Public Health Commons^™

Invasive Therapies For Acute Coronary Syndromes In The Covid-19 Era, Sanket Borgaonkar, Joshua Hahn, Marilyne Daher, Waleed Kayani, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic.

RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Conditional Survival Among Patients With Oropharyngeal Cancer Treated With Radiation Therapy And Alive Without Recurrence 5 Years After Diagnosis, Kristina R Dahlstrom, Juhee Song, Peter F Thall, Clifton D Fuller, Katherine A Hutcheson, Faye M Johnson, G Brandon Gunn, Jack Phan, Steven J Frank, William H Morrison, Renata Ferrarotto, David I Rosenthal, Erich M Sturgis, Adam S Garden

Faculty, Staff and Students Publications

BACKGROUND: Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis.

METHODS: This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and …

The Impact Of Covid-19 On Kidney Transplantation And The Kidney Transplant Recipient – One Year Into The Pandemic, Pascale Khairallah, Nidhi Aggarwal, Ahmed A Awan, Chandan Vangala, Medha Airy, Jenny S Pan, Bhamidipati V R Murthy, Wolfgang C Winkelmayer, Venkat Ramanathan

Faculty, Staff and Students Publications

The COVID‐19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses …

Myd88 L265p Elicits Mutation-Specific Ubiquitination To Drive Nf-Κb Activation And Lymphomagenesis, Xinfang Yu, Wei Li, Qipan Deng, Haidan Liu, Xu Wang, Hui Hu, Ya Cao, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Zhongxin Lu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate …

Racial And Geographic Disparities In Influenza Vaccination In The Us Among Individuals With Atherosclerotic Cardiovascular Disease: Renewed Importance In The Setting Of Covid-19, Mahmoud Al Rifai, Umair Khalid, Arunima Misra, Jing Liu, Khurram Nasir, Miguel Cainzos-Achirica, Dhruv Mahtta, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

INTRODUCTION: The importance of receiving an annual influenza vaccine among patients with atherosclerotic cardiovascular disease (ASCVD) is well established. With the rapid community spread and the possibility of another wave of COVID-19 infections in the fall, receiving an influenza vaccine is of particular importance to mitigate the risk associated with overlapping influenza and COVID-19 infections.

METHODS: We utilized cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative U.S. telephone-based survey of adults 18 years or older. Race/ethnicity was our exposure of interest. We assessed the relative difference in influenza vaccination by race/ethnicity for …

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.

On The Application, Reporting, And Sharing Of In Silico Simulations For Genetic Studies, Kaleigh Riggs, Huann-Sheng Chen, Melissa Rotunno, Bing Li, Naoko I Simonds, Leah E Mechanic, Bo Peng

Faculty, Staff and Students Publications

In silico simulations play an indispensable role in the development and application of statistical models and methods for genetic studies. Simulation tools allow for the evaluation of methods and investigation of models in a controlled manner. With the growing popularity of evolutionary models and simulation-based statistical methods, genetic simulations have been applied to a wide variety of research disciplines such as population genetics, evolutionary genetics, genetic epidemiology, ecology, and conservation biology. In this review, we surveyed 1409 articles from five journals that publish on major application areas of genetic simulations. We identified 432 papers in which genetic simulations were used …

A Prospective Surveillance Study On The Kinetics Of The Humoral Immune Response To The Respiratory Syncytial Virus Fusion Protein In Adults In Houston, Texas, Brittani N Blunck, Letisha Aideyan, Xunyan Ye, Vasanthi Avadhanula, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV)-specific serum antibody has been correlated to protection of infection and reduction of severe disease, but reinfection is still frequent. In this study, we evaluated RSV-specific serum antibody activity following natural RSV re-infection to examine the longevity of the humoral immune response in adults. Nineteen healthy adult volunteers under sixty-five years of age were enrolled during the 2018-2019 RSV season in Houston, TX. Blood was collected at three study visits. The kinetics of RSV-neutralizing, RSV F site-specific competitive, and RSV-binding antibodies in serum samples were measured by microneutralization and enzyme-linked immunosorbent assays. Three distinct profiles of RSV-specific …

Vulvar Lichen Sclerosus In Women Of Reproductive Age, Elysha Kolitz, Laura Gammon, Melissa Mauskar

