Digital Commons Network^™

Comparative Effectiveness Of Diversion Of Cerebrospinal Fluid For Children With Severe Traumatic Brain Injury, Michael J Bell, Jose Pineda, Et Al.

2020-Current year OA Pubs

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies.

Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI.

Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and …

The Overestimation Of Concentric Hypertrophy In Patients With Hfpef As Determined By 2d-Echocardiography, Mohammad F. Mathbout, Hussam Al Hennawi, Anwar Khedr, Gaurang N. Vaidya, Marcus Stoddard

Division of Internal Medicine Faculty Papers & Presentations

Background: Heart failure with preserved ejection fraction continues to pose multiple challenges in terms of accurate diagnosis, treatment, and associated morbidity. Accurate left ventricular (LV) mass calculation yields essential prognostic information relating to structural heart disease. Two-dimensional (2D) echocardiography-based calculations are solely limited to LV geometric assumptions of symmetry, whereas three-dimensional (3D) echocardiography could overcome these limitations. This study aims to compare the performance of 2D and 3D LV mass calculations. Methods: A prospective review of echocardiography findings at the University of Louisville, Kentucky, was conducted and assessed. Normal ejection fraction (EF) was defined as >=52% in males and >=54% …

Effect Of Musculature On Mortality, A Retrospective Cohort Study, Amy L Shaver, Mary E Platek, Anurag K Singh, Sung Jun Ma, Mark Farrugia, Gregory Wilding, Andrew D Ray, Heather M Ochs-Balcom, Katia Noyes

Department of Medical Oncology Faculty Papers

Background: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early. The primary objective of this study was to determine if pre-treatment musculature was associated with all-cause mortality.

Methods: Patient demographic and clinical characteristics were abstracted from the cancer center electronic database (n = 403). Musculature was ascertained from pre-treatment CT scans. Propensity score matching was utilized to adjust for confounding …

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling To Promote Health And Longevity, Mahmoud Abdellatif, Tobias Pendl, Sebastian J Hofer, Moydul Islam, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Et Al

2020-Current year OA Pubs

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic …

Effects Of Paternal High-Fat Diet And Maternal Rearing Environment On The Gut Microbiota And Behavior., Austin C Korgan, Christine L Foxx, Heraa Hashmi, Saydie A Sago, Christopher E Stamper, Jared D Heinze, Elizabeth O'Leary, Jillian L King, Tara S Perrot, Christopher A Lowry, Ian C G Weaver

Faculty Research 2022

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome's potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects …

Symptomatic, Clinical And Biomarker Associations For Mortality In Hospitalized Covid-19 Patients Enriched For African Americans, Hassan Ashktorab, Antonio Pizuorno, Folake Adeleye, Adeyinka Laiyemo, Maryam Mehdipour Dalivand, Farshad Aduli, Zaki A Sherif, Gholamreza Oskrochi, Kibreab Angesom, Philip Oppong-Twene, Suryanarayana Reddy Challa, Nnaemeka Okorie, Esther S Moon, Edward Romos, Boubini Jones-Wonni, Abdoul Madjid Kone, Sheldon Rankine, Camelita Thrift, Derek Scholes, Chiamaka Ekwunazu, Abigail Banson, Brianna Mitchell, Guttu Maskalo, Jillian Ross, Julencia Curtis, Rachel Kim, Chandler Gilliard, Geetha Ahuja, Joseph Mathew, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R. Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph B. Miller Md, Lakshmi Gayathri Chirumamilla, Fatimah Jackson, John M. Carethers, Farin Kamangar, Hassan Brim

Emergency Medicine Articles

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality.

METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected.

RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, …

Gut Dysbiosis And Age-Related Neurological Diseases In Females, Janelle M Korf, Bhanu P Ganesh, Louise D Mccullough

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Navigation Programs Relevant For African American Men With Prostate Cancer: A Scoping Review Protocol, Nynikka R. Palmer, Ashley Nicole Smith, Brittany A. Campbell, Ghilamichael Andemeskel, Peggy Tahir, Tisha M. Felder Phd, Msw, Barbara Cicerelli

Publications

BACKGROUND:

The excess incidence and mortality due to prostate cancer that impacts African American men constitutes the largest of all cancer disparities. Patient navigation is a patient-centered healthcare system intervention to eliminate barriers to timely, high-quality care across the cancer continuum and improves health outcomes among vulnerable patients. However, little is known regarding the extent to which navigation programs include cultural humility to address prostate cancer disparities among African American men. We present a scoping review protocol of an in-depth examination of navigation programs in prostate cancer care-including navigation activities/procedures, training, and management-with a special focus on cultural context and …

Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of

Tomatoes, Lycopene, And Prostate Cancer: What Have We Learned From Experimental Models?, Nancy E Moran, Jennifer M Thomas-Ahner, Lei Wan, Krystle E Zuniga, John W Erdman, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Human epidemiology suggests a protective effect of tomatoes or tomato phytochemicals, such as lycopene, on prostate cancer risk. However, human epidemiology alone cannot reveal causal relations. Laboratory animal models of prostate cancer provide opportunities to investigate hypotheses regarding dietary components in precisely controlled, experimental systems, contributing to our understanding of diet and cancer risk relations. We review the published studies evaluating the impact of tomatoes and/or lycopene in preclinical models of prostate carcinogenesis and tumorigenesis. The feeding of tomatoes or tomato components demonstrates anti-prostate cancer activity in both transplantable xenograft models of tumorigenesis and models of chemically- and genetically-driven carcinogenesis. …

Estrogen Hormone Is An Essential Sex Factor Inhibiting Inflammation And Immune Response In Covid-19, Fuhai Li, Adrianus C M Boon, Andrew P Michelson, Randi E Foraker, Ming Zhan, Philip R O Payne

Open Access Publications

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality of COVID-19 patients already infected with SARS-CoV-2. The global data on COVID-19 showed that men have a higher mortality rate than women. We further observed that the proportion of mortality of females increases starting from around the age of 55 significantly. Thus, sex is an essential factor associated with COVID-19 mortality, and sex related genetic factors could be interesting mechanisms and targets for COVID-19 treatment. However, the associated sex factors and signaling pathways remain unclear. Here, we propose …

Political Environment And Mortality Rates In The United States, 2001-19: Population Based Cross Sectional Analysis, Haider J Warraich, Pankaj Kumar, Khurram Nasir, Karen E Joynt Maddox, Rishi K Wadhera

Open Access Publications

OBJECTIVE: To assess recent trends in age adjusted mortality rates (AAMRs) in the United States based on county level presidential voting patterns.

DESIGN: Cross sectional study.

SETTING: USA, 2001-19.

PARTICIPANTS: 99.8% of the US population.

MAIN OUTCOME MEASURES: AAMR per 100 000 population and average annual percentage change (APC).

METHODS: The Centers for Disease Control and Prevention WONDER database was linked to county level data on US presidential elections. County political environment was classified as either Democratic or Republican for the four years that followed a November presidential election. Additional sensitivity analyses analyzed AAMR trends for counties that voted only …

Amiodarone Use And All-Cause Mortality In Patients With A Continuous-Flow Left Ventricular Assist Device, Rakesh Gopinathannair, Naga Venkata K. Pothineni, Jaimin R. Trivedi, Henri Roukoz, Jennifer A. Cowger, Mustafa Ahmed, Adarsh Bhan, Ashwin K. Ravichandran, Geetha Bhat, Amin Al Ahmad, Andrea Natale, Luigi Di Biase, Mark S. Slaughter, Dhanunjaya Lakkireddy

Cardiology Articles

Background: Atrial and ventricular arrhythmias are commonly encountered in patients with advanced heart failure, with amiodarone being the most commonly used antiarrhythmic drug in continuous-flow left ventricular assist device (CF-LVAD) recipients. The purpose of this study was to assess the impact of amiodarone use on long-term all-cause mortality in patients with a CF-LVAD.

Methods and Results: A retrospective multicenter study of CF-LVAD was conducted at 5 centers including all CF-LVAD implants from 2007 to 2015. Patients were stratified based on pre-CF-LVAD implant amiodarone use. Additional use of amiodarone after CF-LVAD implantation was also evaluated. Primary outcome was all-cause mortality during …

Cetuximab And Anemia Prevention In Head And Neck Cancer Patients Undergoing Radiotherapy, Lucas G. Maahs, Ahmed I. Ghanem, Radhika Gutta, Amy Tang, Swarn Arya, Zaid Al-Saheli, Haythem Y. Ali, Steven S. Chang, Samantha Tam, Vivian Wu, Farzan Siddiqui, Jawad Z. Sheqwara

Hematology/Oncology Articles

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia.

METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some …

French-Fried Potato Consumption And Energy Balance: A Randomized Controlled Trial, Daniel L Smith, Rebecca L Hanson, Stephanie L Dickinson, Xiwei Chen, Amy M Goss, John B Cleek, W Timothy Garvey, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed.

Objectives: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption.

Methods: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries …

Effect Of Awake Prone Positioning On Endotracheal Intubation In Patients With Covid-19 And Acute Respiratory Failure: A Randomized Clinical Trial, Waleed Alhazzani, Ken Kuljit S Parhar, Jason Weatherald, Zainab Al Duhailib, Mohammed Alshahrani, Abdulrahman Al-Fares, Sarah Buabbas, Sujith V Cherian, Laveena Munshi, Eddy Fan, Fahad Al-Hameed, Jamal Chalabi, Amera A Rahmatullah, Erick Duan, Jennifer L Y Tsang, Kimberley Lewis, François Lauzier, John Centofanti, Bram Rochwerg, Sarah Culgin, Katlynne Nelson, Sheryl Ann Abdukahil, Kirsten M Fiest, Henry T Stelfox, Haytham Tlayjeh, Maureen O Meade, Dan Perri, Kevin Solverson, Daniel J Niven, Rachel Lim, Morten Hylander Møller, Emilie Belley-Cote, Lehana Thabane, Hani Tamim, Deborah J Cook, Yaseen M Arabi, Covi-Prone Trial Investigators And The Saudi Critical Care Trials Group

Faculty, Staff and Student Publications

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, setting, and participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention: Patients were …

Synchronized Diaphragmatic Stimulation: A Case Report Of A Novel Extra-Cardiac Intervention For Chronic Heart Failure., Lee R Goldberg, Ana Jorbenadze, Tamaz Shaburishvilli, Michael Mirro Md, Marat Fudim, Michel Zuber, Simon F Stämpfli, Felix C Tanner, Paul Erne, John G Cleland

Parkview Heart Institute

Synchronized diaphragmatic stimulation (SDS) is a novel extra-cardiac device-based therapy for symptomatic heart failure with reduced ejection fraction. SDS provides imperceptible chronic stimulation of the diaphragm through a laparoscopically implanted system consisting of an implantable pulse generator and two sensing/stimulating leads affixed to the inferior surface of the diaphragm delivering imperceptible R-wave gaited pulses that alter intrathoracic pressure improving ventricular filling and cardiac output. We describe, in a man with a history of myocardial infarctions resulting in heart failure and persistent New York Heart Association Class III symptoms despite standard therapies, the successful implantation of SDS resulting in improved quality …

Circadian Disruption Of Hippocampus In An Early Senescence Male Mouse Model, Jennifer A Davis, Jodi R Paul, Mugdha V Mokashi, Stefani A Yates, Daniel J Mount, Hira A Munir, Lacy K Goode, Martin E Young, David B Allison, Karen L Gamble

Children’s Nutrition Research Center Staff Publications

Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice. Here we test the hypothesis that in this early senescence model, disruption of the molecular circadian clock in SAMP8 animals drives disrupted behavior and physiology. We found normal rhythms in …

Association Of Alcohol Use And Physical Activity With Body Mass Index In Mexican-Origin Adults, Natalia I Heredia, Qiong Dong, Shine Chang, Lorna H Mcneill

Faculty, Staff and Student Publications

BACKGROUND: Studies across racial/ethnic groups indicate that physical activity (PA) and alcohol consumption are positively associated, and that alcohol consumption is negatively associated with body mass index (BMI), but this relationship is less often evaluated in Hispanics. The purpose of this study was to assess the relationships between alcohol consumption, PA, and BMI in Hispanic adults.

METHODS: In this secondary data analysis of a Mexican-American cohort, we collected self-reported PA, alcohol consumption, and demographics, and measured height and weight. Linear regression assessed the association between PA and alcohol consumption with BMI, controlling for covariates. Total sample for analyses was n …

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Faculty, Staff and Student Publications

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10

Assessment Of Oral And Overall Health Parameters Using The Sillha Oral Wellness System, Shawn S Adibi, Ryan Hanson, David F Fray, Tania Abedi, Brianna Neil, Danielle Maher, Gena Tribble, Ben F Warner, Mary C Farach-Carson

Faculty, Staff and Student Publications

OBJECTIVE: The study evaluated use of a multipoint saliva analyzer to assess patient wellness in a contemporary dental practice setting.

STUDY DESIGN: Unstimulated saliva from a diverse 104 patient cohort was analyzed using the SillHa Oral Wellness System. The device measures the following 7 analytes present in the patient's oral rinse: cariogenic bacteria, acidity, buffer capacity, blood, leukocytes, protein, and ammonia. Data obtained were compared with validated clinical assessment data independently provided by credentialed dental professionals.

RESULTS: Measured leukocyte and protein levels were higher in patients with periodontal disease and/or deep gingival pockets. Patients with a history of cancer and/or …

Long-Term Outcomes Among Adolescent And Young Adult Survivors Of Acute Leukemia: A Surveillance, Epidemiology, And End Results Analysis, Amy M Berkman, Clark R Andersen, Branko Cuglievan, David C Mccall, Philip J Lupo, Susan K Parsons, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Tapan M Kadia, J A Livingston, Michael E Roth

Faculty, Staff and Student Publications

Background: There is a growing population of adolescent and young adult (AYA, age 15-39 years) acute leukemia survivors in whom long-term mortality outcomes are largely unknown.

Methods: The current study utilized the Surveillance, Epidemiology, and End Results (SEER) registry to assess long-term outcomes of AYA acute leukemia 5-year survivors. The impact of diagnosis age, sex, race/ethnicity, socioeconomic status, and decade of diagnosis on long-term survival were assessed utilizing an accelerated failure time model.

Results: A total of 1,938 AYA acute lymphoblastic leukemia (ALL) and 2,350 AYA acute myeloid leukemia (AML) survivors diagnosed between 1980 and 2009 were included with a …

Success And Outcomes Following A Second Salvage Attempt For Free Flap Compromise In Patients Undergoing Head And Neck Reconstruction, Allison A Slijepcevic, Gavin Young, Justin Shinn, Steven B Cannady, Matthew Hanasono, Matthew Old, Jeewanjot S Grewal, Tamer Ghanem, Yadranko Ducic, Joseph M Curry, Mark K Wax

Faculty, Staff and Student Publications

Importance: Incidence of perioperative free flap compromise is low, with successful salvage in up to 70%. When the flap is compromised a second time, the value of intervening is unknown.

Objective: To assess the outcomes of a second revascularization attempt for compromised free flaps.

Design, setting, and participants: This multicenter retrospective medical record review included patients undergoing head and neck reconstruction with free flaps at 6 US medical centers from January 1, 2000, through December 30, 2020. Patients were 18 years or older with a history of head and neck defects from cancer, osteoradionecrosis, or other wounds. Of 3510 flaps …

Androgen Receptor Blockade Promotes Response To Braf/Mek-Targeted Therapy, Christopher P Vellano, Michael G White, Miles C Andrews, Manoj Chelvanambi, Russell G Witt, Joseph R Daniele, Mark Titus, Jennifer L Mcquade, Fabio Conforti, Elizabeth M Burton, Matthew J Lastrapes, Gabriel Ologun, Alexandria P Cogdill, Golnaz Morad, Peter Prieto, Alexander J Lazar, Yanshuo Chu, Guangchun Han, M A Wadud Khan, Beth Helmink, Michael A Davies, Rodabe N Amaria, Jeffrey J Kovacs, Scott E Woodman, Sapna Patel, Patrick Hwu, Michael Peoples, Jeffrey E Lee, Zachary A Cooper, Haifeng Zhu, Guang Gao, Hiya Banerjee, Mike Lau, Jeffrey E Gershenwald, Anthony Lucci, Emily Z Keung, Merrick I Ross, Laura Pala, Eleonora Pagan, Rossana Lazcano Segura, Qian Liu, Mikayla S Borthwick, Eric Lau, Melinda S Yates, Shannon N Westin, Khalida Wani, Michael T Tetzlaff, Lauren E Haydu, Mikhila Mahendra, Xiaoyan Ma, Christopher Logothetis, Zachary Kulstad, Sarah Johnson, Courtney W Hudgens, Ningping Feng, Lorenzo Federico, Georgina V Long, P Andrew Futreal, Swathi Arur, Hussein A Tawbi, Amy E Moran, Linghua Wang, Timothy P Heffernan, Joseph R Marszalek, Jennifer A Wargo

Faculty, Staff and Student Publications

Treatment with BRAF/MEK-targeted therapy has revolutionized care in melanoma and other cancers, however therapeutic resistance is common and innovative treatment strategies are needed1,2. We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= <10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts2–4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male …

Nexmif Pathogenic Variants In Individuals Of Korean, Vietnamese, And Mexican Descent, Elizabeth Langley, Laura S Farach, Mary K Koenig, Hope Northrup, David F Rodriguez-Buritica, Kate Mowrey

Faculty, Staff and Student Publications

NEXMIF pathogenic variants have been known to produce a wide spectrum of X-linked intellectual disability (ID) in both males and females. Thus far, few individuals from diverse populations have been described with NEXMIF-related disorders. Herein, we report three individuals with NEXMIF pathogenic variants, the first two are the only males of Korean and Vietnamese descent described with this disorder to our knowledge. The last patient is a Hispanic female who harbors the same pathogenic variant as a previously described Caucasian individual, but with differing clinical presentation. These patients present with many classic symptoms of NEXMIF-related disorders including ID, epilepsy, developmental …

Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán

Faculty, Staff and Student Publications

Background: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.

Methods: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.

Results: A total of 211 patients were included. Mean age was 35.6 years. …

Impact Of Covid19 On Maxillofacial Fractures In The Province Of L’Aquila, Abruzzo, Italy Review Of 296 Patients Treated With Statistical Comparison Of The Two-Year Pre-Covid19 And Covid19, Filippo Giovannetti, Ettore Lupi, Danilo Di Giorgio, Secondo Scarsella, Antonio Oliva, Desiderio Di Fabio, Paolo Prata, Giada Petricca, Valentino Valentini

Faculty, Staff and Student Publications

The aim of this study was to understand the impact of the COVID-19 pandemic on the epidemiology of maxillofacial trauma in a regional trauma center in L'Aquila, Abruzzo, Italy, during the first wave of the pandemic and comparted it to an equivalent period from 2015 to 2018. The authorshave retrospectively analyzed personal data, site of trauma, etiology, and mechanism of injury. Statistical analysis has been carried out utilizing IBM SPSS Statistics software (IBM Corp., Armonk, NY) and significance was accepted for P values of 0.05) as opposed to the etiology in which the road traffic accidents decreased in favor of …

The Androgen Receptor Is A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma, Salah-Eddine Lamhamedi-Cherradi, Mayinuer Maitituoheti, Brian A Menegaz, Sandhya Krishnan, Amelia M Vetter, Pamela Camacho, Chia-Chin Wu, Hannah C Beird, Robert W Porter, Davis R Ingram, Vandhana Ramamoorthy, Sana Mohiuddin, David Mccall, Danh D Truong, Branko Cuglievan, P Andrew Futreal, Alejandra Ruiz Velasco, Nazanin Esmaeili Anvar, Budi Utama, Mark Titus, Alexander J Lazar, Wei-Lien Wang, Cristian Rodriguez-Aguayo, Ravin Ratan, J Andrew Livingston, Kunal Rai, A Robert Macleod, Najat C Daw, Andrea Hayes-Jordan, Joseph A Ludwig

Faculty, Staff and Student Publications

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the …

Genetic, Epigenetic, And Environmental Mechanisms Govern Allele-Specific Gene Expression, Celine L St Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson

2020-Current year OA Pubs

Allele-specific expression (ASE) is a phenomenon in which one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific expression, but how they contribute to this cross talk remains understudied. Here, we explored how genotype, parent-of-origin, tissue, sex, and dietary fat simultaneously influence ASE biases. Male and female mice from a F