Digital Commons Network^™

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Student and Faculty Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Intracellular Islatravir-Triphosphate Half-Life Supports Extended Dosing Intervals, Xiaowei Zang, Wendy Ankrom, Walter K. Kraft, Ryan Vargo, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t½) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 …

Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants: A Patient-Level Meta-Analysis From Combine Af, Linda Johnson, Alexander Benz, Ashkan Shoamanesh, John W Eikelboom, Michael Ezekowitz, Robert Giugliano, Lars Wallentin, Christian Ruff, Renato Lopes, Sanjit Jolly, Richard Whitlock, Christopher Granger, Stuart Connolly, Jeffrey Healey

Division of Cardiology Faculty Papers

Background: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk.

Methods and results: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA₂DS₂-VASc score≥2, across strata of CHA₂DS₂-VASc …

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Pembrolizumab Plus Carboplatin And Paclitaxel As First-Line Therapy For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma (Keynote-B10): A Single-Arm Phase Iv Trial, Marcin Dzienis, Peter Oppelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).

METHODS: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review …

Beta-Hydroxybutyrate Levels And Risk Of Diabetic Ketoacidosis In Adults With Type 1 Diabetes Treated With Sotagliflozin, Schafer Boeder, Michael J Davies, Janet B Mcgill, Richard Pratley, Manon Girard, Phillip Banks, Jeremy Pettus, Satish Garg

2020-Current year OA Pubs

No abstract provided.

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

Detection Of Distant Relatedness In Biobanks To Identify Undiagnosed Cases Of Mendelian Disease As Applied To Long Qt Syndrome, Megan C Lancaster, Hung-Hsin Chen, M Benjamin Shoemaker, Matthew R Fleming, Teresa L Strickland, James T Baker, Grahame F Evans, Hannah G Polikowsky, David C Samuels, Chad D Huff, Dan M Roden, Jennifer E Below

Student and Faculty Publications

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this …

Milvexian Vs Apixaban For Stroke Prevention In Atrial Fibrillation: The Librexia Atrial Fibrillation Trial Rationale And Design, Sneha S Jain, Kenneth W Mahaffey, Karen S Pieper, Wataru Shimizu, Tatjana Potpara, Christian T Ruff, Hooman Kamel, Basil S Lewis, Jan H Cornel, Peter R. Kowey, Jay Horrow, John Strony, Alexei N Plotnikov, Danshi Li, Stephen Weng, Julia Donahue, C Michael Gibson, P Gabriel Steg, Roxana Mehran, Jeffrey I Weitz, S Claiborne Johnston, Graeme J Hankey, Robert A Harrington, Carolyn S P Lam

Department of Medicine Faculty Papers

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.

METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to …

Donor Types And Outcomes Of Transplantation In Myelofibrosis: A Cibmtr Study, Tania Jain, Noel Estrada-Merly, M Queralt Salas, Soyoung Kim, Jakob Devos, Min Chen, Xi Fang, Rajat Kumar, Marcio Andrade-Campos, Hany Elmariah, Vaibhav Agrawal, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M Badawy, Karen Ballen, Amer Beitinjaneh, Vijaya Raj Bhatt, Christopher Bredeson, Zachariah Defilipp, Bhagirathbhai Dholaria, Nosha Farhadfar, Shatha Farhan, Arpita P Gandhi, Siddhartha Ganguly, Usama Gergis, Michael R Grunwald, Nada Hamad, Betty K Hamilton, Yoshihiro Inamoto, Madiha Iqbal, Omer Jamy, Mark Juckett, Mohamed A Kharfan-Dabaja, Maxwell M Krem, Deepesh P Lad, Jane Liesveld, Monzr M Al Malki, Adriana K Malone, Hemant S Murthy, Guillermo Ortí, Sagar S Patel, Attaphol Pawarode, Miguel-Angel Perales, Marjolein Van Der Poel, Olle Ringden, David A Rizzieri, Alicia Rovó, Bipin N Savani, Mary Lynn Savoie, Sachiko Seo, Melhem Solh, Celalettin Ustun, Leo F Verdonck, John R Wingard, Baldeep Wirk, Nelli Bejanyan, Richard J Jones, Taiga Nishihori, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, Vikas Gupta

Department of Medical Oncology Faculty Papers

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …

Single-Cell Analysis Of Chromatin And Expression Reveals Age- And Sex-Associated Alterations In The Human Heart, David F Read, Yiing Lin, Et Al.

2020-Current year OA Pubs

Sex differences and age-related changes in the human heart at the tissue, cell, and molecular level have been well-documented and many may be relevant for cardiovascular disease. However, how molecular programs within individual cell types vary across individuals by age and sex remains poorly characterized. To better understand this variation, we performed single-nucleus combinatorial indexing (sci) ATAC- and RNA-Seq in human heart samples from nine donors. We identify hundreds of differentially expressed genes by age and sex and find epigenetic signatures of variation in ATAC-Seq data in this discovery cohort. We then scale up our single-cell RNA-Seq analysis by combining …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Utilization Of A Novel Scoring System In Predicting 30-Day Mortality In Acute Pulmonary Embolism, The Clot-5 Pilot Study, Alexandru Marginean, Punit Arora, Kevin Walsh, Elizabeth Bruno, Cathryn Sawalski, Riya Gupta, Frances Greathouse, Jacob Clarke, Quinn Mallery, Myoung Hyun Choi, Waddah Malas, Parth Shah, David Sutherland, Amudha Kumar, Igor Wroblewski, Ahmed Elkaryoni, Parth Desai, Yevgeniy Brailovsky, Amir Darki

Division of Cardiology Faculty Papers

OBJECTIVES: To construct a new scoring system utilizing biomarkers, vitals, and imaging data to predict 30-day mortality in acute pulmonary embolism (PE).

BACKGROUND: Acute PE, a well-known manifestation of venous thromboembolic disease, is responsible for over 100,000 deaths worldwide yearly. Contemporary management algorithms rely on a multidisciplinary approach to care via PE response teams (PERT) in the identification of low, intermediate, and high-risk patients. The PESI and sPESI scores have been used as cornerstones of the triage process in assigning risk of 30-day mortality for patients presenting with acute PE; however, the specificity of these scoring systems has often come …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

2020-Current year OA Pubs

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in

Appropriateness Of Imaging For Low-Risk Prostate Cancer-Real World Data From The Pennsylvania Urologic Regional Collaboration (Purc), Raidizon Mercedes, Dennis Head, Elizabeth Zook, Eric Eidelman, Jeffrey Tomaszewski, Serge Ginzburg, Robert Uzzo, Marc Smaldone, John Danella, Thomas Guzzo, Daniel Lee, Laurence Belkoff, Jeffrey Walker, Adam Reese, Mihir Shah, Bruce Jacobs, Jay Raman

Einstein Health Papers

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) …

A Systematic Review Of Oral Vertical Dyskinesia ("Rabbit" Syndrome), Jamir Pitton Rissardo, Krish Kherajani, Nilofar Murtaza Vora, Venkatesh Yatakarla, Ana Letícia Fornari Caprara, Jeffrey Ratliff, Md, Stanley N Caroff

Department of Neurology Faculty Papers

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as “rabbit” syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among …

Prospective Analysis Of Stratafix™ Symmetric Pds Plus Suture For Fascial Closure In Spinal Surgery: A Pilot Study, Steven R. Glener, Pious D. Patel, Stephanie N. Serva, Dwight Mitchell Self, Joshua E. Heller

Department of Neurosurgery Faculty Papers

Wound closure is an integral part of every spinal procedure. Effective and secure wound closure is paramount in the prevention of infection, wound dehiscence and the preservation of cosmesis. Barbed suture technologies such as STRATAFIX™ Symmetric have been studied and are used in a variety of specialties, including obstetrics and orthopedic surgery, but is underutilized in neurosurgery. This study aims to assess the time and rate of closure using STRATAFIX™ Symmetric technology for fascial closure and compare this method to the more traditionally used method of fascial closure using braided absorbable sutures below the epidermis. 20 patients were recruited for …

Monitoring Response To Neoadjuvant Chemotherapy In Triple Negative Breast Cancer Using Circulating Tumor Dna, Jennifer H Chen, Sridevi Addanki, Dhruvajyoti Roy, Roland Bassett, Ekaterina Kalashnikova, Erik Spickard, Henry M Kuerer, Salyna Meas, Vanessa N Sarli, Anil Korkut, Jason B White, Gaiane M Rauch, Debu Tripathy, Banu K Arun, Carlos H Barcenas, Clinton Yam, Himanshu Sethi, Angel A Rodriguez, Minetta C Liu, Stacy L Moulder, Anthony Lucci

Student and Faculty Publications

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera

RESULTS: In total, 37 patients were enrolled. The mean age was 50 …

Outpatient Administration Of Car T-Cell Therapies Using A Strategy Of No Remote Monitoring And Early Crs Intervention, Fateeha Furqan, Vineel Bhatlapenumarthi, Binod Dhakal, Timothy S. Fenske, Faiqa Farrukh, Walter Longo, Othman Akhtar, Anita D'Souza, Marcelo Pasquini, Guru Subramanian Guru Murthy, Lyndsey Runaas, Sameem Abedin, Meera Mohan, Nirav N. Shah, Mehdi Hamadani

