Medical Specialties Commons^™

Consensus-Based Development Of A Pediatric Echocardiography Complexity Score: Design, Rationale, And Results Of A Quality Improvement Collaborative, Sowmya Balasubramanian, Sunkyung Yu, Sarina K Behera, Aarti H Bhat, Joseph A Camarda, Nadine F Choueiter, Pei-Ni Jone, Leo Lopez, Shobha S Natarajan, David A Parra, Anitha Parthiban, Ritu Sachdeva, Shubhika Srivastava, Elif Seda Selamet Tierney

Faculty, Staff and Students Publications

BACKGROUND: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score.

METHODS AND RESULTS: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. …

Kidney Function Trajectories And Right Heart Failure Following Lvad Implantation, Carl P Walther, Andrew B Civitello, Harveen K Lamba, Nandan K Mondal, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this.

METHODS AND RESULTS: We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles., Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Neuroscience Articles

IMPORTANCE: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

OBJECTIVE: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

DESIGN, SETTING, AND PARTICIPANTS: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

A Rare Encounter: Extracranial Meningioma Mimicking Musculoskeletal Neoplasms, Liza Salloum, Jennifer Rojas Huen, Ricardo Serna, Andrew Kolodziej

Research Symposium

Background: Meningiomas are the most common primary brain tumor in adults. While commonly encountered intracranially, 2% manifest extracranially. Although usually benign, 10% of meningiomas can become malignant. Despite their relatively high incidence, they are often difficult to diagnose due to long asymptomatic periods, often diagnosed after mass effect symptoms occur. This case explores the intricacies of diagnosing and managing an extracranial meningioma that mimicked musculoskeletal neoplasms.

Case Presentation: A 70-year-old female, with a history of hypertension and dyslipidemia, presented with diplopia, blurry vision, and intermittent right orbital pain. A recent CT had identified a slow-growing right temporal mass, yet she …

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 …

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 …

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, …

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 …

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 …

Changes In Real-World Dispensing Of Adhd Stimulants In Youth From 2019 To 2021 In California, Anika Patel, Rishikesh Chavan, Cyril Rakovski, Richard C. Beuttler, Sun Yang

Mathematics, Physics, and Computer Science Faculty Articles and Research

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric neurobehavioral disorders in the U.S. Stimulants, classified as controlled substances, are commonly used for ADHD management. We conducted an analysis of real-world stimulants dispensing data to evaluate the pandemic’s impact on young patients (≤ 26 years) in California.

Methods: Annual prevalence of patients on stimulants per capita across various California counties from 2019 and 2021 were analyzed and further compared across different years, sexes, and age groups. New patients initiating simulants therapy were also examined. A case study was conducted to determine the impact of socioeconomic status on patient …

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 …

Craniofacial Bone Anomalies Related To Cholesterol Synthesis Defects, Chihiro Iwaya, Akiko Suzuki, Junbo Shim, Aemin Kim, Junichi Iwata

Faculty, Staff and Student Publications

DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7

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. …

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 …

Adaptive Darwinian Off-Target Resistance Mechanisms To Selective Ret Inhibition In Ret Driven Cancer, Vivek Subbiah, Mohamed A Gouda, J Bryan Iorgulescu, Ramona Dadu, Keyur Patel, Steven Sherman, Maria Cabanillas, Mimi Hu, Luz E Castellanos, Behrang Amini, Funda Meric-Bernstam, Tao Shen, Jie Wu

Faculty, Staff and Student Publications

Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with …

Values, Challenges, And Responses Associated With High-Priced Potential Cures: Perspectives Of Diverse Stakeholders In South Korea, Jihyung Hong, Eun-Young Bae, Hye-Jae Lee, Tae-Jin Lee, Philip Clarke

Faculty, Staff and Student Publications

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies.

METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online …

Surgery Of The Palatomaxillary Structure, Jessica R Burgess, Kathleen C Heneghan, Tarra G Barot, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Patients with opioid use disorder (OUD) are increasing, challenging surgeons to adjust post-operative pain management guidelines. A literature review identified limited information on how to best care for these patients. The purpose of this study was to determine surgical perioperative management of OUD, challenges, and support needed for optimal care.

METHODS: This study utilized an anonymous voluntary survey that was distributed to members of the American College of Surgeons through the association's electronic weekly newsletter. The survey was advertised weekly for three consecutive weeks. The survey included questions regarding surgeons' management of perioperative pain in patients with opioid use …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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). …

Integrating Genome Sequencing And Untargeted Metabolomics In Monozygotic Twins With A Rare Complex Neurological Disorder, Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan Alrayahi, Adam D Kennedy, Karen L Debalsi, Sura Hussein, Najwa Elbashir, Sujitha S Padmajeya, Sasirekha Palaniswamy, Sarah H Elsea, Ammira A Akil, Noha A Yousri, Khalid A Fakhro

Faculty, Staff and Students Publications

Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy–Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in ADGRG1(p.Arg565Trp) and a novel variant in CNTNAP1(p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without …

The Development Of 2 Clonally And Histologically Distinct Subtypes Of Extranodal B-Cell Lymphomas In The Brain And Skin In 1 Individual, Daniel Joffe, Thomas Z. Rohan, Jenna Mandel, Jayson Suriano, Lauren Banner, Alexander Valiga, Pierluigi Porcu, Jerald Z. Gong, Jason B. Lee, Onder Alpdogan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

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.