Medicine and Health Sciences Commons^™

Outcomes Following In-Hospital Cardiopulmonary Resuscitation In People Receiving Maintenance Dialysis, Fahad Saeed, Haris F Murad, Richard E Wing, Jianbo Li, Jesse D Schold, Kevin A Fiscella

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis.

STUDY DESIGN: Retrospective chart review.

SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014.

EXPOSURE: Initial in-hospital CPR.

OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same …

Protocol For The Perioperative Outcome Risk Assessment With Computer Learning Enhancement (Periop Oracle) Randomized Study, Bradley Fritz, Christopher King, Yixin Chen, Alex Kronzer, Joanna Abraham, Arbi Ben Abdallah, Thomas Kannampallil, Thaddeus Budelier, Arianna Montes De Oca, Sherry Mckinnon, Bethany Tellor Pennington, Troy Wildes, Michael Avidan

2020-Current year OA Pubs

No abstract provided.

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.

Automatic Wide Complex Tachycardia Differentiation Using Mathematically Synthesized Vectorcardiogram Signals, Anthony H Kashou, Sarah Lococo, Trevon D Mcgill, Christopher M Evenson, Abhishek J Deshmukh, David O Hodge, Daniel H Cooper, Sandeep S Sodhi, Phillip S Cuculich, Samuel J Asirvatham, Peter A Noseworthy, Christopher V Desimone, Adam M May

2020-Current year OA Pubs

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification.

METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT …

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

Mechanisms Of Persistent Atrial Fibrillation And Recurrences Within 12 Months Post-Ablation: Non-Invasive Mapping With Electrocardiographic Imaging, Ramya Vijayakumar, Mitchell N Faddis, Phillip S Cuculich, Yoram Rudy

2020-Current year OA Pubs

INTRODUCTION: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.

METHODS: Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 …

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that

Islet Cilia And Glucose Homeostasis, Isabella Melena, Jing W Hughes

2020-Current year OA Pubs

Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin …

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Adam E. Locke, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Bernhard Banas, Carsten A. Boger, Bettina Jung, D C. Rao, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Relevance Of Rich Club Regions For Functional Outcome Post-Stroke Is Enhanced In Women, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al.

2020-Current year OA Pubs

No abstract provided.

White Matter Abnormalities In The Hdc Knockout Mouse, A Model Of Tic And Ocd Pathophysiology, Kantiya Jindachomthong, Chengran Yang, Yuegao Huang, Daniel Coman, Maximiliano Rapanelli, Fahmeed Hyder, Joseph Dougherty, Luciana Frick, Christopher Pittenger

2020-Current year OA Pubs

INTRODUCTION: An inactivating mutation in the

MATERIALS AND METHODS: We performed exploratory RNA-seq to identify pathological alterations in several brain regions in

RESULTS: Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain

DISCUSSION: While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with …

Primates Chunk Simultaneously-Presented Memoranda, Charles D Holmes, Shinung Ching, Lawrence H Snyder

2020-Current year OA Pubs

Though much research has characterized both the behavior and electrophysiology of spatial memory for single targets in non-human primates, we know much less about how multiple memoranda are handled. Multiple memoranda may interact in the brain, affecting the underlying representations. Mnemonic resources are famously limited, so items may compete for "space" in memory or may be encoded cooperatively or in a combined fashion. Understanding the mode of interaction will inform future neural studies. As a first step, we quantified interactions during a multi-item spatial memory task. Two monkeys were shown 1-4 target locations. After a delay, the targets reappeared with …

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 …

Top-Down And Bottom-Up Propagation Of Disease In The Neuronal Ceroid Lipofuscinoses, John R Ostergaard, Hemanth R Nelvagal, Jonathan D Cooper

2020-Current year OA Pubs

BACKGROUND: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related diseases that share lipofuscin pathobiology as the common core feature, but otherwise distinguished by different a) initial anatomic location, and b) disease propagation.

METHODS: We have tested this hypothesis by comparing known differences in symptomatology and pathology of the CLN1 phenotype caused by complete loss of

RESULTS: Despite displaying similar pathological endpoints, the clinical phenotypes and the evidence of imaging and

DISCUSSION: The propagation of disease in these two …

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 …

A Perspective On Implementation Outcomes And Strategies To Promote The Uptake Of Covid-19 Vaccines, Meagan Pilar, A Rani Elwy, Larissa Lushniak, Grace Huang, Gabriella M Mcloughlin, Cole Hooley, Nisha Nadesan-Reddy, Brittney Sandler, Mosa Moshabela, Olakunle Alonge, Elvin Geng, Enola Proctor

2020-Current year OA Pubs

Recent articles have highlighted the importance of incorporating implementation science concepts into pandemic-related research. However, limited research has been documented to date regarding implementation outcomes that may be unique to COVID-19 vaccinations and how to utilize implementation strategies to address vaccine program-related implementation challenges. To address these gaps, we formed a global COVID-19 implementation workgroup of implementation scientists who met weekly for over a year to review the available literature and learn about ongoing research during the pandemic. We developed a hierarchy to prioritize the applicability of "lessons learned" from the vaccination-related implementation literature. We identified applications of existing implementation …

"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 …

Positive Predictive Value Of Erbb2 Copy Number Gain By Tissue Or Circulating Tumor Dna Next-Generation Sequencing Across Advanced Cancers, Ami N Shah, Ashwin Sunderraj, Brian Finkelman, Sharlene H See, Andrew A Davis, Lorenzo Gerratana, Firas Wehbe, Neelima Katam, Deva Mahalingam, William J Gradishar, Amir Behdad, Luis Blanco, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.

MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.

RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (

CONCLUSIONS: ERBB2 …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Analysis Of Variation In Pre-Procedural Fasting Duration For Common Inpatient Gastrointestinal Procedures, Vorada Sakulsaengprapha, Michael Daniel, Jiarui Cai, Diego A. Martinez, Simon C. Mathews

2020-Current year OA Pubs

BACKGROUND: Gastrointestinal procedures generally require pre-procedural fasting to optimize sedation safety. While the American Society of Anesthesiologists (ASA) recommends no intake of clear liquids and solid food 2-4 and 6-8 hours respectively prior to endoscopic procedures, the actual nil per os (NPO) duration for these procedures in practice is unknown. Our objective was to analyze NPO duration for patients undergoing these procedures and to determine its association with clinical and administrative variables.

METHODS: Inpatient data from 2016-2018 for the three procedures was extracted from electronic medical records and administrative data at a single-center tertiary academic medical center. Various statistical tests …

The Incidence Of Candidate Binding Sites For Β-Arrestin In Drosophila Neuropeptide Gpcrs, Paul H. Taghert

2020-Current year OA Pubs

To support studies of neuropeptide neuromodulation, I have studied beta-arrestin binding sites (BBS's) by evaluating the incidence of BBS sequences among the C terminal tails (CTs) of each of the 49 Drosophila melanogaster neuropeptide GPCRs. BBS were identified by matches with a prediction derived from structural analysis of rhodopsin:arrestin and vasopressin receptor: arrestin complexes [1]. To increase the rigor of the identification, I determined the conservation of BBS sequences between two long-diverged species D. melanogaster and D. virilis. There is great diversity in the profile of BBS's in this group of GPCRs. I present evidence for conserved BBS's in a …

Creation Of Philadelphia Chromosome By Crispr/Cas9-Mediated Double Cleavages On Bcr And Abl1 Genes As A Model For Initial Event In Leukemogenesis, Minori Tamai, Kenji Kamimoto, Kohei Omachi, Et Al.

2020-Current year OA Pubs

The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was …

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 …

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan

2020-Current year OA Pubs

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most …

Reciprocal Regulation Of Mitofusin 2-Mediated Mitophagy And Mitochondrial Fusion By Different Pink1 Phosphorylation Events, Jiajia Li, Xiawei Dang, Antonietta Franco, Gerald W Dorn

2020-Current year OA Pubs

Mitochondrial repair is essential to metabolic homeostasis. Outer mitochondrial membrane mitofusin (MFN) proteins orchestrate mitochondrial fusion that opposes mitochondrial degeneration caused by senescence. Depending upon physiological context, MFN2 can either mediate mitochondrial fusion or recruit cytosolic Parkin to initiate mitophagic elimination. Because it is not clear how these events are counter-regulated we engineered and expressed MFN2 mutants that mimic phosphorylated or non-phosphorylatable MFN2 at its PINK1 phosphorylation sites: T111, S378, and S442. By interrogating mitochondrial fusion, polarization status, and Parkin binding/mitophagy as a function of inferred MFN2 phosphorylation, we discovered that individual MFN2 phosphorylation events act as a biological "bar-code", …

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 …

Predicting Coronary Stenosis Progression Using Plaque Fatigue From Ivus-Based Thin-Slice Models: A Machine Learning Random Forest Approach, Xiaoya Guo, Akiko Maehara, Mingming Yang, Liang Wang, Jie Zheng, Habib Samady, Gary S Mintz, Don P Giddens, Dalin Tang

2020-Current year OA Pubs

No abstract provided.

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 …