Medical Specialties Commons^™

Estrogen/Progesterone Receptor And Her2 Discordance Between Primary Tumor And Brain Metastases In Breast Cancer And Its Effect On Treatment And Survival, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).

METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the …

The Vaso-Occlusive Pain Crisis In Sickle Cell Disease: Definition, Pathophysiology, And Management., Deepika S. Darbari, Vivien A. Sheehan, Samir K. Ballas

Cardeza Foundation for Hematologic Research

Early diagnosis, treatment, and prevention of a vaso-occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC-associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L-glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late-stage clinical development in both the United States and the European Union. The development of agents …

Associations Between High-Density Lipoprotein Particles And Ischemic Events By Vascular Domain, Sex, And Ethnicity: A Pooled Cohort Analysis, Kavisha Singh, Alvin Chandra, Thomas Sperry, Parag H. Joshi, Amit Khera, Salim S. Virani, Christie M. Ballantyne, James D. Otvos, Robin P F. Dullaart, Eke G. Gruppen

Office of the Provost

Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C.
Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA …

Ewing Sarcoma Family Of Tumors-Derived Small Extracellular Vesicle Proteomics Identify Potential Clinical Biomarkers., Glenson Samuel, Jennifer Crow, Jon B. Klein, Michael L. Merchant, Emily Nissen, Devin C. Koestler, Kris Laurence, Xiaobo Liang, Kathleen Neville, Vincent S. Staggs, Atif Ahmed, Safinur Atay, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs).

Materials and methods: We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and …

The Landscape Of Rna Polymerase Ii-Associated Chromatin Interactions In Prostate Cancer, Susmita G Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou Bk Lambros, Kathleen E Houlahan, Suzanne Carreira, Wei Yuan, Guemhee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V Raj, Chao Xing, Paul C Boutros, Johann De Bono, Michael Q Zhang, Ram S Mani

College of Science & Mathematics Departmental Research

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing …

Myocardial Infarction Can Be Safely Excluded By High-Sensitivity Troponin I Testing 3 Hours After Emergency Department Presentation., W Frank Peacock, Robert Christenson, Deborah B Diercks, Christian Fromm, Gary F Headden, Christopher J Hogan, Erik B Kulstad, Frank Lovecchio, Richard M Nowak, Jon W Schrock, Adam J Singer, Alan B Storrow, Joely Straseski, Alan H B Wu, Daniel P Zelinski

Heart and Vascular Articles

BACKGROUND: The accuracy and speed by which acute myocardial infarction (AMI) is excluded are an important determinant of emergency department (ED) length of stay and resource utilization. While high-sensitivity troponin I (hsTnI) >99th percentile (upper reference level [URL]) represents a "rule-in" cutpoint, our purpose was to evaluate the ability of the Beckman Coulter hsTnI assay, using various level-of-quantification (LoQ) cutpoints, to rule out AMI within 3 hours of ED presentation in suspected acute coronary syndrome (ACS) patients.

METHODS: This multicenter evaluation enrolled adults with >5 minutes of ACS symptoms and an electrocardiogram obtained per standard care. Exclusions were ST-segment elevation …

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

Aav-Crispr Gene Editing Is Negated By Pre-Existing Immunity To Cas9, Ang Li, Mark R Tanner, Ciaran M Lee, Ayrea E Hurley, Marco De Giorgi, Kelsey E Jarrett, Timothy H Davis, Alexandria M Doerfler, Gang Bao, Christine Beeton, William R Lagor

Faculty, Staff and Students Publications

Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by …

Postnatal Loss Of The Insulin Receptor In Osteoprogenitor Cells Does Not Impart A Metabolic Phenotype, John L. Fowlkes, R. Clay Bunn, Evangelia Kalaitzoglou, Phil Ray, Iuliana Popescu, Kathryn M. Thrailkill

Barnstable Brown Diabetes Center Faculty Publications

The relationship between osteoblast-specific insulin signaling, osteocalcin activation and gluco-metabolic homeostasis has proven to be complex and potentially inconsistent across animal-model systems and in humans. Moreover, the impact of postnatally acquired, osteoblast-specific insulin deficiency on the pancreas-to-skeleton-to-pancreas circuit has not been studied. To explore this relationship, we created a model of postnatal elimination of insulin signaling in osteoprogenitors. Osteoprogenitor-selective ablation of the insulin receptor was induced after ~10 weeks of age in IR^l°^x/lox/Osx-Cre^+/− genotypic male and female mice (designated postnatal-OIRKO). At ~21 weeks of age, mice were then phenotypically and metabolically characterized. Postnatal-OIRKO mice demonstrated …

Discovery Of A Bacterial Peptide As A Modulator Of Glp-1 And Metabolic Disease, Catherine Tomaro-Duchesneau, Stephanie L Levalley, Daniel Roeth, Liang Sun, Frank T Horrigan, Markus Kalkum, Joseph M Hyser, Robert A Britton

Faculty, Staff and Students Publications

Early work in rodents highlighted the gut microbiota's importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1), an incretin secreted by L-cells lining the gastrointestinal epithelium, has important functions: promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to identify microbial strains with GLP-1 stimulatory activity as potential metabolic disease therapeutics. Over 1500 human-derived strains were isolated from healthy individuals and screened for GLP-1 modulation by incubating bacterial cell-free supernatants with NCI H716 L-cells. Approximately 45 strains capable of increasing GLP-1 were discovered. All GLP-1 positive …

Circulating Leptin Levels Are Associated With Adiposity In Survivors Of Childhood Brain Tumors., E Danielle Sims, William J. Jennings, Brianna Empringham, Adam Fleming, Carol Portwine, Donna L. Johnston, Shayna M. Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of …

The Role Of Noninvasive Tests For Differentiating Nash From Nafl And Diagnosing Advanced Fibrosis Among Patients With Nafld, Maya Balakrishnan, Rohit Loomba

Faculty, Staff and Students Publications

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used …

Proteome Alterations In Pancreatic Ductal Adenocarcinoma, Sheng Pan, Teresa A Brentnall, Ru Chen

Faculty, Staff and Students Publications

Proteins are the essential functional biomolecules profoundly implicated in all aspects of pancreatic tumorigenesis and its progression. While common genomic factors, such as KRAS, TP53, SMAD4, and CDKN2A have been well recognized in association of pancreatic ductal adenocarcinoma (PDAC), our understanding of functional changes at the proteome level merits further investigation. Malignance associated proteome alterations can be attributed to the convoluted outcomes from genetic, epigenetic and environmental factors in initiating and progressing PDAC, and may reflect on changes in protein expressional level, structure, localization, as well as post-translational modifications (PTMs) status. The study of localized or systemic proteome alterations in …

Significance Of Blood And Cerebrospinal Fluid Biomarkers For Alzheimer's Disease: Sensitivity, Specificity And Potential For Clinical Use, C. D'Abramo, L. D'Adamio, L. Giliberto

Journal Articles

No abstract provided.

Aml Risk Stratification Models Utilizing Eln-2017 Guidelines And Additional Prognostic Factors: A Swog Report., Era L Pogosova-Agadjanyan, Anna Moseley, Megan Othus, Frederick R Appelbaum, Thomas R Chauncey, I-Ming L Chen, Harry P Erba, John E Godwin, Isaac C Jenkins, Min Fang, Mike Huynh, Kenneth J Kopecky, Alan F List, Jasmine Naru, Jerald P Radich, Emily Stevens, Brooke E Willborg, Cheryl L Willman, Brent L Wood, Qing Zhang, Soheil Meshinchi, Derek L Stirewalt

Articles, Abstracts, and Reports

Background: The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice.

Methods: In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort,

Results: Models …

Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini

Open Access Theses & Dissertations

Chagas disease (ChD) is a neglected tropical disease (NTD) caused by the protozoan parasite, Trypanosoma cruzi. It is transmitted by the insect-vector triatomine (popular known as kissing bug), blood transfusion, organ transplantation, congenitally, and contaminated foods and juices. T. cruzi has evolved several strategies to invade the host cells, including the release extracellular vesicles (EVs), which assist pathogen survival and its replication within the host. T. cruzi is covered with highly glycosylated surface molecules such as glycoproteins and glycolipids, which are shown to be involved in the interaction with host immune cells. These molecules are highly immunogenic and reactive with …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

Potential Roles Of Extracellular Vesicles In The Pathophysiology, Diagnosis, And Treatment Of Autoimmune Diseases., Jing Tian, Giacomo Casella, Yuan Zhang, Abdolmohamad Rostami, Xing Li

Department of Neurology Faculty Papers

Since extracellular vesicles (EVs) were discovered in 1983 in sheep reticulocytes samples, they have gradually attracted scientific attention and become a topic of great interest in the life sciences field. EVs are small membrane particles, released by virtually every cell that carries a variety of functional molecules. Their main function is to deliver messages to the surrounding area in both physiological and pathological conditions. Initially, they were thought to be either cell debris, signs of cell death, or unspecific structures. However, accumulating evidence support a theory that EVs are a universal mechanism of communication. Thanks to their biological characteristics and …

Enhancing The Identification Of Rheumatoid Arthritis-Associated Lung Disease, Bryant England

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic autoimmune disease that predisposes afflicted individuals to reduced quality of life, physical disability, and premature mortality. While joint involvement is the primary manifestation of RA, extra-articular features including lung disease are responsible for a significant portion of the excess mortality. In this dissertation I demonstrate the contribution of chronic lung diseases to premature mortality in RA, contrasting with the more widely recognized comorbidity in RA of cardiovascular disease. Then, I establish that a novel serum biomarker, anti-malondialdehyde-acetaldehyde adduct (MAA) antibody, is associated with the presence of interstitial lung disease (ILD) in RA subjects. Further …

Precision Medicine In Pancreatic Disease-Knowledge Gaps And Research Opportunities: Summary Of A National Institute Of Diabetes And Digestive And Kidney Diseases Workshop., Mark E Lowe, Dana K Andersen, Richard M Caprioli, Jyoti Choudhary, Zobeida Cruz-Monserrate, Anil K Dasyam, Christopher E Forsmark, Fred S Gorelick, Joe W Gray, Mark Haupt, Kimberly A Kelly, Kenneth P Olive, Sylvia K Plevritis, Noa Rappaport, Holger R Roth, Hanno Steen, S Joshua Swamidass, Temel Tirkes, Aliye Uc, Kirill Veselkov, David C Whitcomb, Aida Habtezion

Articles, Abstracts, and Reports

A workshop on research gaps and opportunities for Precision Medicine in Pancreatic Disease was sponsored by the National Institute of Diabetes and Digestive Kidney Diseases on July 24, 2019, in Pittsburgh. The workshop included an overview lecture on precision medicine in cancer and 4 sessions: (1) general considerations for the application of bioinformatics and artificial intelligence; (2) omics, the combination of risk factors and biomarkers; (3) precision imaging; and (4) gaps, barriers, and needs to move from precision to personalized medicine for pancreatic disease. Current precision medicine approaches and tools were reviewed, and participants identified knowledge gaps and research needs …

Acetaminophen Protein Adducts In Hospitalized Children Receiving Multiple Doses Of Acetaminophen., Sibo Jiang, Valvanera Vozmediano, Susan M. Abdel-Rahman, Stephan Schmidt, Laura P. James

Manuscripts, Articles, Book Chapters and Other Papers

Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen-induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18 years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half-life of adducts (2.17 …

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Fetal Fibronectin Testing For Reducing The Risk Of Preterm Birth., Vincenzo Berghella, Gabriele Saccone

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for …

Patient Registries In Idiopathic Pulmonary Fibrosis., Daniel A. Culver, Jürgen Behr, John A. Belperio, Tamera J. Corte, Joao A. De Andrade, Kevin R. Flaherty, Mridu Gulati, Tristan J. Huie, Lisa H. Lancaster, Jesse Roman, Christopher J. Ryerson, Hyun J. Kim

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data …

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Incidence And Predictors Of Obstructive Coronary Artery Disease And The Role Of Cardiac Troponin Assays In Patients With Unstable Angina, Sushan Yang, Nirmanmoh Bhatia, Meng Xu, John A Mcpherson

The Texas Heart Institute Journal

In a time when cardiac troponin assays are widely used to detect myocardial injury, data remain scarce concerning the incidence and predictors of substantial obstructive coronary artery disease that causes unstable angina. This retrospective single-center study included consecutive patients hospitalized for unstable angina from January 2015 through January 2016. Patients with troponin I levels above the upper reference limit and those who did not undergo angiography were excluded. Multivariate logistic regression analysis was used to identify predictors of obstructive coronary artery disease that warranted revascularization and of major adverse cardiac events up to 6 months after discharge from the hospital. …

Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.

Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and …

Heart Failure Symptom Biology In Response To Ventricular Assist Device Implantation., Christopher S Lee, James O Mudd, Karen S Lyons, Quin E Denfeld, Corrine Y Jurgens, Bradley E Aouizerat, Jill M Gelow, Christopher V Chien, Emily Aarons, Kathleen L Grady

Articles, Abstracts, and Reports

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation.

OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF.

METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], …