their training data, but they also differed greatly in their processing methods and predictive algorithms. Specifically, one brain age model was …

Spontaneous Coronary Artery Dissection Complicated By Left Ventricular Free Wall Rupture In Turner Syndrome, Brendan F Caprio, Kunal Kotkar, Alan Zajarias, Alan C Braverman

2020-Current year OA Pubs

A 38-year-old with Turner syndrome presented with acute myocardial infarction due to multivessel spontaneous coronary artery dissection (SCAD) complicated by left ventricular free wall rupture. Conservative management for SCAD was pursued. She underwent sutureless repair for an oozing-type left ventricular free wall rupture. SCAD has not been previously reported in Turner syndrome. (

Fmr1 Mutation Alters The Early Development Of Sensory Coding And Hunting And Social Behaviors In Larval Zebrafish, Shuyu I Zhu, Michael H Mccullough, Zac Pujic, Jordan Sibberas, Biao Sun, Thomas Darveniza, Bianca Bucknall, Lilach Avitan, Geoffrey J Goodhill

2020-Current year OA Pubs

Autism spectrum disorders (ASDs) are developmental in origin; however, little is known about how they affect the early development of behavior and sensory coding. The most common inherited form of autism is Fragile X syndrome (FXS), caused by a mutation in

Svep1 Is An Endogenous Ligand For The Orphan Receptor Pear1, Jared S Elenbaas, Upasana Pudupakkam, Katrina J Ashworth, Chul Joo Kang, Ved Patel, Katherine Santana, In-Hyuk Jung, Paul C Lee, Kendall H Burks, Junedh M Amrute, Robert P Mecham, Carmen M Halabi, Arturo Aliso, Jorge Di Paola, Nathan O Stitziel

2020-Current year OA Pubs

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet …

Staphylococcus Aureus Breast Implant Infection Isolates Display Recalcitrance To Antibiotic Pocket Irrigants, Jesus M. Duran Ramirez, Jana Gomez, Blake M. Hanson, Taha Isa, Terence M. Myckatyn, Jennifer N. Walker

2020-Current year OA Pubs

Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstructive failure due to infection results in significant patient distress and health care expenditures. Thus, effective BIAI prevention strategies are urgently needed. This study tests the efficacy of one infection prevention strategy: the use of a triple antibiotic pocket irrigant (TAPI) against Staphylococcus aureus, the most common cause of BIAIs. TAPI, which consists of 50,000 U bacitracin, 1 g cefazolin, and 80 mg gentamicin diluted in 500 mL of saline, is used to irrigate the breast implant …

Barriers To Using Legally Authorized Representatives In Clinical Research With Older Adults, Jessica Mozersky, Erin D Solomon, Kari Baldwin, Matthew Wroblewski, Meredith Parsons, Melody Goodman, James M Dubois

2020-Current year OA Pubs

BACKGROUND: Older adults are at increased risk of cognitive impairments including Alzheimer's disease dementia. Legally authorized representatives (LARs) can provide informed consent when a participant is no longer able to, but little is known about barriers to incorporating them in research.

OBJECTIVE: Explore reasons for not asking and documenting participant decisions to appoint LARs among researchers conducting clinical intervention trials studying older adults or individuals with cognitive impairments.

METHODS: Mixed method design consisting of a survey (

RESULTS: 37% (

CONCLUSION: Resources and education to increase awareness and knowledge of LARs are needed. Researchers studying older adults should, at minimum, …

Mrna Vaccine Mitigates Sars-Cov-2 Infections And Covid-19, Christina M. Kackos, Sherri L. Surman, Bart G. Jones, Robert E. Sealy, Trushar Jeevan, Christopher J H Davitt, Sergei Pustylnikov, Tamarand L. Darling, Adrianus C M Boon, Julia L. Hurwitz, Marcelo M. Samsa, Richard J. Webby

2020-Current year OA Pubs

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to contain the spread of the virus and reduce disease. The production and distribution of these vaccines occurred at a remarkable pace, largely through the employment of the novel mRNA platform. However, interruptions in supply chain and high demand for clinical grade reagents have impeded the manufacture and distribution of mRNA vaccines at a time when accelerated vaccine deployment is crucial. Furthermore, the emergence of SARS-CoV-2 …