Abington Jefferson Health Papers

Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days …

Neoantigen Landscape Supports Feasibility Of Personalized Cancer Vaccine For Follicular Lymphoma, Cody A Ramirez, Michelle Becker-Hapak, Kartik Singhal, David A Russler-Germain, Erica K Barnell, Ethan D Mcclain, Sweta Desai, Timothy Schappe, Onyinyechi C Onyeador, Susanna Kiwala, Jasreet Hundal, Zachary L Skidmore, Marcus P Watkins, Thomas B Mooney, Jason R Walker, Kilannin Krysiak, Felicia Gomez, Catrina C Fronick, Robert S Fulton, Robert D Schreiber, Neha Mehta-Shah, Amanda F Cashen, Brad S Kahl, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR …

A Social Media Game To Increase Physical Activity Among Older Adult Women: Protocol Of A Randomized Controlled Trial To Evaluate Challenge, Michael C Robertson, Maria Chang Swartz, Karen M Basen-Engquist, Yisheng Li, Kristofer Jennings, Debbe Thompson, Tom Baranowski, Elena Volpi, Elizabeth J Lyons

Student and Faculty Publications

BACKGROUND: Older adult women often do not engage in sufficient physical activity (PA) and can encounter biological changes that exacerbate the negative effects of inadequate activity. Wearable activity monitors can facilitate PA initiation, but evidence of sustained behavior change is lacking. Supplementing wearable technologies with intervention content that evokes enjoyment, interest, meaning, and personal values associated with PA may support long term adherence. In this paper, we present the protocol of an NIA-funded study designed to evaluate the efficacy of CHALLENGE for increasing step count and motivation for PA in insufficiently active older women (Challenges for Healthy Aging: Leveraging Limits …

Multi-Omic Analysis Of Huntington's Disease Reveals A Compensatory Astrocyte State, Fahad Paryani, Ji-Sun Kwon, Andrew S Yoo, Et Al.

2020-Current year OA Pubs

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, …

Video And Phone Visit Use Differed By Language Preference Among Us Latino And Chinese Adults During The First 9 Months Of The Covid-19 Pandemic: A Cross-Sectional Electronic Health Record Study, Nancy P Gordon, Teresa Y Lin, Antonia Torreblanca, Mary E Reed

Student and Faculty Publications

BACKGROUND: During the first nine months of the COVID-19 emergency, patients were encouraged to use virtual versus clinic visits if in-person care was not deemed necessary by clinical staff. This study examined the association of spoken language preference and ethnicity with use of video versus phone virtual visits by US Latino and Chinese adult patients who got care in the same healthcare system.

METHODS: We analyzed electronic health record data for four groups of adults aged 26-85y who had ≥ 1 primary or specialty care outpatient clinician visits during April-December 2020: 80,869 Latino adults preferring Spanish (LEP Latino); 214,765 Latino …

Identification Of Genetic Subtypes In Follicular Lymphoma, Victoria Shelton, Brad Kahl, Et Al.

2020-Current year OA Pubs

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated …

Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh

Student and Faculty Publications

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire.

METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group.

RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by …

Maturation Of Germinal Center B Cells After Influenza Virus Vaccination In Humans, Katherine M Mcintire, Wooseob Kim, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Jackson S Turner, Ali H. Ellebedy, Et Al.

2020-Current year OA Pubs

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity …

Cluster-Based Toxicity Estimation Of Osteoradionecrosis Via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability By Using Whole Dose-Volume Histograms For Cohort Risk Stratification, Seyedmohammadhossein Hosseinian, Mehdi Hemmati, Cem Dede, Travis C Salzillo, Lisanne V Van Dijk, Abdallah S R Mohamed, Stephen Y Lai, Andrew J Schaefer, Clifton D Fuller

Student and Faculty Publications

PURPOSE: Given the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis that incorporates the whole radiation dose distribution on the mandible.

METHODS AND MATERIALS: The analysis was conducted on retrospective data of 1259 patients with head and neck cancer treated at The University of Texas MD Anderson Cancer Center between 2005 and 2015. During a minimum 12-month posttherapy follow-up period, 173 patients …

Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian

The Texas Heart Institute Journal

Despite substantial advances in the management of hypertrophic cardiomyopathy, advanced heart failure remains a major cause of morbidity in this patient population. This narrative review presents the case of a patient with hypertrophic obstructive cardiomyopathy who underwent alcohol septal ablation to frame a discussion of modern therapies for hypertrophic cardiomyopathy. The current treatment landscape includes medications, both old and new, and surgical and procedural interventions to relieve mechanical obstruction. Several promising new modalities for relieving obstruction are in the nascent stages of development.