Epidemiology Commons^™

Is Covid-19-Induced Platelet Activation A Cause Of Concern For Patients With Cancer?, Lenard M Lichtenberger, K Vinod Vijayan

Faculty, Staff and Students Publications

Patients with cancer are more susceptible to be infected by SARS-CoV-2 and develop severe outcomes including ICU admittance, mechanical ventilator support, and a high rate of mortality. Like mid-to late-stage cancer, SARS-CoV-2 infection is associated with platelet hyperactivity, systemic inflammation, thrombotic complications, and coagulopathy. Platelets also promote cancer cell growth, survival in circulation, and angiogenesis at sites of metastases. In this article, we will discuss the potential for platelets in the development of systemic inflammation and thrombosis in SARS-CoV-2-infected patients with cancer, with the concern that the platelet-induced pathogenic events are likely magnified in cancer patients with COVID-19.

Thyroid Storm In A Patient With Covid-19, Angela N Rao, Ruaa Y Al-Ward, Ruchi Gaba

Faculty, Staff and Students Publications

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19.

METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed.

RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with …

Characteristics And Outcomes Of In-Hospital Cardiac Arrest In Covid-19 A Systematic Review And Meta-Analysis, Lukasz Szarpak, Magdalena Borkowska, Frank W Peacock, Zubaid Rafique, Aleksandra Gasecka, Jacek Smereka, Katarzyna Pytkowska, Marta Jachowicz, Lukasz Iskrzycki, Natasza Gilis-Malinowska, Milosz J Jaguszewski

Faculty, Staff and Students Publications

BACKGROUND: The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period.

METHODS: A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with …

Large-Scale Characterization Of Drug Responses Of Clinically Relevant Proteins In Cancer Cell Lines, Wei Zhao, Jun Li, Mei-Ju M Chen, Yikai Luo, Zhenlin Ju, Nicole K Nesser, Katie Johnson-Camacho, Christopher T Boniface, Yancey Lawrence, Nupur T Pande, Michael A Davies, Meenhard Herlyn, Taru Muranen, Ioannis K Zervantonakis, Erika Von Euw, Andre Schultz, Shwetha V Kumar, Anil Korkut, Paul T Spellman, Rehan Akbani, Dennis J Slamon, Joe W Gray, Joan S Brugge, Yiling Lu, Gordon B Mills, Han Liang

Faculty, Staff and Students Publications

Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ∼210 clinically relevant proteins in >12,000 cancer cell line samples in response to ∼170 drug compounds using reverse-phase protein arrays. We show that integrating perturbed protein response signals provides mechanistic insights into drug resistance, increases the predictive power for drug sensitivity, and helps identify effective drug combinations. We build a systematic map of "protein-drug" connectivity …

Postacute Covid-19: An Overview And Approach To Classification, Eva M Amenta, Amy Spallone, Maria C Rodriguez-Barradas, Hana M El Sahly, Robert L Atmar, Prathit A Kulkarni

Faculty, Staff and Students Publications

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other …

Safety And Effectiveness Of Hydroxychloroquine And Azithromycin Combination Therapy For Treatment Of Hospitalized Patients With Covid-19: A Propensity-Matched Study, Henry D Huang, Hani Jneid, Mariam Aziz, Venkatesh Ravi, Parikshit S Sharma, Timothy Larsen, Neal Chatterjee, Basil Saour, Zaid Aziz, Hemal Nayak, Richard G Trohman, Kousik Krishnan

Faculty, Staff and Students Publications

INTRODUCTION: We sought to determine the effectiveness and safety of hydroxychloroquine-azithromycin (HCQ-AZM) therapy in hospitalized patients with COVID-19.

METHODS: This was a retrospective cohort study of 613 patients hospitalized (integrated health system involving three hospitals) for RT-PCR-confirmed COVID-19 infection between March 1, 2020 and April 25, 2020. Intervention was treatment with HCQ-AZM in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Outcomes of interest were in-hospital all-cause mortality, cardiovascular mortality, pulseless electrical activity (PEA) arrest, non-lethal arrhythmias, and length of hospital stay. Secondary measures included in-hospital corrected QT (QTc) interval parameters and serum biomarkers levels.

RESULTS: Propensity-matched …

Donor And Transplant Candidate Selection For Solid Organ Transplantation During The Covid-19 Pandemic, N Thao N Galvan, Nicolas F Moreno, Jay E Garza, Susan Bourgeois, Marion Hemmersbach-Miller, Bhamidipati Murthy, Katherine Timmins, Christine A O'Mahony, James Anton, Andrew Civitello, Puneet Garcha, Gabe Loor, Kenneth Liao, Alexis Shaffi, John Vierling, Rise Stribling, Abbas Rana, John A Goss

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating …

Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute

Faculty, Staff and Students Publications

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …

Tumor Somatic Mutations Also Existing As Germline Polymorphisms May Help To Identify Functional Snps From Genome-Wide Association Studies, Ivan P Gorlov, Xiangjun Xia, Spiridon Tsavachidis, Olga Y Gorlova, Christopher I Amos

Faculty, Staff and Students Publications

We hypothesized that a joint analysis of cancer risk-associated single-nucleotide polymorphism (SNP) and somatic mutations in tumor samples can predict functional and potentially causal SNPs from GWASs. We used mutations reported in the Catalog of Somatic Mutations in Cancer (COSMIC). Confirmed somatic mutations were subdivided into two groups: (1) mutations reported as SNPs, which we call mutational/SNPs and (2) somatic mutations that are not reported as SNPs, which we call mutational/noSNPs. It is generally accepted that the number of times a somatic mutation is reported in COSMIC correlates with its selective advantage to tumors, with more frequently reported mutations being …

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Ivan P Gorlov, Christopher I Amos, Spiridon Tsavachidis, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Aaim Recommendations For The 2020-2021 Internal Medicine Residency Application Cycle In Response To The Covid-19 Pandemic, Katherine C Chretien, Jaya M Raj, Reeni A Abraham, Paul Aronowitz, Donna J Astiz, Shobhina G Chheda, Ernie L Esquivel, Maria M Garcia, Nadia Ismail, Susan Lane, Suzanne E Mclaughlin, Anne Pereira, Amy W Shaheen, Abby L Spencer, Kimberly M Tartaglia, Lisa L Willett

Faculty, Staff and Students Publications

This statement was released in June 2020 by the Alliance for Academic Internal Medicine to provide guidance for the 2020-2021 residency application cycle in light of the COVID-19 pandemic. While many of the recommendations are specific to this cycle, others, such as the Department Summary Letter of Evaluation, are meant to be an enduring change to the internal medicine residency application process. AAIM realizes that some schools may not yet have the tools or resources to implement the template fully this cycle and look toward collaboration within the internal medicine education community to facilitate adoption in the cycles to come.

Targeting Pd-L1 In Non-Small Cell Lung Cancer Using Car T Cells, Ming Liu, Xu Wang, Wei Li, Xinfang Yu, Pedro Flores-Villanueva, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Ken H Young, Xiaodong Ma, Yong Li

Faculty, Staff and Students Publications

Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC. In this work, we constructed CAR T cells that target PD-L1 and evaluated their efficacy in NSCLC …

Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang

Faculty, Staff and Students Publications

SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes with the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched toward the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an …

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

Whole Exome Sequencing Of Highly Aggregated Lung Cancer Families Reveals Linked Loci For Increased Cancer Risk On Chromosomes 12q, 7p, And 4q, Anthony M Musolf, Bilal A Moiz, Haiming Sun, Claudio W Pikielny, Yohan Bossé, Diptasri Mandal, Mariza De Andrade, Colette Gaba, Ping Yang, Yafang Li, Ming You, Ramaswamy Govindan, Richard K Wilson, Elena Y Kupert, Marshall W Anderson, Ann G Schwartz, Susan M Pinney, Christopher I Amos, Joan E Bailey-Wilson

Faculty, Staff and Students Publications

BACKGROUND: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer.

METHODS: Parametric genetic linkage analysis was performed on these samples using two distinct analyses-the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were …

Global Burden Of Disease Study 2010: Interpretation And Implications For The Neglected Tropical Diseases, Peter J. Hotez, Miriam Alvarado, Maria Gloria Basanez, Ian Bolliger, Et Al.

Faculty, Staff and Students Publications

No abstract provided.