Medicine and Health Sciences Commons^™

Mortality In Pediatric Oncology And Stem Cell Transplant Patients With Bloodstream Infections, Daniel N Willis, Mary Claire Mcglynn, Patrick J Reich, Robert J Hayashi

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) continue to represent a significant source of morbidity for pediatric oncology patients, however less is known regarding this population's risk of death. We sought to evaluate the risk of BSI and death at a large pediatric cancer center.

METHODS: We retrospectively collected inpatient data from pediatric oncology and hematopoietic stem cell transplant (HSCT) patients over a 9-year period. We performed univariate and multivariable modeling to assess risk of BSI and mortality examining the following variables: demographics, underlying malignancy, history of HSCT, central line type, and febrile neutropenia (FN).

RESULTS: During the study period, 6763 admissions from …

Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian

2020-Current year OA Pubs

PURPOSE: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.

METHODS: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.

RESULTS: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with …

"Provider Discretionary Power Practices To Support Implementation Of Patient-Centered Hiv Care In Lusaka, Zambia", Chanda Mwamba, Njekwa Mukamba, Anjali Sharma, Kasapo Lumbo, Marksman Foloko, Herbert Nyirenda, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Aaloke Mody, Elvin Geng, Laura K Beres

2020-Current year OA Pubs

INTRODUCTION: Traditional patient-provider relationships privilege the providers, as they possess the formal authority and clinical knowledge applied to address illness, but providers also have discretion over how they exercise their power to influence patients' services, benefits, and sanctions. In this study, we assessed providers' exercise of discretionary power in implementing patient-centered care (PCC) practices in Lusaka, Zambia.

METHODS: HIV clinical encounters between patients on antiretroviral therapy (ART) and providers across 24 public health facilities in Lusaka Province were audio recorded and transcribed verbatim. Using qualitative content analysis, we identified practices of discretionary power (DP) employed in the implementation of PCC …

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 …

Management Of Acute Promyelocytic Leukemia In The Setting Of Acute Covid-19 Infection, Kevin G Shim, Mallory Crain, Kristan Augustin, Karolyn A Oetjen

2020-Current year OA Pubs

Acute promyelocytic leukemia (APL) often presents with significant coagulopathy which may result in both hemorrhagic and thrombotic complications. The emergence of the COVID-19 pandemic has complicated the initial treatment and diagnosis of APL owing to the viral infection's own associated coagulopathy. Here we report two cases of APL newly diagnosed in the setting of COVID-19 infection and considerations in their management. Included is a discussion of strategies for the dosing of arsenic trioxide in patients with significant obesity and renal insufficiency. The case series submitted does not represent a study on patients and thus no specific informed consents or permissions …

A Promising Genetic Target For A Deadly Disease: Single Immunoglobulin Interleukin 1 (Sigirr) Mutations In Necrotizing Enterocolitis, Misty Good, Camilia R Martin

2020-Current year OA Pubs

No abstract provided.

Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco

2020-Current year OA Pubs

Most neuroimaging studies of post-stroke recovery rely on analyses derived from standard node-centric functional connectivity to map the distributed effects in stroke patients. Here, given the importance of nonlocal and diffuse damage, we use an edge-centric approach to functional connectivity in order to provide an alternative description of the effects of this disorder. These techniques allow for the rendering of metrics such as normalized entropy, which describes the diversity of edge communities at each node. Moreover, the approach enables the identification of high amplitude co-fluctuations in fMRI time series. We found that normalized entropy is associated with stroke lesion severity …

Sepsis Prediction For The General Ward Setting, Sean C Yu, Aditi Gupta, Kevin D Betthauser, Patrick G Lyons, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

OBJECTIVE: To develop and evaluate a sepsis prediction model for the general ward setting and extend the evaluation through a novel pseudo-prospective trial design.

DESIGN: Retrospective analysis of data extracted from electronic health records (EHR).

SETTING: Single, tertiary-care academic medical center in St. Louis, MO, USA.

PATIENTS: Adult, non-surgical inpatients admitted between January 1, 2012 and June 1, 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of the 70,034 included patient encounters, 3.1% were septic based on the Sepsis-3 criteria. Features were generated from the EHR data and were used to develop a machine learning model to predict sepsis 6-h ahead …

Low-Dose Interleukin-2 Reverses Chronic Migraine-Related Sensitizations Through Peripheral Interleukin-10 And Transforming Growth Factor Beta-1 Signaling, Zhaohua Guo, Jintao Zhang, Xuemei Liu, Jacqueline Unsinger, Richard S. Hotchkiss, Yu-Qing Cao

2020-Current year OA Pubs

Low-dose interleukin-2 (LD-IL-2) treatment has been shown to effectively reverse chronic migraine-related behaviors and the sensitization of trigeminal ganglion (TG) neurons through expansion and activation of peripheral regulatory T cells (Tregs) in mice. In this study, we investigated the molecular mechanisms underlying the effects of LD-IL-2 and Treg cells. LD-IL-2 treatment increases the production of cytokines interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) in T cells, especially Treg cells, suggesting that they may mediate the therapeutic effect of LD-IL-2. Indeed, neutralizing antibodies against either IL-10 or TGFβ completely blocked the effects of LD-IL-2 on the facial mechanical hypersensitivity as …

Analysis Of Neuronal Injury Transcriptional Response Identifies Ctcf And Yy1 As Co-Operating Factors Regulating Axon Regeneration, Oshri Avraham, Jimmy Le, Kathleen Leahy, Tiandao Li, Guoyan Zhao, Valeria Cavalli

2020-Current year OA Pubs

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons

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

Mesenchymal Gene Expression Subtyping Analysis For Early-Stage Human Papillomavirus-Negative Head And Neck Squamous Cell Carcinoma Reveals Prognostic And Predictive Applications, Gregory M Mayhew, Joshua M Uronis, David Neil Hayes, Jose P Zevallos

2020-Current year OA Pubs

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(-), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(-) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, …

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

Examining Virtual Driving Test Performance And Its Relationship To Individuals With Hiv-Associated Neurocognitive Disorders, David Grethlein, Vanessa Pirrone, Kathryn N Devlin, Will Dampier, Zsofia Szep, Flaura K Winston, Santiago Ontañón, Elizabeth A Walshe, Kim Malone, Shinika Tillman, Beau M Ances, Venk Kandadai, Dennis L Kolson, Brian Wigdahl

2020-Current year OA Pubs

SIGNIFICANCE: Existing screening tools for HIV-associated neurocognitive disorders (HAND) are often clinically impractical for detecting milder forms of impairment. The formal diagnosis of HAND requires an assessment of both cognition and impairment in activities of daily living (ADL). To address the critical need for identifying patients who may have disability associated with HAND, we implemented a low-cost screening tool, the Virtual Driving Test (VDT) platform, in a vulnerable cohort of people with HIV (PWH). The VDT presents an opportunity to cost-effectively screen for milder forms of impairment while providing practical guidance for a cognitively demanding ADL.

OBJECTIVES: We aimed to: …

Toward A Fully Implantable Ecosystem For Adaptive Neuromodulation In Humans: Preliminary Experience With The Cortec Braininterchange Device In A Canine Model, Gerwin Schalk, Samuel Worrell, Filip Mivalt, Alexander Belsten, Inyong Kim, Jonathan M Morris, Dora Hermes, Bryan T Klassen, Nathan P Staff, Steven Messina, Timothy Kaufmann, Jörn Rickert, Peter Brunner, Gregory A Worrell, Kai J Miller

2020-Current year OA Pubs

This article describes initial work toward an ecosystem for adaptive neuromodulation in humans by documenting the experience of implanting CorTec's BrainInterchange (BIC) device in a beagle canine and using the BCI2000 environment to interact with the BIC device. It begins with laying out the substantial opportunity presented by a useful, easy-to-use, and widely available hardware/software ecosystem in the current landscape of the field of adaptive neuromodulation, and then describes experience with implantation, software integration, and post-surgical validation of recording of brain signals and implant parameters. Initial experience suggests that the hardware capabilities of the BIC device are fully supported by …

Reduced Expression In Preterm Birth Of Sflt-1 And Plgf With A High Sflt-1/Plgf Ratio In Extracellular Vesicles Suggests A Potential Biomarker, Sama Hussein, Weina Ju, Stephanie Pizzella, Michael Flory, Chu Chu, Yong Wang, Nanbert Zhong

2020-Current year OA Pubs

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases …

Epidermolysis Bullosa With Congenital Absence Of Skin: Congenital Corneal Cloudiness And Esophagogastric Obstruction Including Extended Genotypic Spectrum Of Plec, Lamc2, Itgb4 And Col7a1, Pharuhad Pongmee, Sanchawan Wittayakornrerk, Ramrada Lekwuttikarn, Sasikarn Pakdeeto, Piangor Watcharakuldilok, Chatchay Prempunpong, Thipwimol Tim-Aroon, Chawintee Puttanapitak, Piyawan Wattanasoontornsakul, Thitiporn Junhasavasdikul, Parith Wongkittichote, Saisuda Noojarern, Duangrurdee Wattanasirichaigoon

2020-Current year OA Pubs

Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of

Phase 1 Clinical Trial Evaluating The Safety And Anti-Tumor Activity Of Adp-A2m10 Spear T-Cells In Patients With Mage-A10+ Head And Neck, Melanoma, Or Urothelial Tumors, David S Hong, Russell K Pachynski, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered autologous T-cells that express a high-affinity melanoma-associated antigen (MAGE)-A10-specific T-cell receptor (TCR) targeting MAGE-A10-positive tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-004 is a phase 1, dose-escalation trial to evaluate the safety and anti-tumor activity of ADP-A2M10 in three malignancies (https://clinicaltrials.gov: NCT02989064).

METHODS: Eligible patients were HLA-A*02 positive with advanced head and neck squamous cell carcinoma (HNSCC), melanoma, or urothelial carcinoma (UC) expressing MAGE-A10. Patients underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the MAGE-A10 TCR, and expanded. Patients underwent lymphodepletion with fludarabine …

Investing In Late-Life Brain Capital, Walter D Dawson, Eric J Lenze, Et Al.

2020-Current year OA Pubs

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused …

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Kenneth E Remy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Skeletal Muscle Contractile Function In Heart Failure With Reduced Ejection Fraction - A Focus On Nitric Oxide, Lauren K Park, Andrew R Coggan, Linda R Peterson

2020-Current year OA Pubs

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Induction Egfr Tyrosine Kinase Inhibitors Prior To Definitive Chemoradiotherapy In Unresectable Stage Iii Egfr-Mutated Non-Small Cell Lung Cancer, Jacqueline V Aredo, Heather A Wakelee, Angela Bik-Yu Hui, Sukhmani K Padda, Nitin D Joshi, H Henry Guo, Aadel Chaudhuri, Maximilian Diehn, Billy W Loo Jr, Joel W Neal

2020-Current year OA Pubs

INTRODUCTION: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy.

METHODS: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes.

RESULTS: Of six patients, three received erlotinib and three osimertinib as induction …

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Mary F Feitosa, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, C Charles Gu, Et Al.

2020-Current year OA Pubs

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …

Evaluating The Implementation Of A Multi-Level Mhealth Study To Improve Hydroxyurea Utilization In Sickle Cell Disease, J S Hankins, A A King, A A Baumann, L M. Klesges, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the …

Abnormal Synergies And Associated Reactions Post-Hemiparetic Stroke Reflect Muscle Activation Patterns Of Brainstem Motor Pathways, Laura M Mcpherson, Julius P A Dewald

2020-Current year OA Pubs

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when …