Faculty, Staff and Students Publications

Vulvar lichen sclerosus (vLS) is an inflammatory skin condition that predominantly affects the vulvar and perianal regions. Approximately 50% of cases present prior to menopause; however, there is a paucity of data on vLS in women of reproductive age as well as during their pregnancies. A retrospective review was performed at two tertiary referral centers to better describe cases of vLS in women of reproductive age. Thirty-three patients with a mean age of 40 years met inclusion criteria. In this group, vulvar pruritus was the most common presenting symptom (52%); 61% had biopsy-proven vLS, 42% had at least one autoimmune …

Education Of Infectious Diseases Fellows During The Covid-19 Pandemic Crisis: Challenges And Opportunities, Lisa M Chirch, Wendy S Armstrong, Gayle P Balba, Prathit A Kulkarni, Constance A Benson, Victoria Konold, Vera P Luther, Obinna N Nnedu, Sarah Perloff, Raymund R Razonable, Wendy Stead, George R Thompson, Michael T Melia

Faculty, Staff and Students Publications

One of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate …

Houston Hurricane Harvey Health (Houston-3h) Study: Assessment Of Allergic Symptoms And Stress After Hurricane Harvey Flooding, Abiodun O Oluyomi, Kristen Panthagani, Jesus Sotelo, Xiangjun Gu, Georgina Armstrong, Dan Na Luo, Kristi L Hoffman, Diana Rohlman, Lane Tidwell, Winifred J Hamilton, Elaine Symanski, Kimberly Anderson, Joseph F Petrosino, Cheryl Lyn Walker, Melissa Bondy

Faculty, Staff and Students Publications

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 …

Disparities In Cardiovascular Disease Outcomes Among Pregnant And Post-Partum Women, Mohamed M Gad, Islam Y Elgendy, Ahmed N Mahmoud, Anas M Saad, Toshiaki Isogai, Isadora Sande Mathias, Rabel Misbah Rameez, Johnny Chahine, Hani Jneid, Samir R Kapadia

Faculty, Staff and Students Publications

Background

The incidence of cardiovascular disease among pregnant women is rising in the United States. Data on racial disparities for the major cardiovascular events during pregnancy are limited.

Methods and Results

Pregnant and post‐partum women hospitalized from January 2007 to December 2017 were identified from the Nationwide Inpatient Sample. The outcomes of interest included: in‐hospital mortality, myocardial infarction, stroke, pulmonary embolism, and peripartum cardiomyopathy. Multivariate regression analysis was used to assess the independent association between race and in‐hospital outcomes. Among 46 700 637 pregnancy‐related hospitalizations, 21 663 575 (46.4%) were White, 6 302 089 (13.5%) were Black, and 8 914 …

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 …

Patient-Perceived Versus Actual Risk Of Cardiovascular Disease And Associated Willingness To Consider And Use Prevention Therapy, Ann Marie Navar, Tracy Y Wang, Shuang Li, Xiaojuan Mi, Zhuokai Li, Jennifer G Robinson, Salim S Virani, Eric D Peterson

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient …

Lifestyle Risk Factors, Quality Of Life, And Intervention Preferences Of Barrett's Esophagus Patients: A Prospective Cohort Study, Xiaotao Zhang, Sharmila Anandasabapathy, Julian Abrams, Mohamed Othman, Hoda J Badr

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population.

METHODS: Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported …

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), Katherine R Shaw, Jennifer M Lynch, George H Balazs, T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

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 …

Application Of Human Factors Methods To Understand Missed Follow-Up Of Abnormal Test Results, Deevakar Rogith, Tyler Satterly, Hardeep Singh, Dean F Sittig, Elise Russo, Michael W Smith, Don Roosan, Viraj Bhise, Daniel R Murphy

Faculty, Staff and Students Publications

OBJECTIVE: This study demonstrates application of human factors methods for understanding causes for lack of timely follow-up of abnormal test results ("missed results") in outpatient settings.

METHODS: We identified 30 cases of missed test results by querying electronic health record data, developed a critical decision method (CDM)-based interview guide to understand decision-making processes, and interviewed physicians who ordered these tests. We analyzed transcribed responses using a contextual inquiry (CI)-based methodology to identify contextual factors contributing to missed results. We then developed a CI-based flow model and conducted a fault tree analysis (FTA) to identify hierarchical relationships between factors that delayed …

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 …