Brain Aerobic Glycolysis And Resilience In Alzheimer Disease, Manu S Goyal, Tyler Blazey, Nicholas V Metcalf, Mark P Mcavoy, Jeremy F Strain, Maryam Rahmani, Tony J Durbin, Chengjie Xiong, Tammie L-S Benzinger, John C Morris, Marcus E Raichle, Andrei G Vlassenko

2020-Current year OA Pubs

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher …

Self-Renewing Macrophages In Dorsal Root Ganglia Contribute To Promote Nerve Regeneration, Rui Feng, Vishnu Muraleedharan Saraswathy, Mayssa H Mokalled, Valeria Cavalli

2020-Current year OA Pubs

Sensory neurons located in dorsal root ganglia (DRG) convey sensory information from peripheral tissue to the brain. After peripheral nerve injury, sensory neurons switch to a regenerative state to enable axon regeneration and functional recovery. This process is not cell autonomous and requires glial and immune cells. Macrophages in the DRG (DRGMacs) accumulate in response to nerve injury, but their origin and function remain unclear. Here, we mapped the fate and response of DRGMacs to nerve injury using macrophage depletion, fate-mapping, and single-cell transcriptomics. We identified three subtypes of DRGMacs after nerve injury in addition to a small population of …

Apolipoprotein E4 Has Extensive Conformational Heterogeneity In Lipid-Free And Lipid-Bound Forms, Melissa D Stuchell-Brereton, Maxwell I Zimmerman, Justin J Miller, Upasana L Mallimadugula, J Jeremías Incicco, Debjit Roy, Louis G Smith, Jasmine Cubuk, Berevan Baban, Gregory T Dekoster, Carl Frieden, Gregory R Bowman, Andrea Soranno

2020-Current year OA Pubs

The ε4-allele variant of apolipoprotein E (ApoE4) is the strongest genetic risk factor for Alzheimer's disease, although it only differs from its neutral counterpart ApoE3 by a single amino acid substitution. While ApoE4 influences the formation of plaques and neurofibrillary tangles, the structural determinants of pathogenicity remain undetermined due to limited structural information. Previous studies have led to conflicting models of the C-terminal region positioning with respect to the N-terminal domain across isoforms largely because the data are potentially confounded by the presence of heterogeneous oligomers. Here, we apply a combination of single-molecule spectroscopy and molecular dynamics simulations to construct …

Rate Of Tarsal And Metatarsal Bone Mineral Density Change In Adults With Diabetes Mellitus And Peripheral Neuropathy: A Longitudinal Study, Nicholas J Youmans, Rachana S Vaidya, Ling Chen, Hyo-Jung Jeong, Alexa York, Paul K Commean, Mary K Hastings, Jennifer A Zellers

2020-Current year OA Pubs

BACKGROUND: In people with diabetes (DM) and peripheral neuropathy (PN), loss of bone mineral density (BMD) in the tarsals and metatarsals contribute to foot complications; however, changes in BMD of the calcaneal bone is most commonly reported. This study reports rate of change in BMD of all the individual bones in the foot, in participants with DM and PN. Our aim was to investigate whether the rate of BMD change is similar across all the bones of the foot.

METHODS: Participants with DM and PN (n = 60) were included in this longitudinal cohort study. Rate of BMD change of …

Community Research Fellows Training Program: Evaluation Of A Covid-19-Precipitated Virtual Adaptation, Nicole Ackermann, Sarah Humble, Jacquelyn V Coats, Carlette Lewis Rhone, Craig Schmid, Vetta Sanders Thompson, Kia L Davis

2020-Current year OA Pubs

Community engagement is important for promoting health equity. However, effective community engagement requires trust, collaboration, and the opportunity for all stakeholders to share in decision-making. Community-based training in public health research can build trust and increase community comfort with shared decision-making in academic and community partnerships. The Community Research Fellows Training (CRFT) Program is a community-based training program that promotes the role of underserved populations in research by enhancing participant knowledge and understanding of public health research and other relevant topics in health. This paper describes the process of modifying the original 15-week in-person training program to a 12-week online, …

Outcomes In Participants With Ventilated Nosocomial Pneumonia And Organ Failure Treated With Ceftolozane/Tazobactam Versus Meropenem: A Subset Analysis Of The Phase 3, Randomized, Controlled Aspect-Np Trial, Ignacio Martin-Loeches, Andrew F Shorr, Richard G Wunderink, Marin H Kollef, Jean-François Timsit, Brian Yu, Jennifer A Huntington, Erin Jensen, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction.

METHODS: This was a subset analysis of data from ASPECT-NP, a randomized, double-blind, non-inferiority trial (ClinicalTrials.gov NCT02070757). Adults with vHABP/VABP were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem every 8 h for 8-14 days. Outcomes in participants with a baseline respiratory component of the Sequential Organ Failure Assessment (SOFA) score (R-SOFA) ≥ 2 (indicative of severe respiratory failure), cardiovascular component of the SOFA score (CV-SOFA) …

Phase Ib Study Of Telisotuzumab Vedotin In Combination With Erlotinib In Patients With C-Met Protein-Expressing Non-Small-Cell Lung Cancer, D Ross Camidge, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

PURPOSE: Overexpression of c-Met protein and epidermal growth factor receptor (

PATIENTS AND METHODS: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an

RESULTS: As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months …

Retinoid X Receptor Promotes Hematopoietic Stem Cell Fitness And Quiescence And Preserves Hematopoietic Homeostasis, María Piedad Menéndez-Gutiérrez, Jesús Porcuna, Ramesh Nayak, Ana Paredes, Haixia Niu, Vanessa Núñez, Aditi Paranjpe, Manuel J Gómez, Anukana Bhattacharjee, Daniel J Schnell, Fátima Sánchez-Cabo, John S Welch, Nathan Salomonis, Jose A Cancelas, Mercedes Ricote

2020-Current year OA Pubs

Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an …

Chikungunya Virus And Its Envelope Protein E2 Induce Hyperalgesia In Mice: Inhibition By Anti-E2 Monoclonal Antibodies And By Targeting Trpv1, Carina Z Segato-Vendrameto, Felipe A Pinho-Ribeiro, Et Al.

2020-Current year OA Pubs

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) …

Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting Pd-L1 And Tgf-Β, In Patients With Pretreated Colorectal Cancer: Results From A Phase I Trial, Alexander Spira, Michael S Wertheim, Edward J Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L Gulley, Scott Kopetz

2020-Current year OA Pubs

Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor β (TGF-β) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received bintrafusp alfa …

Protection Of Messenger Rna Vaccines Against Hospitalized Coronavirus Disease 2019 In Adults Over The First Year Following Authorization In The United States, Mark W Tenforde, Hilary M Babcock, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.

METHODS: Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing …

The Impact Of Universal Glove And Gown Use On Clostridioides Difficile Acquisition: A Cluster-Randomized Trial, Daniel J Morgan, Erik R Dubberke, Tiffany Hink, Gwen Paszkiewicz, Carey-Ann D Burnham, Lisa Pineles, Larry Magder, J Kristie Johnson, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infections in the United States. It is unknown whether universal gown and glove use in intensive care units (ICUs) decreases acquisition of C. difficile.

METHODS: This was a secondary analysis of a cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from 4 January 2012 to 4 October 2012. After a baseline period, ICUs were randomized to standard practice for glove and gown use versus the intervention of all healthcare workers being required to wear gloves and gowns for all patient contact and when entering any patient …

Prognostic Significance Of Early Platelet Dynamics In Staphylococcus Aureus Bacteremia, Rachid Douglas-Louis, Mimi Lou, Brian Lee, Emi Minejima, Juliane Bubeck-Wardenburg, Annie Wong-Beringer

2020-Current year OA Pubs

BACKGROUND: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB).

METHOD: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence.

RESULTS: Among the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2-3 following SAB onset, and Day 4 was a determining …