Medicine and Health Sciences Commons^™

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.

2023 American College Of Rheumatology (Acr)/American College Of Chest Physicians (Chest) Guideline For The Treatment Of Interstitial Lung Disease In People With Systemic Autoimmune Rheumatic Diseases, Sindhu R Johnson, Elana J Bernstein, Marcy B Bolster, Jonathan H Chung, Sonye K Danoff, Michael D George, Dinesh Khanna, Gordon Guyatt, Reza D Mirza, Rohit Aggarwal, Aberdeen Allen, Shervin Assassi, Lenore Buckley, Hassan A Chami, Douglas S Corwin, Paul F Dellaripa, Robyn T Domsic, Tracy J Doyle, Catherine Marie Falardeau, Tracy M Frech, Fiona K Gibbons, Monique Hinchcliff, Cheilonda Johnson, Jeffrey P Kanne, John S Kim, Sian Yik Lim, Scott Matson, Zsuzsanna H Mcmahan, Samantha J Merck, Kiana Nesbitt, Mary Beth Scholand, Lee Shapiro, Christine D Sharkey, Ross Summer, John Varga, Anil Warrier, Sandeep K Agarwal, Danielle Antin-Ozerkis, Bradford Bemiss, Vaidehi Chowdhary, Jane E Dematte D'Amico, Robert Hallowell, Alicia M Hinze, Patil A Injean, Nikhil Jiwrajka, Elena K Joerns, Joyce S Lee, Ashima Makol, Gregory C Mcdermott, Jake G Natalini, Justin M Oldham, Didem Saygin, Kimberly Showalter Lakin, Namrata Singh, Joshua J Solomon, Jeffrey A Sparks, Marat Turgunbaev, Samera Vaseer, Amy Turner, Stacey Uhl, Ilya Ivlev

Faculty, Staff and Student Publications

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs).

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations.

Results: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong …

Increasing Incidence Of Streptococcus Anginosus Group Intracranial Infections Associated With Sinusitis, Otitis Media, And Mastoiditis In Children, Elisabeth A Hoyer, Marritta Joseph, James Dunn, Howard L Weiner, Amy Dimachkieh, Anthony R Flores, Misu A Sanson, Hossaena Ayele, Blake M Hanson, Sheldon L Kaplan, Jesus G Vallejo, J Chase Mcneil

Faculty, Staff and Student Publications

BACKGROUND: The Streptococcus anginosus group (SAG) pathogens have the potential to cause head and neck space infections, including intracranial abscesses. Several centers noted an increase in intracranial abscesses in children during the SARS-CoV-2 pandemic, prompting a Centers for Disease Control and Prevention health alert in May 2022. We examined the epidemiology of pediatric intracranial abscesses at a tertiary care center with a focus on SAG pre- and post-pandemic.

METHODS: Cases of intracranial abscesses of any microbiologic etiology admitted from January 2011 to December 2022 were identified using International Classification of Diseases 10 codes. Subjects were cross-referenced with culture results from …

Measuring Perceived Utility Of Genomic Sequencing: Development And Validation Of The Genetic Utility (Gene-U) Scale For Pediatric Diagnostic Testing, Hadley Stevens Smith, Caryn Kseniya Rubanovich, Jill Oliver Robinson, Ariel N Levchenko, Sarah A Classen, Janet Malek, Barbara Biesecker, Kyle B Brothers, Benjamin S Wilfond, Christine Rini, Sara J Knight, Amy L Mcguire, Cinnamon S Bloss

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Measuring the effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS.

Methods: Informed by a 5-domain conceptual model, the study comprised 5 steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Parents of pediatric patients who had received results of clinically indicated GS participated in structured cognitive interviews and 2 rounds of surveys. After eliminating items based on theory and quantitative performance, we conducted …

Large-Scale Genotype Prediction From Rna Sequence Data Necessitates A New Ethical And Policy Framework, Mary A Majumder, Jeffrey T Leek, Kasper D Hansen, Afrooz Razi, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Genotype prediction from RNA-seq data has become widespread. RNA-seq data, unlike DNA-seq data, are available as raw reads for many projects, with related protocols and consent terms typically inaccessible. However, there is a lack of clarity in current policy and inconsistency in practice with regard to the handling of these data. Here, we call for a framework for management of RNA-seq data and the predicted genotypes that includes registered access for RNA-seq data, controlled access for predicted genotypes, and a code of conduct for data access and use, as well as enhanced downstream protections.

Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris

2020-Current year OA Pubs

Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults, necessitating concerted efforts to advance our understanding and management of these conditions. AD is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and tau neurofibrillary tangles that are the primary cause of dementia in older individuals. Early and accurate diagnosis of AD dementia is crucial for effective intervention and treatment but has proven challenging to accomplish. Although testing for AD brain pathology with cerebrospinal fluid (CSF) or positron emission tomography (PET) has been available for over 2 decades, …

The Smc5/6 Complex Prevents Genotoxicity Upon Apobec3a-Mediated Replication Stress, Dylan F Fingerman, David R O'Leary, Ava R Hansen, Thi Tran, Brooke R Harris, Rachel A Deweerd, Mithila Tennakoon, Alice Meroni, Jessica Devenport, Danielle Lavigne, Jeffrey Bednarski, Alessandro Vindigni, Abby M Green, Et Al.

2020-Current year OA Pubs

Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent genotoxin that causes substantial DNA damage in experimental systems and human tumors. However, the mechanisms that ensure genome stability in cells with active APOBEC3A are unknown. Through an unbiased genome-wide screen, we define the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex as essential for cell viability when APOBEC3A is active. We observe an absence of APOBEC3A mutagenesis in human tumors with SMC5/6 dysfunction, consistent with synthetic lethality. Cancer cells depleted of SMC5/6 incur substantial genome damage from …

Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock

2020-Current year OA Pubs

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as …

Immune-Mediated Myositis Following Gene Therapy For Duchenne Muscular Dystrophy: A Case Report, Susan T Iannaccone, Chunyu Cai, Brittney Rhem, Kaitlin Batley, Veena Rajaram, Benjamin M Greenberg, Sachi Dharia, Craig M Zaidman

2020-Current year OA Pubs

No abstract provided.

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

2020-Current year OA Pubs

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

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

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

2020-Current year OA Pubs

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

Active Mutual Conjoint Estimation Of Multiple Contrast Sensitivity Functions, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour

2020-Current year OA Pubs

Recent advances in nonparametric contrast sensitivity function (CSF) estimation have yielded a new tradeoff between accuracy and efficiency not available to classical parametric estimators. An additional advantage of this new framework is the ability to independently tune multiple aspects of the estimator to seek further improvements. Machine learning CSF estimation with Gaussian processes allows for design optimization in the kernel, acquisition function, and underlying task representation, to name a few. This article describes a novel kernel for CSF estimation that is more flexible than a kernel based on strictly functional forms. Despite being more flexible, it can result in a …

The Clinical Utility Of Diffusion-Weighted Imaging In Diagnosing And Predicting Treatment Response Of Laryngeal And Hypopharyngeal Carcinoma: A Systematic Review And Meta-Analysis, Mohammadamin Parsaei, Hossein Sanjari Moghaddam, Parisa Mazaheri

2020-Current year OA Pubs

PURPOSE: Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC.

METHODS: A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies.

RESULTS: A total …

High-Dimensional Single-Cell Analysis Of Human Natural Killer Cell Heterogeneity, Lucas Rebuffet, Marco Colonna, Et Al.

2020-Current year OA Pubs

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic …

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

2020-Current year OA Pubs

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

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

2020-Current year OA Pubs

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

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

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

2020-Current year OA Pubs

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

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

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

A Training Protocol Compliance Of 13% Was Observed In A Research Study Of Clinical Research Professionals, Erin D Solomon, Jessica Mozersky, Meredith V Parsons, Kari Baldwin, Melody Goodman, James M Dubois

2020-Current year OA Pubs

OBJECTIVE: We attempted to conduct a randomized controlled trial of three different informed consent training formats to evaluate their effectiveness. We recruited 503 clinical research professionals, who received $50 for participation. Incidental findings showed unexpectedly low rates of compliance with completing the study training protocols, resulting in insufficient statistical power to test our original hypotheses. In this report, we conducted a secondary analysis of the data in which we characterize and evaluate the observed low compliance. This involved using literature on average reading times, speed-reading times, and video play speeds to calculate the timeframes required to complete the three training …

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

2020-Current year OA Pubs

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

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

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

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

2020-Current year OA Pubs

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

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

Association Between Interpregnancy Interval And The Labor Curve, Julia Burd, Candice Woolfolk, Antonina Frolova, Amanda Zofkie, Anthony Odibo, Ebony B Carter, Jeannie C Kelly, Alison G Cahill, Nandini Raghuraman

2020-Current year OA Pubs

BACKGROUND: Both short and long interpregnancy intervals are associated with adverse pregnancy outcomes; however, the impact of interpregnancy intervals on labor progression is unknown.

OBJECTIVE: We examined the impact of interpregnancy intervals on the labor curve, hypothesizing that those with a longer interpregnancy intervals would have slower labor progression.

STUDY DESIGN: This is a retrospective cohort study of patients with a history of one prior vaginal delivery admitted for induction of labor or spontaneous labor with a singleton gestation ≥37 weeks at an academic medical center between 2004 and 2015. Repeated measures regression was used to construct labor curves, which …

Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise …

A Group 3 Medulloblastoma Stem Cell Program Is Maintained By Otx2-Mediated Alternative Splicing, Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam D Hendrikse, Paul Layug, Victor Gordon, Kimberly A Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi M Gonzales, Gareth Palidwor, Christopher J Porter, Stéphane Richard, Tanveer Sharif, Kathleen J Millen, Brad W Doble, Michael D Taylor, Tamra E Werbowetski-Ogilvie

Faculty, Staff and Students Publications

OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among …

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …

Hypoxaemia And Risk Of Death Among Children: Rethinking Oxygen Saturation, Risk-Stratification, And The Role Of Pulse Oximetry In Primary Care, Hamish R Graham, Carina King, Trevor Duke, Salahuddin Ahmed, Abdullah H Baqui, Tim Colbourn, Adegoke G Falade, Helena Hildenwall, Shubhada Hooli, Yewande Kamuntu, Rami Subhi, Eric D Mccollum

Faculty, Staff and Students Publications

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO2] 90–93%) and severe hypoxaemia (ie, …

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

Faculty, Staff and Students Publications

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

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

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

Preeclampsia In The Context Of Covid-19: Mechanisms, Pathophysiology, And Clinical Outcomes, Guilherme M Nobrega, Brittany R Jones, Indira U Mysorekar, Maria Laura Costa

Center on Aging Staff Publications

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with …

Secondary Endpoint Utilization And Publication Rate Among Phase Iii Oncology Trials, Esther J Beck, Alexander D Sherry, Marcus A Florez, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Roshal R Patel, Fumiko Chino, Victoria Serpas Higbie, Christine M Parseghian, Michael J Overman, Bruce D Minsky, Charles R Thomas, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

UNLABELLED: Secondary endpoints (SEP) provide crucial information in the interpretation of clinical trials, but their features are not yet well understood. Thus, we sought to empirically characterize the scope and publication rate of SEPs among late-phase oncology trials. We assessed SEPs for each randomized, published phase III oncology trial across all publications and ClinicalTrials.gov, performing logistic regressions to evaluate associations between trial characteristics and SEP publication rates. After screening, a total of 280 trials enrolling 244,576 patients and containing 2,562 SEPs met the inclusion criteria. Only 22% of trials (62/280) listed all SEPs consistently between ClinicalTrials.gov and the trial protocol. …

Chick Embryo Chorioallantoic Membrane As A Platform For Assessing The In Vivo Efficacy Of Chimeric Antigen Receptor T-Cell Therapy In Solid Tumors, Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil Da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora

Faculty, Staff and Student Publications

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied …