Medicine and Health Sciences Commons^™

Proteomic Associations Of Adverse Outcomes In Human Heart Failure, Marie-Joe Dib, Ahmed Diab, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying novel molecular drivers of disease progression in heart failure (HF) is a high-priority goal that may provide new therapeutic targets to improve patient outcomes. The authors investigated the relationship between plasma proteins and adverse outcomes in HF and their putative causal role using Mendelian randomization.

METHODS AND RESULTS: The authors measured 4776 plasma proteins among 1964 participants with HF with a reduced left ventricular ejection fraction enrolled in PHFS (Penn Heart Failure Study). Assessed were the observational relationship between plasma proteins and (1) all-cause death or (2) death or HF-related hospital admission (DHFA). The authors replicated nominally significant …

Associations Of Geographic-Based Socioeconomic Factors And Hpv Vaccination Among Male And Female Children In Five Us States, Serena Xiong, Sarah Humble, Alan Barnette, Heather Brandt, Vetta Thompson, Lisa M Klesges, Michelle I Silver

2020-Current year OA Pubs

BACKGROUND: We assessed whether five geographic-based socioeconomic factors (medically underserved area (MUA); healthcare provider shortage area (HPSA); persistent poverty; persistent child poverty; and social vulnerability index (SVI)) were associated with the odds of HPV vaccination initiation, series completion, and parental vaccine hesitancy, and whether the observed relationships varied by gender of the child.

METHODS: An online panel service, administered through Qualtrics®, was used to recruit parents of adolescents 9-17 years of age to complete a one-time survey in 2021. Coverage of the panel included five US states: Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois. Generalized estimating equation (GEE) models were …

Prevalence, Morbidity, And Mortality Of Men With Sex Chromosome Aneuploidy In The Million Veteran Program Cohort, Shanlee Davis, Craig Teerlink, Julie Lynch, Bryan Gorman, Meghana Pagadala, Aoxing Liu, Matthew Panizzon, Victoria Merritt, Giulio Genovese, Judith Ross, Richard Hauger

Department of Pediatrics Faculty Papers

IMPORTANCE: The reported phenotypes of men with 47,XXY and 47,XYY syndromes include tall stature, multisystem comorbidities, and poor health-related quality of life (HRQOL). However, knowledge about these sex chromosome aneuploidy (SCA) conditions has been derived from studies in the less than 15% of patients who are clinically diagnosed and also lack diversity in age and genetic ancestry.

OBJECTIVES: To determine the prevalence of clinically diagnosed and undiagnosed X or Y chromosome aneuploidy among men enrolled in the Million Veteran Program (MVP); to describe military service metrics of men with SCAs; and to compare morbidity and mortality outcomes between men with …

Adipose Tissue Dysfunction And Energy Balance Paradigms In People Living With Hiv, Claudia E Ramirez Bustamante, Neeti Agarwal, Aaron R Cox, Sean M Hartig, Jordan E Lake, Ashok Balasubramanyam

Faculty, Staff and Students Publications

Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy, including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy. These conditions may coexist with generalized obesity in PLWH and reflect disturbances of energy balance regulation caused by HIV persistence and antiretroviral therapy drugs. Adipocyte hypertrophy characterizes visceral …

Intraoperative Evaluation Of Breast Tissues During Breast Cancer Operations Using The Masspec Pen, Kyana Y Garza, Mary E King, Chandandeep Nagi, Rachel J Dehoog, Jialing Zhang, Marta Sans, Anna Krieger, Clara L Feider, Alena V Bensussan, Michael F Keating, John Q Lin, Min Woo Sun, Robert Tibshirani, Christopher Pirko, Kirtan A Brahmbhatt, Ahmed R Al-Fartosi, Alastair M Thompson, Elizabeth Bonefas, James Suliburk, Stacey A Carter, Livia S Eberlin

Faculty, Staff and Students Publications

IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult …

Reports Of Covid-19 Vaccine Adverse Events In Predominantly Republican Vs Democratic States, David A Asch, Chongliang Luo, Yong Chen

2020-Current year OA Pubs

IMPORTANCE: Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored.

OBJECTIVE: To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican …

Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton

Faculty, Staff and Student Publications

IMPORTANCE: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed.

OBJECTIVE: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the …

A Genotyping Array For The Globally Invasive Vector Mosquito, Aedes Albopictus, Luciano Veiga Cosme, Margaret Corley, Thomas Johnson, Dave W Severson, Guiyun Yan, Xiaoming Wang, Nigel Beebe, Andrew Maynard, Mariangela Bonizzoni, Ayda Khorramnejad, Ademir Jesus Martins, José Bento Pereira Lima, Leonard E Munstermann, Sinnathamby N Surendran, Chun-Hong Chen, Kevin Maringer, Isra Wahid, Shomen Mukherjee, Jiannon Xu, Michael C Fontaine, Elizabet L Estallo, Marina Stein, Todd Livdahl, Patricia Y Scaraffia, Brendan H Carter, Motoyoshi Mogi, Nobuko Tuno, James W Mains, Kim A Medley, David E Bowles, Richard J Gill, Roger Eritja, Ranulfo González-Obando, Huynh T T Trang, Sébastien Boyer, Ann-Marie Abunyewa, Kayleigh Hackett, Tina Wu, Justin Nguyễn, Jiangnan Shen, Hongyu Zhao, Jacob E Crawford, Peter Armbruster, Adalgisa Caccone

Faculty, Staff and Student Publications

BACKGROUND: Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising up to 72% repetitive elements, and therefore we set out to develop a single-nucleotide polymorphism (SNP) chip to be more cost-effective. Aedes albopictus is an invasive species originating from Southeast Asia that has recently spread around the world and is a vector for many human diseases. Developing an accessible genotyping platform is essential in …

Associations Between Recurrence Patterns And Outcome In Glioblastoma Patients Undergoing Re-Resection: A Complementary Report Of The Rano Resect Group, Philipp Karschnia, Antonio Dono, Jacob S Young, Stephanie T Juenger, Nico Teske, Levin Häni, Tommaso Sciortino, Christine Y Mau, Francesco Bruno, Luis Nunez, Ramin A Morshed, Alexander F Haddad, Michael Weller, Martin Van Den Bent, Niklas Thon, Juergen Beck, Shawn Hervey-Jumper, Annette M Molinaro, Nitin Tandon, Roberta Rudà, Michael A Vogelbaum, Lorenzo Bello, Oliver Schnell, Stefan J Grau, Susan M Chang, Mitchel S Berger, Yoshua Esquenazi, Joerg-Christian Tonn

Faculty, Staff and Student Publications

No abstract provided.

Postconcussive Symptoms After Early Childhood Concussion, Dominique Dupont, Ken Tang, Cindy Beaudoin, Fanny Dégeilh, Isabelle Gagnon, Keith Owen Yeates, Sean C Rose, Jocelyn Gravel, Brett Burstein, Antonia S Stang, Rachel M Stanley, Roger L Zemek, Miriam H Beauchamp, Perc Koala Study

Faculty, Staff and Student Publications

IMPORTANCE: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children.

OBJECTIVE: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. …

Neuroinvasive West Nile Virus Infection In Immunosuppressed And Immunocompetent Adults., Amir A Mbonde, David Gritsch, Ehab Y Harahsheh, Sabirah N Kasule, Shemonti Hasan, Angela M Parsons, Nan Zhang, Richard Butterfield, Harn Shiue, Kathryn A Norville, Jenna L Reynolds, Holenarasipur R Vikram, Brian Chong, Marie F Grill

Neuroscience Articles

IMPORTANCE: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored.

OBJECTIVE: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS.

DESIGN, SETTING, …

Congenital Tooth Agenesis And Risk Of Early-Onset Cancer, Saga Elise Eiset, Jeremy Schraw, Gitte Vrelits Sørensen, Pernille Axél Gregersen, Sonja A Rasmussen, Cecilia H Ramlau-Hansen, Philip J Lupo, Henrik Hasle

Faculty, Staff and Students Publications

IMPORTANCE: There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting.

OBJECTIVE: To examine the association between tooth agenesis and specific cancer types before 40 years of age.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 …

Expanded Clinical Phenotype And Untargeted Metabolomics Analysis In Rars2-Related Mitochondrial Disorder: A Case Report, Ameya S Walimbe, Keren Machol, Stephen F Kralik, Elizabeth A Mizerik, Yoel Gofin, Mir Reza Bekheirnia, Charul Gijavanekar, Sarah H Elsea, Lisa T Emrick, Fernando Scaglia

Faculty, Staff and Students Publications

Background

RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE). …

Germline Genetic Testing And Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From The Children's Oncology Group, Bailey A Martin-Giacalone, He Li, Michael E Scheurer, Dana L Casey, Shannon Dugan-Perez, Deborah A Marquez-Do, Donna Muzny, Richard A Gibbs, Donald A Barkauskas, David Hall, Douglas R Stewart, Joshua D Schiffman, Matthew T Mcevoy, Javed Khan, David Malkin, Corinne M Linardic, Brian D Crompton, Jack F Shern, Stephen X Skapek, Rajkumar Venkatramani, Douglas S Hawkins, Aniko Sabo, Sharon E Plon, Philip J Lupo

Faculty, Staff and Students Publications

IMPORTANCE: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

OBJECTIVE: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023.

EXPOSURE: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set …

Adipose Triglyceride Lipase Is A Therapeutic Target In Advanced Prostate Cancer That Promotes Metabolic Plasticity, Dominik Awad, Pham Hong Anh Cao, Thomas L Pulliam, Meredith Spradlin, Elavarasan Subramani, Tristen V Tellman, Caroline F Ribeiro, Riccardo Muzzioli, Brittany E Jewell, Hubert Pakula, Jeffrey J Ackroyd, Mollianne M Murray, Jenny J Han, Mei Leng, Antrix Jain, Badrajee Piyarathna, Jingjing Liu, Xingzhi Song, Jianhua Zhang, Albert R Klekers, Justin M Drake, Michael M Ittmann, Cristian Coarfa, David Piwnica-Worms, Mary C Farach-Carson, Massimo Loda, Livia S Eberlin, Daniel E Frigo

Faculty, Staff and Students Publications

UNLABELLED: Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. A better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate …

A Humanized Mouse Model For Adeno-Associated Viral Gene Therapy, Mercedes Barzi, Tong Chen, Trevor J Gonzalez, Francis P Pankowicz, Seh Hoon Oh, Helen L Streff, Alan Rosales, Yunhan Ma, Sabrina Collias, Sarah E Woodfield, Anna Mae Diehl, Sanjeev A Vasudevan, Thao N Galvan, John Goss, Charles A Gersbach, Beatrice Bissig-Choisat, Aravind Asokan, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg−/−/Rag2−/−/Fah−/−/Aavr−/− (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the …

Efficacy Of Single-Agent Chemotherapy In Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma, Jason A Mouabbi, Wei Qaio, Yu Shen, Akshara Singareeka Raghavendra, Debasish Tripathy, Rachel M Layman

Faculty, Staff and Student Publications

Background: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

Materials and methods: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic …

Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Importance: Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited.

Objective: To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials.

Design, setting, and participants: This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov.

Main outcomes and measures: Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard …

Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

IMPORTANCE: Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited.

OBJECTIVE: To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov.

MAIN OUTCOMES AND MEASURES: Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard …

The Identification Of A Distinct Astrocyte Subtype That Diminishes In Alzheimer's Disease, Haichao Wei, Joseph Withrow, Jyotirmoy Rakshit, Faiz Ul Amin, Joshua Nahm, Francesca E Mowry, Zhengmei Mao, Meenakshi B Bhattacharjee, Jay-Jiguang Zhu, Yongjie Yang, Jia Qian Wu

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is characterized by the presence of two hallmark pathologies: the accumulation of Amyloid beta (Aβ) and tau proteins in the brain. There is a growing body of evidence suggesting that astrocytes, a type of glial cell in the brain, play crucial roles in clearing Aβ and binding to tau proteins. However, due to the heterogeneity of astrocytes, the specific roles of different astrocyte subpopulations in response to Aβ and tau remain unclear. To enhance the understanding of astrocyte subpopulations in AD, we investigated astrocyte lineage cells based on single-nuclei transcriptomic data obtained from both human and mouse …

The Epigenetic Evolution Of Glioma Is Determined By The Idh1 Mutation Status And Treatment Regimen, Tathiane M Malta, Thais S Sabedot, Natalia S Morosini, Indrani Datta, Luciano Garofano, Wies Vallentgoed, Frederick S Varn, Kenneth Aldape, Fulvio D'Angelo, Spyridon Bakas, Jill S Barnholtz-Sloan, Hui K Gan, Mohammad Hasanain, Ann-Christin Hau, Kevin C Johnson, Simona Cazacu, Ana C Decarvalho, Mustafa Khasraw, Emre Kocakavuk, Mathilde C M Kouwenhoven, Simona Migliozzi, Simone P Niclou, Johanna M Niers, D Ryan Ormond, Sun Ha Paek, Guido Reifenberger, Peter A Sillevis Smitt, Marion Smits, Lucy F Stead, Martin J Van Den Bent, Erwin G Van Meir, Annemiek Walenkamp, Tobias Weiss, Michael Weller, Bart A Westerman, Bauke Ylstra, Pieter Wesseling, Anna Lasorella, Pim J French, Laila M Poisson, Consortium The Glass, Roel G W Verhaak, Antonio Iavarone, Houtan Noushmehr

Faculty, Staff and Student Publications

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of …

Lilrb3 Supports Immunosuppressive Activity Of Myeloid Cells And Tumor Development, Ryan Huang, Xiaoye Liu, Jaehyup Kim, Hui Deng, Mi Deng, Xun Gui, Heyu Chen, Guojin Wu, Wei Xiong, Jingjing Xie, Cheryl Lewis, Jade Homsi, Xing Yang, Chengcheng Zhang, Yubo He, Qi Lou, Caroline Smith, Samuel John, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the …

Medical Home Implementation And Follow-Up Of Cancer-Related Abnormal Test Results In The Veterans Health Administration, Suja S Rajan, Shashank Sarvepalli, Li Wei, Ashley N D Meyer, Daniel R Murphy, Debra T Choi, Hardeep Singh

Faculty, Staff and Student Publications

IMPORTANCE: Lack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs' (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012.

OBJECTIVE: To evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers.

DESIGN, SETTING, AND PARTICIPANTS: This multiyear retrospective cohort study …

The Genetic Basis Of Hydrocephalus: Genes, Pathways, Mechanisms, And Global Impact, Andrew T Hale, Jennifer M Strahle, Et Al.

2020-Current year OA Pubs

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the …

Survival In Patients With De Novo Metastatic Prostate Cancer, Martin W Schoen, R Bruce Montgomery, Lukas Owens, Saira Khan, Kristen M Sanfilippo, Ruth B Etzioni

2020-Current year OA Pubs

No abstract provided.

Microglia At Sites Of Atrophy Restrict The Progression Of Retinal Degeneration Via Galectin-3 And Trem2, Chen Yu, Yun Chen, Jinchao Hou, Marco Colonna, Et Al.

2020-Current year OA Pubs

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 …

Genetic Sex Validation For Sample Tracking In Next-Generation Sequencing Clinical Testing, Jianhong Hu, Viktoriya Korchina, Hana Zouk, Maegan V Harden, David Murdock, Alyssa Macbeth, Steven M Harrison, Niall Lennon, Christie Kovar, Adithya Balasubramanian, Lan Zhang, Gauthami Chandanavelli, Divya Pasham, Robb Rowley, Ken Wiley, Maureen E Smith, Adam Gordon, Gail P Jarvik, Patrick Sleiman, Melissa A Kelly, Harris T Bland, Mullai Murugan, Eric Venner, Eric Boerwinkle, Emerge Iii Consortium, Cynthia Prows, Lisa Mahanta, Heidi L Rehm, Richard A Gibbs, Donna M Muzny

Faculty, Staff and Students Publications

OBJECTIVE: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.

RESULTS: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that …

Rebound Intracranial Hypertension, Simy K. Parikh

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: Rebound intracranial hypertension (RIH) is a post-procedural treatment complication in patients with spontaneous intracranial hypotension (SIH) characterized by transient high-pressure headache symptoms. This article reviews the epidemiology, clinical features, risk factors, and treatment options for RIH.

RECENT FINDINGS: This article discusses how changes in underlying venous pressure and craniospinal elastance can explain symptoms of RIH, idiopathic intracranial hypertension (IIH), and SIH.

SUMMARY: The pathophysiology of RIH provides a clue for how high and low intracranial pressure disorders, such as IIH and SIH, are connected on a shared spectrum.

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Pooja Popli, Zian Liao, Eryk Andreas, Michelle Dias, Tianyuan Wang, Stephanie J Gunderson, Patricia T Jimenez, Denise G Lanza, Rainer B Lanz, Charles E Foulds, Diana Monsivais, Francesco J Demayo, Hari Krishna Yalamanchili, Emily S Jungheim, Jason D Heaney, John P Lydon, Kelle H Moley, Bert W O'Malley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …

Outcomes In Biomarker-Selected Subgroups From The Kestrel Study Of Durvalumab And Tremelimumab In Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma, Tanguy Y Seiwert, Sophie Wildsmith, Jérôme Fayette, Kevin Harrington, Maura Gillison, Myung-Ju Ahn, Shunji Takahashi, Jared Weiss, Jean-Pascal Machiels, Shrujal Baxi, Valerie Baker, Brent Evans, Nassim Morsli, Jill Walker, Katia Real, Anne L'Hernault, Amanda Psyrri

Faculty, Staff and Student Publications

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective …