Medical Specialties Commons^™

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …

Current State And Future Directions Of Genomic Medicine In Aortic Dissection: A Path To Prevention And Personalized Care, Alana C Cecchi, Madeline Drake, Chrisanne Campos, Jake Howitt, Jonathan Medina, Scott M Damrauer, Sherene Shalhub, Dianna M Milewicz, Aortic Dissection Collaborative

Faculty, Staff and Student Publications

Aortic dissection confers high mortality and morbidity rates despite advances in treatment, impacts quality of life, and contributes immense burden to the healthcare system globally. Efforts to prevent aortic dissection through screening and management of modifiable risk factors and early detection of aneurysms should incorporate genomic information, as it is integral to stratifying risk. However, effective integration of genomic-guided risk assessment into clinical practice will require addressing implementation barriers that currently permeate our healthcare systems. The Aortic Dissection Collaborative was established to define aortic dissection research priorities through patient engagement. Using a collaborative patient-centered feedback model, our Genomic Medicine Working …

Value Of Measurable Residual Disease Monitoring In Patients With Acute Promyelocytic Leukemia In The Era Of Frontline ‘Chemotherapy-Free’ Therapy, Jorge M Ramos Perez, Keyur P Patel, Sanam Loghavi, Guillermo Garcia-Manero, Gautam Borthakur, Elias Jabbour, William Wierda, Sherry Pierce, Mark Brandt, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney D Dinardo, Nitin Jain, Musa Yilmaz, Nicholas Short, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Daniel Rivera, David Mccue, Hagop M Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t(15;17) and the resulting gene PML-RARA, used for measurable residual disease (MRD) monitoring. Despite highly effective therapy for APL, MRD monitoring practices are not fully established. We aimed to assess the value of MRD monitoring by RT-qPCR in patients with APL treated with ATRA and arsenic trioxide +/- GO. We reviewed 223 patients with APL treated with this regimen. RT-qPCR for PML-RARA was measured every 3 months, and at 12, 18, and 24 months after therapy. Seven patients relapsed. Time to relapse was 7.9-12.4 months in 6 patients, and …

A Multidisciplinary Approach And Consensus Statement To Establish Standards Of Care For Angelman Syndrome, Jessica Duis, Mark Nespeca, Jane Summers, Lynne Bird, Karen G C B Bindels-De Heus, M J Valstar, Marie-Claire Y De Wit, C Navis, Maartje Ten Hooven-Radstaake, Bianca M Van Iperen-Kolk, Susan Ernst, Melina Dendrinos, Terry Katz, Gloria Diaz-Medina, Akshat Katyayan, Srishti Nangia, Ronald Thibert, Daniel Glaze, Christopher Keary, Karine Pelc, Nicole Simon, Anjali Sadhwani, Helen Heussler, Anne Wheeler, Caroline Woeber, Margaret Deramus, Amy Thomas, Emily Kertcher, Lauren Devalk, Kristen Kalemeris, Kara Arps, Carol Baym, Nicole Harris, John P Gorham, Brenda L Bohnsack, Reid C Chambers, Sarah Harris, Henry G Chambers, Katherine Okoniewski, Elizabeth R Jalazo, Allyson Berent, Carlos A Bacino, Charles Williams, Anne Anderson

Duncan NRI Faculty and Staff Publications

Background: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a …

Continuous Thoracic Paravertebral Block To Treat Electrical Storm, Daryl I Smith, Sarah A Kralovic, Rafeek A Hegazy, Hai Tran

The Texas Heart Institute Journal

Continuous ganglion block is increasingly being used to help manage ventricular tachyarrhythmias. We present the cases of 2 patients in whom we used continuous left thoracic paravertebral block to achieve sympathetic denervation and improvement in drug-refractory ventricular tachyarrhythmias. Whether as destination therapy or bridging therapy, we conclude that the block is safe, improves patients' comfort, and is superior in several ways to stellate ganglion block and other single-injection techniques.

Radiation Doses In Patients Undergoing Computed Tomographic Coronary Artery Calcium Evaluation With A 64-Slice Scanner Versus A 256-Slice Scanner, Paul Madaj, Dong Li, Rine Nakanishi, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Rachael O'Rourke, Christian Hamilton-Craig, Manojna Nimmagadda, Nicholas Kim, Badiha Fatima, Christopher Dailing, Kashif Shaikh, Chandana Shekar, Ju Hwan Lee, Matthew J Budoff

The Texas Heart Institute Journal

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression.

The mean dose-length product was 21% lower in the study group than in …

Prognostic And Predictive Biomarkers In Patients With Coronavirus Disease 2019 Treated With Tocilizumab In A Randomized Controlled Trial, Jennifer Tom, Min Bao, Larry Tsai, Aditi Qamra, David Summers, Montserrat Carrasco-Triguero, Jacqueline Mcbride, Carrie M Rosenberger, Celia J F Lin, William Stubbings, Kevin G Blyth, Jordi Carratalà, Bruno François, Thomas Benfield, Derrick Haslem, Paolo Bonfanti, Cor H Van Der Leest, Nidhi Rohatgi, Lothar Wiese, Charles Edouard Luyt, Farrah Kheradmand, Ivan O Rosas, Fang Cai

Faculty, Staff and Students Publications

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia.

DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.

SETTING: Hospitals in North America and Europe.

PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care.

INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo.

MEASUREMENTS AND MAIN …

Evaluation Of Factors Underlying Sex-Based Disparities In Cardiovascular Care In Adults With Self-Reported Premature Atherosclerotic Cardiovascular Disease, Vardhmaan Jain, Mahmoud Al Rifai, Rodman Turpin, Hatice Nur Eken, Ankit Agrawal, Dhruv Mahtta, Zainab Samad, Stephanie Coulter, Fatima Rodriguez, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There are limited data regarding sex-based differences in physical and mental health domains and health care access in adults with premature atherosclerotic cardiovascular disease (ASCVD).

OBJECTIVE: To study the association of sex with physical and mental health domains as well as health care access-related factors among adults with self-reported premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of 748 090 adults aged 18 to 55 years in the Behavioral Risk Factor Surveillance System 2016 to 2019 in the US. Data were analyzed from June to July 2021.

EXPOSURES: Self-reported ASCVD, defined as having a history of coronary artery …

Identifying Causative Microorganisms In Left Ventricular Assist Device Infections As A Guide For Developing Bacteriophage Therapy, Ishan Kamat, Harveen Lamba, Casey Hines-Munson, Samuel Hudson, Kenneth Liao, Kenneth L Muldrew, Sabrina Green, Austen Terwilliger, Heidi B Kaplan, Robert F Ramig, Anthony Maresso, Barbara W Trautner

Faculty, Staff and Students Publications

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center.

MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains …

Clinical Opinion: The Diagnosis And Management Of Suspected Fetal Growth Restriction: An Evidence-Based Approach, Christoph C Lees, Roberto Romero, Tamara Stampalija, Andrea Dall'asta, Greggory A Devore, Federico Prefumo, Tiziana Frusca, Gerard H A Visser, John C Hobbins, Ahmet A Baschat, Caterina M Bilardo, Henry L Galan, Stuart Campbell, Dev Maulik, Francesc Figueras, Wesley Lee, Julia Unterscheider, Herbert Valensise, Fabricio Da Silva Costa, Laurent J Salomon, Liona C Poon, Enrico Ferrazzi, Giancarlo Mari, Giuseppe Rizzo, John C Kingdom, Torvid Kiserud, Kurt Hecher

Faculty, Staff and Students Publications

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is …

Randomised Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain, Robert J Shulman, Bruno P Chumpitazi, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, Gregory L Kearns

Faculty, Staff and Students Publications

AIMS: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

METHODS: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, …

Design, Usability, And Acceptability Of A Needs-Based, Automated Dashboard To Provide Individualized Patient-Care Data To Pediatric Residents, Julia K W Yarahuan, Huay-Ying Lo, Lanessa Bass, Jeff Wright, Lauren M Hess

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Pediatric residency programs are required by the Accreditation Council for Graduate Medical Education to provide residents with patient-care and quality metrics to facilitate self-identification of knowledge gaps to prioritize improvement efforts. Trainees are interested in receiving this data, but this is a largely unmet need. Our objectives were to (1) design and implement an automated dashboard providing individualized data to residents, and (2) examine the usability and acceptability of the dashboard among pediatric residents.

METHODS: We developed a dashboard containing individualized patient-care data for pediatric residents with emphasis on needs identified by residents and residency leadership. To …

Symptom Clusters, Physical Activity, And Quality Of Life: A Latent Class Analysis Of Children During Maintenance Therapy For Leukemia, Mary C Hooke, Michelle A Mathiason, Audrey Blommer, Jessica Hutter, Pauline Mitby, Olga Taylor, Michael E Scheurer, Alicia S Kunin-Batson, Wei Pan, Marilyn J Hockenberry

Faculty, Staff and Students Publications

BACKGROUND: Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL).

OBJECTIVES: This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL.

METHODS: Self-report of fatigue, sleep disturbance, and depression; QOL; and PA were measured at the beginning and end of maintenance in 42 children aged 3 to 18 years with ALL. Children were categorized into symptom cluster groups based …

Constipation In Patients With Symptoms Of Gastroparesis: Analysis Of Symptoms And Gastrointestinal Transit, Henry P Parkman, Emily Sharkey, Richard W Mccallum, William L Hasler, Kenneth L Koch, Irene Sarosiek, Thomas L Abell, Braden Kuo, Robert J Shulman, Madhusudan Grover, Gianrico Farrugia, Ron Schey, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Nih/Niddk Gastroparesis Consortium

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC).

METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper …

Effect Of Domperidone Therapy On Gastroparesis Symptoms: Results Of A Dynamic Cohort Study By Niddk Gastroparesis Consortium, Irene Sarosiek, Mark Van Natta, Henry P Parkman, Thomas Abell, Kenneth L Koch, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A Hamilton, Pankaj J Pasricha, Katherine P Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W Mccallum

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).

METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. …

Factors Associated With Penicillin Allergy Labels In Electronic Health Records Of Children In 2 Large Us Pediatric Primary Care Networks, Margaret G Taylor, Torsten Joerger, Yun Li, Michael E Scheurer, Michael E Russo, Jeffrey S Gerber, Debra L Palazzi

Faculty, Staff and Students Publications

IMPORTANCE: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.

OBJECTIVE: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, …

The Impact Of Response To Iron Therapy On Maternal And Neonatal Outcomes Among Pregnant Women With Anemia, Sarah E Detlefs, Michael D Jochum, Bahram Salmanian, Jennifer R Mckinney, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Anemia during pregnancy is associated with increased risks of preterm birth, preeclampsia, cesarean delivery, and maternal morbidity. The most prevalent modifiable cause of pregnancy-associated anemia is iron deficiency. However, it is still unclear whether iron therapy can reduce the risks of adverse outcomes in women with anemia.

OBJECTIVE: This study aimed to determine whether response to iron therapy among women with anemia is associated with a change in odds of adverse maternal and neonatal outcomes.

STUDY DESIGN: This was a population-based cohort study (2011-2019) using an institutional database composed of obstetrical patients from 2 delivery hospitals. Patients with adequate …

Cross-Roads For Meta-Analysis And Network Meta-Analysis Of H Pylori Therapy, David Y Graham, Ruben Hernaez, Theodore Rokkas

Faculty, Staff and Students Publications

Helicobacter pylori infections are responsible for tremendous morbidity and mortality worldwide, leading to efforts to eradicate the organism. However, the effectiveness of antimicrobial therapy has been undermined by the progressive development of antimicrobial resistance. Treatments and treatment guidelines have been based on traditional pairwise meta-analyses of randomized controlled trials. More recently, network meta-analyses have also been utilized in an attempt to provide useful information to the clinician regarding which therapies appear best and which to avoid as the least efficacious. However, both forms of meta-analysis have been undermined by the same problems including the poor quality of the clinical trials …

Clinical Exome Sequencing Data Reveal High Diagnostic Yields For Congenital Diaphragmatic Hernia Plus (Cdh+) And New Phenotypic Expansions Involving Cdh, Tiana M Scott, Ian M Campbell, Andres Hernandez-Garcia, Seema R Lalani, Pengfei Liu, Chad A Shaw, Jill A Rosenfeld, Daryl A Scott

Duncan NRI Faculty and Staff Publications

Background: Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that often co-occurs with non-hernia-related anomalies (CDH+). While copy number variant (CNV) analysis is often employed as a diagnostic test for CDH+, clinical exome sequencing (ES) has not been universally adopted.

Methods: We analysed a clinical database of ~12 000 test results to determine the diagnostic yields of ES in CDH+ and to identify new phenotypic expansions.

Results: Among the 76 cases with an indication of CDH+, a molecular diagnosis was made in 28 cases for a diagnostic yield of 37% (28/76). A provisional diagnosis was made in seven other …

Genetic Subtyping And Phenotypic Characterization Of The Immune Microenvironment And Myc/Bcl2 Double Expression Reveal Heterogeneity In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Li Wei, Xiaosheng Fang, Qingyan Au, Harry Nunns, Máté Nagy, Alexandar Tzankov, Feng Zhu, Carlo Visco, Govind Bhagat, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Xiaoping Sun, Xin Han, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, J Han Van Krieken, Miguel A Piris, Jane N Winter, Yong Li, Bing Xu, Maher Albitar, Hua You, Ken H Young

Faculty, Staff and Students Publications

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, cell-of-origin, or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double expression (DE) is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers.

EXPERIMENTAL DESIGN: We performed targeted next-generation sequencing; IHC for MYC, BCL2, and FN1; and fluorescent multiplex IHC for microenvironmental markers in a large cohort of …

A Call For An Integrated Approach To Improve Efficiency, Equity And Sustainability In Rare Disease Research In The United States, Meghan C Halley, Hadley Stevens Smith, Euan A Ashley, Aaron J Goldenberg, Holly K Tabor

Faculty, Staff and Students Publications

To build a more efficient, equitable, and sustainable approach to rare disease research in the United States, we must prioritize integrated research infrastructure and approaches that focus on understanding connections across rare diseases.

P16 Represses Dna Damage Repair Via A /Novel Ubiquitin-Dependent Signaling Cascade, David P Molkentine, Jessica M Molkentine, Kathleen A Bridges, David R Valdecanas, Annika Dhawan, Reshub Bahri, Andrew J Hefner, Manish Kumar, Liangpeng Yang, Mohamed Abdelhakiem, Phillip M Pifer, Vlad Sandulache, Aakash Sheth, Beth M Beadle, Howard D Thames, Kathryn A Mason, Curtis R Pickering, Raymond E Meyn, Heath D Skinner

Faculty, Staff and Students Publications

Squamous cell carcinoma driven by human papillomavirus (HPV) is more sensitive to DNA-damaging therapies than its HPV-negative counterpart. Here, we show that p16, the clinically used surrogate for HPV positivity, renders cells more sensitive to radiotherapy via a ubiquitin-dependent signaling pathway, linking high levels of this protein to increased activity of the transcription factor SP1, increased HUWE1 transcription, and degradation of ubiquitin-specific protease 7 (USP7) and TRIP12. Activation of this pathway in HPV-positive disease led to decreased homologous recombination and improved response to radiotherapy, a phenomenon that can be recapitulated in HPV-negative disease using USP7 inhibitors in clinical development. This …

Safety And Activity Of Pembrolizumab In Combination With Rituximab In Relapsed Or Refractory Follicular Lymphoma, Loretta J Nastoupil, Collin K Chin, Jason R Westin, Nathan H Fowler, Felipe Samaniego, Xiaoyun Cheng, Man Chun John Ma, Zhiqiang Wang, Fuliang Chu, Ly Dsouza, Chizobam Obi, Jennifer Mims, Lei Feng, Shouhao Zhou, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were …

Transitions Of Care: Completeness Of The Interoperability Data Standard For Communication From Home Health Care To Primary Care., Edgar Chou, Paulina S Sockolow

Department of Medicine Faculty Papers

Data sharing is necessary to address communication deficits along the transitions of care among community settings. Evidence-based practice supports home healthcare (HHC) patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. A small subset of patient data collected at HHC admission is mandated to be transmitted to primary care, predominantly by fax. Using qualitative analysis, we assessed completeness of the United States Core Data for Interoperability (USCDI) interoperability standard, as compared to the patient data collected by the primary care team (topics) and HHC (classes) during the initial visit; and …

Activation Of Ras/Mapk Pathway Confers Mcl-1 Mediated Acquired Resistance To Bcl-2 Inhibitor Venetoclax In Acute Myeloid Leukemia, Qi Zhang, Bridget Riley-Gillis, Lina Han, Yannan Jia, Alessia Lodi, Haijiao Zhang, Saravanan Ganesan, Rongqing Pan, Sergej N Konoplev, Shannon R Sweeney, Jeremy A Ryan, Yulia Jitkova, Kenneth Dunner, Shaun E Grosskurth, Priyanka Vijay, Sujana Ghosh, Charles Lu, Wencai Ma, Stephen Kurtz, Vivian R Ruvolo, Helen Ma, Connie C Weng, Cassandra L Ramage, Natalia Baran, Ce Shi, Tianyu Cai, Richard Eric Davis, Venkata L Battula, Yingchang Mi, Jing Wang, Courtney D Dinardo, Michael Andreeff, Jeffery W Tyner, Aaron Schimmer, Anthony Letai, Rose Ann Padua, Carlos E Bueso-Ramos, Stefano Tiziani, Joel Leverson, Relja Popovic, Marina Konopleva

Faculty, Staff and Student Publications

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity. In support of the importance …

The Influence Of Preoperative Dialysis On Survival After Continuous-Flow Left Ventricular Assist Device Implantation, Harveen K Lamba, Fadi I Musfee, Subhasis Chatterjee, Ajith P Nair, Andrew B Civitello, Leo Simpson, O H Frazier, George V Letsou

Faculty, Staff and Students Publications

OBJECTIVES: Dialysis is considered a contraindication to continuous-flow left ventricular assist device (CF-LVAD) implantation. We evaluated clinical outcomes and survival in carefully selected, low-risk patients with renal failure who required dialysis before CF-LVAD implantation.

METHODS: We extracted medical record data of patients who underwent CF-LVAD placement at our centre between 1 January 2006 and 31 August 2017, with 2 clinical scenarios: those who required long-term (>14 days) dialysis and those who required short-term (≤14 days) dialysis immediately before implantation. Demographic, clinical and intraoperative characteristics and survival outcomes were assessed.

RESULTS: Of 621 patients who underwent CF-LVAD implantation during the …

Mild Encephalitis/Encephalopathy With A Reversible Splenial Lesion Associated With Systemic Mycoplasma Pneumoniae Infection In North America: A Case Report, Nafee T Talukder, Ashlea Feezel, Jeremy E Lankford

Faculty, Staff and Student Publications

BACKGROUND: Mild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent.

CASE PRESENTATIONS: A 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, …

Syndecan-2 Regulates Pad2 To Exert Antifibrotic Effects On Ra-Ild Fibroblasts, Konstantin Tsoyi, Anthony J Esposito, Bo Sun, Ryan G Bowen, Kevin Xiong, Fernando Poli, Rafael Cardenas, Sarah G Chu, Xiaoliang Liang, Stefan W Ryter, Christine Beeton, Tracy J Doyle, Matthew J Robertson, Lindsay J Celada, Freddy Romero, Souheil Y El-Chemaly, Mark A Perrella, I-Cheng Ho, Ivan O Rosas

Faculty, Staff and Students Publications

Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix …

Applying Evidence-Based Intervention (Ebi) Mapping To Identify The Components And Logic Of Colorectal Cancer Screening Interventions, Jacob Szeszulski, Derek W Craig, Timothy J Walker, Maya Foster, Patricia Dolan Mullen, Maria E Fernandez

Faculty, Staff and Student Publications

Implementation of evidence-based interventions (EBIs) can help to increase colorectal cancer screening (CRCS). Potential users of CRCS EBIs are often unclear about the specific features, logic, and core elements of existing EBIs, making it challenging to use or adapt them. We used EBI Mapping, a systematic process developed from Intervention Mapping that identifies an EBI's components and logic, to characterize existing CRCS EBIs from the National Cancer Institute's Evidence-Based Cancer Control Programs website. The resulting information can facilitate intervention adoption, adaptation, and/or implementation. Two trained coders independently coded intervention materials to describe intervention components and logic (n = 20). We …

Differences In Psychosocial Constructs Among Elementary School Staff That Implement Physical Activity Programs: A Step In Designing Implementation Strategies, Jacob Szeszulski, Timothy J Walker, Michael C Robertson, Maria E Fernandez

Faculty, Staff and Student Publications

Multiple types of school staff members (e.g., classroom teachers, principals) are involved in implementing physical activity programs (e.g., classroom-based, gym), but factors specific to their job responsibilities may inhibit their ability to implement programming effectively. Thus, implementation strategies tailored by job type may be needed. We compare perceptions of behavioral constructs related to implementation of school-based physical activity programs, by job type, among school staff. School staff (n = 139), including principals/assistant principals (n = 21), physical education teachers (n = 41), and classroom teachers (n = 77), from elementary schools (n = 25), completed a cross-sectional survey measuring perceptions …