Digital Commons Network^™

Novel Scoring Systems To Predict The Need For Oxygenation And Icu Care, And Mortality In Hospitalized Covid-19 Patients: A Risk Stratification Tool, Vishakh C Keri, Pankaj Jorwal, Rohit Verma, Piyush Ranjan, Ashish D Upadhyay, Anivita Aggarwal, Radhika Sarda, Kunal Sharma, Shubham Sahni, Chaithra Rajanna

Faculty, Staff and Student Publications

INTRODUCTION: A rapid surge in cases during the COVID-19 pandemic can overwhelm any healthcare system. It is imperative to triage patients who would require oxygen and ICU care, and predict mortality. Specific parameters at admission may help in identifying them.

METHODOLOGY: A prospective observational study was undertaken in a COVID-19 ward of a tertiary care center. All baseline clinical and laboratory data were captured. Patients were followed till death or discharge. Univariable and multivariable logistic regression was used to find predictors of the need for oxygen, need for ICU care, and mortality. Objective scoring systems were developed for the same …

Bone Mineral Density, Serum Calcium, And Vitamin D Levels In Adult Thalassemia Major Patients: Experience From A Single Center In Eastern India, Soumya Santra, Kunal Sharma, Ipsita Dash, Shaikat Mondal, Himel Mondal

Faculty, Staff and Student Publications

Background and objective Patients suffering from thalassemia major are at higher risk of osteoporosis. Due to their decreased life expectancy, the number of adult patients is low. However, their bone health is rarely checked in developing countries like India. There is no data available in the literature on the bone mineral density (BMD) of adult (aged ≥18 years) thalassemia major patients in eastern India. In this study, we aimed to measure the BMD and serum calcium and vitamin D levels in adult thalassemia major patients and to compare them with healthy controls. Materials and methods We conducted this cross-sectional observational …

Impact Of Risk-Based Sexually Transmitted Infection Screening In The Emergency Department, Fahd A Ahmad, Kayleigh Fischer, Hongjie Gu, Thomas C Bailey, Donna B Jeffe, Christopher R Carpenter, Philip R O Payne

Faculty, Staff and Student Publications

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents.

METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing …

Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, Sean D Rose, David W Jordan, Nicholas B Bevins, Jaydev K Dave, David E Hintenlang, Brad K Lofton, Pankaj Patel

Faculty, Staff and Student Publications

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United …

Biological Treatment Usage In Patients With Hiv And Rheumatic Disease, 2003-2021: Long-Term Safety And Follow-Up, Benjamin Sornrung Naovarat, Gloria Salazar, Mariko Ishimori, Francis M Williams, John D Reveille

Faculty, Staff and Student Publications

OBJECTIVE: This study examined the safety and efficacy of biological agents, especially tumour necrosis factor (TNF) inhibitors, for HIV-positive rheumatology patients refractory to standard therapy.

METHODS: This study is a retrospective case series including patients derived from a community HIV clinic as well as from two academic centres. Initial visit data collected included: sociodemographic characteristics, CD4 counts, HIV viral load and medication use. Patients with persistent disease activity despite standard conservative therapy were begun on biological agents.The main outcomes were patient and physician global assessment of treatment response and medication side effects in patients with rheumatological disorders treated with biological …

Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Guilin Tang, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment. We analyzed three prospective frontline clinical trials that allowed the use of cytoreduction before treatment initiation. Among 274 patients with a median age of 62 (range, 18-89), there was no significant difference in short- and long-term outcome and safety among patients who did …

Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nicholas Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian

Faculty, Staff and Student Publications

Progress with intensive chemotherapy and supportive care measures has improved survival in newly diagnosed acute myeloid leukemia (AML). Predicting outcome helps in treatment decision making. We analyzed survival as the treatment endpoint in 3728 patients with newly diagnosed AML treated with intensive chemotherapy from 1980 to 2021. We divided the total study group (3:1 basis) into a training (n = 2790) and a validation group (n = 938). The associations between survival and 27 characteristics were investigated. In the training cohort, the multivariate analysis identified 12 consistent adverse prognostic variables independently associated with worse survival: older age, therapy-related myeloid neoplasm, …

Treatment-Free Remission In Patients With Chronic Myeloid Leukemia Following The Discontinuation Of Tyrosine Kinase Inhibitors, Fadi G Haddad, Koji Sasaki, Ghayas C Issa, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Marina Konopleva, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney Dinardo, Nitin Jain, Naval Daver, Nicholas J Short, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, …

Stalled Replication Fork Protection Limits Cgas-Sting And P-Body-Dependent Innate Immune Signalling, Ahmed Emam, Xiao Wu, Shengfeng Xu, Longqiang Wang, Shichang Liu, Bin Wang

Faculty, Staff and Student Publications

Protection of stalled replication forks is crucial for cells to respond to replication stress and maintain genome stability. Genome instability and replication stress have been linked to immune activation. Here we show that Abro1 and FANCD2 protect replication forks, which is linked with the restriction of innate immune responses. We reveal that stalled replication fork degradation induced by Abro1 or FANCD2 deficiency leads to accumulation of cytosolic single-stranded DNA and activation of a cGAS-STING-dependent innate immune response that is dependent on DNA2 nuclease. We further show that the increased cytosolic single-stranded DNA contains ribosomal DNA that can bind to cGAS. …

Redirecting Host Preexisting Influenza A Virus Immunity For Cancer Immunotherapy, Bharat K R Chaganty, Songbo Qiu, Yang Lu, Gabriel Lopez-Berestein, Bulent Ozpolat, Zhen Fan

Faculty, Staff and Student Publications

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing …

Bloodstream Infections In Hematologic Malignancy Patients With Fever And Neutropenia: Are Empirical Antibiotic Therapies In The United States Still Effective?, Andrea J Zimmer, Erica Stohs, Jane Meza, Christopher Arnold, John W Baddley, Pranatharthi Chandrasekar, Zeinab El Boghdadly, Carlos A Gomez, Eileen K Maziarz, Jose G Montoya, Steven Pergam, Kenneth V Rolston, Michael J Satlin, Gowri Satyanarayana, Shmuel Shoham, Lynne Strasfeld, Randy Taplitz, Thomas J Walsh, Jo-Anne H Young, Yuning Zhang, Alison G Freifeld

Faculty, Staff and Student Publications

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.

Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.

Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with …

Mice Lacking Wnt9a Or Wnt4 Are Prone To Develop Spontaneous Osteoarthritis With Age And Display Alteration In Either The Trabecular Or Cortical Bone Compartment, Stefan Teufel, Lena Wolff, Ulrich König, Akio Kobayashi, Richard Behringer, Christine Hartmann

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype. Previously, it was shown that WNT9a is involved in maintaining synovial cell identity in the elbow joint during embryogenesis. Here, we report that the conditional loss of Wnt9a in the Prx1-Cre expressing limb mesenchyme or Prg4-CreER …

Opposing Roles Of Hdac6 In Liver Regeneration And Hepatocarcinogenesis, Sophors Phorl, Azra Memon, Yuri Seo, Thi Oanh Hoang, Trung Nghia Tran, Le Minh Tri Nguyen, Chang Hoon Lee, Woon Kyu Lee, Joo-Yong Lee

Faculty, Staff and Student Publications

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro-survival acetylation, in all tested animal models but …

Haploidentical Versus Matched Unrelated Versus Matched Sibling Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide, Rohtesh S Mehta, Rima M Saliba, Sassine Ghanem, Amin M Alousi, Gabriela Rondon, Paolo Anderlini, Gheath Al-Atrash, Qaiser Bashir, Chitra M Hosing, Jin S Im, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall

Faculty, Staff and Student Publications

With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% …

Molecular Characterization And Prospective Evaluation Of Pathologic Response And Outcomes With Neoadjuvant Therapy In Metaplastic Triple-Negative Breast Cancer, Clinton Yam, Nour Abuhadra, Ryan Sun, Beatriz E Adrada, Qing-Qing Ding, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Vicente Valero, Debu Tripathy, Senthilkumar Damodaran, Banu K Arun, Jennifer K Litton, Naoto T Ueno, Rashmi K Murthy, Bora Lim, Luis Baez, Xiaoxian Li, Aman U Buzdar, Gabriel N Hortobagyi, Alistair M Thompson, Elizabeth A Mittendorf, Gaiane M Rauch, Rosalind P Candelaria, Lei Huo, Stacy L Moulder, Jeffrey T Chang

Faculty, Staff and Student Publications

PURPOSE: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.

EXPERIMENTAL DESIGN: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy.

RESULTS: Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience …

Hap40 Is A Conserved Central Regulator Of Huntingtin And A Potential Modulator Of Huntington’S Disease Pathogenesis, Shiyu Xu, Gang Li, Xin Ye, Dongsheng Chen, Zhihua Chen, Zhen Xu, Moretti Daniele, Sara Tambone, Alessandra Ceccacci, Licia Tomei, Lili Ye, Yue Yu, Amanda Solbach, Stephen M Farmer, Erin Furr Stimming, George Mcallister, Deanna M Marchionini, Sheng Zhang

Faculty, Staff and Student Publications

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, …

Efficacy Of Niraparib By Time Of Surgery And Postoperative Residual Disease Status: A Post Hoc Analysis Of Patients In The Prima/Engot-Ov26/Gog-3012 Study, Roisin E O'Cearbhaill, Jose-Alejandro Pérez-Fidalgo, Bradley J Monk, Ignacio Tusquets, Colleen Mccormick, Jose Fuentes, Richard G Moore, Christof Vulsteke, Mark S Shahin, Frédéric Forget, William H Bradley, Sakari Hietanen, David M O'Malley, Anne Dørum, Brian M Slomovitz, Klaus Baumann, Frédéric Selle, Paula M Calvert, Grazia Artioli, Tally Levy, Aalok Kumar, Izabela A Malinowska, Yong Li, Divya Gupta, Antonio González-Martín

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.

METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual …

Skin Cancer Education Interventions For Primary Care Providers: A Scoping Review, Ashley E Brown, Maleka Najmi, Taylor Duke, Daniel A Grabell, Misha V Koshelev, Kelly C Nelson

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are often the first line of defense against skin cancers. Despite this, many PCPs do not receive a comprehensive training in skin conditions. Educational interventions aimed at skin cancer screening instruction for PCPs offer an opportunity to detect skin cancer at earlier stages and subsequent improved morbidity and mortality. A scoping review was conducted to collect data about previously reported skin cancer screening interventions for PCPs. A structured literature search found 51 studies describing 37 unique educational interventions. Curriculum elements utilized by the interventions were divided into categories that would facilitate comparison including curriculum components, delivery …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Respiratory Effects Of Thyrotropin-Releasing Hormone And Its Analogue Taltirelin On Opioid-Induced Respiratory Depression, Marijke H Algera, Joseph F Cotten, Monique Van Velzen, Marieke Niesters, Martijn Boon, Daniel S Shoham, Kaye E Dandrea, Rutger Van Der Schrier, Albert Dahan

Faculty, Staff and Student Publications

No abstract provided.

Lenalidomide Enhances Cd23car T Cell Therapy In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release …

Prolonged Cardiac Nr4a2 Aactivation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Guidelines On Models Of Diabetic Heart Disease, Lisa C Heather, Anne D Hafstad, Ganesh V Halade, Romain Harmancey, Kimberley M Mellor, Paras K Mishra, Erin E Mulvihill, Miranda Nabben, Michinari Nakamura, Oliver J Rider, Matthieu Ruiz, Adam R Wende, John R Ussher

Faculty, Staff and Student Publications

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the …

Adding Customized Electron Energy Beams To Truebeam Linear Accelerators, Song Gao, Manickam Muruganandham, Weiliang Du, Jared Ohrt, Rajat J Kudchadker, Peter A Balter

Faculty, Staff and Student Publications

Purpose: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs.

Methods: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) …

Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Teresa T Nguyen, Dong Ho Shin, Sagar Sohoni, Sanjay K Singh, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Background: Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.

Methods: We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation …

Impact Of Venetoclax And Azacitidine In Treatment-Naïve Patients With Acute Myeloid Leukemia And Idh1/2 Mutations, Daniel A Pollyea, Courtney D Dinardo, Martha L Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A Rizzieri, B Douglas Smith, Atsushi Shinagawa, Roberto M Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L Miller, Hagop M Kantarjian

Faculty, Staff and Student Publications

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle).

Results: …

Computed Tomography Of The Chest To Screen For Interstitial Lung Disease In Patients With Systemic Sclerosis At Expert Scleroderma Centers In The United States, Elana J Bernstein, Shervin Assassi, Flavia V Castelino, Lorinda Chung, Chase Correia, Luke B Evnin, Tracy M Frech, Jessica K Gordon, Brian A Skaug, Faye N Hant, Laura K Hummers, Nora Sandorfi, Ami A Shah, Victoria K Shanmugam, Virginia D Steen, Dinesh Khanna

Faculty, Staff and Student Publications

OBJECTIVE: Although a high-resolution computed tomography (HRCT) scan of the chest is the gold standard test for the detection of interstitial lung disease (ILD), there is no consensus among rheumatologists regarding the use of HRCT to screen for ILD in their patients with systemic sclerosis (SSc). The aims of this study were to describe the HRCT ordering practices at SSc centers in the United States and to determine which patient characteristics are associated with HRCT performance.

METHODS: We performed a prospective cohort study of patients with SSc enrolled in the US-based Collaborative National Quality and Efficacy Registry (CONQUER). We performed …

Third Year Medical Student Knowledge Gaps After A Virtual Surgical Rotation, Sophia Hernandez, Siyou Song, Ogonna N Nnamani Silva, Chelsie Anderson, Alexander S Kim, Andre R Campbell, Edward H Kim, Adnan Alseidi, Elizabeth C Wick, Julie Ann Sosa, Jessica Gosnell, Matthew Y C Lin, Sanziana A Roman

Faculty, Staff and Student Publications

INTRODUCTION: This study describes perceived knowledge gaps of third-year medical students after participating in a virtual surgical didactic rotation (EMLR) and shortened in-person surgery rotation during the COVID-19 Pandemic.

METHODS: Open-ended and Likert questions were administered at the end of the virtual rotation and inperson-surgical rotation to medical students. Three blinded coders identified themes by semantic analysis.

RESULTS: 82 students (51% of all MS3s) participated in the EMLR. Semantic analysis revealed gaps in perioperative management (Post-EMLR:18.4%, Post-Inpatient:26.5%), anatomy (Post-EMLR:8.2%, PostInpatient:26.5%). and surgical skills (Post-EMLR: 43.0%, Post-Inpatient: 44.1%). Students also described gaps related to OR etiquette (Post-EMLR: 12.2%, Post-Inpatient: 8.8%) and …

Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Ganne Chaitanya, Johnson P Hampson, Emilia Toth, Norma J Hupp, Jaison S Hampson, John C Mosher, Sandipan Pati, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.

Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out …

A Missing Piece Of The Puzzle: Patient And Provider Perspectives On Pain Management Needs And Opioid Prescribing In Inflammatory Bowel Disease Care, Salva N Balbale, Cassandra B Iroz, Willemijn L A Schäfer, Julie K Johnson, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Recent data have shown high rates of opioid misuse among inflammatory bowel disease (IBD) patients. We conducted a qualitative study to explore IBD patient and provider perceptions and experiences with pain management and opioid prescribing.

METHODS: We conducted a focus group with IBD patients and semistructured interviews with IBD-focused physicians and nurses. We used an inductive approach for analysis and the constant comparison method to develop and refine codes and identify prominent themes. We analyzed interview and focus group data concurrently to triangulate themes.

RESULTS: Nine patients and 10 providers participated. We grouped themes into 3 categories: (1) current …