Digital Commons Network^™

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Nivolumab Plus Relatlimab For Patients With Relapsed Or Progressed B-Cell Malignancies In Relativity-022, Ajay K Gopal, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during …

Bridging Radiotherapy Before Chimeric Antigen Receptor T Cells For B-Cell Lymphomas: An Ilrog Multicenter Study, Nikhil Yegya-Raman, Joanna C Yang, Et Al.

2020-Current year OA Pubs

Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (BCLs) who received Br-RT followed by CAR-T from 2018 to 2020 across 10 institutions. Br-RT toxicities were graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy Consensus Guidelines. One hundred seventy-two patients (168 large BCL) received Br-RT before axicabtagene ciloleucel (73%), tisagenlecleucel (24%), or brexucabtagene autoleucel (2%). At …

The Landscape Of Autosomal-Dominant Alzheimer's Disease: Global Distribution And Age Of Onset, Haiyan Liu, Thomas W Marsh, Xinyu Shi, Kevin M Bowling, Ellen Ziegemeier, Guoqiao Wang, Yuchen Cao, Alexa Dickson, Richard J Perrin, Michelle Doering, Alisha Daniels, Brian A Gordon, Tammie L S Benzinger, Jason Hassenstab, Laura Ibanez, Charlene Supnet-Bell, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Carlos Cruchaga, Eric Mcdade, Jorge J Llibre-Guerra, Et Al.

2020-Current year OA Pubs

We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying …

Exploring Sex-Specific Clinical Features In Chinese Patients With Takotsubo Syndrome, Hong-Yi Duan, Ling-Lin Wang, Ling-Chun Lyu, Zhen-Hua Shi, Xiao-Ping Lin, Zheng-Yang Yu, Guo-Hua Fan, Jing Chen, Xin-Hong Yang, Wei Deng, Chang-Wu Xu, Yan Huang, Qing Zhou, Jin-Ling Chen, Hong-Ning Song, Dong Hu, Jin-Qiu Liu, Hector Barajas-Martinez, Charles Antzelevitch, Kan Liu, Hong Jiang, Dan Hu

Department of Medicine Faculty Papers

BACKGROUND: Takotsubo syndrome (TTS) is considered as a transient acute heart failure syndrome predominant in females. However, data on Chinese TTS patients are limited. Therefore, this study aimed to investigate the clinical characteristics of Chinese TTS patients, identify prognostic markers.

METHODS: A total of 258 TTS patients were enrolled. Data on clinical characteristics and in-hospital major adverse cardiovascular events (MACE) were collected and analyzed. The latter included severe heart failure, shock, malignant arrhythmia, and death.

RESULTS: The average age of TTS patients was 59.3 ± 19.2 years. Female patients accounted for 68.9%. MACE occurred in 41.4% of patients during hospitalization. …

Prediction Of Generalized Anxiety Disorder Treatment Outcomes With Neurobehavioral Responses To Approach-Avoidance Conflict: A Randomized Clinical Trial., Hannah Berg, Timothy J. Mcdermott, Rayus Kuplicki, Hung-Wen Yeh, Wesley K. Thompson, Ryan Smith, Elisabeth Akeman, Namik Kirlic, Ashley Clausen, Mallory Cannon, Evan White, Christopher R. Martell, Kate B. Wolitzky-Taylor, Michelle G. Craske, James L. Abelson, Martin P. Paulus, Robin L. Aupperle

Manuscripts, Articles, Book Chapters and Other Papers

Treatments for generalized anxiety disorder (GAD) often aim to address maladaptive approach-avoidance behavior patterns. Approach-avoidance conflict (AAC) offers a potential framework for identifying treatment outcome predictors and informing optimization of GAD treatment. The current study examined whether pre-treatment neurobehavioral AAC indices predict symptom improvement in behavioral activation (BA) and exposure therapy (EXP) for GAD. Treatment-seeking adults meeting criteria for GAD completed a randomized clinical trial with pre-treatment blinding, conducted from 2016-2021. Participants were randomized to complete 10 manualized sessions of BA or EXP. Participants completed an AAC task during functional magnetic resonance imaging pre-treatment. Computational parameters of task behavior were …

Exploring Sex-Specific Clinical Features In Chinese Patients With Takotsubo Syndrome, Hong-Yi Duan, Kan Liu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) is considered as a transient acute heart failure syndrome predominant in females. However, data on Chinese TTS patients are limited. Therefore, this study aimed to investigate the clinical characteristics of Chinese TTS patients, identify prognostic markers.

METHODS: A total of 258 TTS patients were enrolled. Data on clinical characteristics and in-hospital major adverse cardiovascular events (MACE) were collected and analyzed. The latter included severe heart failure, shock, malignant arrhythmia, and death.

RESULTS: The average age of TTS patients was 59.3 ± 19.2 years. Female patients accounted for 68.9%. MACE occurred in 41.4% of patients during hospitalization. …

Improving Genetics Equity: Identifying Women Eligible For Genetic Care Services Using Mammography Clinics In Underserved Areas As Screening Hubs, Darya Kizub, Rachel Bluebond, Sierra Green, Jessica Duckworth, Sreejesh Shanker, Autumn Vara, Banu Arun

Faculty, Staff and Student Publications

PURPOSE: Fewer than 20% of underserved individuals undergo guideline-concordant hereditary breast and ovarian cancer (HBOC) genetic testing (GT). Our study aimed to determine the proportion of women eligible for HBOC GT using a cancer genetics risk assessment (CGRA) tool at breast cancer (BC) screening clinics in underserved communities and to describe the program's impact.

METHODS: Participants were women who presented for BC screening at The Rose clinics, serving low-income underserved communities in southeast Texas, and completed the CGRA. High-risk individuals received bilingual educational materials and a saliva-based GT kit. Those with a pathogenic variant (PV) or a variant of uncertain …

Supporting Patients With Advanced Cancer And Their Spouses In Parenting Minor Children: Results Of A Randomized Controlled Trial, Kathrin Milbury, Sujin Ann-Yi, Meagan S Whisenant, Morgan Jones, Yisheng Li, Victoria Necroto, Sania D Yousuf, Mariana Chavez-Macgregor, Larrisa Meyers, Eduardo Bruera

Faculty, Staff and Student Publications

Introduction: Patients with advanced cancer and their spousal caregivers who parent minor children report unmet parenting concerns and increased psychological distress. Seeking to address these important supportive care needs, this RCT examined the feasibility, acceptability, and initial evidence for the efficacy of a novel psychosocial intervention.

Patients and methods: Patients with a metastatic solid malignancy and their spouses completed self-reported validated assessments of psychological symptoms and cancer-related parenting outcomes and were then randomized to the parent support intervention or a usual care (UC) group. Both groups were reassessed 6 and 12 weeks later. Dyads randomized to the counselor-led intervention attended …

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Association Study For Lung Cancer In 6531 African Americans Reveals New Susceptibility Loci, Jinyoung Byun, Younghun Han, Jiyeon Choi, Ryan Sun, Vikram R Shaw, Catherine Zhu, Xiangjun Xiao, Christine Lusk, Hoda Badr, Hyun-Sung Lee, Hee-Jin Jang, Yafang Li, Hyeyeun Lim, Erping Long, Yanhong Liu, Linda Kachuri, Kyle M Walsh, John K Wiencke, Demetrius Albanes, Stephen Lam, Adonina Tardon, Marian L Neuhouser, Matt J Barnett, Chu Chen, Stig Bojesen, Hermann Brenner, Maria Teresa Landi, Mattias Johansson, Angela Risch, H-Erich Wichmann, Heike Bickeböller, David C Christiani, Gad Rennert, Susanne Arnold, John K Field, Sanjay Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Fiona Taylor, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Alpa Patel, Xihong Lin, Krista A Zanetti, Curtis C Harris, Stephen Chanock, James Mckay, Ann G Schwartz, Rayjean J Hung, Christopher I Amos

Faculty, Staff and Student Publications

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Daily Physical Activity And Cardiorespiratory Fitness In Adults With Down Syndrome With And Without Congenital Heart Disease., Julianne G. Clina, David A. White, Joseph R. Sherman, Jessica C. Danon, Daniel Forsha, Brian C. Helsel, Richard A. Washburn, Joseph E. Donnelly, Lauren T. Ptomey

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Individuals with Down syndrome (DS) typically exhibit lower cardiorespiratory fitness and reduced moderate-to-vigorous physical activity (MVPA) compared to persons without disability. Approximately 50-55 % of individuals with DS have congenital heart disease (CHD), which is associated with cardiopulmonary deficiencies and reduced MVPA participation in non-DS populations. It is unknown if CHD related comorbidities compound with DS associated deficits in physical activity and fitness.

OBJECTIVE: To compare physical activity, cardiorespiratory fitness, and cardiovascular function, of persons with DS with and without CHD.

METHODS: Baseline data were used from a 12-month randomized controlled physical activity intervention of adults with DS. Participants …

Systemic Exogenous Progestins With Or Without Estrogens Are Associated With Decreased Rates Of Venous Procedures For Varicose Veins, Paarth Jain, Adam M. Ostrovsky, Paul J Dimuzio, Luis H. Eraso, Michael Nooromid, Dawn Salvatore, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVES: Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

METHODS: The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. …

Individualized Functional And Structural Language Lateralities In Temporal Lobe Epilepsy And Their Impact On Memory, Ankeeta Ankeeta, Qirui Zhang, Sam Sharifzadeh Javidi, Shilpi Modi, Michael R. Sperling, Joseph I. Tracy

Department of Neurology Faculty Papers

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Dietary Patterns, Serum Metabolites, And Risk Of Cardiovascular Disease In United States Hispanic/Latino Adults: A Prospective Analysis Of The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Hongbo Yang, Yi Wang, Kai Luo, Yasmin Mossavar-Rahmani, Christina Cordero, Robert J Ostfeld, Claudia Martinez, Luis Maldonado, Amber Pirzada, Martha Daviglus, Bing Yu, Frank B Hu, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Background: Healthy dietary patterns are recommended to prevent cardiovascular disease (CVD), yet the relationships among healthy dietary patterns, blood metabolite profile, and incident CVD are not well understood.

Objectives: This study aimed to assess the associations of healthy dietary patterns and related serum metabolite profiles with incident CVD in United States Hispanic/Latino adults.

Methods: The study included 13,922 participants aged 18-74 y from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores, including Healthy Eating Index (HEI)-2020, healthful Plant-based Diet Index (hPDI), and alternate Mediterranean diet score (aMED), were constructed at baseline (2008-2011) based on 2 24-h dietary recalls. …

Pulmonary Complications Associated With Sugammadex Or Neostigmine In Patients Recovering From Advanced Diagnostic Or Interventional Bronchoscopy: A Retrospective Two-Centre Analysis, Ehab Farag, Karan Shah, Maged Argalious, Basem Abdelmalak, Thomas Gildea, John Seif, Shuyi Li, Edward J Mascha, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Many diagnostic and interventional procedures are performed in bronchoscopy suites in high-risk patients. Minor impairment in respiratory muscle function caused by incomplete reversal of neuromuscular block can contribute to postoperative pulmonary complications (PPCs). We assessed whether there are fewer serious PPCs after diagnostic or therapeutic bronchoscopy when neuromuscular block is reversed with sugammadex rather than neostigmine.

Methods: This is a retrospective cohort study for bronchoscopy under general anaesthesia with the use of neuromuscular blockers between July 2016 and June 2022. The primary outcome was a composite of PPCs. The secondary outcome was hypoxaemia. We used inverse probability of treatment …

High-Impact Chronic Pain And Cognitive Decline Among Mexicans Aged 60 And Older From 2012 To 2018, Sadaf Arefi Milani, Sirena Gutierrez, Brandon O'Grady, Rebeca Wong, Rafael Samper-Ternent, Brian Downer

Faculty, Staff and Student Publications

Pain is associated with cognitive decline, but prior research has not considered differences between high- and low-impact chronic pain or low-and middle-income countries, such as Mexico. Our objective was to evaluate the association between high-impact chronic pain and cognitive decline among older adults in Mexico. We used data from the 2012-2018 Mexican Health and Aging Study (MHAS), a nationally representative study of older Mexican adults (60+). Pain, measured at each wave, was categorized as high-impact chronic pain (pain that limits daily activities), low-impact chronic pain (pain that did not limit daily activities), and no chronic pain. Cognition was measured at …

Diet, Gut Microbiota, And Histidine Metabolism Toward Imidazole Propionate Production In Relation To Type 2 Diabetes, Hongbo Yang, Kai Luo, Brandilyn A Peters, Yi Wang, Yanbo Zhang, Martha Daviglus, Amber Pirzada, Christina Cordero, Bing Yu, Robert D Burk, Robert Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Objective: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

Research design and methods: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake. …

Prevalence, Treatment Patterns, Burden, And Factors Related To Treatment Failure With Sodium-Glucose Cotransporter 2 Inhibitor In Adults With Type 2 Diabetes In The United States, Xi Tan, Yiwen Cao, Yan Wang, Joanna Boland, Mico Guevarra, Lin Xie, Yan Song, Min Ji Kwak

Faculty, Staff and Student Publications

Aims: To evaluate treatment failure of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among adults with type 2 diabetes (T2D) and assess associated risk factors and clinical and economic outcomes in the real-world setting.

Methods: Adults with T2D who initiated SGLT2i were selected from the Komodo's Healthcare Map, an administrative claims database (2016-2024). Treatment failure was defined as discontinuation, add-on/switching, or uncontrolled glycated hemoglobin (HbA1c) without action. Risk factors, treatment patterns, and clinical and economic burden were assessed.

Results: Among 237,295 eligible adults, the overall rate of treatment failure with SGLT2i was 77.3 %, with a median time to failure of 9.14 …

Efficacy And Safety Of Mechanical Thrombectomy In Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients On Low-Dose Aspirin, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and …

Endovascular Therapy For Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis Of The Clear Study, Simon Winzer, Daniel P O Kaiser, Muhammad M Qureshi, Alicia C Castonguay, Daniel Strbian, Raul G Nogueira, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Hiroshi Yamagami, Kanta Tanaka, Sunil A Sheth, Anne Dusart, Patrik Michel, Marta Olive Gadea, Marc Ribo, Osama O Zaidat, Diogo C Haussen, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, James E Siegler, Ajit S Puri, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Milagros Galecio-Castillo, Sergio Salazar-Marioni, Pekka Virtanen, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Abiya Qureshi, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Mikko Sillanpää, Wei Hu, Eugene Lin, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Urs Fischer, Santiago Ortega-Gutierrez, Robin Lemmens, Peter A Ringleb, Thanh N Nguyen, Volker Puetz

Faculty, Staff and Student Publications

Background: There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The …

Automated Mycoplasma Genitalium Molecular Macrolide Resistance Detection And Nucleic Acid Target Semi-Quantitation: Patient Demographic Considerations, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Michael E Newcomb, Brian Mustanski, Erik Munson

Faculty, Staff and Student Publications

Recent work has optimized parameters of a real-time reverse transcriptase PCR-based laboratory-developed test on the Panther Fusion system which detects Mycoplasma genitalium-specific macrolide resistance-associated mutations LDT (MRM-LDT) from primary swab and urine specimens. In this study, MRM-LDT was applied to a large multi-demographic study set to further characterize M. genitalium resistance in the United States. A total of 2,145 primary clinical specimens testing positive for M. genitalium 16S rRNA by transcription-mediated amplification (TMA) were initially titered by the same assay using serial 10-fold dilutions to determine relative target nucleic acid burden. Specimens were then processed for MRM-LDT. Findings were stratified …

A Case Of Aqp4-Igg Neuromyelitis Optica Presenting With Orbital Inflammatory Syndrome, Lucy A Bailey, Roy F Riascos, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

A 45-year-old healthy African-American man experienced 2 months of right-eye soreness followed by acute onset of right painful vision loss with binocular, oblique diplopia. Visual acuity was count fingers OD and 20/20 OS. He had a partial, right, pupil-involving cranial nerve III palsy with a right relative afferent pupillary defect and optic disc edema with tortuous vessels. Magnetic resonance imaging showed increased T2 signal with tortuosity and thickening of the retrobulbar right optic nerve with associated restricted diffusion and enhancement, enhancement of orbital fat adjacent to the optic nerve sheath, and relative right proptosis. Workup was positive for aquaporin-4 antibody …

Long-Term Exposure To Multiple Air Pollutants And Multi-Level Socioeconomic Status: Joint Effects On Age-Related Macular Degeneration, Subsequent Ocular Comorbidity, And Death In Middle-Aged And Older Adults, Yang Yang, Liangkai Chen, Qichen Liu, Min Mu, Jing Huang, Guangming Zhang, Qianqian Song

Faculty, Staff and Student Publications

Background: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.

Methods: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Involved But Not Essential: Cognitive Activity In Periventricular Nodules And Neuropsychological Outcomes Following Their Ablation, Yosefa A Modiano, Oscar Woolnough, Ryan M Mccormack, Kathryn Snyder, Ellery Wheeler, Samden D Lhatoo, Nuria Lacuey, Sandipan Pati, Katherine Harris, Jay Gavvala, Jessica A Johnson, Nitin Tandon

Faculty, Staff and Student Publications

Objective: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development with high rates of epilepsy. The extent to which nodules participate in normal cerebral functions in addition to pathological processes is unclear. The authors assessed the functional utility (i.e., cognitive impacts) of surgically ablated epileptogenic PVNH tissue via comprehensive neuropsychological testing.

Methods: The sample included 32 patients with PVNH who underwent presurgical neuropsychological evaluation and a subsample of 16 patients who underwent MR-guided laser interstitial thermal therapy (MRgLITT) of nodules, with postsurgical neuropsychological testing. In 11 patients in whom intracranial recordings were performed, reading and naming tasks were tested …

Chronic Pain Is Associated With Greater Brain Entropy In The Prefrontal Cortex, Gianpaolo Del Mauro, Yiran Li, Jiaao Yu, Peter Kochunov, Landrew Samuel Sevel, Jeff Boissoneault, Shuo Chen, Ze Wang

Faculty, Staff and Student Publications

Chronic pain is a debilitating clinical condition and a severe public health issue that demands to be addressed. Neuroimaging-based techniques have been widely adopted to investigate the neural underpinnings of chronic pain. Despite the efforts the complex nature of pain experience as well as the heterogeneity of chronic pain have made the identification of neuroimaging-based biomarkers extremely challenging. In this study, resting-state fMRI-based brain entropy, a measure reflecting the "irregularity" of brain activity, was adopted as a biomarker of chronic pain by comparing individuals with chronic pain and healthy controls in a sample of middle-to-old-age participants (n > 30,000) drawn from …

Assessment Of Complement Cascade Components In Patients With Major Depressive Disorder, Brandi Quintanilla, Dede Greenstein, Ashutosh Tripathi, Alona Bartosh, Peixiong Yuan, Carlos A Zarate, Anilkumar Pillai

Faculty, Staff and Student Publications

Recent evidence suggests that the rapid-acting antidepressant ketamine has immune regulatory functions. The complement system is an important component of the innate immune response and plays a key role in synaptic plasticity. An increase in complement component 3 (C3) expression was previously found in the prefrontal cortex of individuals with depression. Given the complement system's role in depression and ketamine's potential anti-inflammatory properties, there is reason to suspect overlap between the complement system and ketamine's mechanism of action. This post-hoc study analyzed data from 39 individuals with major depressive disorder (MDD) and 25 healthy volunteers who previously participated in a …