Digital Commons Network^™

Three-Year Outcomes Of Post-Acute Sequelae Of Covid-19, Miao Cai, Yan Xie, Eric J Topol, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 …

Plasma Extracellular Vesicle Tau And Tdp-43 As Diagnostic Biomarkers In Ftd And Als, Madhurima Chatterjee, Nicolas R Barthélemy, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy …

Two Genome-Wide Interaction Loci Modify The Association Of Nonsteroidal Anti-Inflammatory Drugs With Colorectal Cancer, David A Drew, Andre E Kim, Yi Lin, Conghui Qu, John Morrison, Juan Pablo Lewinger, Eric Kawaguchi, Jun Wang, Yubo Fu, Natalia Zemlianskaia, Virginia Díez-Obrero, Stephanie A Bien, Niki Dimou, Demetrius Albanes, James W Baurley, Anna H Wu, Daniel D Buchanan, John D Potter, Ross L Prentice, Sophia Harlid, Volker Arndt, Elizabeth L Barry, Sonja I Berndt, Emmanouil Bouras, Hermann Brenner, Arif Budiarto, Andrea Burnett-Hartman, Peter T Campbell, Robert Carreras-Torres, Graham Casey, Jenny Chang-Claude, David V Conti, Matthew A M Devall, Jane C Figueiredo, Stephen B Gruber, Andrea Gsur, Marc J Gunter, Tabitha A Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R Huyghe, Mark A Jenkins, Kristina M Jordahl, Anshul Kundaje, Loic Le Marchand, Li Li, Brigid M Lynch, Neil Murphy, Rami Nassir, Polly A Newcomb, Christina C Newton, Mireia Obón-Santacana, Shuji Ogino, Jennifer Ose, Rish K Pai, Julie R Palmer, Nikos Papadimitriou, Bens Pardamean, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, Gad Rennert, Edward Ruiz-Narvaez, Lori C Sakoda, Peter C Scacheri, Stephanie L Schmit, Robert E Schoen, Mariana C Stern, Yu-Ru Su, Duncan C Thomas, Yu Tian, Konstantinos K Tsilidis, Cornelia M Ulrich, Caroline Y Um, Fränzel J B Van Duijnhoven, Bethany Van Guelpen, Emily White, Li Hsu, Victor Moreno, Ulrike Peters, Andrew T Chan, W James Gauderman

Faculty, Staff and Student Publications

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit

Nivolumab Plus Relatlimab In Patients With Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase Ii Checkmate 142 Study, Michael J Overman, Fabio Gelsomino, Massimo Aglietta, Mark Wong, Maria Luisa Limon Miron, Gregory Leonard, Pilar García-Alfonso, Andrew G Hill, Antonio Cubillo Gracian, Eric Van Cutsem, Bassel El-Rayes, Stephen M Mccraith, Beilei He, Ming Lei, Sara Lonardi

Faculty, Staff and Student Publications

BACKGROUND: Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.

METHODS: In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC …

Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha

Faculty, Staff and Student Publications

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue …

Machine Learning Models For Predicting Blood Pressure Phenotypes By Combining Multiple Polygenic Risk Scores, Yana Hrytsenko, Benjamin Shea, Michael Elgart, Nuzulul Kurniansyah, Genevieve Lyons, Alanna C Morrison, April P Carson, Bernhard Haring, Braxton D Mitchell, Bruce M Psaty, Byron C Jaeger, C Charles Gu, Charles Kooperberg, Daniel Levy, Donald Lloyd-Jones, Eunhee Choi, Jennifer A Brody, Jennifer A Smith, Jerome I Rotter, Matthew Moll, Myriam Fornage, Noah Simon, Peter Castaldi, Ramon Casanova, Ren-Hua Chung, Robert Kaplan, Ruth J F Loos, Sharon L R Kardia, Stephen S Rich, Susan Redline, Tanika Kelly, Timothy O'Connor, Wei Zhao, Wonji Kim, Xiuqing Guo, Yii-Der Ida Chen, Trans-Omics In Precision Medicine Consortium, Tamar Sofer

Faculty, Staff and Student Publications

We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model's performance as percentage variance explained (PVE) on a held-out test …

Propofol Enhancement Of Slow Wave Sleep To Target The Nexus Of Geriatric Depression And Cognitive Dysfunction: Protocol For A Phase I Open Label Trial, Rachel Lynn Rios, Michael Green, S Kendall Smith, Mohammadmehdi Kafashan, Shinung Ching, Nuri B Farber, Nan Lin, Brendan P Lucey, Charles F Reynolds, Eric J Lenze, Ben Julian Agustin Palanca, Swiped Study Team

2020-Current year OA Pubs

INTRODUCTION: Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has …

Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller

Kimmel Cancer Center Faculty Papers

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.

METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local …

Efficacy And Safety Of Atezolizumab And Bevacizumab In Appendiceal Adenocarcinoma, Nicholas J Hornstein, Mohammad A Zeineddine, Betul B Gunes, Andrew J Pellatt, Mark Knafl, Haifeng Zhu, Anneleis F Willett, Abdelrahman Yousef, Suyu Liu, Ryan Sun, Andrew Futreal, Scott E Woodman, Melissa W Taggart, Michael J Overman, Daniel M Halperin, Kanwal P Raghav, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously.

EXPERIMENTAL DESIGN: We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA.

RESULTS: Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of …

Vascular Risk Profile And Changes Of Arterial Hypertension After Surgical Revascularization In Adult Moyamoya Patients, Patrick Haas, Lucas Moritz Wiggenhauser, Jonas Tellermann, Helene Hurth, Daniel Feucht, Marcos Tatagiba, Nadia Khan, Constantin Roder

Faculty, Staff and Student Publications

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Faculty, Staff and Student Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

Spontaneous Coronary Artery Dissection Outcomes Among Pregnant Vs. Non-Pregnant Women, Chayakrit Krittanawong, Neelkumar Patel, Dhrubajyoti Bandyopadhyay, Neil Sagar Maitra, Muzamil Khawaja, Zhen Wang, Mahboob Alam, Jacob Shani, Robert Frankel, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

Aims: Spontaneous coronary artery dissection (SCAD) has become increasingly recognized. It accounts for < 1-4% of acute coronary syndrome presentations. Overall, however, it makes up over 40% of pregnancy-associated myocardial infarction. Furthermore, pregnancy-associated spontaneous coronary artery dissection (P-SCAD) is described to have a greater degree of clinical manifestations, including left ventricular dysfunction, shock, and left main or multivessel involvement. The findings are disconcerting, though many studies evaluating P-SCAD are based on case series data or are single centre studies.

Methods and results: The aim of this study was to evaluate a larger national dataset to evaluate the outcomes of SCAD and specifically P-SCAD in an attempt to better characterize the severity and clinical nature of this condition. To conduct this study, we analysed the National Readmission Database from January 2016 to December 2020. Propensity matching was done using the Greedy 1:1 method. Multivariate logistics and time-to-event Cox regression analysis models were built by including all confounders significantly associated with the outcome on univariable analysis with a …

Smoking Cessation After Initial Treatment Failure With Varenicline Or Nicotine Replacement: A Randomized Clinical Trial, Paul M Cinciripini, Charles E Green, Sanjay Shete, Jennifer A Minnix, Jason D Robinson, Yong Cui, Seokhun Kim, George Kypriotakis, Diane Beneventi, Janice A Blalock, Francesco Versace, Maher Karam-Hage

Faculty, Staff and Student Publications

Importance: Most people who smoke do not quit on their initial attempt.

Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT).

Design, setting, and participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic.

Interventions: The initial treatment was 2 mg/d of varenicline or …

Differentiation Syndrome Associated With Treatment With Idh2 Inhibitor Enasidenib: Pooled Analysis From Clinical Trials, Pau Montesinos, Amir T Fathi, Stéphane De Botton, Eytan M Stein, Amer M Zeidan, Yue Zhu, Thomas Prebet, Carlos E Vigil, Iryna Bluemmert, Xin Yu, Courtney D Dinardo

Faculty, Staff and Student Publications

Treatment with enasidenib, a selective mutant isocitrate dehydrogenase isoform 2 (IDH2) inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging because of nonspecific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy. Across the total AML population, 67 …

Factors Associated With Intention To Implement Sbi And Sud Treatment: A Survey Of Primary Care Clinicians In Texas Enrolled In An Online Course, Alicia Kowalchuk, Tiffany G Ostovar-Kermani, Kylie Schaper, Larissa Grigoryan, Jacqueline M Hirth, Maria Carmenza Mejia, Kiara K Spooner, Roger J Zoorob

Faculty, Staff and Students Publications

BACKGROUND: Substance use disorder (SUD) presents a range of public health challenges and consequences. Despite the prevention potential of screening and brief intervention (SBI) in the primary care setting, implementation is low. The purpose of this study was to assess associations of primary care clinicians' knowledge of SBI and SUD treatment, subjective norms, and perceived behavioral control with intention to incorporate SBI and SUD treatment into regular clinical practice.

METHODS: This online survey was administered to primary care clinicians who practice in Texas between March 1, 2021, and February 5, 2023. Survey questions were mapped to factors in the Theory …

Noncontrast Ct Selected Thrombectomy Vs Medical Management For Late-Window Anterior Large Vessel Occlusion, Thanh N Nguyen, Raul G Nogueira, Muhammad M Qureshi, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Sunil A Sheth, Volker Puetz, Anne Dusart, Patrik Michel, Marc Ribo, Osama O Zaidat, James E Siegler, Diogo C Haussen, Daniel Strbian, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, Marta Olive-Gadea, Ajit S Puri, Simon Winzer, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad A Jumaa, Syed F Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Mudassir Farooqui, Sergio Salazar-Marioni, Pekka Virtanen, Daniel P O Kaiser, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Alicia C Castonguay, Zain Mansoor, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Erno Peltola, Wei Hu, Eugene Lin, Kanta Tanaka, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Hiroshi Yamagami, Urs Fischer, Tudor G Jovin, Robin Lemmens, Peter A Ringleb, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background and objectives: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well …

Safety And Efficacy Of Metabolic Modulation With Ninerafaxstat In Patients With Nonobstructive Hypertrophic Cardiomyopathy, Martin S Maron, Sharon Cresci, Et Al.

2020-Current year OA Pubs

BACKGROUND: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics.

OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.

METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient < 30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption < 80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.

RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) …

A Technology-Assisted Web Application For Consumer Access To A Nonprescription Statin Medication, Steven E Nissen, Howard G Hutchinson, Kathy Wolski, Karol Watson, Seth S Martin, Erin D Michos, William S Weintraub, Melanie Morris, Leslie Cho, Luke Laffin, Douglas Jacoby, Christie M Ballantyne, Jan Ekelund, Filip Birve, Venu Menon, Michelle Strzelecki, Paul M Ridker

Faculty, Staff and Students Publications

Background: Although statins reduce adverse cardiovascular outcomes, less than one-half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins.

Objectives: This study sought to assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a technology assisted self-selection Web application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels.

Methods: This study was a prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate-intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, …

Quantifying The Effects Of Sleep On Sensor-Derived Variables From Upper Limb Accelerometry In People With And Without Upper Limb Impairment, Allison E Miller, Catherine E Lang, Marghuretta D Bland, Keith R Lohse

2020-Current year OA Pubs

BACKGROUND: Despite the promise of wearable sensors for both rehabilitation research and clinical care, these technologies pose significant burden on data collectors and analysts. Investigations of factors that may influence the wearable sensor data processing pipeline are needed to support continued use of these technologies in rehabilitation research and integration into clinical care settings. The purpose of this study was to investigate the effect of one such factor, sleep, on sensor-derived variables from upper limb accelerometry in people with and without upper limb impairment and across a two-day wearing period.

METHODS: This was a secondary analysis of data collected during …

Nivolumab Plus Brentuximab Vedotin For Relapsed/Refractory Peripheral T-Cell Lymphoma And Cutaneous T-Cell Lymphoma, Pier Luigi Zinzani, Neha Mehta-Shah, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Impact Of The Optn Policy Change On Patients With A Durable Left Ventricular Assist Device And Chronic Kidney Disease: Analysis Of The Unos Database, Eric D. Warner, Christopher Pritting, Sawan Dutta, Matt Bierowski, Waqas Ullah, Yevgeniy Brailovsky, Michelle Kittleson, René J. Alvarez, J. Eduardo Rame, Alexander Hajduczok, Vineeta Kumar, Danial Ahmad, Vakhtang Tchantchaleishvili, Indranee N. Rajapreyar

Division of Cardiology Faculty Papers

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD).

OBJECTIVE: To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD).

METHODS: We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant …

Invasive Hemodynamic Changes Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Abiodun Idowu, Olayinka Adebolu, Casipit Bruce, Bede Nriagu, Endurance Evbayekha, Kevin Bryan Lo, Olayinka Afolabi-Brown, Janani Rangaswami

Einstein Health Papers

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanisms of benefit in relation to invasive hemodynamics remain unclear. Using PRISMA guidelines, we systematically reviewed multiple online databases for randomized trials evaluating the effect of SGLT2i on invasive hemodynamics. Rest and peak exercise invasive hemodynamics were measured via right heart catheterization pre- and postintervention. Random effects model meta-analysis at a 95% confidence interval was done using RevMan 5.0. A total of 3 studies with a total of 145 patients were included in the meta-analysis. SGLT2i was significantly associated with a reduction …

Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal

Faculty, Staff and Student Publications

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial …

Estimating The Likelihood Of Epilepsy From Clinically Noncontributory Electroencephalograms Using Computational Analysis: A Retrospective, Multisite Case–Control Study, Luke Tait, Lydia E. Staniaszek, Elizabeth Galizia, David Martin-Lopez, Matthew C. Walker, Al Anzari Abdul Azeez, Kay Meiklejohn, David Allen, Chris Price, Sophie Georgiou, Manny Bagary, Sakh Khalsa, Francesco Manfredonia, Phil Tittensor, Charlotte Lawthom, Benjamin B. Howes, Rohit Shankar, John R. Terry, Wessel Woldman

Peninsula Medical School

Objective: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case–control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). Methods: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = …

Accessibility, Relevance, And Impact Of A Symptom Monitoring Tool For Home Hospice Care: Theory Elaboration And Qualitative Assessment, Karla T Washington, Debra Parker Oliver, Allison K Donehower, Patrick White, Jacquelyn J Benson, Patrick G Lyons, George Demiris

2020-Current year OA Pubs

BACKGROUND: Early users found Engagement and Visualization to Improve Symptoms in Oncology Care (ENVISION), a web-based application designed to improve home management of hospice patients' symptoms and support patients' and family caregivers' well-being, to be generally useful and easy to use. However, they also raised concerns about potential challenges users with limited technological proficiency might experience.

OBJECTIVE: We sought to concurrently accomplish two interrelated study aims: (1) to develop a conceptual framework of digital inclusivity for health information systems and (2) to apply the framework in evaluating the digital inclusivity of the ENVISION application.

METHODS: We engaged ENVISION users (N=34) …

The Inform (International Framework For Rehabilitation Medics) Project To Strengthen The Medical Specialty, Man Hung, Himani Patel, Samantha Lee, Justin Nguyen, Amir Mohajeri

Faculty, Staff and Student Publications

(1) Background: This study examines vitamin D’s impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as …

Sustained Response To Atogepant In Episodic Migraine: Post Hoc Analyses Of A 12-Week Randomized Trial And A 52-Week Long-Term Safety Trial, Richard Lipton, Stephanie J. Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter Mcallister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David Dodick

Department of Neurology Faculty Papers

BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.

METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety …

Comprehensive Proteogenomic Characterization Of Rare Kidney Tumors, Ginny Xiaohe Li, Lijun Chen, Yi Hsiao, Rahul Mannan, Yuping Zhang, Jie Luo, Francesca Petralia, Hanbyul Cho, Noshad Hosseini, Felipe Da Veiga Leprevost, Anna Calinawan, Yize Li, Shankara Anand, Aniket Dagar, Yifat Geffen, Chandan Kumar-Sinha, Seema Chugh, Anne Le, Sean Ponce, Shenghao Guo, Cissy Zhang, Michael Schnaubelt, Nataly Naser Al Deen, Feng Chen, Wagma Caravan, Andrew Houston, Alex Hopkins, Chelsea J Newton, Xiaoming Wang, Daniel A Polasky, Sarah Haynes, Fengchao Yu, Xiaojun Jing, Siqi Chen, Ana I Robles, Mehdi Mesri, Mathangi Thiagarajan, Eunkyung An, Gad A Getz, W Marston Linehan, Galen Hostetter, Scott D Jewell, Daniel W Chan, Pei Wang, Gilbert S Omenn, Rohit Mehra, Christopher J Ricketts, Li Ding, Arul M Chinnaiyan, Marcin P Cieslik, Saravana M Dhanasekaran, Hui Zhang, Alexey I Nesvizhskii, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC …

Lacl3-Based Sodium Halide Solid Electrolytes With High Ionic Conductivity For All-Solid-State Batteries, Chengyu Fu, Yifan Li, Wenjie Xu, Xuyong Feng, Weijian Gu, Jue Liu, Wenwen Deng, Wei Wang, A M Milinda Abeykoon, Laisuo Su, Lingyun Zhu, Xiaojun Wu, Hongfa Xiang

Faculty, Staff and Student Publications

To enable high performance of all solid-state batteries, a catholyte should demonstrate high ionic conductivity, good compressibility and oxidative stability. Here, a LaCl3-based Na+ superionic conductor (Na1−xZrxLa1−xCl4) with high ionic conductivity of 2.9 × 10−4 S cm−1 (30 °C), good compressibility and high oxidative potential (3.80 V vs. Na2Sn) is prepared via solid state reaction combining mechanochemical method. X-ray diffraction reveals a hexagonal structure (P63/m) of Na1−xZrxLa1−xCl4, with Na+ ions forming a one-dimensional diffusion channel along the c-axis. First-principle calculations combining with …