Digital Commons Network^™

Clinical And Genetic Markers Of Vascular Toxicity In Glioblastoma Patients: Insights From Nrg Oncology Rtog-0825, Joshua D Strauss, Mark R Gilbert, Minesh Mehta, Ang Li, Renke Zhou, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Volker W Stieber, Vinay K Puduvalli, Serah Choi, Nina L Martinez, H Ian Robins, Grant K Hunter, Chi-Fan Lin, Vivian A Guedes, Melissa A Richard, Stephanie L Pugh, Terri S Armstrong, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment.

Methods: In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the …

Oncology Provider And Patient Perspectives On A Cardiovascular Health Assessment Tool Used During Posttreatment Survivorship Care In Community Oncology (Results From Wf-1804cd): Mixed Methods Observational Study, Chandylen L Nightingale, Maura Kepper, Randi E Foraker, Et Al.

2020-Current year OA Pubs

BACKGROUND: Most survivors of cancer have multiple cardiovascular risk factors, increasing their risk of poor cardiovascular and cancer outcomes. The Automated Heart-Health Assessment (AH-HA) tool is a novel electronic health record clinical decision support tool based on the American Heart Association's Life's Simple 7 cardiovascular health metrics to promote cardiovascular health assessment and discussion in outpatient oncology. Before proceeding to future implementation trials, it is critical to establish the acceptability of the tool among providers and survivors.

OBJECTIVE: This study aims to assess provider and survivor acceptability of the AH-HA tool and provider training at practices randomized to the AH-HA …

Social Media As A Platform For Cancer Care Decision-Making Among Women: Internet Survey-Based Study On Trust, Engagement, And Preferences, Anna Rose Johnson, Grace Anne Longfellow, Clara N Lee, Benjamin Ormseth, Gary B Skolnick, Mary C Politi, Yonaira M Rivera, Terence Myckatyn

2020-Current year OA Pubs

BACKGROUND: Decision aids improve patient and clinician decision-making but are underused and often restricted to clinical settings.

OBJECTIVE: Given limited studies analyzing the feasibility of disseminating decision aids through social media, this study aimed to evaluate the acceptability, trust, and engagement of women with social media as a tool to deliver online decision aids for cancer treatment.

METHODS: To prepare for potential dissemination of a breast cancer decision aid via social media, a cross-sectional survey in February 2023 was conducted via Prime Panels, an online market research platform, of women aged 35-75 years in the United States. Demographics, health, cancer …

Comparison Between Maia And Mp-3 In Healthy Subjects And Patients With Diabetes, Diabetic Retinopathy, And Age-Related Macular Degeneration, Anna Marmalidou, Haleema Siddiqui, Muhammad Usman Jamil, Kwang Min Woo, Antonio Yaghy, A. Yasin Alibhai, Hiroyuki Takahashi, Stephanie Kaiser, Keith Effert, Peter Zhao, Shilpa Desai, Christopher Robinson, Jay Duker, Nadia Waheed

SKMC Student Presentations and Publications

PURPOSE: The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.

METHODS: This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to …

Exploring Social Impairment In Those With Opioid Use Disorder: Linking Impulsivity, Childhood Trauma, And The Prefrontal Cortex, Thais Costa Macedo De Arruda, Laura Sinko, Paul Regier, Altona Tufanoglu, Adrian Curtin, Anne M. Teitelman, Hasan Ayaz, Peter F. Cronholm, Anna Rose Childress

College of Nursing Faculty Papers & Presentations

BACKGROUND: Challenges with social functioning, which is a hallmark of opioid use disorder (OUD), are a drawback in treatment adherence and maintenance. Yet, little research has explored the underlying mechanisms of this impairment. Impulsivity and corresponding neural alterations may be at the center of this issue. Childhood adversity, which has been linked to both impulsivity and poorer treatment outcomes, could also affect this relationship. This study explores the relationship between impulsivity, social functioning, and their neural correlates in the prefrontal cortex, while examining the potential moderating effects of childhood trauma in individuals recovering from OUD.

METHODS: Participants with (N = …

Researcher Perceptions Of Inclusion Of Study Participants Who Use Languages Other Than English., Henry Hoffman, Tran T. Doan, Olivia Migliori, Alisa Khan, Jaime Sidani, Sabrina Liu, Abby Jo Perez, Lani Mears, Benoit Kihumbu, Khara Timsina, Diego Chaves-Gnecco, John Cowden, Maya I. Ragavan

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite constituting 8% of the US population, people who speak languages other than English (LOE) are consistently underrepresented in health-focused research. To make research more inclusive and generalizable, it is crucial to better understand researcher perspectives on barriers to inclusion of participants using LOE and solutions to promote language justice.

OBJECTIVE: To assess researcher perspectives on barriers to and best practices for inclusion of participants using LOE and to generate strategies to make research more inclusive.

DESIGN, SETTING, AND PARTICIPANTS: This exploratory cross-sectional survey study used an anonymous digital Qualtrics survey distributed between March 1 and June 30, 2023. …

First-In-Human Clinical Trial Of A Small-Molecule Ebna1 Inhibitor, Vk-2019, In Patients With Epstein-Barr-Positive Nasopharyngeal Cancer, With Pharmacokinetic And Pharmacodynamic Studies, A Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun Lee, Maura L Gillison, Saad A Khan, Rong Lu, Benjamin A Pinsky, Samantha S Soldan, Olga Vladmirova, Paul M Lieberman, Troy E Messick

Faculty, Staff and Student Publications

Purpose: A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients and methods: Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

Results: VK-2019 was …

Targeted Normoxemia And Supplemental Oxygen-Free Days In Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial, David J Douin, John D Rice, Erin L Anderson, Conner L Jackson, Alex C Cheng, Mengli Xiao, Jessica Cwik, Laurel E Beaty, Jessica L Wild, Mohamud R Daya, Pratik B Doshi, Shannon C Eastham, Michael D Goodman, Scott R Gunn, Jason S Haukoos, Jessica A Hudson, Jan O Jansen, Jason T Mcmullan, Julie A Rizzo, Martin A Schreiber, Wesley H Self, Matthew W Semler, Aimee Steinwand, Nicole Werner, Vikhyat S Bebarta, Steven G Schauer, Adit A Ginde

Faculty, Staff and Student Publications

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, setting, and participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US. These trauma centers were randomized at 3-month intervals when they crossed over from usual care to targeting normoxemia. …

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 …

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 …

Sex Differences In Apolipoprotein E And Alzheimer Disease Pathology Across Ancestries, Xiaoyi Xu, Jiseon Kwon, Ruiqi Yan, Catherine Apio, Soomin Song, Gyujin Heo, Qijun Yang, Jigyasha Timsina, Menghan Liu, John Budde, John C Morris, Carlos Cruchaga, Yun Ju Sung, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.

OBJECTIVE: To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 …

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 …

Geographic Access To Cancer Care And Treatment And Outcomes Of Early-Stage Non-Small Cell Lung Cancer, Pratibha Shrestha, Ying Liu, James Struthers, Benjamin Kozower, Min Lian

2020-Current year OA Pubs

IMPORTANCE: Data on the impact of geographic access to cancer care on early-stage non-small cell lung cancer (NSCLC) treatment and outcomes are limited.

OBJECTIVE: To examine the associations of geographic access to cancer care with guideline-recommended treatment and outcomes in patients with early-stage NSCLC.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included patients with early-stage NSCLC newly diagnosed between January 1, 2007, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. Data analysis was performed from March to November 2024.

EXPOSURES: Geographic access to thoracic surgeons and radiation …

Assessment Of The Sensitivity Of A Smartphone App To Assist Patients In The Identification Of Stroke And Myocardial Infarction: Cross-Sectional Study, Amar Dhand, Rama Mangipudi, Anubodh S Varshney, Jonathan R Crowe, Andria L Ford, Nancy K Sweitzer, Min Shin, Samuel Tate, Haissam Haddad, Michael E Kelly, James Muller, Jay S Shavadia

2020-Current year OA Pubs

BACKGROUND: Most people do not recognize symptoms of neurological and cardiac emergencies in a timely manner. This leads to delays in hospital arrival and reduced access to therapies that can open arteries. We created a smartphone app to help patients and families evaluate if symptoms may be high risk for stroke or heart attack (myocardial infarction, MI). The ECHAS (Emergency Call for Heart Attack and Stroke) app guides users to assess their risk through evidence-based questions and a test of weakness in one arm by evaluating finger-tapping on the smartphone.

OBJECTIVE: This study is an initial step in the accuracy …

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

Trends In Kidney Allograft Failure Among First-Time Transplant Recipients In The United States, Pascale Khairallah, Elizabeth C Lorenz, Amy Waterman, Nidhi Aggarwal, Akshta Pai, Wolfgang C Winkelmayer, Jingbo Niu

Faculty, Staff and Students Publications

Rationale & objective: The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality.

