Medicine and Health Sciences Commons^™

Comparison Of Open Thoracoabdominal Repair For Chronic Aortic Dissections And Aneurysms, Ian O Cook, Susan Y Green, Kimberly R Rebello, Qianzi Zhang, Veronica A Glover, Rodrigo Zea-Vera, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: Aortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm.

Methods: We retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death …

Fathers In The United States Are Getting Older, Larry I Lipshultz, Blair T Stocks

Faculty, Staff and Students Publications

No abstract provided.

Asynchronous Online Training Increased Knowledge, Confidence, And Intent To Screen And Treat Substance Use Disorders Among Primary Care Clinicians Practicing In Texas, Roger Zoorob, Sung In Kim-Vences, Jacqueline M Hirth, Kylie Schaper, Larissa Grigoryan, Sandra Gonzalez, Alicia Kowalchuk

Faculty, Staff and Students Publications

Introduction: Despite increasing prevalence of substance use disorders (SUD), few patients are diagnosed and treated in primary care settings. This study evaluated changes in knowledge, confidence, and intention to implement screening and brief intervention (SBI) and SUD treatment after clinicians participated in an asynchronous online education course.

Methods: A self-selected sample of primary care clinicians in Texas participated in online SBI and SUD education March 2021-July 2023. Baseline and post-training surveys evaluated changes in knowledge, confidence, and intent to implement SBI and SUD treatment. Changes were compared using paired t-tests. Multivariable linear regression examined factors potentially associated with confidence and …

A Rare Variant In Mrc2 Associated With Familial Supraventricular Tachycardia And Wolff-Parkinson-White Syndrome, Adam S Potter, Christina Y Miyake, Claudia Gonzaga-Jauregui, Yuriana Aguilar-Sanchez, Mohit M Hulsurkar, Satadru K Lahiri, Lucia M Moreira, Neelam Mehta, Mahshid S Azamian, James R Lupski, Svetlana Reilly, Seema R Lalani, Xander H T Wehrens

Faculty, Staff and Students Publications

Background: Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model.

Methods: Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified MRC2 as a candidate gene. Serial electrocardiograms, …

Trajectory Of C-Reactive Protein And Incident Heart Failure In Black Adults: The Jackson Heart Study, Arsalan Hamid, Wondwosen K Yimer, Adebamike A Oshunbade, Muhammad Shahzeb Khan, Daisuke Kamimura, Rodney K Kipchumba, Ambarish Pandey, Donald Clark, Robert J Mentz, Ervin R Fox, Jarett D Berry, R Brandon Stacey, Amil Shah, Adolfo Correa, Salim S Virani, Javed Butler, Michael E Hall

Faculty, Staff and Students Publications

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization.

Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective …

Individual Variation In The Distribution Of Apolipoprotein B Levels Across The Spectrum Of Ldl-C Or Non-Hdl-C Levels, Ahmed Sayed, Eric D Peterson, Salim S Virani, Allan D Sniderman, Ann Marie Navar

Faculty, Staff and Students Publications

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown.

Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups.

Design, setting, …

Validation Of Electronic Diagnostic Codes For Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Carlos H Schenck, Mehrnaz Azarian, Ricardo E Jorge, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of veterans with rapid eye movement sleep behavior disorder. The charts of 139 randomly sampled veterans with ≥ 1 ICD-9 and ICD-10 code(s) for rapid eye movement sleep behavior disorder were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) patients with rapid eye movement sleep behavior disorder electronic diagnoses had not undergone polysomnography, and 29 (20.9%) had polysomnography reports without commentary on rapid eye movement sleep without atonia. Sleep centers are therefore encouraged …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility To Pulmonary Fibrosis, Kai Xu, Linke Ding, Wenwen Li, Yaxuan Wang, Shuaichen Ma, Hui Lian, Xiaoyue Pan, Ruyan Wan, Weiming Zhao, Juntang Yang, Ivan Rosas, Lan Wang, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by pulmonary fibroblast overactivation, resulting in the accumulation of abnormal extracellular matrix and lung parenchymal damage. Although the pathogenesis of IPF remains unclear, aging was proposed as the most prominent nongenetic risk factor. Propionate metabolism undergoes reprogramming in the aging population, leading to the accumulation of the by-product methylmalonic acid (MMA). This study aimed to explore alterations in propionate metabolism in IPF and the impact of the by-product MMA on pulmonary fibrosis. It revealed alterations in the expression of enzymes involved in propionate metabolism within IPF lung tissues, characterized …

Early-Life Social Determinants Of Sca6 Age At Onset, Severity, And Progression, Tiffany X Chen, Hannah L Casey, Chi-Ying R Lin, Theresa A Boyle, Jeremy D Schmahmann, Gilbert J L'Italien, Sheng-Han Kuo, Christopher M Gomez

Faculty, Staff and Students Publications

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) …

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial, Jason L Sperry, Francis X Guyette, Bedda L Rosario-Rivera, Matthew E Kutcher, Lucy Z Kornblith, Bryan A Cotton, Chad T Wilson, Kenji Inaba, Eva V Zadorozny, Laura E Vincent, Ashley M Harner, Emily T Love, Joseph E Doherty, Joseph Cuschieri, Aaron E Kornblith, Erin E Fox, Yu Bai, Marcus K Hoffman, Catherine P Seger, Jay Hudgins, Sheila Mallett-Smith, Matthew D Neal, Christine M Leeper, Philip C Spinella, Mark H Yazer, Stephen R Wisniewski, Cold Stored Platelet For Hemorrhagic Shock (Crisp-Hs) Study Group

Faculty, Staff and Student Publications

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock.

BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury.

METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Opioid Use Disorder Risk Alleles In Self-Reported Assigned African American/Afro-Caribbean And European Biogeographical Genetic Ancestry Groups And In Males And Females, Jon E Sprague, Caroline E Freiermuth, Joshua Lambert, Robert Braun, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Lauren Beaumont, Michael S Lyons, Michael V Pantalon, Brittany E Punches, Rachel Ancona, David F Kisor

2020-Current year OA Pubs

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the …

Medicare Utilization And Cost Trends For Car T Cell Therapies Across Settings Of Care In The Treatment Of Diffuse Large B-Cell Lymphoma, James Wu, Armin Ghobadi, Richard Maziarz, Krish Patel, Hil Hsu, Zihao Liu, Caitlin Sheetz, Peter Kardel, Christine Fu

2020-Current year OA Pubs

INTRODUCTION: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways.

METHODS: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products-lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)-which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of …

Treatment Patterns In Women With Postmenopausal Osteoporosis Using Abaloparatide: A Real-World Observational Study, Deborah T Gold, Tammy Beckett, Chad Deal, Andrew L James, Mahshid Mohseni, Abigail Mcmillan, Tom Bailey, Leny Pearman, John Caminis, Yamei Wang, Setareh A Williams, Jacqueline M Kernaghan

2020-Current year OA Pubs

UNLABELLED: Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed.

PURPOSE: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history.

METHODS: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six …

Comparing Balance Using The Bestest In Alzheimer, Huntington And Parkinson Disease, Lauren E Tueth, Ryan P Duncan, Beth E Crowner, Gammon M Earhart

2020-Current year OA Pubs

No abstract provided.

Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …

Psilocybin Desynchronizes The Human Brain, Joshua S Siegel, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Eric J Lenze, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

Posttraumatic Stress Disorder And Type 2 Diabetes Outcomes In Veterans, Jeffrey F Scherrer, Joanne Salas, Wenjin Wang, Kenneth E Freedland, Patrick J Lustman, Paula P Schnurr, Beth E Cohen, Allan S Jaffe, Matthew J Friedman

2020-Current year OA Pubs

IMPORTANCE: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown.

OBJECTIVE: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to …

Predicting Post-Surgical Functional Status In High-Grade Glioma With Resting State Fmri And Machine Learning, Patrick H Luckett, Michael O Olufawo, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.

METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of …

Overall Survival In Patients With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel In The Randomized Engot-En6/Gog-3031/Ruby Trial, M A Powell, C Mccourt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis.

PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were …

Obicetrapib On Top Of Maximally Tolerated Lipid-Modifying Therapies In Participants With Or At High Risk For Atherosclerotic Cardiovascular Disease: Rationale And Designs Of Broadway And Brooklyn, Stephen J Nicholls, Anne C Goldberg, Et Al.

2020-Current year OA Pubs

BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events.

METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing …

Population Pharmacokinetic Modelling And Simulation Of Tranexamic Acid In Adult Trauma Patients, Gideon Stitt, Philip C Spinella, Grant V Bochicchio, Ian Roberts, Kevin J Downes, Athena F Zuppa

2020-Current year OA Pubs

AIMS: The aim of this study is to describe the disposition of tranexamic acid (TXA) in adult trauma patients and derive a dosing regimen that optimizes exposure based on a predefined exposure target.

METHODS: We performed a population pharmacokinetic (popPK) analysis of participants enrolled in the Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial (≥18 years with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room) who were randomized to a single dose of either 2 or 4 g of TXA ≤2 h from time of injury. PopPK analysis was conducted using nonlinear …

Association Of Surgical Approaches And Outcomes In Total Mesorectal Excision And Margin Status For Rectal Cancer, Muhammad Bilal Mirza, Adriana C Gamboa, Rebecca Irlmeier, Benjamin Hopkins, Scott E Regenbogen, Katherine A Hrebinko, Jennifer Holder-Murray, Jason T Wiseman, Aslam Ejaz, Paul E Wise, Fei Ye, Kamran Idrees, Alexander T Hawkins, Glen C Balch, Aimal Khan

2020-Current year OA Pubs

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer.

METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected …

Analytical Validation Of The Multitarget Stool Rna Test For Colorectal Cancer Screening, Erica K Barnell, Jack Land, Kimberly Kruse, Maya C Scott, Ben Wedeking, Catherine Morrison, Clayton Grass, Ann Zuniga, Elizabeth M Wurtzler, Eric J Duncavage

2020-Current year OA Pubs

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of < 0.6, < 0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and < 20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non-colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Diestro, Rachel Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann Lay, Adrien Guenego, Leonardo Renieri, Nicole Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin Vranic, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Jay Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad Hafeez, Joshua Catapano, Muhammad Waqas, Vincent Tutino, Mohamed Ibrahim, Marwa Mohammed, M. Ozgur Ozates, Giyas Ayberk, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Stéphanie Elens, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian Jankowitz, Jan-Karl Burkhardt, Ricardo Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Essibayi, Sunil Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo Cuellar-Saenz, Pascal Jabbour, Vitor Pereira, Aman Patel, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …