Digital Commons Network^™

Crowdsourced Assessment Of Surgical Skill Proficiency In Cataract Surgery, Grace L Paley, Rebecca Grove, Tejas C Sekhar, Jack Pruett, Michael V Stock, Tony N Pira, Steven M Shields, Evan L Waxman, Bradley S Wilson, Mae O Gordon, Susan M Culican

2020-Current year OA Pubs

OBJECTIVE: To test whether crowdsourced lay raters can accurately assess cataract surgical skills.

DESIGN: Two-armed study: independent cross-sectional and longitudinal cohorts.

SETTING: Washington University Department of Ophthalmology.

PARTICIPANTS AND METHODS: Sixteen cataract surgeons with varying experience levels submitted cataract surgery videos to be graded by 5 experts and 300+ crowdworkers masked to surgeon experience. Cross-sectional study: 50 videos from surgeons ranging from first-year resident to attending physician, pooled by years of training. Longitudinal study: 28 videos obtained at regular intervals as residents progressed through 180 cases. Surgical skill was graded using the modified Objective Structured Assessment of Technical Skill (mOSATS). …

Electrophysiological And Molecular Mechanisms Of Sinoatrial Node Mechanosensitivity, Daniel Turner, Chen Kang, Pietro Mesirca, Juan Hong, Matteo E Mangoni, Alexey V Glukhov, Rajan Sah

2020-Current year OA Pubs

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels …

Clinical Challenges In The Management Of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review, Gayathri Nagaraj, Cynthia X Ma

2020-Current year OA Pubs

Endocrine therapy (ET) is integral to the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Aromatase inhibitors (AIs; e.g., anastrozole, letrozole, exemestane), selective estrogen receptor modulators (e.g., tamoxifen), and the selective estrogen receptor degrader, fulvestrant, inhibit tumor cell proliferation by targeting ER signaling. However, the efficacy of ET could be limited by intrinsic and acquired resistance mechanisms, which has prompted the development of targeted agents and combination strategies. In recent years, the treatment landscape for HR+, HER2- MBC has evolved rapidly. AIs, historically the first-line treatment for postmenopausal patients with HR+, HER2- …

Just Culture For Medical Students: Understanding Response To Providers In Adverse Events, Brijen J Shah, Bonnie Portnoy, Dennis Chang, Marc Napp

2020-Current year OA Pubs

INTRODUCTION: Individual and organizational response to an adverse event is a key part of the life cycle of a patient safety event. Just culture is a safety concept that emphasizes system drivers of human behavior. We developed a learning activity for medical students to teach and discuss just culture as part of a patient safety curriculum.

METHODS: This small-group, discussion-based learning activity was aimed at third-year medical students. Over 5 years, 628 students participated in it. The session had three components: a presession case-based survey, a didactic lecture, and a facilitated small-group discussion. Participants evaluated the session using our institution's …

Temozolomide Chronotherapy In Patients With Glioblastoma: A Retrospective Single-Institute Study, Anna R Damato, Jingqin Luo, Ruth G N Katumba, Grayson R Talcott, Joshua B Rubin, Erik D Herzog, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival.

METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox …

Validation Of Diffusion Mri As A Biomarker For Efficacy Using Randomized Phase Iii Trial Of Bevacizumab With Or Without Vb-111 In Recurrent Glioblastoma, Benjamin M Ellingson, Jian L Campian, Et Al.

2020-Current year OA Pubs

BACKGROUND: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.

METHODS: Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as …

Homotopic Functional Connectivity Disruptions In Glioma Patients Are Associated With Tumor Malignancy And Overall Survival, Andy G S Daniel, Carl D Hacker, John J Lee, Donna Dierker, Joseph B Humphries, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of

METHODS: We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a …

The Free And Cued Selective Reminding Test Predicts Braak Stage, Ellen Grober, Qi Qi, Lynn Kuo, Jason Hassenstab, Richard J Perrin, Richard B Lipton

2020-Current year OA Pubs

BACKGROUND: The ultimate validation of a clinical marker for Alzheimer's disease (AD) is its association with AD neuropathology.

OBJECTIVE: To identify clinical measures that predict pathology, we evaluated the relationships of the picture version of the Free and Cued Selective Reminding Test (pFCSRT + IR), the Mini-Mental State Exam (MMSE), and the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) to Braak stage.

METHODS: 315 cases from the clinicopathologic series at the Knight Alzheimer's Disease Research Center were classified according to Braak stage. Boxplots of each predictor were compared to identify the earliest stage at which decline was observed and …

Stages Of Objective Memory Impairment Predict Alzheimer's Disease Neuropathology: Comparison With The Clinical Dementia Rating Scale-Sum Of Boxes, Ellen Grober, Qi Qi, Lynn Kuo, Jason Hassenstab, Richard J Perrin, Richard B Lipton

2020-Current year OA Pubs

BACKGROUND: The ultimate validation of a clinical marker for Alzheimer's disease (AD) is its association with AD neuropathology.

OBJECTIVE: To examine how well the Stages of Objective Memory Impairment (SOMI) system predicts intermediate/high AD neuropathologic change and extent of neurofibrillary tangle (NFT) pathology defined by Braak stage, in comparison to the Clinical Dementia Rating (CDR) Scale sum of boxes (CDR-SB).

METHODS: 251 well-characterized participants from the Knight ADRC clinicopathologic series were classified into SOMI stage at their last assessment prior to death using the free recall and total recall scores from the picture version of the Free and Cued Selective …

Unfriendly Fire: How The Tobacco Industry Is Destroying The Future Of Our Children, Andrew Bush, Thomas Ferkol, Et Al.

2020-Current year OA Pubs

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned …

Clinicopathologic Implications Of Complement Genetic Variants In Kidney Transplantation, Zhen Ren, Stephen J Perkins, Latisha Love-Gregory, John P Atkinson, Anuja Java

2020-Current year OA Pubs

Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as variants of uncertain significance (VUS). Clinical risk assessment of patients carrying a VUS remains challenging primarily due to a lack of functional information, especially in the context of multiple confounding factors in the setting of kidney transplantation. Our objective was to evaluate the clinicopathologic significance of genetic variants in TMA and C3G in a kidney transplant cohort. We used whole exome next-generation sequencing to analyze complement genes in 76 patients, comprising 60 patients with a TMA and …

Health Disparities And Treatment Approaches In Portopulmonary Hypertension And Idiopathic Pulmonary Arterial Hypertension: An Analysis Of The Pulmonary Hypertension Association Registry, Hilary M Dubrock, Murali Chakinala, Et Al.

2020-Current year OA Pubs

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = …

Does Circulating Progesterone Mediate The Associations Of Single Nucleotide Polymorphisms In Progesterone Receptor (Pgr)-Related Genes With Mammographic Breast Density In Premenopausal Women?, Favour A Akinjiyan, Yunan Han, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

UNLABELLED: Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP …

Loss Of Angiotensin Ii Type 2 Receptor Improves Blood Pressure In Elastin Insufficiency, Michelle Lin, Robyn A Roth, Beth A Kozel, Robert P Mecham, Carmen M Halabi

2020-Current year OA Pubs

There is ample evidence supporting a role for angiotensin II type 2 receptor (AT

Effective Connectivity Extracts Clinically Relevant Prognostic Information From Resting State Activity In Stroke, Mohit H Adhikari, Joseph Griffis, Joshua S Siegel, Michel Thiebaut De Schotten, Gustavo Deco, Andrea Instabato, Matthieu Gilson, Maurizio Corbetta

2020-Current year OA Pubs

Recent resting-state functional MRI studies in stroke patients have identified two robust biomarkers of acute brain dysfunction: a reduction of inter-hemispheric functional connectivity between homotopic regions of the same network, and an abnormal increase of ipsi-lesional functional connectivity between task-negative and task-positive resting-state networks. Whole-brain computational modelling studies, at the individual subject level, using undirected effective connectivity derived from empirically measured functional connectivity, have shown a reduction of measures of integration and segregation in stroke as compared to healthy brains. Here we employ a novel method, first, to infer whole-brain directional effective connectivity from zero-lagged and lagged covariance matrices, then, …

Smaller Spared Subcortical Nuclei Are Associated With Worse Post-Stroke Sensorimotor Outcomes In 28 Cohorts Worldwide, Sook-Lei Liew, Catherine E Lang, Anup K Bhattacharya, Et Al.

2020-Current year OA Pubs

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T

Perceived Barriers To Assessing Understanding And Appreciation Of Informed Consent In Clinical Trials: A Mixed-Method Study, Erin D Solomon, Jessica Mozersky, Kari Baldwin, Matthew P Wroblewski, Meredith V Parsons, Melody Goodman, James M Dubois

2020-Current year OA Pubs

INTRODUCTION: Participants and research professionals often overestimate how well participants understand and appreciate consent information for clinical trials, and experts often vary in their determinations of participant's capacity to consent to research. Past research has developed and validated instruments designed to assess participant understanding and appreciation, but the frequency with which they are utilized is unknown.

METHODS: We administered a survey to clinical researchers working with older adults or those at risk of cognitive impairment (

RESULTS: We found that using a validated assessment of consent is relatively uncommon, being used by only 44% of researchers who had an opportunity. …

Teaching For Implementation: A Framework For Building Implementation Research And Practice Capacity Within The Translational Science Workforce, Aaron L Leppin, Ana A Baumann, Maria E Fernandez, Brittany N Rudd, Kathleen R Stevens, David O Warner, Bethany M Kwan, Rachel C Shelton

2020-Current year OA Pubs

Implementation science offers a compelling value proposition to translational science. As such, many translational science stakeholders are seeking to recruit, teach, and train an implementation science workforce. The type of workforce that will make implementation happen consists of both implementation researchers and practitioners, yet little guidance exists on how to train such a workforce. We-members of the Advancing Dissemination and Implementation Sciences in CTSAs Working Group-present the Teaching For Implementation Framework to address this gap. We describe the differences between implementation researchers and practitioners and demonstrate what and how to teach them individually and in co-learning opportunities. We briefly comment …

A Genetic Mouse Model With Postnatal Nf1 And P53 Loss Recapitulates The Histology And Transcriptome Of Human Malignant Peripheral Nerve Sheath Tumor, Akira Inoue, Laura J Janke, Brian L Gudenas, Hongjian Jin, Yiping Fan, Joshua Paré, Michael R Clay, Paul A Northcott, Angela C Hirbe, Xinwei Cao

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of

METHODS: We combined 2 genetically modified alleles, an

RESULTS: Postnatal

CONCLUSIONS: The NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly.

A Phase Ii Study Of Laser Interstitial Thermal Therapy Combined With Doxorubicin In Patients With Recurrent Glioblastoma, Omar H Butt, Alice Y Zhou, Jiayi Huang, William A Leidig, Alice E Silberstein, Milan G Chheda, Tanner M Johanns, George Ansstas, Jingxia Liu, Grayson Talcott, Ruth Nakiwala, Joshua S Shimony, Albert H Kim, Eric C Leuthardt, Jian L Campian, Et Al.

2020-Current year OA Pubs

BACKGROUND: The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.

METHODS: Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared …

The Next Generation Of Ocular Pathogen Detection, Sharon L. Sabapathypillai, Hayley R. James, Rachael R. L. Lyerla, Lynn Hassman

2020-Current year OA Pubs

Metagenomic next-generation sequencing is a powerful method for pathogen detection that combines advanced genome sequencing technology with cutting-edge bioinformatics to analyze microbial populations. Metagenomic next-generation sequencing has the potential to identify uncommon, unculturable, and even previously unidentified pathogens from a clinical isolate. Of particular interest to ophthalmology, this robust data extraction can occur from very small volume clinical samples. Here we discuss the opportunities and limitations of this technique and their current and future application to ophthalmic diagnostics.

Detection Of Β-Amyloid Positivity In Alzheimer's Disease Neuroimaging Initiative Participants With Demographics, Cognition, Mri And Plasma Biomarkers, Duygu Tosun, James Bollinger, Vitaliy Ovod, Kwasi G Mawuenyega, Randall J Bateman, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Modified Delphi Approach To Develop A Trial Protocol For Antibiotic De-Escalation In Patients With Suspected Sepsis, Michael E Yarrington, Rebekah W Moehring, Michael Z David, Keith W Hamilton, Michael Klompas, Chanu Rhee, Kevin Hsueh, Elizabeth Dodds Ashley, Ronda L Sinkowitz-Cochran, Matthew Ryan, Deverick J Anderson, Detours Expert Panel Of The Cdc Prevention Epicenters Program

2020-Current year OA Pubs

Background: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown.

Methods: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health …

Evaluation Of A Hybrid Antimicrobial Restriction Process At A Large Academic Medical Center, Jesse D Smith, Linh H Nguyen, Tamara Krekel, Jerrica Waggoner, David J Ritchie, Michael J Durkin, Kevin Hsueh, Elizabeth A Neuner

2020-Current year OA Pubs

We conducted a retrospective review of a hybrid antimicrobial restriction process demonstrating adherence to appropriate use criteria in 72% of provisional-only orders, in 100% of provisional orders followed by ID orders, and in 97% of ID-initiated orders. Therapy interruptions occurred in 24% of provisional orders followed by ID orders.

Transmission Dynamics: Data Sharing In The Covid-19 Era, Randi E Foraker, Albert M Lai, Thomas G Kannampallil, Keith F Woeltje, Anne M Trolard, Philip R O Payne

2020-Current year OA Pubs

Problem: The current coronavirus disease 2019 (COVID-19) pandemic underscores the need for building and sustaining public health data infrastructure to support a rapid local, regional, national, and international response. Despite a historical context of public health crises, data sharing agreements and transactional standards do not uniformly exist between institutions which hamper a foundational infrastructure to meet data sharing and integration needs for the advancement of public health.

Approach: There is a growing need to apply population health knowledge with technological solutions to data transfer, integration, and reasoning, to improve health in a broader learning health system ecosystem. To achieve this, …

Incidentally Found Rib Hemangioma: Case Report And Discussion Of Management, Deniz B. Morkan, Jason M. Gauthier, Daniel Kreisel, Varun Puri, Ruben G. Nava

2020-Current year OA Pubs

Rib hemangioma is a rare chest wall tumor for which few reports in the literature exist to help guide treatment. The clinical presentation, radiographic findings, and treatment strategies vary in the literature, with the majority of patients undergoing surgical resection to definitively rule out malignancy. Here, we report a 23-year-old woman with an incidentally discovered rib hemangioma, who had a history of migraines, during the workup of a severe headache refractory to medical treatment. Imaging revealed a solitary, expansile tumor arising from the posterior left third rib. Spinal magnetic resonance imaging (MRI) showed a fat-containing lesion with multiple vascular flow …

Differentiating Wide Complex Tachycardias: A Historical Perspective, Anthony H Kashou, Christopher M Evenson, Peter A Noseworthy, Thoddi R Muralidharan, Christopher V Desimone, Abhishek J Deshmukh, Samuel J Asirvatham, Adam M May

2020-Current year OA Pubs

One of the most critical and challenging skills is the distinction of wide complex tachycardias into ventricular tachycardia or supraventricular wide complex tachycardia. Prompt and accurate differentiation of wide complex tachycardias naturally influences short- and long-term management decisions and may directly affect patient outcomes. Currently, there are many useful electrocardiographic criteria and algorithms designed to distinguish ventricular tachycardia and supraventricular wide complex tachycardia accurately; however, no single approach guarantees diagnostic certainty. In this review, we offer an in-depth analysis of available methods to differentiate wide complex tachycardias by retrospectively examining its rich literature base - one that spans several decades.

Gene Therapy Potential For Genetic Disorders Of Surfactant Dysfunction, Ashley L Cooney, Jennifer A Wambach, Patrick L Sinn, Paul B Mccray

2020-Current year OA Pubs

Pulmonary surfactant is critically important to prevent atelectasis by lowering the surface tension of the alveolar lining liquid. While respiratory distress syndrome (RDS) is common in premature infants, severe RDS in term and late preterm infants suggests an underlying genetic etiology. Pathogenic variants in the genes encoding key components of pulmonary surfactant including surfactant protein B (SP-B,

Rethinking Immune Checkpoint Blockade: Beyond The T Cell, Xiuting Liu, Graham D Hogg, David G Denardo

2020-Current year OA Pubs

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune …

Disease-Modifying Therapy Prescription Patterns In People With Multiple Sclerosis By Age, Yinan Zhang, Amber Salter, Shan Jin, William J Culpepper, Gary R Cutter, Mitchell Wallin, Olaf Stuve

2020-Current year OA Pubs

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for their ability to reduce disease activity, namely clinical relapses and signal changes on magnetic resonance imaging (MRI). Disease activity appears age dependent. Thus, the greatest benefit would be expected in younger people with MS (PwMS) whereas benefits in the elderly are uncertain.

METHODS: Real-world data were obtained from PwMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR).

RESULTS: 6948 PwMS were surveyed from NARCOMS, and the MSSR had 1719 participants. In younger adult PwMS …