Medical Specialties Commons^™

The Evolution Of Non-Small Cell Lung Cancer Metastases In Tracerx, Maise Al Bakir, Ariana Huebner, Carlos Martínez-Ruiz, Kristiana Grigoriadis, Thomas B K Watkins, Oriol Pich, David A Moore, Selvaraju Veeriah, Sophia Ward, Joanne Laycock, Diana Johnson, Andrew Rowan, Maryam Razaq, Mita Akther, Cristina Naceur-Lombardelli, Paulina Prymas, Antonia Toncheva, Sonya Hessey, Michelle Dietzen, Emma Colliver, Alexander M Frankell, Abigail Bunkum, Emilia L Lim, Takahiro Karasaki, Christopher Abbosh, Crispin T Hiley, Mark S Hill, Daniel E Cook, Gareth A Wilson, Roberto Salgado, Emma Nye, Richard Kevin Stone, Dean A Fennell, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Yvonne Summers, Colin R Lindsay, Fiona H Blackhall, Judith Cave, Kevin G Blyth, Arjun Nair, Asia Ahmed, Magali N Taylor, Alexander James Procter, Mary Falzon, David Lawrence, Neal Navani, Ricky M Thakrar, Sam M Janes, Dionysis Papadatos-Pastos, Martin D Forster, Siow Ming Lee, Tanya Ahmad, Sergio A Quezada, Karl S Peggs, Peter Van Loo, Caroline Dive, Allan Hackshaw, Nicolai J Birkbak, Simone Zaccaria, Tracerx Consortium, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% …

Evolutionary Characterization Of Lung Adenocarcinoma Morphology In Tracerx, Takahiro Karasaki, David A Moore, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Neil Magno, Sophia Ward, Maise Al Bakir, Thomas B K Watkins, Kristiana Grigoriadis, Ariana Huebner, Mark S Hill, Alexander M Frankell, Christopher Abbosh, Clare Puttick, Haoran Zhai, Francisco Gimeno-Valiente, Sadegh Saghafinia, Nnennaya Kanu, Michelle Dietzen, Oriol Pich, Emilia L Lim, Carlos Martínez-Ruiz, James R M Black, Dhruva Biswas, Brittany B Campbell, Claudia Lee, Emma Colliver, Katey S S Enfield, Sonya Hessey, Crispin T Hiley, Simone Zaccaria, Kevin Litchfield, Nicolai J Birkbak, Elizabeth Larose Cadieux, Jonas Demeulemeester, Peter Van Loo, Prasad S Adusumilli, Kay See Tan, Waseem Cheema, Francisco Sanchez-Vega, David R Jones, Natasha Rekhtman, William D Travis, Allan Hackshaw, Teresa Marafioti, Roberto Salgado, John Le Quesne, Andrew G Nicholson, Tracerx Consortium, Nicholas Mcgranahan, Charles Swanton, Mariam Jamal-Hanjani

Faculty, Staff and Student Publications

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions …

Genomic-Transcriptomic Evolution In Lung Cancer And Metastasis, Carlos Martínez-Ruiz, James R M Black, Clare Puttick, Mark S Hill, Jonas Demeulemeester, Elizabeth Larose Cadieux, Kerstin Thol, Thomas P Jones, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Paulina Prymas, Andrew Rowan, Sophia Ward, Laura Cubitt, Foteini Athanasopoulou, Oriol Pich, Takahiro Karasaki, David A Moore, Roberto Salgado, Emma Colliver, Carla Castignani, Michelle Dietzen, Ariana Huebner, Maise Al Bakir, Miljana Tanić, Thomas B K Watkins, Emilia L Lim, Ali M Al-Rashed, Danny Lang, James Clements, Daniel E Cook, Rachel Rosenthal, Gareth A Wilson, Alexander M Frankell, Sophie De Carné Trécesson, Philip East, Nnennaya Kanu, Kevin Litchfield, Nicolai J Birkbak, Allan Hackshaw, Stephan Beck, Peter Van Loo, Mariam Jamal-Hanjani, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression …

The Evolution Of Lung Cancer And Impact Of Subclonal Selection In Tracerx, Alexander M Frankell, Michelle Dietzen, Maise Al Bakir, Emilia L Lim, Takahiro Karasaki, Sophia Ward, Selvaraju Veeriah, Emma Colliver, Ariana Huebner, Abigail Bunkum, Mark S Hill, Kristiana Grigoriadis, David A Moore, James R M Black, Wing Kin Liu, Kerstin Thol, Oriol Pich, Thomas B K Watkins, Cristina Naceur-Lombardelli, Daniel E Cook, Roberto Salgado, Gareth A Wilson, Chris Bailey, Mihaela Angelova, Robert Bentham, Carlos Martínez-Ruiz, Christopher Abbosh, Andrew G Nicholson, John Le Quesne, Dhruva Biswas, Rachel Rosenthal, Clare Puttick, Sonya Hessey, Claudia Lee, Paulina Prymas, Antonia Toncheva, Jon Smith, Wei Xing, Jerome Nicod, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Kevin G Blyth, Dean A Fennell, Martin D Forster, Siow Ming Lee, Mary Falzon, Madeleine Hewish, Michael J Shackcloth, Eric Lim, Sarah Benafif, Peter Russell, Ekaterini Boleti, Matthew G Krebs, Jason F Lester, Dionysis Papadatos-Pastos, Tanya Ahmad, Ricky M Thakrar, David Lawrence, Neal Navani, Sam M Janes, Caroline Dive, Fiona H Blackhall, Yvonne Summers, Judith Cave, Teresa Marafioti, Javier Herrero, Sergio A Quezada, Karl S Peggs, Roland F Schwarz, Peter Van Loo, Daniël M Miedema, Nicolai J Birkbak, Crispin T Hiley, Allan Hackshaw, Simone Zaccaria, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) …

Treatment Outcomes For Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study Of The Impact Of Immunosuppression On Pulmonary Function Trajectory, Scott M Matson, Misbah Baqir, Teng Moua, Michael Marll, Jessica Kent, Nicholas S Iannazzo, Ryan D Boente, John M Donatelli, Junqiang Dai, Francisco J Diaz, M Kristen Demoruelle, Mark B Hamblin, Susan K Mathai, Jay H Ryu, Kristen Pope, Christopher M Walker, Joyce S Lee

Faculty, Staff and Student Publications

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice.

RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD?

STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear …

Prospective, Early Longitudinal Assessment Of Lymphedema-Related Quality Of Life Among Patients With Locally Advanced Breast Cancer: The Foundation For Building A Patient-Centered Screening Program, Anusha Gandhi, Tianlin Xu, Sarah M Desnyder, Grace L Smith, Ruitao Lin, Carlos H Barcenas, Michael C Stauder, Karen E Hoffman, Eric A Strom, Susan Ferguson, Benjamin D Smith, Wendy A Woodward, George H Perkins, Melissa P Mitchell, Desmond Garner, Chelain R Goodman, Melissa Aldrich, Marigold Travis, Susan Lilly, Isabelle Bedrosian, Simona F Shaitelman

Faculty, Staff and Student Publications

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs.

METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models.

RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having …

Quantification Of The Role Of Lead Foil In Flattening Filter Free Beam Reference Dosimetry, Song Gao, Christopher Nelson, Congjun Wang, Vindu Kathriarachchi, Michael Choi, Rishik Saxena, Robin Kendall, Peter Balter

Faculty, Staff and Student Publications

PURPOSE: To quantify the potential error in outputs for flattening filter free (FFF) beams associated with use of a lead foil in beam quality determination per the addendum protocol for TG-51, we examined differences in measurements of the beam quality conversion factor k

METHODS: Two FFF beams, a 6 MV FFF and a 10 MV FFF, were calibrated on eight Varian TrueBeams and two Elekta Versa HD linear accelerators (linacs) according to the TG-51 addendum protocol by using Farmer ionization chambers [TN 30013 (PTW) and SNC600c (Sun Nuclear)] with traceable absorbed dose-to-water calibrations. In determining k

RESULTS: Differences in %dd(10)x …

Model-Constrained Reconstruction Accelerated With Fourier-Based Undersampling For Hyperpolarized [1-13c] Pyruvate Imaging, Zhan Xu, Keith A Michel, Christopher M Walker, Collin J Harlan, Gary V Martinez, Jeremy W Gordon, Hsin-Yu Chen, Daniel B Vigneron, James A Bankson

Faculty, Staff and Student Publications

PURPOSE: Model-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-

METHODS: The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity …

Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam

Faculty, Staff and Student Publications

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein …

Causal Effects On Complex Traits Are Similar For Common Variants Across Segments Of Different Continental Ancestries Within Admixed Individuals, Kangcheng Hou, Yi Ding, Ziqi Xu, Yue Wu, Arjun Bhattacharya, Rachel Mester, Gillian M Belbin, Steve Buyske, David V Conti, Burcu F Darst, Myriam Fornage, Chris Gignoux, Xiuqing Guo, Christopher Haiman, Eimear E Kenny, Michelle Kim, Charles Kooperberg, Leslie Lange, Ani Manichaikul, Kari E North, Ulrike Peters, Laura J Rasmussen-Torvik, Stephen S Rich, Jerome I Rotter, Heather E Wheeler, Genevieve L Wojcik, Ying Zhou, Sriram Sankararaman, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods …

Consensus-Based Evaluation Of Outcome Measures In Pediatric Stroke Care: A Toolkit, Samantha J Feldman, Lauren A Beslow, Ryan J Felling, Laura A Malone, Michaela Waak, Stuart Fraser, Nihal Bakeer, Jo Ellen M Lee, Victoria Sherman, Melissa M Howard, Beth Anne Cavanaugh, Robyn Westmacott, Lori C Jordan

Faculty, Staff and Student Publications

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, …

The Risk Of Hepatocellular Carcinoma In Entecavir Versus Tenofovir Treated Us Cohort With Chronic Hepatitis B Virus, Jennifer R Kramer, Peter A Richardson, Hyunseok Kim, Yao-Chun Hsu, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

The comparative effectiveness of tenofovir (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al. initially suggested lower than expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups, and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF⁴. Most of these studies examined Asian patients from Korea, Taiwan, …

Machine Learning And Health Care: Potential Benefits And Issues, J Graham Atkinson, Elizabeth G Atkinson

Faculty, Staff and Students Publications

We discuss the potential for machine learning (ML) and artificial intelligence (AI) to improve health care, while detailing caveats and important considerations to ensure unbiased and equitable implementation. If disparities exist in the data used to train ML algorithms, they must be recognized and accounted for, so they do not bias performance accuracy or are not interpreted by the algorithm as simply a lack of need. We pay particular attention to an area in which bias in data composition is particularly striking, that is in large-scale genetics databases, as people of European descent are vastly overrepresented in the existing resources.

In-Hospital Mortality Risk Stratification In Children Aged Under 5 Years With Pneumonia With Or Without Pulse Oximetry: A Secondary Analysis Of The Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Dataset, Shubhada Hooli, Carina King, Eric D Mccollum, Tim Colbourn, Norman Lufesi, Charles Mwansambo, Christopher J Gregory, Somsak Thamthitiwat, Clare Cutland, Shabir Ahmed Madhi, Marta C Nunes, Bradford D Gessner, Tabish Hazir, Joseph L Mathew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Syed Ma Zaman, Raul O Ruvinsky, Marilla Lucero, Cissy B Kartasasmita, Claudia Turner, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Sudha Basnet, Tor A Strand, Mark I Neuman, Luis Martinez Arroyo, Marcela Echavarria, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Angela Gentile, Mandeep Chadha, Siddhivinayak Hirve, Kerry-Ann F O'Grady, Alexey W Clara, Chris A Rees, Harry Campbell, Harish Nair, Jennifer Falconer, Linda J Williams, Margaret Horne, Shamim A Qazi, Yasir Bin Nisar, Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Study Group

Faculty, Staff and Students Publications

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.

METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.

RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five …

Commentary: Atrial Fibrillation: Surgeons Can Do More Than Operate, Lauren Barron, Marc R Moon

Faculty, Staff and Students Publications

No abstract provided.

Therapeutic Plasma Exchange Is Associated With Improved Major Adverse Kidney Events In Children And Young Adults With Thrombocytopenia At The Time Of Continuous Kidney Replacement Therapy Initiation, Dana Y Fuhrman, Sameer Thadani, Claire Hanson, Joseph A Carcillo, John A Kellum, Hyun Jung Park, Liling Lu, Nahmah Kim-Campbell, Christopher M Horvat, Ayse Akcan Arikan

Faculty, Staff and Students Publications

Therapeutic plasma exchange (TPE) has been shown to improve organ dysfunction and survival in patients with thrombotic microangiopathy and thrombocytopenia associated with multiple organ failure. There are no known therapies for the prevention of major adverse kidney events after continuous kidney replacement therapy (CKRT). The primary objective of this study was to evaluate the effect of TPE on the rate of adverse kidney events in children and young adults with thrombocytopenia at the time of CKRT initiation.

DESIGN: Retrospective cohort.

SETTING: Two large quaternary care pediatric hospitals.

PATIENTS: All patients less than or equal to 26 years old who received …

Efficacy And Safety Of Lumasiran For Infants And Young Children With Primary Hyperoxaluria Type 1: 12-Month Analysis Of The Phase 3 Illuminate-B Trial, Wesley Hayes, David J Sas, Daniella Magen, Hadas Shasha-Lavsky, Mini Michael, Anne-Laure Sellier-Leclerc, Julien Hogan, Taylor Ngo, Marianne T Sweetser, John M Gansner, Tracy L Mcgregor, Yaacov Frishberg

Faculty, Staff and Students Publications

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here.

METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months).

RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, …

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …

Telemental Health In Emergency Care Settings: A Qualitative Analysis Of Considerations For Sustainability And Spread, Mckenzie K Roddy, Patricia Chen, Alvin D Jeffery, Jeydith Gutierrez, Melissa Rubenstein, Corey Campbell, Eric Blake, Michael J Ward

Faculty, Staff and Students Publications

Objectives: Following rapid uptake of telehealth during the COVID-19 pandemic, we examined barriers and facilitators for sustainability and spread of telemental health video (TMH-V) as policies regarding precautions from the pandemic waned.

Methods: We conducted a qualitative study using semistructured interviews and observations guided by RE-AIM. We asked four groups, local clinicians, facility leadership, Veterans, and external partners, about barriers and facilitators impacting patient willingness to engage in TMH-V (reach), quality of care (effectiveness), barriers and facilitators impacting provider uptake (adoption), possible adaptations to TMH-V (implementation), and possibilities for long-term use of TMH-V (maintenance). Interviews were recorded, transcribed, and analyzed …

Advancing Diagnostic Equity Through Clinician Engagement, Community Partnerships, And Connected Care, Traber D Giardina, Lechauncy D Woodard, Hardeep Singh

Faculty, Staff and Students Publications

No abstract provided.

Quantifying The Number Of Us Men With Erectile Dysfunction Who Are Potential Candidates For Penile Prosthesis Implantation, Sirikan Rojanasarot, Abimbola O Williams, Natalie Edwards, Mohit Khera

Faculty, Staff and Students Publications

INTRODUCTION: Penile prosthesis implantation (PPI) is a treatment option recommended in clinical guidelines for erectile dysfunction (ED). However, a limited number of urologists perform PPI procedures in the United States.

AIM: To quantify the number of insured men with ED in the United States and project the number of potential candidates for PPI in 2022.

METHODS: An Excel-based disease impact model was constructed using a top-down estimation approach. The starting US male population consisted of adult men from 2022 US Census data after exclusion of age-specific mortality rates from the National Vital Statistics Reports. Men with health insurance were included …

Kinase Inhibitors And Atrial Fibrillation: Mechanisms Of Action And Clinical Implications, Adam S Potter, Mohit M Hulsurkar, Lingling Wu, Bharat Narasimhan, Kaveh Karimzad, Efstratios Koutroumpakis, Nicolas Palaskas, Anita Deswal, Bharat K Kantharia, Xander H T Wehrens

Faculty, Staff and Students Publications

Recent advances have significantly expanded the options of available therapeutics for cancer treatment, including novel targeted cancer therapies. Within this broad category of targeted therapies is the class of kinase inhibitors (KIs), which target kinases that have undergone aberrant activation in cancerous cells. Although KIs have shown a benefit in treating various forms of malignancy, they have also been shown to cause a wide array of cardiovascular toxicities, with cardiac arrhythmias, in particular atrial fibrillation (AF), being 1 of the predominant side effects. The occurrence of AF in patients undergoing cancer treatment can complicate the treatment approach and poses unique …

Pilot Clinical Trial Of Macimorelin To Assess Safety And Efficacy In Patients With Cancer Cachexia, Megan Herodes, Lindsey J Anderson, Samuel Shober, Ellen A Schur, Solomon A Graf, Nicola Ammer, Ramiro Salas, Marco Marcelli, Jose M Garcia

Faculty, Staff and Students Publications

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: …

Loss Of Neuron Navigator 2 Impairs Brain And Cerebellar Development, Andrea Accogli, Shenzhao Lu, Ilaria Musante, Paolo Scudieri, Jill A Rosenfeld, Mariasavina Severino, Simona Baldassari, Michele Iacomino, Antonella Riva, Ganna Balagura, Gianluca Piccolo, Carlo Minetti, Denis Roberto, Fan Xia, Razaali Razak, Emily Lawrence, Mohamed Hussein, Emmanuel Yih-Herng Chang, Michelle Holick, Elisa Calì, Emanuela Aliberto, Rosalba De-Sarro, Antonio Gambardella, Undiagnosed Diseases Network, Synaps Study Group, Lisa Emrick, Peter J A Mccaffery, Margaret Clagett-Dame, Paul C Marcogliese, Hugo J Bellen, Seema R Lalani, Federico Zara, Pasquale Striano, Vincenzo Salpietro

Faculty, Staff and Students Publications

Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In …

Association Of Coronary Artery Calcium Density And Volume With Predicted Atherosclerotic Cardiovascular Disease Risk And Cardiometabolic Risk Factors In South Asians: The Mediators Of Atherosclerosis In South Asians Living In America (Masala) Study, Mahmoud Al Rifai, Alka M Kanaya, Namratha R Kandula, Jaideep Patel, Mouaz H Al-Mallah, Matthew Budoff, Miguel Cainzos-Achirica, Michael H Criqui, Salim S Virani

Faculty, Staff and Students Publications

Background:

Individuals of South Asians (SA) ancestry are predisposed to higher risk of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) volume and density can identify coronary plaque characteristics unique to SA that may provide important prognostic information to identify high risk individuals beyond traditional CAC scores.

Methods:

We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA). CAC density and volume were calculated according to established protocols. ASCVD risk was estimated using the pooled cohort equations (PCE). Multivariable-adjusted linear regression models were used to study the association between the PCE and advanced CAC measures, …

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Construction Of Semi-Supervised Spatial Projections To Identify The Source Of Beta- And High Frequency Oscillations In Parkinson’S Disease, Luciano R F Branco, Ashwin Viswanathan, Arjun Tarakad, Nuri F Ince

Faculty, Staff and Students Publications

Traditional deep brain stimulation (DBS) treatment for Parkinson's disease (PD) targets the placement of DBS leads into subthalamic nucleus (STN). Extraction of neurobiomarkers from STN local field potential activity can be used for the optimization of DBS. Beta (12-30 Hz) and high frequency oscillations (200-450 Hz, HFO) of STN and their phase-amplitude coupling have been previously correlated with symptom severity in PD. The typical approach is to take bipolar derivations of electrode contacts in order to enhance recordings of local brain activity and suppress noise levels. This approach can often cancel the signals in correlated neighboring contacts and create ambiguity …

Approaching Object Acceleration Differentially Affects The Predictions Of Neuronal Collision Avoidance Models, Fabrizio Gabbiani, Thomas Preuss, Richard B Dewell

Faculty, Staff and Students Publications

The processing of visual information for collision avoidance has been investigated at the biophysical level in several model systems. In grasshoppers, the (so-called) [Formula: see text] model captures reasonably well the visual processing performed by an identified neuron called the lobular giant movement detector as it tracks approaching objects. Similar phenomenological models have been used to describe either the firing rate or the membrane potential of neurons responsible for visually guided collision avoidance in other animals. Specifically, in goldfish, the [Formula: see text] model has been proposed to describe the Mauthner cell, an identified neuron involved in startle escape responses. …

Intranasal Fentanyl And Discharge From The Emergency Department Among Children With Sickle Cell Disease And Vaso-Occlusive Pain: A Multicenter Pediatric Emergency Medicine Perspective, Chris A Rees, David C Brousseau, Fahd A Ahmad, Jonathan Bennett, Seema Bhatt, Amanda Bogie, Kathleen M Brown, T Charles Casper, Laura L Chapman, Corrie E Chumpitazi, Daniel M Cohen, Carlton Dampier, Angela M Ellison, Hartmut Grasemann, Dunia Hatabah, Robert W Hickey, Lewis L Hsu, Nitya Bakshi, Sara Leibovich, Prabhumallikarjun Patil, Elizabeth C Powell, Rachel Richards, Syana Sarnaik, Debra L Weiner, Claudia R Morris, Scd Arginine Study Group And Pecarn

Faculty, Staff and Students Publications

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included …