Digital Commons Network^™

Leveraging Mhealth To Mitigate The Impact Of Covid-19 In Black American Communities: Qualitative Analysis, Kelly M Harris, Tilicia Mayo Gamble, Madelyn G Yoo, Lindsay A Spell, Timira N Minor, Holly Jones, Donald Lynch

2020-Current year OA Pubs

BACKGROUND: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations.

OBJECTIVE: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Single-Cell Atlas Of Healthy Human Blood Unveils Age-Related Loss Of Nkg2c+Gzmb−Cd8+ Memory T Cells And Accumulation Of Type 2 Memory T Cells, Marina Terekhova, Amanda Swain, Pavla Bohacova, Ekaterina Aladyeva, Laura Arthur, Anwesha Laha, Denis A Mogilenko, Samantha Burdess, Vladimir Sukhov, Denis Kleverov, Barbora Echalar, Petr Tsurinov, Roman Chernyatchik, Kamila Husarcikova, Maxim N Artyomov

2020-Current year OA Pubs

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK

[Intra-Articular Corticoid Therapy With Triamcinolone Hexacetonide], M Talke

Student and Faculty Publications

Objective

Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt–Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter‐individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD.

Methods

Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Rab1a Haploinsufficiency Phenocopies The 2p14-P15 Microdeletion And Is Associated With Impaired Neuronal Differentiation, Jonathan J Rios, Yang Li, Nandina Paria, Ryan J Bohlender, Chad Huff, Jill A Rosenfeld, Pengfei Liu, Weimin Bi, Kentaro Haga, Mitsunori Fukuda, Shayal Vashisth, Kiran Kaur, Maria H Chahrour, Michael B Bober, Angela L Duker, Farah A Ladha, Neil A Hanchard, Kristhen Atala, Anas M Khanshour, Linsley Smith, Carol A Wise, Mauricio R Delgado

Student and Faculty Publications

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and …

Delayed Giant Pseudoaneurysm With Left-To-Right Shunt Following Postinfarct Ventricular Septal Perforation Repair, Yojiro Machii, Makoto Taoka, Yuki Hayashi, Atsushi Harada, Keita Kamata, Masashi Tanaka

The Texas Heart Institute Journal

Left ventricular pseudoaneurysm with a left-to-right shunt is extremely rare, requiring surgery if symptomatic; however, surgery has a high risk. Here, the case of a 77-year-old man with heart failure symptoms is reported, in which he develops a giant left ventricular pseudoaneurysm 16 months after ventricular septal perforation repair as a result of acute myocardial infarction, with mild shunt blood flow from the pseudoaneurysm to the right ventricle. Intraoperative findings showed a free wall rupture along the area where the patch was secured during the initial surgery. The patient was discharged on postoperative day 13, and postoperative examination revealed no …

Chromosome 10q24.32 Variants Associate With Brain Arterial Diameters In Diverse Populations: A Genome-Wide Association Study, Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez

Student and Faculty Publications

Background: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown.

Methods and results: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide …

Role Of Sex In The Association Of Socioeconomic Status With Cardiovascular Health In Black Americans: The Jackson Heart Study, Joshua J Joseph, Amaris Williams, Rosevine A Azap, Songzhu Zhao, Guy Brock, David Kline, James B Odei, Randi Foraker, Mario Sims, Laprincess C Brewer, Darrell M Gray Ii, Timiya S Nolan

2020-Current year OA Pubs

BACKGROUND: Socioeconomic status (SES) is associated with cardiovascular health (CVH). Potential differences by sex in this association remain incompletely understood in Black Americans, where SES disparities are posited to be partially responsible for cardiovascular inequities. The association of SES measures (income, education, occupation, and insurance) with CVH scores was examined in the Jackson Heart Study.

METHODS AND RESULTS: American Heart Association CVH components (non-high-density-lipoprotein cholesterol, blood pressure, diet, tobacco use, physical activity, sleep, glycemia, and body mass index) were scored cross-sectionally at baseline (scale: 0-100). Differences in CVH and 95% CIs (Estimate, 95% CI) were calculated using linear regression, adjusting …

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery Of 187 Novel Risk Variants, Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, David E Neal, Jenny L Donovan, Freddie C Hamdy, Richard M Martin, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A Clements, Wayne Tilly, Gail P Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M Dunning, Maya Ghoussaini, Ruth C Travis, Tim J Key, Elio Riboli, Jong Y Park, Thomas A Sellers, Hui-Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B Cook, Lorelei A Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J Hunter, Kathryn L Penney, Constance Turman, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, Robert J Hamilton, Neil E Fleshner, Antonio Finelli, Marie-Élise Parent, Janet L Stanford, Elaine A Ostrander, Stella Koutros, Laura E Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L Andriole, Robert N Hoover, Mitchell J Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J Blot, Wei Zheng, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-Chao Zhao, Zan Sun, Stephen N Thibodeau, Shannon K Mcdonnell, Daniel J Schaid, Catharine M L West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M John, Eli Marie Grindedal, Lovise Maehle, Kay-Tee Khaw, Sue A Ingles, Mariana C Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S Rosenstein, Sarah L Kerns, Harry Ostrer, Manuel R Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T Bensen, Ebonee N Butler, James L Mohler, Jack A Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C Teerlink, Chad D Huff, Patrick Pilie, Yao Yu, Ryan J Bohlender, Jian Gu, Sara S Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A Klein, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Jeri Kim, Susan L Neuhausen, Linda Steele, Yuan Chun Ding, William B Isaacs, Barbara Nemesure, Anselm J M Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Lisa F Newcomb, Daniel W Lin, Jay H Fowke, Christine M Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A Townsend, Claire Aukim-Hastie, William S Bush, Melinda C Aldrich, Dana C Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P Chokkalingam, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M Gundell, Monique J Roobol, Guido Jenster, Ron H N Van Schaik, Jennifer J Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean-Cowdin, Mina Torres, Michael H Preuss, Ruth J F Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K Van Den Eeden, Douglas F Easton, Stefan Ambs, Todd L Edwards, Reedik Mägi, Timothy R Rebbeck, Lars Fritsche, Stephen J Chanock, Sonja I Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S Witte, J Michael Gaziano, Amy C Justice, Nick Mancuso, Chikashi Terao, Rosalind A Eeles, Zsofia Kote-Jarai, Ravi K Madduri, David V Conti, Christopher A Haiman

Student and Faculty Publications

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in …

Characteristics And Outcomes Of Patients With Pregnancy-Related End-Stage Kidney Disease., Lauren Kucirka, Ana Angarita, Tracy Manuck, Kim Boggess, Vimal Derebail, Mollie Wood, Michelle Meyer, Dorry Segev, Monica Reynolds

Department of Obstetrics and Gynecology Faculty Papers

IMPORTANCE: The incidence of pregnancy-related acute kidney injury is increasing and is associated with significant maternal morbidity including progression to end-stage kidney disease (ESKD). Little is known about characteristics and long-term outcomes of patients who develop pregnancy-related ESKD.

OBJECTIVES: To examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study of 183 640 reproductive-aged women with incident ESKD between January 1, 2000, and November 20, 2020, from the US Renal Data System and maternal data from births captured in the …

Genomic Profiles And Clinical Outcomes Of Penile Squamous Cell Carcinoma With Elevated Tumor Mutational Burden, Andrea Necchi, Philippe E Spiess, Tiago Costa De Padua, Roger Li, Petros Grivas, Richard S P Huang, Douglas I Lin, Natalie Danziger, Jeffrey S Ross, Joseph M Jacob, Rebecca A Sager, Alina Basnet, Gerald Li, Ryon P Graf, Dean C Pavlick, Gennady Bratslavsky

Student and Faculty Publications

IMPORTANCE: Tumor mutational burden (TMB) is a putative biomarker of efficacy for immune checkpoint inhibitor (ICI) therapies of solid tumors, but not specifically for penile squamous cell carcinoma (PSCC).

OBJECTIVE: To characterize biomarker features and ICI therapy outcomes associated with high TMB in PSCC in the routine clinical practice setting.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 397 PSCC cases were analyzed to identify genomic alterations in more than 300 cancer-associated genes and genomic signatures, including TMB, using a hybrid capture-based comprehensive genomic profiling assay. Tumor mutational burden was categorized as low ([mut/Mb]), high (10-19 mut/Mb), or very high …

Mortality And Morbidity Among Individuals With Hypertension Receiving A Diuretic, Ace Inhibitor, Or Calcium Channel Blocker: A Secondary Analysis Of A Randomized Clinical Trial, Jose-Miguel Yamal, Journey Martinez, Mikala C Osani, Xianglin L Du, Lara M Simpson, Barry R Davis

Student and Faculty Publications

IMPORTANCE: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood.

OBJECTIVE: to determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at …

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M Humphries, Kwangmi Ahn, Rachel L Kember, Fabiana L Lopes, Evelina Mocci, Juan M Peralta, John Blangero, David C Glahn, Fernando S Goes, Peter P Zandi, Peter Kochunov, Cristopher Van Hout, Alan R Shuldiner, Toni I Pollin, Braxton D Mitchell, Maja Bucan, L Elliot Hong, Francis J Mcmahon, Seth A Ament

Student and Faculty Publications

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network …

Quantitative Analysis Of Anesthesia Utilization In Ambulatory Hand Surgery, Lucas P Bowen, Dean W Smith, Jacob Siahaan

Student and Faculty Publications

Background: Though evidence demonstrating benefits of local anesthetic continues to compound, a consensus among surgeons regarding optimal anesthetic modality has not been reached. General and regional anesthetic may still be preferred for patient anxiety, concomitant procedures, increased complexity, or poor patient pain tolerance. Therefore, the primary purpose of this study was to analyze trends in anesthetic utilization using a large-scale state healthcare database for common outpatient hand procedures. We hypothesize that over the 10 years between 2010-2019, local anesthetic [including Wide-Awake Local Anesthesia with no Tourniquet (WALANT)] utilization use for common hand procedures has increased, while the use of general …

Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is …

Local Treatment And Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer, Saira Khan, Su-Hsin Chang, Mei Wang, Eric H Kim, Martin W Schoen, Carleena Rocuskie-Marker, Bettina F Drake

2020-Current year OA Pubs

IMPORTANCE: Recent data suggest that local treatment with radical prostatectomy or radiation may improve survival outcomes in men with advanced prostate cancer. However, evidence is lacking on treatment-related adverse effects among men with advanced prostate cancer.

OBJECTIVE: To assess the association of local treatment on treatment-related adverse effects among men diagnosed with advanced prostate cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed men diagnosed with advanced prostate cancer (defined as T4, N1, and/or M1 prostate cancer) between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2021, who were treated at Veterans Health Administration medical centers. …

Dopamine, Norepinephrine And Serotonin Participate Differently In Methylphenidate Action In Concomitant Behavioral And Ventral Tegmental Area, Locus Coeruleus And Dorsal Raphe Neuronal Study In Young Rats, Cruz Reyes-Vasquez, Zachary Jones, Bin Tang, Nachum Dafny

Student and Faculty Publications

Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1–6), followed by a …

Two Phase 3 Trials Of Gantenerumab In Early Alzheimer's Disease, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease.

METHODS: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab …

A Multi-Institutional Phase 2 Trial Of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy For Borderline Resectable And Locally Advanced Pancreatic Cancer, Parag Jitendra Parikh, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.

2020-Current year OA Pubs

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).

METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to …

Repeated Multi-Domain Cognitive Training Prevents Cognitive Decline, Anxiety And Amyloid Pathology Found In A Mouse Model Of Alzheimer Disease, Jogender Mehla, Scott H Deibel, Hadil Karem, Nancy S Hong, Shakhawat R Hossain, Sean G Lacoursiere, Robert J Sutherland, Majid H Mohajerani, Robert J Mcdonald

2020-Current year OA Pubs

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APP

Relationship Of Race With Functional And Clinical Outcomes With The Rehab-Hf Multidomain Physical Rehabilitation Intervention For Older Patients With Acute Heart Failure, Olivia N. Gilbert, Robert J. Mentz, Alain G. Bertoni, Dalane W. Kitzman, David J. Whellan, Gordon R. Reeves, Pamela W. Duncan, Michael Benjamin Nelson, Vanessa Blumer, Haiying Chen, Shelby D. Reed, Bharathi Upadhya, Christopher M. O'Connor, Amy M. Pastva

Department of Medicine Faculty Papers

Background

The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3‐month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health‐related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown.

Methods and Results

In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6‐Minute Walk Distance), cognition, depression, frailty, health‐related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5‐Dimension‐5‐Level Questionnaire) and at 6 months for …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Student and Faculty Publications

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Segregated Patterns Of Hospital Care Delivery And Health Outcomes, Sunny C Lin, J. Gmerice Hammond, Michael Esposito, Cassandra Majewski, Randi E Foraker, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Residential segregation has been shown to be a root cause of racial inequities in health outcomes, yet little is known about current patterns of racial segregation in where patients receive hospital care or whether hospital segregation is associated with health outcomes. Filling this knowledge gap is critical to implementing policies that improve racial equity in health care.

OBJECTIVE: To characterize contemporary patterns of racial segregation in hospital care delivery, identify market-level correlates, and determine the association between hospital segregation and health outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of US hospital referral regions (HRRs) used 2018 Medicare claims, …

Automated Large Vessel Occlusion Detection Software And Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial, Juan Carlos Martinez-Gutierrez, Youngran Kim, Sergio Salazar-Marioni, Muhammad Bilal Tariq, Rania Abdelkhaleq, Arash Niktabe, Anjan N Ballekere, Ananya S Iyyangar, Mai Le, Hussain Azeem, Charles C Miller, Jon E Tyson, Sandi Shaw, Peri Smith, Mallory Cowan, Isabel Gonzales, Louise D Mccullough, Andrew D Barreto, Luca Giancardo, Sunil A Sheth

Student and Faculty Publications

Importance

The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical.

Objective

To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows.

Design, Setting, and Participants

This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Student and Faculty Publications

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

Resilience Of Patients Undergoing Knee And Shoulder Arthroscopy Procedures, Jillian Mazzocca, Natalie Lowenstein, Connor Crutchfield, Jamie Collins, Elizabeth Matzkin

Student Papers, Posters & Projects

INTRODUCTION: Resilience is a person's capacity to overcome adversity. The purpose was to determine what patient factors correlate with resilience using the Brief Resilience Score. We hypothesize that characteristics of female sex, younger age, Workers' Compensation status, and preoperative opioid use are predictors of a lower preoperative resilience score and that patients with positive psychosocial factors would have higher resilience scores.

METHODS: Eight hundred nine patients undergoing knee or shoulder arthroscopy were preoperatively categorized into low, normal, and high-resilience groups. Preoperative patient-reported outcome measures (PROMs) and demographics were assessed. Statistical analyses evaluated differences in demographics and PROMs between resilience groups. …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Student and Faculty Publications

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

Ascertainment Of Minimal Clinically Important Differences In The Diabetes Distress Scale-17: A Secondary Analysis Of A Randomized Clinical Trial, Jack Banks, Amber B Amspoker, Elizabeth M Vaughan, Lechauncy Woodard, Aanand D Naik

Student and Faculty Publications

IMPORTANCE: The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17.

OBJECTIVE: to establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress).

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated …

Health-Related Quality-Of-Life In Treatment-Naive Cll/Sll Patients Treated With Zanubrutinib Versus Bendamustine Plus Rituximab, Paolo Ghia, Gisoo Barnes, Keri Yang, Constantine S Tam, Tadeusz Robak, Jennifer R Brown, Brad S Kahl, Tian Tian, Andy Szeto, Jason C Paik, Mazyar Shadman

2020-Current year OA Pubs

OBJECTIVE: Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality-of-life (HRQoL).

METHODS: In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires' scales and a mixed …