Medicine and Health Sciences Commons^™

Connectome-Based Predictive Modeling Of Ptsd Development Among Recent Trauma Survivors, Ziv Ben-Zion, Alexander J Simon, Matthew Rosenblatt, Nachshon Korem, Or Duek, Israel Liberzon, Arieh Y Shalev, Talma Hendler, Ifat Levy, Ilan Harpaz-Rotem, Dustin Scheinost

Staff and Researcher Publications

Importance: The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments.

Objective: To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors.

Design, setting, and participants: This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Clinical Performance Of An N-Terminal Pro-B-Type Natriuretic Peptide Assay In Acute Heart Failure Diagnosis, Lori B Daniels, Patience Ajongwen, Robert H Christenson, Carol L Clark, Deborah B Diercks, Gregory J Fermann, Sharon E Mace, Simon A Mahler, Peter S Pang, Zubaid Rafique, Michael S Runyon, James Tauras, Christopher R Defilippi

Faculty, Staff and Students Publications

Background: We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea.

Methods: Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL). Additional measures were area under the curve (AUC) for receiver operating characteristic (ROC) curves. Results were also interpreted in patient subgroups with relevant …

Epstein-Barr Virus Sequence Variations Among The Understudied Nasopharyngeal Carcinoma Patients Of Diverse Ancestries In Southeast Asia, Hwee Sze Tee, Jingtong Liang, Norazlin Abdul Aziz, Xiang Zhou, Hamidah Akmal Hisham, Ke-En Tan, Yanhong Chen, Zuriani Burhanuddin, Johnny S.H. Kwan, Kwok-Wai Lo, Faridah Hassan, Sha'ariyah Bt Mohd Mokhtar, Alan Soo Beng Khoo, Miao Xu, Yat-Yuen Lim, Lu Ping Tan

Department of Medical Oncology Faculty Papers

Epstein-Barr virus (EBV) is associated with cancers, including lymphomas and nasopharyngeal carcinoma (NPC). To date, risk variants for NPC were mainly identified from Chinese populations, which dominated the world's total number of cases. Although Southeast Asia (SEA) countries have among the world's top yet intriguingly diverse NPC age-standardized incidence rates across subpopulations, data on EBV from SEA remains scarce. In this study, we examined 83 NPC patients of different ancestries for the presence of risk haplotypes associated with the Southern Chinese NPC and generated and analyzed 67 EBV sequences (from tissue, patient-derived xenografts and lymphoblastoid cell lines of 60 NPC …

Visual Field Progression In The Ocular Hypertension Treatment Study, Mae O Gordon, Dale K Heuer, Eve J Higginbotham, Richard K Parrish, Lei Liu, James D Brandt, Julia B Huecker, J Phillip Miller, Chamila Perera, Chris Xie, John L Keltner, Chris A Johnson, Stuart K Gardiner, Jeffrey M Liebmann, Michael A Kass

2020-Current year OA Pubs

PURPOSE: To determine the rate of visual field (VF) loss before and after the diagnosis of primary open angle glaucoma (POAG) in the Ocular Hypertension Treatment Study (OHTS).

DESIGN: Prespecified analyses of data collected prospectively in a clinical trial with extended follow-up.

SETTING AND PARTICIPANTS: Participants who developed POAG during OHTS 1 and 2 (February 1994 to December 2008) constitute an inception cohort. Follow-up data were collected in OHTS 3 (January 2016-April 2019). Analyses were performed from July 2021 to August 2022.

INTERVENTION: In OHTS 1 and 2, visual field (VF) tests were performed every 6 months and stereoscopic optic …

The Vivid Trial 12-Month Outcomes Of The Venous Stent For The Iliofemoral Vein Using The Duo Venous Stent System., Mahmood Razavi, Michael Lichtenberg, Kush Desai, David Dexter, Peter Soukas, Nicolas Shammas, Ankur Lodha, Paul Gagne, Anna Nordell, Raghu Kolluri, Mark Garcia

Heart and Vascular Articles

OBJECTIVE: There are varying anatomical and mechanical demands of stent placement in the iliofemoral venous segment; the Duo Venous Stent System is designed to address these issues. The purpose of the VIVID (Venous stent for the Iliofemoral Vein Investigational clinical trial using the Duo Venous Stent System) study was to investigate the safety and efficacy of the Duo Venous Stent System for the treatment of patients with nonmalignant iliofemoral venous obstructive disease.

METHODS: This was an international, prospective, multicenter, single-arm study that enrolled patients with symptomatic nonthrombotic (NT), post-thrombotic (PTS), or acute deep vein thrombotic (aDVT) iliofemoral venous outflow obstruction. …

Rationale And Design Of The Defiance Study: A Randomized Controlled Trial Of Mechanical Thrombectomy Versus Anticoagulation Alone For Iliofemoral Deep Vein Thrombosis., Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black

Heart and Vascular Articles

BACKGROUND: Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.

METHODS: The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, …

Just As Expected? Older Adults’ Aging Expectations Are Associated With Subjective Cognition, Nikki Hill, Sakshi Bhargava, Justin Do, Emily Bratlee-Whitaker, Monique Brown, Renata Komalasari, Rachel Wu, Jacqueline Mogle

SKMC Student Presentations and Publications

OBJECTIVES: This study investigated the relationship between older adults' expectations regarding aging and subjective cognition. Specifically, we examined whether the three domains of aging expectations (physical health, mental health, and cognitive function) were associated with two aspects of subjective cognition: current subjective cognition and subjective cognitive decline (SCD).

METHOD: An online survey was conducted among U.S. adults aged 65-90 (N = 581; M_age=71.4, SD ± 4.81; 51% female). Measures included the 12-item Expectations Regarding Aging scale, the 8-item PROMIS Cognitive Abilities scale (current subjective cognition), and the 12-item Everyday Cognition scale (SCD). We used generalized linear models …

"Inpatient Pharmacological Thromboprophylaxis In The Antepartum Period: An Argument For Universal Thromboprophylaxis", Julia Burd, Amanda Zofkie

2020-Current year OA Pubs

Venous thromboembolism (VTE), a largely preventable condition, accounts for almost 15% of maternal mortalities. The physiologic changes of pregnancy, including quantitative changes in coagulation factors and compression of vasculature by the gravid uterus, cause an increase in risk of VTE, including deep vein thromboembolism (DVT), pulmonary embolism, and stroke (CVA). Long term antepartum admission for preeclampsia, preterm prelabor rupture of membranes (PPROM) or other high-risk pregnancy needs present additional risk factors for VTE due to the patient's medical condition and their inpatient status. Given the near-universal support for anticoagulation in patients with a history of venous thromboembolism or high-risk thrombophilia, …

Local Genetic Covariance Analysis With Lipid Traits Identifies Novel Loci For Early-Onset Alzheimer's Disease, Nicholas R. Ray, Joseph Bradley, Elanur Yilmaz, Caghan Kizil, Jiji T. Kurup, Eden R. Martin, Hans-Ulrich Klein, Brian W Kunkle, David A. Bennett, Philip L. De Jager, Alzheimer’S Disease Genetics Consortium, Gary W. Beecham, Carlos Cruchaga, Christiane Reitz

2020-Current year OA Pubs

The genetic component of early-onset Alzheimer disease (EOAD), accounting for ~10% of all Alzheimer's disease (AD) cases, is largely unexplained. Recent studies suggest that EOAD may be enriched for variants acting in the lipid pathway. The current study examines the shared genetic heritability between EOAD and the lipid pathway using genome-wide multi-trait genetic covariance analyses. Summary statistics were obtained from the GWAS meta-analyses of EOAD by the Alzheimer's Disease Genetics Consortium (n=19,668) and five blood lipid traits by the Global Lipids Genetics Consortium (n=1,320,016). The significant results were compared between the EOAD and lipids GWAS and genetic covariance analyses were …

Transcranial Vibration Stimulation At 40 Hz Induced Neural Activity And Promoted The Coupling Of Global Brain Activity And Cerebrospinal Fluid Flow, Linghan Kong, Wei Jin, Yue Jiang, Fuhua Yan, Jun Liu, Eric C Leuthardt, Guang-Zhong Yang, Yuan Feng

2020-Current year OA Pubs

BACKGROUND: Neuroscience advances have highlighted the potential of non-invasive brain stimulation in influencing cognitive and emotional processes. Conventional stimulation methods such as electrical, magnetic, and ultrasound have been studied intensively, but little is known about the mechanical stimulation.

OBJECTIVE: To investigate the effects of 40 Hz transcranial vibration stimulation (TVS) on human brain activity, specifically focusing on changes in the Amplitude of Low-Frequency Fluctuation (ALFF), fractional ALFF (fALFF) and Regional Homogeneity (ReHo) as measures of spontaneous brain activity. Additionally, this study investigates alterations in the global blood-oxygen-level-dependent (gBOLD) signal and cerebrospinal fluid (CSF) inflow coupling, which serve as indicators of …

Prognostic, Biological, And Structural Implications Of Flt3-Jmd Point Mutations In Acute Myeloid Leukemia: An Analysis Of Alliance Studies, Nadeen Anabtawi, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients. Patients with FLT3-JMD mutations had a higher relapse rate and shorter disease-free survival than those with FLT3-TKD, whereas their relapse rate, disease-free and overall survival were not significantly different from those of …

Zanubrutinib Versus Bendamustine And Rituximab In Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up Of Sequoia, Mazyar Shadman, Brad S Kahl, Et Al.

2020-Current year OA Pubs

No abstract provided.

Decreased Voluntary Alcohol Intake And Ventral Striatal Epigenetic And Transcriptional Remodeling In Male Acss2 Ko Mice, Gabor Egervari, Greg Donahue, Natalia A Quijano Cardé, Desi C Alexander, Connor Hogan, Jessica K Shaw, Erica M Periandri, Vanessa Fleites, Mariella De Biasi, Shelley L Berger

2020-Current year OA Pubs

Metabolic-epigenetic interactions are emerging as key pathways in regulating alcohol-related transcriptional changes in the brain. Recently, we have shown that this is mediated by the metabolic enzyme Acetyl-CoA synthetase 2 (Acss2), which is nuclear and chromatin-bound in neurons. Mice lacking ACSS2 fail to deposit alcohol-derived acetate onto histones in the brain and show no conditioned place preference for ethanol reward. Here, we further explored the role of this pathway during voluntary alcohol intake. We found that Acss2 KO mice consume significantly less alcohol in a model of binge drinking, an effect primarily driven by males. Genome-wide transcriptional profiling of 7 …

Care Utilization For Acute Respiratory Infections In Children Requiring Invasive Long-Term Mechanical Ventilation, Carolyn C Foster, Todd A Florin, Derek J Williams, Katherine L Freundlich, Rebecca L Steuart, Julia A Heneghan, Cara Cecil, Nathan M Pajor, Robert J Graham, Sriram Ramgopal

Faculty, Staff and Student Publications

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.S. children's hospital emergency department (ED) and hospital encounters for patients (< 21 years) with LTMV and an ARI diagnosis code (10/1/2016-6/30/2023). We examined mortality and ED/hospital utilization outcomes, defining short-stay hospitalizations as ≤ 2 calendar days. We stratified analyses by high intensity neurologic impairment (HINI) using a validated coding algorithm.

Results: We included 4866 patients (median age 4.5 years; 58.6% male) with LTMV and ≥ 1 ARI encounter. Most (95.1%) were hospitalized on their index encounter, and …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

The Changing Faces Of Academic Family Medicine Leadership: A Cera Secondary Analysis., Bryce A Ringwald, Yasamine Edwards, Sarah Vengal, Jon Montemayor, Carter Ringwald

Medical Education Articles

BACKGROUND AND OBJECTIVES: Diversity, equity, and inclusion (DEI) efforts strive to create a physician workforce that represents the general population. Barriers remain, however, regarding the promotion of women and underrepresented in medicine (URiM) physicians. We sought to describe gender and race trends in academic family medicine leadership over the past decade.

METHODS: We performed a secondary analysis of Council of Academic Family Medicine Educational Research Alliance clearinghouse data, examining demographic survey responses from available surveys of family medicine clerkship directors (CDs), program directors (PDs), and department chairs from 2011 to 2023.

RESULTS: During the time studied, family medicine CDs female …

Training Protocol And Calibration Of The International Caries Detection And Assessment System In A School-Based Clinical Trial Of Elementary School-Age Children, Jose-Miguel Yamal, Dania Mofleh, Ru-Jye Chuang, Mengxi Wang, Kila Johnson, Alejandra Garcia-Quintana, Tolulope Titiloye, Suchitra Nelson, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting.

Methods: ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify …

Predicting Fatal Opioid-Involved Overdoses: A Social-Ecological Framework Matched To A Linked-Data Warehouse, Ric Bayly, Jack Cordes, Dana Bernson, Leland K Ackerson, Marc R Larochelle, Ghada H Hassan, Cici X Bauer, Thomas J Stopka

Faculty, Staff and Student Publications

Background: An estimated 60 million people used opioids non-medically worldwide in 2021. In 2019, opioid use disorder caused the loss of over 12.5 million healthy years of life due to disability and premature deaths, including those resulting from opioid-involved overdoses. Factors associated with opioid-involved overdoses are numerous, multi-layered, and interrelated. Using the social-ecological model as a foundation, we sought to comprehensively identify risk and preventive factors of fatal opioid-involved overdoses and operationalize them with quantifiable measures.

Methods: With our Community Advisory Board, investigators' expertise, and an examination of the literature, we created an expansive, opioid-overdose specific social-ecological model structured as …

Risk Of Traumatic Brain Injury In Deployment And Nondeployment Settings Among Members Of The Millennium Cohort Study, Kalyn C Jannace, Lisa Pompeii, David Gimeno Ruiz De Porras, William Brett Perkison, Jose-Miguel Yamal, Daniel W Trone, Rudolph P Rull

Faculty, Staff and Student Publications

Objective: To describe and quantify the prevalence and risk of deployment and nondeployment service-related traumatic brain injury (TBI) among participants of the Millennium Cohort Study.

Setting: Survey data.

Participants: 28 759 Millennium Cohort Study participants who were active duty, Reserves, or National Guard at the time of the survey.

Design: Cross-sectional secondary data analysis.

Main measures: Estimates of prevalence and rates of TBI were calculated. Multivariable Poisson regression estimated rate ratios of TBI overall and stratified by deployment and nondeployment settings.

Results: The rate of TBI over the 362 535 person-years (PY) was 2.95 p/100 PY. the nondeployment rate was …

An Adaptive Antiretroviral Therapy Adherence Intervention For Youth With Hiv Through Text Message And Cell Phone Support With And Without Incentives: A Sequential Multiple Assignment Randomized Trial (Smart), Marvin E Belzer, Karen Macdonell, Demetria Cain, Samiran Ghosh, Richard Zhao, Julie Mcavoy-Banerjea, Sitaji Gurung, Sylvie Naar

Faculty, Staff and Student Publications

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL < 200 or adherence > 80% after the initial 3 months were rerandomized to usual care …

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …

Regional Lung Ventilation During Supraglottic And Subglottic Jet Ventilation: A Randomized Cross-Over Trial, Marita Windpassinger, Michal Prusak, Jana Gemeiner, Maximilian Edlinger-Stanger, Imme Roesner, Doris-Maria Denk-Linnert, Olga Plattner, Ahmed Khattab, Eugenijus Kaniusas, Lu Wang, Daniel I Sessler

Faculty, Staff and Student Publications

Objective: Test the hypothesis that the center of ventilation, a measure of ventro-dorsal atelectasis, is posterior during supraglottic ventilation indicating better dependent-lung ventilation. Secondarily, we tested the hypothesis that supraglottic ventilation improves oxygenation and carbon dioxide elimination.

Background: Supraglottic and subglottic jet ventilation are both used during laryngotracheal surgery. Supraglottic jet ventilation may better prevent atelectasis and provide superior ventilation.

Design: Randomized, cross-over trial.

Setting: Operating rooms.

Patients: Patients having elective micro-laryngotracheal surgery.

Interventions: Patients were sequentially ventilated for 5 min with one randomly selected type of jet ventilation before being switched to the alternative method.

Measurements: Regional ventilation distribution …

Bevacizumab Beyond Progression: Impact Of Subsequent Bevacizumab Re-Treatment In Patients With Ovarian, Fallopian Tube, And Peritoneal Cancer After Progression, Amma Asare, Rebecca Ann Previs, Daniel Spinosa, Bryan Fellman, Amelia L Scott, Isabelle Mulder, May Mahmoud, Ahmed Enbaya, Jean Hansen Siedel, Lauren Cobb, Pamela T Soliman, Anil K Sood, Robert L Coleman, Angeles Alvarez Secord, Shannon N Westin

Faculty, Staff and Student Publications

Background: This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.

Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results: Among 226 patients with OC …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Exome Sequencing Identifies Helb As A Novel Susceptibility Gene For Non-Mucinous, Non-High-Grade-Serous Epithelial Ovarian Cancer, Ed M Dicks, Jonthan P Tyrer, Suzana Ezquina, Michelle Jones, John Baierl, Pei-Chen Peng, Michael Diaz, Ellen Goode, Stacey J Winham, Thilo Dörk, Toon Van Gorp, Anna De Fazio, David D L Bowtell, Dale W Garsed, Kunle Odunsi, Kirsten Moysich, Marina Pavanello, Florentia Fostira, Penelope M Webb, Jana Soukupová, Paul A Cohen, Weiva Sieh, Renée Turzanski Fortner, Charite Ricker, Beth Karlan, Ian Campbell, James D Brenton, Susan J Ramus, Simon A Gayther, Paul D P Pharoah

Faculty, Staff and Student Publications

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which …

Immunelens Characterizes Systemic Immune Dysregulation In Aging And Cancer, Robert Bentham, Thomas P Jones, James R M Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas B K Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, Genomics England Consortium, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower …

Cervical Necrotizing Fasciitis And Shock In The Post-Operative Pediatric Patient., Paul Bryan Hankey, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Cervical necrotizing fasciitis (CNF) is a rare infection that can quickly lead to devastating patient outcomes. Considering the vital importance of surrounding neck structures, rapid control of the infection is essential. Infection is most frequently polymicrobial and occurs in the adult patient in the context of certain medical comorbidities. Complications are typically limited to tissue destruction in the form of necrosis. There are no current reports describing CNF complicated by acute shock in the post-operative pediatric patient. Here, we present a pediatric case of CNF complicated by acute shock following Sistrunk procedure for removal of a supposed thyroglossal duct cyst. …

Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong

Faculty, Staff and Student Publications

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Methods: Human serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1KO) mice were fed a 45% high-fat diet, with serum samples collected every 2 weeks to monitor LRG1 and insulin levels throughout diet-induced obesity. MIN6 beta cells were used to investigate the effects …

Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography, Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Significance: Systemic sclerosis (SSc) is a chronic idiopathic disease that causes immune dysregulation, vasculopathy, and organ fibrosis that affects more than 3 million people in the US alone. The modified Rodnan skin score (mRSS) is the current gold standard for diagnosing and staging skin fibrosis in SSc. However, mRSS is subjective, requires extensive training, and has high observer variability.

Aim: We aim to provide a quantitative method for the assessment of fibrosis.

Approach: We utilized optical coherence tomography (OCT), its extensions, optical coherence elastography (OCE), and OCT angiography (OCTA) to evaluate SSc-like fibrosis and therapy response in a mouse model. …