Study design: Retrospective cohort study.

Setting & participants: Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019.

Exposure: The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019.

Outcome: (1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure.

Analytical approach: Competing risk …

Rising Mortality Rates Linked To Type-2 Diabetes And Obesity In The United States: An Observational Analysis From 1999 To 2022, Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow

Faculty, Staff and Students Publications

Background: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.

Methods: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.

Results: From 1999 to 2022, a …

Self-Collection For Primary Hpv Testing: Acceptability In A Large Urban Emergency Department, Itunu O Sokale, Dick C Kuo, Claire M Hoppenot, Lorraine R Reitzel, Luis H Juarez, Katherine J Hernandez, Susan L Parker, Chris Amos, Maria Daheri, Kelly R Keene, Jane R Montealegre, Aaron P Thrift

Faculty, Staff and Students Publications

Study objective: Overdue cervical cancer screening increases the risk of invasive cervical cancer. It is important to identify settings where self-collection for primary human papillomavirus (HPV) testing can be implemented to have high effect on cervical cancer screening among hard-to-reach women with overdue screening. Herein, we examined the acceptability of HPV self-collection, including completion rates, attitudes, and experiences among women seeking noncritical care at a high-volume urban safety-net hospital emergency department (ED) in Houston, Texas, United States.

Methods: In this single-arm intervention pilot study, we recruited women overdue for cervical cancer screening in the waiting areas of a safety-net hospital …

Reply: A Positive Step Toward Cost-Effective And Accessible Hcc Detection Awaits Further Validation, Hashem B El-Serag, Qingchun Jin, Tayob Nabihah

Faculty, Staff and Students Publications

No abstract provided.

Exploration Of Cytokines And Microbiome Among Males And Females With Diarrhea-Predominant Irritable Bowel Syndrome, Li Juen Chen, Anna M Plantinga, Robert Burr, Kevin Cain, Pamela Barney, Tor Savidge, Robert J Shulman, Margaret Heitkemper, Kendra Kamp

Faculty, Staff and Students Publications

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine …

Shifting Tuberculosis Dynamics In The Eu/Eea: Geographical And Drug Resistance Trends Among People Of Foreign Origin, 2019 To 2023, Anca Vasiliu, Veronica Cristea, Krista Stoycheva, Senia Rosales-Klintz, Christoph Lange, Dominik Zenner, Csaba Ködmön

Faculty, Staff and Students Publications

We observed shifting trends in tuberculosis (TB) epidemiology in the EU/EEA between 2019 and 2023. In 2023, TB notifications among people of foreign origin increased by 24.6% after decreasing between 2019 and 2020. The majority originated from African and East Mediterranean regions, with a 316.4% upsurge in TB among Ukrainians in 2022-23. Rifampicin-resistant/multidrug-resistant TB increased by ≥ 60% in 2019-23, mainly among Ukrainians. Rapid response to shifting epidemiological patterns is crucial for efficient TB prevention and control within the EU/EEA.

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 …

Genetic Characterization Of A Large Cohort Of Individuals With A Clinical Suspicion Of Hypophosphatasia In The United States., Eric T. Rush, Guillermo Del Angel, Juan Dong, Toby Bates, Robert D. Steiner, Allison Cox

Manuscripts, Articles, Book Chapters and Other Papers

Hypophosphatasia (HPP) is a rare metabolic disease resulting from variants in ALPL, inherited in an either autosomal recessive or autosomal dominant manner. Sponsored clinical ALPL testing was offered in the US for individuals with a clinical suspicion of HPP. Gene variants were assessed to determine the likelihood of identifying disease-causing variants, uncover genotype-phenotype relationships, and for further understanding of ALPL variants in the US HPP population. Variants were detected by Sanger sequencing and classified as pathogenic or likely pathogenic (P/LP; positive test result), variant(s) of uncertain significance (indeterminate test result), benign or likely benign (negative test result), or no variants …

Liver Involvement In A Large Cohort Of Patients With Erythropoietic Protoporphyria Or X-Linked Protoporphyria, Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine Mcdonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan Mcguire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani, Porphyrias Consortium Of The Rare Diseases Clinical Research Network

Faculty, Staff and Student Publications

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at …

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …