Medical Specialties Commons^™

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Identification Of Bradycardia Following Remdesivir Administration Through The Us Food And Drug Administration American College Of Medical Toxicology Covid-19 Toxic Pharmacovigilance Project, Jason M Devgun, Rongmei Zhang, Jeffrey Brent, Paul Wax, Keith Burkhart, Alison Meyn, Sharan Campleman, Stephanie Abston, Kim Aldy

Faculty, Staff and Student Publications

IMPORTANCE: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information.

OBJECTIVE: To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 …

Emergency Department Virtual Happy Hour: A Novel Approach To Peer Group Support During A Pandemic, Adeola A Kosoko, Shabana Walia, Ryan Huebinger

Faculty, Staff and Student Publications

Introduction Communities responded to the coronavirus disease 2019 (COVID-19) pandemic with mandatory social-distancing regulations. Pandemic and disaster research shows that social isolation can often cause negative emotions and medical provider burnout. The primary objective of this study was to create and evaluate a novel wellness program, the Happy Hour Wellness Initiative (HHWI), based on peer support group concepts to foster resilience for emergency healthcare providers in response to a novel disaster. Methods The study was performed at a large emergency department with physicians, advanced practice providers, and staff invited to attend weekly "virtual happy hour" sessions. Participants individually opted into …

Expression And Functions Of Transient Receptor Potential Channels In Liver Diseases, Wenhui Wang, Pengyu Liu, Yalin Zhang, Li Yan, Michael X Zhu, Jin Wang, Ye Yu

Faculty, Staff and Student Publications

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental …

Percutaneous Revascularization For The Treatment Of Refractory Digital Ischemia In Systemic Sclerosis, Lily A Romero-Karam, Kevin A Honan, Salman A Arain, Maureen D Mayes

Faculty, Staff and Student Publications

OBJECTIVE: The objective of this study is to explore the role of adjunctive percutaneous revascularization of the hand in the management of patients with systemic sclerosis-associated refractory digital ischemia.

METHODS: We present our initial experience of using percutaneous upper extremity interventions to treat patients with systemic sclerosis and symptomatic Raynaud's phenomenon who presented with either refractory digital ischemia or non-healing ulcers. We discuss patient characteristics, procedural findings, and short-term clinical outcomes of these interventions.

RESULTS: We performed 14 interventions in 6 patients with non-healing digital ulcers or refractory ischemia secondary to systemic sclerosis. Angioplasty was performed at or below the …

Association Of Frailty And The Expanded Operative Stress Score With Preoperative Acute Serious Conditions, Complications, And Mortality In Males Compared To Females: A Retrospective Observational Study, Qi Yan, Jeongsoo Kim, Daniel E Hall, Myrick C Shinall, Katherine Moll Reitz, Karyn B Stitzenberg, Lillian S Kao, Elizabeth L George, Ada Youk, Chen-Pin Wang, Jonathan C Silverstein, Elmer V Bernstam, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males.

SUMMARY BACKGROUND DATA: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1).

METHODS: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90-, and 180-day mortality.

RESULTS: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% …

Prospective Evaluation Of The Fungitell® (1-->3) Beta-D-Glucan Assay As A Diagnostic Tool For Invasive Fungal Disease In Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report From The Children’S Oncology Group, William R Otto, Christopher C Dvorak, Craig L K Boge, Luis Ostrosky-Zeichner, Adam J Esbenshade, Michael L Nieder, Sarah Alexander, William J Steinbach, Ha Dang, Doojduen Villaluna, Lu Chen, Micah Skeens, Theoklis E Zaoutis, Lillian Sung, Brian T Fisher

Faculty, Staff and Student Publications

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period.

METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at …

Assessment Of Symptom, Disability, And Financial Trajectories In Patients Hospitalized For Covid-19 At 6 Months, Andrew J Admon, Theodore J Iwashyna, Lee A Kamphuis, Stephanie J Gundel, Sarina K Sahetya, Ithan D Peltan, Steven Y Chang, Jin H Han, Kelly C Vranas, Kirby P Mayer, Aluko A Hope, Sarah E Jolley, Ellen Caldwell, Max L Monahan, Katrina Hauschildt, Samuel M Brown, Neil R Aggarwal, B Taylor Thompson, Catherine L Hough

Faculty, Staff and Student Publications

IMPORTANCE: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited.

OBJECTIVE: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization.

DESIGN, SETTING, AND PARTICIPANTS: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization …

Child Opportunity Index And Hospital Utilization In Children With Traumatic Brain Injury Admitted To The Picu, Monica M. Gray, Kurt C. Stange, Elaine A. Borawski, Steven L. Shein, Katherine N. Slain

Faculty Scholarship

IMPORTANCE: The need to understand how Community-based disparities impact morbidity and mortality in pediatric critical illness, such as traumatic brain injury. Test the hypothesis that ZIP code-based disparities in hospital utilization, including length of stay (LOS) and hospital costs, exist in a cohort of children with traumatic brain injury (TBI) admitted to a PICU using the Child Opportunity Index (COI). DESIGN: Multicenter retrospective cohort study. SETTING: Pediatric Health Information System (PHIS) database. PATIENTS: Children 0-18 years old admitted to a PHIS hospital with a diagnosis of TBI from January 2016 to December 2020 requiring PICU care. To identify the most …

Effects Of Subnormothermic Regulated Hepatic Reperfusion On Mitochondrial And Transcriptomic Profiles In A Porcine Model, Joohyun Kim, Michael A Zimmerman, Woo Young Shin, Brent T Boettcher, Ju-Seog Lee, Jong-In Park, Muhammed Ali, Meiying Yang, Jyotsna Mishra, Catherine E Hagen, Joseph E Mcgraw, Angela Mathison, Harvey J Woehlck, Gwen Lomberk, Amadou K S Camara, Raul A Urrutia, David F Stowe, Johnny C Hong

Faculty, Staff and Student Publications

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model.

SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation.

METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), …

Profiling Human Pathogenic Repeat Expansion Regions By Synergistic And Multi-Level Impacts On Molecular Connections, Cong Fan, Ken Chen, Yukai Wang, Edward V Ball, Peter D Stenson, Matthew Mort, Albino Bacolla, Hildegard Kehrer-Sawatzki, John A Tainer, David N Cooper, Huiying Zhao

Faculty, Staff and Student Publications

Whilst DNA repeat expansions cause numerous heritable human disorders, their origins and underlying pathological mechanisms are often unclear. We collated a dataset comprising 224 human repeat expansions encompassing 203 different genes, and performed a systematic analysis with respect to key topological features at the DNA, RNA and protein levels. Comparison with controls without known pathogenicity and genomic regions lacking repeats, allowed the construction of the first tool to discriminate repeat regions harboring pathogenic repeat expansions (DPREx). At the DNA level, pathogenic repeat expansions exhibited stronger signals for DNA regulatory factors (e.g. H3K4me3, transcription factor-binding sites) in exons, promoters, 5'UTRs and …

Fucosylation Of Hla-Drb1 Regulates Cd4+ T Cell-Mediated Anti-Melanoma Immunity And Enhances Immunotherapy Efficacy, Daniel K Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B Williamson, Dennie T Frederick, Tatyana Sharova, Michael G White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan Mccarthy, Carlos Moransegura, Jane Messina, Kerry L Thomas, Lancia Darville, Victoria Izumi, John M Koomen, Shari A Pilon-Thomas, Brian Ruffell, Vincent C Luca, Robert S Haltiwanger, Xuefeng Wang, Jennifer A Wargo, Genevieve M Boland, Eric K Lau

Faculty, Staff and Student Publications

Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of l-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance …

A 24-Month Updated Analysis Of The Comparative Effectiveness Of Zuma-5 (Axi-Cel) Vs Scholar-5 External Control In Relapsed/Refractory Follicular Lymphoma, M Lia Palomba, Paola Ghione, Anik R Patel, Myrna Nahas, Sara Beygi, Anthony J Hatswell, Steve Kanters, Eve H Limbrick-Oldfield, Sally W Wade, Markqayne D Ray, Jessica Owen, Sattva S Neelapu, John Gribben, John Radford, Sabela Bobillo

Faculty, Staff and Student Publications

Background: In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data.

Research design and methods: The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response …

Disrupted White Matter Microstructure Correlates With Impulsivity In Children And Adolescents With Bipolar Disorder, Tianjia Zhu, Alessio Simonetti, Minhui Ouyang, Sherin Kurian, Johanna Saxena, Jair C Soares, Kirti Saxena, Hao Huang

Faculty, Staff and Student Publications

Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including …

Retrospective Review Of 80 Patients With Chronic Recurrent Multifocal Osteomyelitis Evaluated By Pediatric Orthopaedic Surgeons, Tristen Noble Taylor, Callie Shawhan Bridges, Ekene Uchenna Ezeokoli, Tyler Scott Smith, Nicole Irene Montgomery

Faculty, Staff and Students Publications

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare aseptic autoinflammatory disease with a wide and vague clinical presentation that often mimics infection, malignancy, or benign conditions, leading to a delayed diagnosis. We aimed to evaluate the clinical characteristics, differential diagnoses from evaluating pediatric orthopaedic surgeons, and compared the number of patients that could have avoided a biopsy in 80 patients with CRMO.

Methods: Children diagnosed with CRMO at a single tertiary pediatric hospital in the United States between 2012 and 2022 who were evaluated by a pediatric orthopaedic surgeon were retrospectively reviewed. The differential diagnoses from the surgeons were …

Characterizing Mechanism-Based Pain Phenotypes In Patients With Chronic Pancreatitis: A Cross-Sectional Analysis Of The Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies, Jami L Saloman, Darwin L Conwell, Evan Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Anna Evans Phillips, Mark Topazian, Stephen K Van Den Eeden, Jose Serrano, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N …

Multiple Sclerosis And Neuromyelitis Optica Spectrum Disorder: Onset Following Acute Covid-19 Infection, A Case Series, Mirla Avila, Yuanyuan Tan, Roberto Hernandez, Hafsa Zuberi, Victor M Rivera

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Acute COVID-19 infection has been associated with neurological involvement. We report a case series of newly diagnosed patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) developed in a short period of time after acute COVID-19 infection.

METHODS: New MS patients developing initial symptoms shortly after an acute COVID-19 infection were diagnosed based on the 2017 McDonald Criteria [Garcia-Ramos et al. in Cells, 2021]. The patients diagnosed with NMOSD met the 2015 International Panel criteria for the diagnosis of NMOSD (IPDN) [Thompson et al. in Lancet Neurol 17:162-173, 2018].

RESULTS FROM THE MS PATIENT GROUP: …

Functional And Clinical Studies Reveal Pathophysiological Complexity Of Clcn4-Related Neurodevelopmental Condition, Elizabeth E Palmer, Michael Pusch, Alessandra Picollo, Caitlin Forwood, Matthew H Nguyen, Vanessa Suckow, Jessica Gibbons, Alva Hoff, Lisa Sigfrid, Andre Megarbane, Mathilde Nizon, Benjamin Cogné, Claire Beneteau, Fowzan S Alkuraya, Aziza Chedrawi, Mais O Hashem, Hannah Stamberger, Sarah Weckhuysen, Arnaud Vanlander, Berten Ceulemans, Sulekha Rajagopalan, Kenneth Nunn, Stéphanie Arpin, Martine Raynaud, Constance S Motter, Catherine Ward-Melver, Katrien Janssens, Marije Meuwissen, Diane Beysen, Nicola Dikow, Mona Grimmel, Tobias B Haack, Emma Clement, Amy Mctague, David Hunt, Sharron Townshend, Michelle Ward, Linda J Richards, Cas Simons, Gregory Costain, Lucie Dupuis, Roberto Mendoza-Londono, Tracy Dudding-Byth, Jackie Boyle, Carol Saunders, Emily Fleming, Salima El Chehadeh, Marie-Aude Spitz, Amelie Piton, Bénédicte Gerard, Marie-Thérèse Abi Warde, Gillian Rea, Caoimhe Mckenna, Sofia Douzgou, Siddharth Banka, Cigdem Akman, Jennifer M Bain, Tristan T Sands, Golder N Wilson, Erin J Silvertooth, Lauren Miller, Damien Lederer, Rani Sachdev, Rebecca Macintosh, Olivier Monestier, Deniz Karadurmus, Felicity Collins, Melissa Carter, Luis Rohena, Marjolein H Willemsen, Charlotte W Ockeloen, Rolph Pfundt, Sanne D Kroft, Michael Field, Francisco E R Laranjeira, Ana M Fortuna, Ana R Soares, Vincent Michaud, Sophie Naudion, Sailaja Golla, David D Weaver, Lynne M Bird, Jennifer Friedman, Virginia Clowes, Shelagh Joss, Laura Pölsler, Philippe M Campeau, Maria Blazo, Emilia K Bijlsma, Jill A Rosenfeld, Christian Beetz, Zöe Powis, Kirsty Mcwalter, Tracy Brandt, Erin Torti, Mikaël Mathot, Shekeeb S Mohammad, Ruth Armstrong, Vera M Kalscheuer

Faculty, Staff and Students Publications

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on …

Fecal Elastase In Preterm Infants To Predict Growth Outcomes, Lindsay F Holzapfel, Amy B Hair, Geoffrey A Preidis, Tripti Halder, Heeju Yang, Jana P Unger, Steven Freedman, Camilia R Martin

Faculty, Staff and Student Publications

OBJECTIVES: Preterm infants are born functionally pancreatic insufficient with decreased pancreatic production of lipase and proteases. Developmental pancreatic insufficiency (PI) may contribute to reduced nutrient absorption and growth failure. We sought to determine longitudinal fecal elastase (ELA1) levels in a cohort of preterm infants and whether levels are associated with growth outcomes.

METHODS: Prospective observational study of 30 infants 24-34 weeks gestational age and birth weight ≤1250 g fed the exclusive human milk diet, consisting of human milk with human milk-based fortifier. ELA1 was quantified by ELISA during the first 2 weeks of life [Early; 7.5 ± 1.8 days of …

Relief Of Malignant Gastric Outlet Obstruction With Lumen-Apposing Metallic Stent-Assisted Percutaneous Endoscopic Gastrostomy Tube After Roux-En-Y Gastric Bypass, Scott N Berger, Juan D Gomez Cifuentes, Tara Keihanian, Wasif M Abidi, Kalpesh K Patel

Faculty, Staff and Students Publications

No abstract provided.

Design And Characterization Of An Aerosol Test Chamber For Emergency Response Patient Contamination Control Simulation And Research, Megan L. Steele, Emily M. Spatz, George P. Lemmer, Jacob M. Denney, Casey Cooper, Jeremy M. Slagley, Robert M. Eninger

Faculty Publications

Contaminated or infected patients present a risk of cross-contamination for emergency responders, attending medical personnel and medical facilities as they enter a treatment facility. The controlled conditions of an aerosol test chamber are required to examine factors of contamination, decontamination, and cross-contamination. This study presents the design, construction, and a method for characterizing an aerosol test chamber for a full-sized manikin on a standard North Atlantic Treaty Organization litter. The methodology combined air velocity measurements, aerosol particle counts and size distributions, and computational fluid dynamics modeling to describe the chamber’s performance in three dimensions. This detailed characterization facilitates future experimental …

Sox17: A Highly Sensitive And Specific Immunomarker For Ovarian And Endometrial Carcinomas, Xudong Zhang, Jun Yao, Na Niu, Xiaoran Li, Yan Liu, Lei Huo, Elizabeth D Euscher, Huamin Wang, Diana Bell, Anil K Sood, Guoliang Wang, Barrett C Lawson, Preetha Ramalingam, Anais Malpica, Aysegul A Sahin, Qingqing Ding, Jinsong Liu

Faculty, Staff and Student Publications

PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 …

Erratum: "Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment", Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada

Faculty, Staff and Student Publications

No abstract provided.

Hematopoietic Cell Transplantation In The Management Of Myelodysplastic Syndrome: An Evidence-Based Review From The American Society For Transplantation And Cellular Therapy Committee On Practice Guidelines, Zachariah Defilipp, Stefan O Ciurea, Corey Cutler, Marie Robin, Erica D Warlick, Ryotaro Nakamura, Andrew M Brunner, Bhagirathbhai Dholaria, Alison R Walker, Nicolaus Kröger, Nelli Bejanyan, Ehab Atallah, Roni Tamari, Melhem M Solh, Mary-Elizabeth Percival, Marcos De Lima, Bart Scott, Betul Oran, Guillermo Garcia-Manero, Mehdi Hamadani, Paul Carpenter, Amy E Dezern

Faculty, Staff and Student Publications

The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS …

Structural Valve Deterioration After Self-Expanding Transcatheter Or Surgical Aortic Valve Implantation In Patients At Intermediate Or High Risk., Daniel O'Hair, Steven J Yakubov, Kendra J Grubb, Jae K Oh, Saki Ito, G Michael Deeb, Nicolas M Van Mieghem, David H Adams, Tanvir Bajwa, Neal S Kleiman, Stanley Chetcuti, Lars Søndergaard, Hemal Gada, Mubashir Mumtaz, John Heiser, William M Merhi, George Petrossian, Newell Robinson, Gilbert H L Tang, Joshua D Rovin, Stephen H Little, Renuka Jain, Sarah Verdoliva, Tim Hanson, Shuzhen Li, Jeffrey J Popma, Michael J Reardon

Heart and Vascular Articles

IMPORTANCE: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood.

OBJECTIVE: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

A Complete Methyl-Lysine Binding Aromatic Cage Constructed By Two Domains Of Phf2, John R Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T Bedford, Xiaodong Cheng

Faculty, Staff and Student Publications

The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR2TK4) and VRK1 (PR2VK4) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (KD values) of 160 nM and 42 nM, …

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …