Digital Commons Network^™

Phase 3 Validation Of Paam For Hepatocellular Carcinoma Risk Stratification In Cirrhosis, Naoto Fujiwara, Camden Lopez, Tracey L Marsh, Indu Raman, Cesia A Marquez, Subhojit Paul, Sumit K Mishra, Naoto Kubota, Courtney Katz, Hiroaki Kanzaki, Michael Gonzalez, Lisa Quirk, Sneha Deodhar, Pratibha Selvakumar, Prithvi Raj, Neehar D Parikh, Lewis R Roberts, Myron E Schwartz, Mindie H Nguyen, Alex S Befeler, Stephanie Page-Lester, Sudhir Srivastava, Ziding Feng, K Rajender Reddy, Saira Khaderi, Sumeet K Asrani, Fasiha Kanwal, Hashem B El-Serag, Jorge A Marrero, Amit G Singal, Yujin Hoshida

Faculty, Staff and Students Publications

Background & aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The …

The Association Between Gulf War Illness And Suicidal Thoughts And Behaviors Among Gulf War Era Veterans, Rachele K Lipsky, Drew A Helmer, Jean C Beckham, Patrick S Calhoun, Mary Jo Pugh, Nathan A Kimbrel

Faculty, Staff and Students Publications

The rate of death by suicide is elevated among Veterans of all eras. Chronic symptoms of pain, depression, and sleep disturbances are also common among Veterans, and these symptoms are associated with suicidal thoughts and behaviors. About 25% of the 697,000 Gulf War Era Veterans deployed to the Persian Gulf theater in 1990-1991 remain afflicted with chronic, unexplained symptoms known as Gulf War Illness (GWI). This study used data from a national sample of Gulf War Veterans (N = 1142) who completed a survey of demographic, military, and health information. Multivariable logistic regression models, controlling for confounding variables, tested for …

Epidemiology Of Diagnostic Errors In Pediatric Emergency Departments Using Electronic Triggers, Prashant Mahajan, Emily White, Kathy Shaw, Sarah J Parker, James Chamberlain, Richard M Ruddy, Elizabeth R Alpern, Jacqueline Corboy, Andrew Krack, Brandon Ku, Daphne Morrison Ponce, Asha S Payne, Elizabeth Freiheit, Gregor Horvath, Giselle Kolenic, Michele Carney, Nicole Klekowski, Karen J O'Connell, Hardeep Singh

Faculty, Staff and Students Publications

Objectives: We applied three electronic triggers to study frequency and contributory factors of missed opportunities for improving diagnosis (MOIDs) in pediatric emergency departments (EDs): return visits within 10 days resulting in admission (Trigger 1), care escalation within 24 h of ED presentation (Trigger 2), and death within 24 h of ED visit (Trigger 3).

Methods: We created an electronic query and reporting template for the triggers and applied them to electronic health record systems of five pediatric EDs for visits from 2019. Clinician reviewers manually screened identified charts and initially categorized them as "unlikely for MOIDs" or "unable to rule …

Distinct Single-Cell Transcriptional Profile In Cd4+ T-Lymphocytes Among Obese Children With Asthma, Vickram Tejwani, Rulin Wang, Andres Villabona-Rueda, Karthik Suresh, Tianshi David Wu, Ian M Adcock, Nazanin Z Kermani, Joe Zein, Nadia N Hansel, Srinivasan Yegnasubramanian, Meredith C Mccormack, Franco R D'Alessio

Faculty, Staff and Students Publications

Obesity is a risk factor for asthma morbidity, associated with less responsiveness to inhaled corticosteroids. CD4+ T cells are central to the immunology of asthma and may contribute to the unique obese asthma phenotype. We sought to characterize the single-cell CD4+ transcriptional profile differences in obese children with asthma compared with normal-weight children with asthma. Eight normal-weight and obese participants with asthma were clinically phenotyped and matched based on asthma control. Peripheral blood (PB) CD4+ T cells were sorted, and single-cell RNA sequencing was conducted. Cell clusters were identified by canonical gene expression and differential gene expression and reactome pathway …

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 …

Rhabdoid Tumor Of The Kidney And Soft Tissues: Results From National Wilms Tumor Study-5 And Children's Oncology Group Study Aren0321, James I Geller, Lindsay A Renfro, Paul E Grundy, Elizabeth J Perlman, John A Kalapurakal, Peter F Ehrlich, Jackie Biegel, Vicki Huff, Anne B Warwick, Arnold Paulino, Elizabeth A Mullen, Najat C Daw, Fredric A Hoffer, Zelig Tochner, Kenneth Gow, Eric Gratias, Deborah A Ward, James R Anderson, Conrad V Fernandez, Jeffrey S Dome

Faculty, Staff and Student Publications

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients and methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1). We report event-free survival (EFS) and overall survival (OS) from each study.

Results: Thirty patients received Regimen RTK on NWTS-5; …

Wmh Contributions To Cognitive Impairment: Rationale And Design Of The Diverse Vcid Study, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason Hinman, David K Johnson, Danielle Harvey, Myriam Fornage

Faculty, Staff and Student Publications

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter …

Elder Mistreatment Within Stroke Family Caregiving, Carina Katigbak, Wesley R Browning, Sean Savitz, Carolyn E Z Pickering

Faculty, Staff and Student Publications

This secondary data analysis sought to identify characteristics associated with mistreatment among chronic stroke survivors who transition to dementia. We examined baseline data from a multi-time series survey study (n = 453; where caregivers of those with stroke n = 107, and those without stroke, n = 346) on caregiving experiences influencing dementia family caregivers’ abusive or neglectful behaviors. Inferential statistical analysis indicated that baseline mistreatment rates were similar across stroke and non-stroke subgroups, though this finding was not significant. Caregiver depression was significantly associated with mistreatment. Multi-morbidity, prescription medication use, and limited mobility were more common among stroke …

Outcomes Of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Zhongya Wang, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Naureen Syed, Yosra Aljawai, Hans C Lee, Krina K Patel, Melody R Becnel, Christine Ye, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM …

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

Faculty, Staff and Student Publications

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

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

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

Department of Medical Oncology Faculty Papers

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

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

2020-Current year OA Pubs

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

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

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

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

Androgen Receptor Ubiquitination Links Kctd13 To Genitourinary Tract Defects, Ahmed Chahdi, Carolina Jorgez, Jill A Rosenfeld, Neetu Neetu, Abhishek Seth

Faculty, Staff and Students Publications

The potassium channel tetramerization domain containing 13 (KCTD13) protein is a substrate-specific adapter for cullin3-based E3 ubiquitin ligase. Patients with copy number variants at this locus exhibit genitourinary tract anomalies. In this study, we show that decreased androgen receptor (AR) protein level correlated with increased AR ubiquitination in the testis of Kctd13-deficient mice, suggesting that KCTD13 inhibits AR ubiquitination. KCTD13 increased CUL3-dependent AR ubiquitination but had no effect on CUL3 binding to AR, confirming the role of KCTD13 as an adaptor of CUL3 ligase. Recombinant KCTD13 directly binds to recombinant AR, and the BTB domain of KCTD13 is critical for …

Invasive Haemophilus Influenzae Disease At A Us Children's Hospital In The Sars-Cov-2 Era, J Chase Mcneil, David R Mcdonald, James J Dunn, Sheldon L Kaplan, Kristina G Hulten, Jesus G Vallejo

Faculty, Staff and Students Publications

Background: National data previously demonstrated an increase in invasive disease due to non-type b Haemophilus influenzae from the 2000s to the 2010s. Significant shifts in the epidemiology of respiratory pathogens in children have occurred in the post-SARS-CoV-2 era. We examined pediatric invasive H. influenzae disease in the pre- and post-SARS-CoV-2 years.

Methods: Invasive H. influenzae infections were identified from culture records of the Texas Children's Hospital microbiology laboratory from January 2011 to December 2023. Invasive cases were considered those with isolation of H. influenzae from a sterile site. The annual number of cases/1000 admissions was used as a surrogate for …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev Sen, Omar Alwakaa, Christoph Griessenauer, Pascal Jabbour, Stavropoula Tjoumakaris, Jan-Karl Burkhardt, Robert Starke, Mustafa Baskaya, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng Chen, Spiros Blackburn, Mark Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman Patel, Hugo Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Department of Neurosurgery Faculty Papers

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem M Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam A Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev D Sen, Omar Alwakaa, Christoph J Griessenauer, Pascal Jabbour, Stavropoula I Tjoumakaris, Jan-Karl Burkhardt, Robert M Starke, Mustafa Baskaya, Laligam N Sekhar, Michael R Levitt, David J Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng R Chen, Spiros Blackburn, Mark J Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman B Patel, Hugo H Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Faculty, Staff and Student Publications

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Muscle-Specific Errγ Activation Mitigates Muscle Atrophy After Acl Injury, Aiping Lu, Katie J Sikes, Ping Guo, Matthieu Huard, Shelbi Green, Kelly Santangelo, Jacob Singer, Ashley Groesbeck, Scott Tashman, Vihang A Narkar, Johnny Huard

Faculty, Staff and Student Publications

Anterior cruciate ligament (ACL) injury adversely affects skeletal muscle, leading to muscle atrophy and weakness, significantly impacting clinical outcomes. This study aimed to determine if estrogen-related receptor gamma (ERRγ) overexpression in skeletal muscle could mitigate muscle atrophy after ACL injury. An animal model with selective overexpression of ERRγ in skeletal muscle (ERR-gamma transgenic mice, TG) and WT control mice were used for this study. All the mice received a mechanical ACL rupture and were euthanized at 4- and 8-week post-injury. Muscle histology, atrophy, and function were evaluated and compared between the TG and WT mice. Muscle-specific ERRγ activation in TG …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

The Transition To Adulthood: A Qualitative Study Of Autism Spectrum Disorder From Military And Veteran Parents And Military-Dependent Young Adults, Antonio F Pagán, Mara C Montenegro, Mark Ahlenius, Ana C Ramirez, Miriam Ortiz, Estefani Bernal, Cecilia Montiel-Nava, Jennifer Bittner, Katherine A Loveland, Ron E Acierno

Faculty, Staff and Student Publications

Introduction: Given the unique experiences of military service members and their families, military-dependent young adults (18-25 years old) with autism spectrum disorder (ASD) and their military or veteran families experience unique barriers to accessing quality mental health care during the transition to adulthood. In fact, developing services to address ASD challenges for military families is a burgeoning area of interest for the department of defense. However, there is a limited knowledge on the specific needs of military families as the young adult's transition outside of high school and lose supports.

Materials and methods: The present study conducted 3 focus groups …

Inhibition Of Il-6 Trans-Signaling Promotes Post-Stroke Functional Recovery In A Sex And Dose-Dependent Manner, Cassandra Hall, Dustin T Nguyen, Kate Mendoza, Chunfeng Tan, Anjali Chauhan

Faculty, Staff and Student Publications

Introduction: Elevated circulating IL-6 levels are associated with poorer outcomes after stroke, and increased serum IL-6 levels are linked to a higher risk of stroke. IL-6 binds to soluble IL-6 receptors (sIL-6R) and subsequently to ubiquitously expressed gp130, initiating proinflammatory trans-signaling. This study tested the hypothesis that inhibiting IL-6 trans-signaling by administering soluble (s) gp130 improves long-term functional outcomes in young mice after stroke.

Methods: Recombinant mouse gp130Fc chimera (sgp130) was administered one hour after middle cerebral artery occlusion (MCAO) followed by twice-weekly administration for 2 weeks in mice (8-15 weeks old). Behavioral assessments were done on days 7 and …

Associations Of Long-Term Exposure To Temperature With Coronary Artery Calcification Risk Among Middle-Aged Adults: The Coronary Artery Risk Development In Young Adults (Cardia) Study, Dandan Zhao, Jie Yao, Yuanfei Li, David R Jacobs, Yinan Zheng, Chunyu Liu, Yingbin Fu, Margaret M Deangelis, Donald Lloyd-Jones, Lifang Hou, Kai Zhang

Faculty, Staff and Students Publications

BACKGROUND: The impact of ambient temperature on population health has drawn increasing attention as climate change drives more extreme temperatures globally. However, little research has investigated its connection to subclinical cardiovascular diseases. This study aims to examine the impact of long-term exposure to temperature on coronary artery calcification (CAC) among middle-aged Black and White adults in four U.S. areas with varying climate and weather conditions.

METHODS: This study compiled long-term environmental temperature data and individual coronary artery Agatston score (0 vs. >0) from the Coronary Artery Risk Development in Young Adults study. It employed logistic regression and examined the influences …

Integration Of Metabolomic And Transcriptomic Analyses Reveals Regulatory Functions Of The Chrebp Transcription Factor In Energy Metabolism, Jie An, Inna Astapova, Guofang Zhang, Andrew L Cangelosi, Olga Ilkayeva, Hannah Marchuk, Michael J Muehlbauer, Tabitha George, Joseph Brozinick, Mark A Herman, Christopher B Newgard

Faculty, Staff and Students Publications

The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses …

Incidence And Predictors Of Woven Endobridge (Web) Shape Modification Following Treatment Of Intracranial Aneurysms In A Large Multicenter Study, Nimer Adeeb, Hamza Adel Salim, Basel Musmar, Assala Aslan, Christian Swaid, Miguel Cuellar, Mahmoud Dibas, Nicole Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Amir Essibayi, Sunil Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Eytan Raz, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad Levy, Neil Haranhalli, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula Tjoumakaris, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vivek Yedavalli, Max Wintermark, Vitor Mendes Pereira, Aman Patel, Hugo Cuellar-Saenz, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is FDA-approved for the treatment of bifurcation aneurysms. Despite its wide popularity, it has been under scrutiny for its association with potential aneurysm recanalization and retreatment due to device shape modification. This study aims to analyze the shape modification rate of WEB devices and identify factors associated with this phenomenon, as well as its correlation with aneurysm retreatment. We conducted a retrospective review of the WorldWide WEB Consortium database, including adult patients treated for intracranial aneurysms with the WEB device. We assessed aneurysm occlusion using the WEB Occlusion Scale and defined WEB shape modification as …

Characterization Of Factors Associated With Death In Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey, Alina Ivaniuk, Irina A Anselm, Aaron Bowen, Bruce H Cohen, Fatma Tuba Eminoglu, Jane Estrella, Renata C Gallagher, Rebecca D Ganetzky, Jennifer Gannon, Grainne S Gorman, Carol Greene, Andrea L Gropman, Richard H Haas, Michio Hirano, Seema Kapoor, Amel Karaa, Mary Kay Koenig, Cornelia Kornblum, Engin Kose, Austin Larson, Uta Lichter-Konecki, Piervito Lopriore, Michelangelo Mancuso, Robert Mcfarland, Aye Myat Moe, Eva Morava, Yi Shiau Ng, Russell P Saneto, Fernando Scaglia, Carolyn M Sue, Mark Tarnopolsky, Melissa A Walker, Sumit Parikh, Fung Cheuk-Wing, Tsz-Sum Wong, Kiran Belaramani, Chun-Kong Chan, Wing-Ki Chan, Wai-Lun Larry Chan, Hon-Wing Cheung, Ka-Yin Cheung, Shek-Kwan Chang, Sing-Ngai Cheung, Tsz-Fung Cheung, Yuk-Fai Cheung, Shuk-Ching Josephine Chong, Chi-Kwan Jasmine Chow, Hon-Yin B Chung, Sin-Ying Florence Fan, Wai-Ming Joshua Fok, Ka-Wing Fong, Tsui-Hang Sharon Fung, Kwok-Fai Hui, Ting-Hin Hui, Joannie Hui, Chun Hung Ko, Min-Chung Kwan, Mei-Kwan Anne Kwok, Sung-Shing Jeffrey Kwok, Moon-Sing Lai, Yau-On Lam, Ching-Wan Lam, Ming-Chung Lau, Chun-Yiu Eric Law, Hiu-Fung Law, Wing-Cheong Lee, Han-Chih Hencher Lee, Kin-Hang Leung, Kit-Yan Leung, Siu-Hung Li, Tsz-Ki Jacky Ling, Kam-Tim Timothy Liu, Fai-Man Lo, Colin Lui, Ching-On Luk, Ho-Ming Luk, Che-Kwan Ma, Karen Ma, Kam-Hung Ma, Yuen-Ni Mew, Alex Mo, Sui-Fun Hg, Wing-Kit Grace Poon, Bun Sheng, Cheuk-Ling Charing Szeto, Shuk-Mui Tai, Jing-Liang Tang, Choi-Ting Alan Tse, Li-Yan Lilian Tsung, Ho-Ming June Wong, Wing-Yin Winnie Wong, Kwok-Kui Wong, Suet-Na Sheila Wong, Chun-Nei Virginia Wong, Wai-Shan Sammy Wong, Chi-Kin Felix Wong, Shun-Ping Wu, Hiu-Fung Jerome Wu, Man-Mut Yau, Kin-Cheong Eric Yau, Wai-Lan Yeung, Hon-Ming Jonas Yeung, Kin-Keung Edwin Yip, Hui-Jun Wu, Pui-Hong Terence Young, Gao Yuan, Yuet-Ping Liz Yuen, Chi-Lap Yuen

Faculty, Staff and Student Publications

Background and objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based …

Non-Invasive Real-Time Pulsed Doppler Assessment Of Blood Flow In Mouse Ophthalmic Artery, Iraida Sharina, Radwa Awad, Soren Cobb, Emil Martin, Sean P Marrelli, Anilkumar K Reddy

Faculty, Staff and Student Publications

Non-invasive and high-temporal resolution methods for characterizing blood flow in mouse cranial arteries, such as the ophthalmic artery (OphA), are lacking. We present an application of pulsed Doppler ultrasound to provide real-time, non-invasive measurement of blood flow velocity in the OphA through an identified soft tissue window in the mouse head. We confirmed the identity of the artery and mapped its origin from the internal carotid artery by a combination of microcomputed tomography (microCT) vascular imaging and transient occlusion of the internal carotid artery. Application of our approach demonstrated sex differences in the OphA vasodilative response to agonists. We also …

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Novel Device Therapies In Heart Failure: Focus On Patient Selection, Amrita Balgobind, Daniel Asemota, Emily Rodriguez, Phuuwadith Wattanachayakul, Marat Fudim, Miguel Alvarez Villela

Einstein Health Papers

The increasing prevalence of heart failure (HF) has led to advancements in therapeutic strategies, including the development of new pharmacological treatments and the expansion of guideline recommendations across the spectrum of left ventricular ejection fractions. Despite these advancements, the full benefits of guideline-directed medical therapy (GDMT) are often limited by various barriers that result in incomplete implementation or suboptimal responses. For patients who cannot tolerate or only partially respond to GDMT, therapeutic options remain limited. This gap is particularly significant for those with contraindications to heart replacement therapies (HRT), such as left ventricular assist device (LVAD) or heart transplant. In …

Pitavastatin Is Well-Tolerated With No Detrimental Effects On Physical Function, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Jennifer A Schrack, Edgar T Overton, Carl J Fichtenbaum, Kathleen V Fitch, Jhoanna C Roa, Marissa R Diggs, Kenneth Wood, Markella V Zanni, Gerald S Bloomfield, Carlos Malvestutto, Judith A Aberg, Maria C Rodriguez-Barradas, Rosalba Gomez Morones, Katherine Breaux, Pamela S Douglas, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

Methods: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Findings: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female …

Memorability Of Novel Words Correlates With Anterior Fusiform Activity During Reading, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Our memory for the words we already know is best predicted by their associated meanings. However, the factors that influence whether we will remember a new word after we see it for the first time are unclear. We record memory performance for 2100 novel pseudowords across 1804 participants during a continuous recognition task. Participants show significant agreement across individuals for which novel words were memorable or forgettable, suggesting an intrinsic memorability for individual pseudowords. Pseudowords that are similar to low-frequency known words, with sparse orthographic neighbourhoods and rarely occurring letter pairs, are more memorable. Further, using intracranial recordings in 36 …