Medical Specialties Commons^™

Analysis Of Outcomes Associated With Outpatient Management Of Nonoperatively Treated Patients With Appendicitis, Writing Group For The Coda Collaborative, David A Talan, Gregory J Moran, Anusha Krishnadasan, Sarah E Monsell, Brett A Faine, Lisandra Uribe, Amy H Kaji, Daniel A Deugarte, Wesley H Self, Nathan I Shapiro, Joseph Cuschieri, Jacob Glaser, Pauline K Park, Thea P Price, Nicole Siparsky, Sabrina E Sanchez, David A Machado-Aranda, Jesse Victory, Patricia Ayoung-Chee, William Chiang, Joshua Corsa, Heather L Evans, Lisa Ferrigno, Luis Garcia, Quinton Hatch, Marc D Horton, Jeffrey Johnson, Alan Jones, Lillian S Kao, Anton Kelly, Daniel Kim, Matthew E Kutcher, Mike K Liang, Nima Maghami, Karen Mcgrane, Elizaveta Minko, Cassandra Mohr, Miriam Neufeld, Joe H Patton, Colin Rog, Amy Rushing, Amber K Sabbatini, Matthew Salzberg, Callie M Thompson, Aleksandr Tichter, Jon Wisler, Bonnie Bizzell, Erin Fannon, Sarah O Lawrence, Emily C Voldal, Danielle C Lavallee, Bryan A Comstock, Patrick J Heagerty, Giana H Davidson, David R Flum, Larry G Kessler

Faculty, Staff and Student Publications

IMPORTANCE: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs.

OBJECTIVE: To assess the use and safety of outpatient management of acute appendicitis.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February …

Distress Tolerance: Prospective Associations With Cognitive-Behavioral Therapy Outcomes In Adults With Posttraumatic Stress And Substance Use Disorders, Anka A Vujanovic, Heather E Webber, Shelby J Mcgrew, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage= 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory …

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 …

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 …

Association Of Rare Apoe Missense Variants V236e And R251g With Risk Of Alzheimer Disease, Yann Le Guen, Michael E Belloy, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo-Morales, Iris Jansen, Aude Nicolas, Céline Bellenguez, Carolina Dalmasso, Fahri Küçükali, Sarah J Eger, Katrine Laura Rasmussen, Jesper Qvist Thomassen, Jean-François Deleuze, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Cornelia Van Duijn, Magda Tsolaki, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M Van Der Flier, Alfredo Ramirez, Ole A Andreassen, Ruth Frikke-Schmidt, Julie Williams, Agustín Ruiz, Jean-Charles Lambert, Michael D Greicius, Members Of The Eadb, Gr@Ace, Degesco, Demgene, Gerad, And Eadi Groups, Beatrice Arosio, Luisa Benussi, Anne Boland, Barbara Borroni, Paolo Caffarra, Delphine Daian, Antonio Daniele, Stéphanie Debette, Carole Dufouil, Emrah Düzel, Daniela Galimberti, Vilmantas Giedraitis, Timo Grimmer, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Deckert Jürgen, Teemu Kuulasmaa, Aad Van Der Lugt, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Susanne Moebus, Benedetta Nacmias, Gael Nicolas, Robert Olaso, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Oliver Peters, Yolande A L Pijnenburg, Julius Popp, Innocenzo Rainero, Inez Ramakers, Steffi Riedel-Heller, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Hilkka Soininen, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Thomas J Tegos, Lucio Tremolizzo, Frans Verhey, Martin Vyhnalek, Jens Wiltfang, Mercè Boada, Pablo García-González, Raquel Puerta, Luis M Real, Victoria Álvarez, María J Bullido, Jordi Clarimon, José María García-Alberca, Pablo Mir, Fermin Moreno, Pau Pastor, Gerard Piñol-Ripoll, Laura Molina-Porcel, Jordi Pérez-Tur, Eloy Rodríguez-Rodríguez, Jose Luís Royo, Raquel Sánchez-Valle, Martin Dichgans, Dan Rujescu

Faculty, Staff and Students Publications

IMPORTANCE: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly.

OBJECTIVE: To determine whether rare missense variants on APOE are associated with AD risk.

DESIGN, SETTING, …

Analysis Of An Antibiotic Stewardship Program For Asymptomatic Bacteriuria In The Veterans Affairs Health Care System, Larissa Grigoryan, Aanand D Naik, Paola Lichtenberger, Christopher J Graber, Payal K Patel, Dimitri M Drekonja, Timothy P Gauthier, Bhavarth Shukla, Anne E Sales, Sarah L Krein, John N Van, Laura M Dillon, Sylvia J Hysong, Jennifer R Kramer, Annette Walder, David Ramsey, Barbara W Trautner

Faculty, Staff and Students Publications

IMPORTANCE: Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited.

OBJECTIVE: To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB.

DESIGN, SETTING, AND PARTICIPANTS: This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect …

White Coat Hypertension Persistence In Children And Adolescents: The Pediatric Nephrology Research Consortium Study, Yosuke Miyashita, Coral Hanevold, Anna Faino, Julia Scher, Marc Lande, Ikuyo Yamaguchi, Joel Hernandez, Alisa Acosta, Donald J Weaver, Jason Thomas, Mahmoud Kallash, Michael Ferguson, Ketan N Patel, Andrew M South, Megan Kelton, Joseph T Flynn

Faculty, Staff and Students Publications

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM.

STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We …

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 …

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 …

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. …

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 …

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. …

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 …

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 …

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 …

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 …

Prognosticators Of Visual Acuity After Indirect Traumatic Optic Neuropathy, Alex J Wright, Joanna H Queen, Emilio P Supsupin, Alice Z Chuang, John J Chen, Rod Foroozan, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON).

METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

Discovery Of Potent Bet Bromodomain 1 Stereoselective Inhibitors Using Dna-Encoded Chemical Library Selections, Ram K Modukuri, Zhifeng Yu, Zhi Tan, Hai Minh Ta, Melek Nihan Ucisik, Zhuang Jin, Justin L Anglin, Kiran L Sharma, Pranavanand Nyshadham, Feng Li, Kevin Riehle, John C Faver, Kevin Duong, Sureshbabu Nagarajan, Nicholas Simmons, Stephen S Palmer, Mingxing Teng, Damian W Young, Joanna S Yi, Choel Kim, Martin M Matzuk

Duncan NRI Faculty and Staff Publications

BRDT, BRD2, BRD3, and BRD4 comprise the bromodomain and extraterminal (BET) subfamily which contain two similar tandem bromodomains (BD1 and BD2). Selective BD1 inhibition phenocopies effects of tandem BET BD inhibition both in cancer models and, as we and others have reported of BRDT, in the testes. To find novel BET BD1 binders, we screened >4.5 billion molecules from our DNA-encoded chemical libraries with BRDT-BD1 or BRDT-BD2 proteins in parallel. A compound series enriched only by BRDT-BD1 was resynthesized off-DNA, uncovering a potent chiral compound, CDD-724, with >2,000-fold selectivity for inhibiting BRDT-BD1 over BRDT-BD2. CDD-724 stereoisomers exhibited remarkable differences in …

Poloxamer 407 Induces Hypertriglyceridemia But Decreases Atherosclerosis In Ldlr -/- Mice, Xueying Peng, Zeqin Lian, Xiao-Yuan Dai Perrard, Yunjie Xiao, Jing Ni, Veronica O'Brien, Henry Dong, Henry J Pownall, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

Background: Hypertriglyceridemia (HTG) increases the risk for atherosclerotic cardiovascular disease, but underlying mechanisms are incompletely understood. Circulating monocytes play an important role in atherogenesis by infiltrating arterial walls, where they differentiate into macrophages. We tested the hypothesis that HTG is mechanistically linked to atherogenesis by altering the monocyte phenotype and infiltration into atherosclerotic lesions in a model of diet-induced atherogenesis in Ldlr−/− mice. Methods: HTG was induced in male Ldlr−/− mice, fed a Western, high-fat high-cholesterol diet, by daily injection of poloxamer 407 (P407), a lipoprotein lipase inhibitor, for seven weeks. Atherosclerosis, monocyte phenotypes, and monocyte migration into atherosclerotic lesions …

Early Short Course Of Neuromuscular Blocking Agents In Patients With Covid-19 Ards: A Propensity Score Analysis., Gianluigi Li Bassi, Kristen Gibbons, Jacky Y Suen, Heidi J Dalton, Nicole White, Amanda Corley, Sally Shrapnel, Samuel Hinton, Simon Forsyth, John G Laffey, Eddy Fan, Jonathon P Fanning, Mauro Panigada, Robert Bartlett, Daniel Brodie, Aidan Burrell, Davide Chiumello, Alyaa Elhazmi, Mariano Esperatti, Giacomo Grasselli, Carol Hodgson, Shingo Ichiba, Carlos Luna, Eva Marwali, Laura Merson, Srinivas Murthy, Alistair Nichol, Mark Ogino, Paolo Pelosi, Antoni Torres, Pauline Yeung Ng, John F Fraser

Department of Anesthesiology Faculty Papers

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis.

METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 …

Burden Of Cardiovascular Risk Factors And Disease In Five Asian Groups In Catalonia: A Disaggregated, Population-Based Analysis Of 121 000 First-Generation Asian Immigrants, Priyanka Satish, Emili Vela, Usama Bilal, Montse Cleries, Alka M Kanaya, Namratha Kandula, Salim S Virani, Nadia Islam, Javier Valero-Elizondo, Tamer Yahya, Josep Comin-Colet, Khurram Nasir, Josepa Mauri, Miguel Cainzos-Achirica

Faculty, Staff and Students Publications

AIMS: To evaluate the burden of cardiovascular risk factors and disease (CVD) among five Asian groups living in Catalonia (Spain): Indian, Pakistani, Bangladeshi, Filipino, and Chinese.

METHODS AND RESULTS: Retrospective cohort study using the Catalan Health Surveillance System database including 42 488 Pakistanis, 40 745 Chinese, 21 705 Indians, 9544 Filipinos, and 6907 Bangladeshis; and 5.3 million native individuals ('locals'). We estimated the age-adjusted prevalence (as of 31 December 2019) and incidence (during 2019) of diabetes, hypertension, hyperlipidaemia, obesity, tobacco use, coronary heart disease (CHD), cerebrovascular disease, atrial fibrillation, and heart failure (HF). Bangladeshis had the highest prevalence of diabetes …