Digital Commons Network^™

Switching Warfarin To Direct Oral Anticoagulants In Atrial Fibrillation: Insights From The Ncdr Pinnacle Registry, Christopher T Sciria, Thomas M Maddox, Et Al

Open Access Publications

BACKGROUND: Previous studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin.

HYPOTHESIS: To examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice-level factors associated with switching from chronic warfarin therapy to a DOAC.

METHODS: Prospective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year …

A Color Flow Tract In Ultrasound-Guided Random Renal Core Biopsy Predicts Complications, Marie-Helene Gagnon, Michael F. Lin, Samantha Lancia, Amber Salter, Motoyo Yano

Open Access Publications

OBJECTIVES: To determine patient and procedural risk factors for major complications in ultrasound (US)-guided random renal core biopsy.

METHODS: Random renal biopsies performed by radiologists in the US department at a single institution between 2014 and 2018 were retrospectively reviewed. The patient's age, sex, race, and estimated glomerular filtration rate (eGFR) were recorded. The biopsy approach, needle gauge, length of cores, number of throws, and presence of a color flow tract were recorded. Outcome data included minor and major complications. Associations between variables were tested with χ

RESULTS: A total of 231 biopsies (167 native and 64 allografts) were reviewed. …

The Effect Of Thermal Therapy On The Blood-Brain Barrier And Blood-Tumor Barrier, Bhuvic Patel, Peter H Yang, Albert H Kim

Open Access Publications

The blood-brain and blood-tumor barriers represent highly specialized structures responsible for tight regulation of molecular transit into the central nervous system. Under normal circumstances, the relative impermeability of the blood-brain barrier (BBB) protects the brain from circulating toxins and contributes to a brain microenvironment necessary for optimal neuronal function. However, in the context of tumors and other diseases of central nervous system, the BBB and the more recently appreciated blood-tumor barrier (BTB) represent barriers that prevent effective drug delivery. Overcoming both barriers to optimize treatment of central nervous system diseases remains the subject of intense scientific investigation. Although many newer …

Implementation Of A Novel Remote Physician Stereotactic Body Radiation Therapy Coverage Process During The Coronavirus Pandemic, Alex Price, Lauren E Henke, Borna Maraghechi, Taeho Kim, Matthew B Spraker, Geoffrey D Hugo, Clifford G Robinson, Nels C Knutson

Open Access Publications

Purpose: During the coronavirus 2019 disease (COVID-19) pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO stereotactic body radiation therapy (SBRT) coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice.

Methods and Materials: All observed failure modes were recorded during implementation over the first 15 sequential fractions. The …

Statistics Of Heart Failure And Mechanical Circulatory Support In 2020, Robert E. S. Bowen, Thomas J. Graetz, Daniel A. Emmert, Michael S. Avidan

Open Access Publications

Heart failure is increasing in prevalence, with approximately 26 million patients affected worldwide. This represents a significant cause of morbidity and mortality. Statistics regarding heart failure patient age, hospitalization likelihood, and mortality differ significantly by country. Heart failure patients are typically classified by ejection fraction, with distinct phenotypes associated with reduced ejection fraction (rEF) or preserved ejection fraction (pEF). Heart failure has a significant financial impact related to hospitalization, medication, and procedural expenses. The costs of heart failure also extend to the reduced quality of life conferred by heart failure symptoms. Management of heart failure includes a variety of interventions, …

Whole Exome Sequencing Reveals The Maintained Polyclonal Nature From Primary To Metastatic Malignant Peripheral Nerve Sheath Tumor In Two Patients With Nf1, Abigail Godec, Reyka Jayasinghe, John S A Chrisinger, Bethany Prudner, Tyler Ball, Yuxi Wang, Divya Srihari, Madhurima Kaushal, Hilary Dietz, Xiaochun Zhang, Melike Pekmezci, Sonika Dahiya, Yu Tao, Jinqin Luo, Brian A Van Tine, Li Ding, David H Gutmann, Angela C Hirbe

Open Access Publications

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with high metastatic rates and poor overall patient survival. There are currently no effective therapies, underscoring the pressing need to define the molecular etiologies that underlie MPNST progression. The aim of this study was to examine clonal progression and identify the molecular events critical for MPNST spread.

METHODS: In two patients with temporally and spatially distinct metastatic lesions, we employed whole exome sequencing (WES) to elucidate the genetic events of clonal progression, thus identifying the molecular events critical for MPNST spread.

RESULTS: First, we demonstrated shared clonal origins …

Defining The Substrate For Ventricular Tachycardia Ablation: The Impact Of Rhythm At The Time Of Mapping, Danesh K Kella, Seth H Sheldon, Amit Noheria, Deepak Padmanabhan, Thomas Munger, Samuel J Asirvatham, Suraj Kapa

Open Access Publications

BACKGROUND: Voltage mapping is critical to define substrate during ablation. In ventricular tachycardia, abnormal potentials may be targets. However, wavefront of activation could impact local signal characteristics. This may be particularly true when comparing sinus rhythm versus paced rhythms. We sought to determine how activation wavefront impacts electrogram characteristics.

METHODS: Patients with ischemic cardiomyopathy, ventricular tachycardia, and without fascicular or bundle branch block were included. Point by point mapping was done and at each point, one was obtained during an atrial paced rhythm and one during a right ventricular paced rhythm. Signals were adjudicated after ablation to define late potentials, …

A Patient-Centred, Comprehensive Model For The Care For Heart Failure: The 360° Heart Failure Centre, Ilia G Halatchev, Jay R Mcdonald, Wen-Chin Wu

Open Access Publications

No abstract provided.

Implementing A Novel Remote Physician Treatment Coverage Practice For Adaptive Radiation Therapy During The Coronavirus Pandemic, Alex Price, Hyun Kim, Lauren E Henke, Nels C Knutson, Matthew B Spraker, Jeff Michalski, Geoffrey D Hugo, Clifford G Robinson, Olga Green

Open Access Publications

Purpose: The 2019 coronavirus disease pandemic has placed an increased importance on physical distancing to minimize the risk of transmission in radiation oncology departments. The pandemic has also increased the use of hypofractionated treatment schedules where magnetic resonance-guided online adaptive radiation therapy (ART) can aid in dose escalation. This specialized technique requires increased staffing in close proximity, and thus the need for novel coverage practices to increase physical distancing while still providing specialty care.

Methods and Materials: A remote-physician ART coverage practice was developed and described using commercially available software products. Our remote-physician coverage practice provided control to the physician …

Predictors Of Worsening Neuropathy And Neuropathic Pain After 12 Years In People With Hiv, Ronald J Ellis, Monica Diaz, Ned Sacktor, Christina Marra, Ann C Collier, David B Clifford, Nigel Calcutt, Jerel A Fields, Robert K Heaton, Scott L Letendre, Cns Antiretroviral Therapy Effects Research (Charter) Study Group

Open Access Publications

OBJECTIVE: Distal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact.

METHODS: Ambulatory, community-dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co-morbidities. Adjusted odds ratios were calculated for follow-up neuropathy outcomes.

RESULTS: Of 254 …

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.

Histopathology And Selective Biomarker Expression In Human Meibomian Glands, Lixing W Reneker, Rebecca T Irlmeier, Ying-Bo Shui, Ying Liu, Andrew J W Huang

Open Access Publications

BACKGROUND/AIMS: Meibomian gland dysfunction (MGD) is the most common form of evaporative dry eye disease, but its pathogenesis is poorly understood. This study examined the histopathological features of meibomian gland (MG) tissue from cadaver donors to identify potential pathogenic processes that underlie MGD in humans.

METHODS: Histological analyses was performed on the MGs in the tarsal plates dissected from four cadaver donors, two young and two old adults, including a 36-year-old female (36F) and three males aged 30, 63 and 64 years (30M, 63M and 64M).

RESULTS: The MGs of 36F displayed normal anatomy and structure, whereas the MGs of …

Ocular And Brain Imaging Findings In Peters' Anomaly: A Case Report And Literature Review, Amjad Samara, Rami W Eldaya

Open Access Publications

Peters' anomaly is a rare congenital eye condition characterized by anterior segment dysgenesis and commonly presents as unilateral or bilateral corneal opacity in the early neonatal period. Peters' anomaly is often associated with congenital brain and skull abnormalities, which are frequently overlooked. In this paper, we present a case of a 5-day-old female neonate with Peters' anomaly, and review the literature for similar reports that describe associated brain imaging findings. In our case, imaging studies show abnormalities involving the anterior segments of both globes with absent intracranial manifestations. Although Peters' anomaly is a condition of interest for ophthalmologists, radiological studies …

Clinical And Radiographic Presentations Of Covid-19 Among Patients Receiving Radiation Therapy For Thoracic Malignancies, Pamela Samson, Matthew S Ning, Narek Shaverdian, Annemarie F Shepherd, Daniel R Gomez, Gwendolyn J Mcginnis, Paige L Nitsch, Steven Chmura, Michael S O'Reilly, Percy Lee, Joe Y Chang, Clifford Robinson, Steven H Lin

Open Access Publications

No abstract provided.

The Endosymbiont Wolbachia Rebounds Following Antibiotic Treatment, Emma L. Gunderson, Young-Jun Choi, Makedonka Mitreva, Et Al.

Open Access Publications

Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi …

Maternal Knowledge Of The Risk Of Vertical Transmission And Offspring Acquisition Of Hepatitis B., Mauricio Lisker-Melman, Mandana Khalili, Steven H Belle, Norah A Terrault, Hsing-Hua S Lin, Coleman I Smith, Raymond T Chung, Naoky Tsai, Natalie H Bzowej, Tram T Tran, Sarah Jane Schwarzenberg, Hepatitis B Research Network (Hbrn)

Open Access Publications

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B.

MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) …

Brain Connectivity And Socioeconomic Status At Birth And Externalizing Symptoms At Age 2 Years, Bruce Ramphal, Diana J Whalen, Jeanette K Kenley, Qiongru Yu, Christopher D Smyser, Cynthia E Rogers, Chad M Sylvester

Open Access Publications

Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to …

Robust Principal Component Analysis For Accurate Outlier Sample Detection In Rna-Seq Data, Xiaoying Chen, Bo Zhang, Ting Wang, Azad Bonni, Guoyan Zhao

Open Access Publications

BACKGROUND: High throughput RNA sequencing is a powerful approach to study gene expression. Due to the complex multiple-steps protocols in data acquisition, extreme deviation of a sample from samples of the same treatment group may occur due to technical variation or true biological differences. The high-dimensionality of the data with few biological replicates make it challenging to accurately detect those samples, and this issue is not well studied in the literature currently. Robust statistics is a family of theories and techniques aim to detect the outliers by first fitting the majority of the data and then flagging data points that …

Systemic Inflammatory Response Syndrome In Patients With Acute Obstructive Upper Tract Urinary Stone: A Risk Factor For Urgent Renal Drainage And Revisit To The Emergency Department, Spencer Larkin, Jeremy Johnson, Trisha Venkatesh, Joel Vetter, Ramakrishna Venkatesh

Open Access Publications

BACKGROUND: In patients seen in the emergency department (ED) with acute stone obstruction many risk factors that indicate need for urgent renal drainage are known. However, in patients discharged from ED without renal drainage factors that can minimize revisit to the emergency department are not fully identified. We evaluated SIRS (systemic inflammatory response syndrome) as a risk factor for urgent renal drainage and revisit to the ED in patients with acute stone colic during their ED visit.

METHODS: Retrospective review was performed of patients presenting to a tertiary academic emergency department (ED) from an obstructing ureteral or UPJ stone with …

Parkinson Disease Clinical Subtypes: Key Features & Clinical Milestones, Meghan C Campbell, Peter S Myers, Alexandra J Weigand, Erin R Foster, Nigel J Cairns, Joshua J Jackson, Christina N Lessov-Schlaggar, Joel S Perlmutter

Open Access Publications

OBJECTIVES: Based on multi-domain classification of Parkinson disease (PD) subtypes, we sought to determine the key features that best differentiate subtypes and the utility of PD subtypes to predict clinical milestones.

METHODS: Prospective cohort of 162 PD participants with ongoing, longitudinal follow-up. Latent class analysis (LCA) delineated subtypes based on score patterns across baseline motor, cognitive, and psychiatric measures. Discriminant analyses identified key features that distinguish subtypes at baseline. Cox regression models tested PD subtype differences in longitudinal conversion to clinical milestones, including deep brain stimulation (DBS), dementia, and mortality.

RESULTS: LCA identified distinct subtypes: "motor only" (N = 63) …

Phenotypic Profiling In Subjects Heterozygous For 1 Of 2 Rare Variants In The Hypophosphatasia Gene (Alpl), Daniel R Tilden, Jonathan H Sheehan, John H Newman, Jens Meiler, John A Capra, Andrea Ramirez, Jill Simmons, Kathryn Dahir

Open Access Publications

CONTEXT: Hypophosphatasia (HPP) is a syndrome marked by low serum alkaline phosphatase (AlkP) activity as well as musculoskeletal and/or dental disease. While the majority of subjects with HPP carry a pathogenic variant in the

METHODS: Through BioVU, a DNA biobank that pairs individuals' genetic information with their de-identified medical records, we identified subjects with 2 rare variants with distinct reported clinical phenotypes (p.D294A and p.T273M). We then performed a manual review of these subjects' de-identified medical records along with computational modeling of protein structure to construct a genetic, biochemical and clinical phenotype for each subject and variant.

RESULTS: Twenty subjects …

Exploiting The Circuit Breaker Cancer Evolution Model In Human Clear Cell Renal Cell Carcinoma, James J Hsieh, Emily H Cheng

Open Access Publications

The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20

Behavioral And Neural Signatures Of Working Memory In Childhood, Monica D. Rosenberg, Deanna M. Barch, Et Al

Open Access Publications

Working memory function changes across development and varies across individuals. The patterns of behavior and brain function that track individual differences in working memory during human development, however, are not well understood. Here, we establish associations between working memory, other cognitive abilities, and functional MRI (fMRI) activation in data from over 11,500 9- to 10-year-old children (both sexes) enrolled in the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing longitudinal study in the United States. Behavioral analyses reveal robust relationships between working memory, short-term memory, language skills, and fluid intelligence. Analyses relating out-of-scanner working memory performance to memory-related fMRI activation …

Evaluation Of The Biofire Filmarray Pneumonia Panel For Detection Of Viral And Bacterial Pathogens In Lower Respiratory Tract Specimens In The Setting Of A Tertiary Care Academic Medical Center, Daniel M Webber, Meghan A Wallace, C A Burnham, Neil W Anderson

Open Access Publications

Our objective was to evaluate the diagnostic yield and accuracy of the BioFire FilmArray pneumonia panel (BFPP) for identification of pathogens in lower respiratory tract specimens (

Evaluation Of Ng-Test Carba 5 For Rapid Phenotypic Detection And Differentiation Of Five Common Carbapenemase Families: Results Of A Multicenter Clinical Evaluation, Stephen Jenkins, Carey-Ann D. Burnham, Meghan A Wallace, Et Al

Open Access Publications

NG-Test Carba 5 is a rapid

An Agonistic Anti-Cd137 Antibody Disrupts Lymphoid Follicle Structure And T-Cell-Dependent Antibody Responses, Jun P Hong, Glennys V Reynoso, Prabhakar S Andhey, Amanda Swain, Jackson S Turner, Adrianus C M Boon, Florian Krammer, Ali H Ellebedy, Fabio Zanini, Maxim Artyomov, Heather D Hickman, Michael S Diamond

Open Access Publications

CD137 is a costimulatory receptor expressed on natural killer cells, T cells, and subsets of dendritic cells. An agonistic monoclonal antibody (mAb) against CD137 has been used to reduce tumor burden or reverse autoimmunity in animal models and clinical trials. Here, we show that mice treated with an agonistic anti-CD137 mAb have reduced numbers of germinal center (GC) B cells and follicular dendritic cells (FDCs) in lymphoid tissues, which impair antibody responses to multiple T-cell-dependent antigens, including infectious virus, viral proteins, and conjugated haptens. These effects are not due to enhanced apoptosis or impaired proliferation of B cells but instead …

Pattern Of Relapse And Treatment Response In Wnt-Activated Medulloblastoma, Liana Nobre, Joshua B Rubin, Et Al

Open Access Publications

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic …

Development Of A Single-Stranded Dna-Binding Protein Fluorescent Fusion Toolbox, Katarzyna Dubiel, Camille Henry, Lisanne M. Spenkelink, Alexander G. Kozlov, Elizabeth A. Wood, Slobodan Jergic, Nicholas E. Dixon, Antoine M. Van Oijen, Michael M. Cox, Timothy M. Lohman, Steven J. Sandler, James L. Keck

Open Access Publications

Bacterial single-stranded DNA-binding proteins (SSBs) bind single-stranded DNA and help to recruit heterologous proteins to their sites of action. SSBs perform these essential functions through a modular structural architecture: the N-terminal domain comprises a DNA binding/tetramerization element whereas the C-terminus forms an intrinsically disordered linker (IDL) capped by a protein-interacting SSB-Ct motif. Here we examine the activities of SSB-IDL fusion proteins in which fluorescent domains are inserted within the IDL of Escherichia coli SSB. The SSB-IDL fusions maintain DNA and protein binding activities in vitro, although cooperative DNA binding is impaired. In contrast, an SSB variant with a fluorescent protein …

Pet Radiopharmaceuticals For Imaging Chemotherapy-Induced Cardiotoxicity, Jothilingam Sivapackiam, Monica Sharma, Thomas H Schindler, Vijay Sharma

Open Access Publications

PURPOSE OF REVIEW: Currently, cardiotoxicity is monitored through echocardiography or multigated acquisition scanning and is defined as 10% or higher LVEF reduction. The latter stage may represent irreversible myocardium injury and limits modification of therapeutic paradigms at earliest stages. To stratify patients for anthracycline-related heart failure, highly sensitive and molecularly specific probes capable of interrogating cardiac damage at the subcellular levels have been sought.

RECENT FINDINGS: PET tracers may provide noninvasive assessment of earliest changes within myocardium. These tracers are at nascent stages of development and belong primarily to (a) mitochondrial potential-targeted and (b) general ROS (reactive oxygen species)-targeted radiotracers. …

The Mechanism Of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-Of-Function In Cantú Syndrome, Conor Mcclenaghan, Yan Huang, Scot J Matkovich, Attila Kovacs, Carla J Weinheimer, Ron Perez, Thomas J Broekelmann, Theresa M Harter, Jin-Moo Lee, Maria S Remedi, Colin G Nichols

Open Access Publications

Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (K