Medicine and Health Sciences Commons^™

Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported.

Methods: Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024.

Results: One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and …

Healthcare Utilization Following Implementation Of A Pediatric Social Needs Screening Program, Ashley Gibson, Kaleigh Riggs-Harpur, Midhat Jafry, Mallika Mathur, Yen-Chi Le, Sandra Mckay

Faculty, Staff and Student Publications

Objective: This study evaluated differences in healthcare utilization among a pediatric primary care population following implementation of a universal social needs screening and referral program. It was hypothesized that emergency, sick, and hospitalization visits would decrease post-implementation, with stable or increased preventive care.

Methods: A retrospective, observational study was conducted using electronic health record data from 2 cohorts at different time periods at a large academic pediatric primary care clinic. The pre-implementation group included patients with a well-child visit from 08/2021 to 07/2022; the post-implementation group included patients from 09/2022 to 08/2023. Healthcare utilization measures of emergency department visits, hospitalizations, …

Contemporary Trends In Pediatric Extubation Failure And Noninvasive Respiratory Support Use, Jeremy M Loberger, Mitchell Moore, Matthew Scanlon, Robinder G Khemani, Samer Abu-Sultaneh, Colin M Rogerson

Faculty, Staff and Student Publications

Background: Prolonged invasive mechanical ventilation (IMV) is associated with morbidity and mortality in children. Timely extubation is essential and must balance the competing risks of extubation failure (EF) and prolonged use of noninvasive respiratory support after extubation.

Research question: Did EF risk factors, EF rates, noninvasive respiratory support after extubation practices, and patient-centered outcomes changed between 2013 and 2022?

Study design and methods: Retrospective cross-sectional study of patients younger than 19 years receiving IMV for ≥ 24 hours and extubated between 2013 and 2022 from 158 North American sites in the Virtual Pediatric Intensive Care, LLC, quality improvement database.

Results: …

Risk Factors And Outcomes Of Reintubation Following Combined Heart-Lung Transplantation, Ye In Christopher Kwon, Michael Keller, Alan Lai, Brian Bao, Joshua Pei, Matthew Ambrosio, Jay Patel, Motaz Al-Yafi, Zachary Fitch, Josue Chery, Patricia Nicolato, Vigneshwar Kasirajan, Zubair A Hashmi

Faculty, Staff and Student Publications

Background: Unplanned reintubation after combined heart-lung transplantation (HLT) significantly affects morbidity and mortality, yet national data are limited. We evaluated the incidence, predictors, timing, and outcomes associated with reintubation after HLT.

Methods: We retrospectively reviewed adults undergoing primary HLT in the UNOS registry from January 2004 to September 2024. Patients were stratified by reintubation status (defined as re-established mechanical ventilation (MV) after initial extubation). Propensity matching (1:1) balanced recipient and donor characteristics. Multivariable logistic regression models identified independent risk factors.

Results: Among 609 adult HLT recipients, 165 (27.1%) required postoperative reintubation. After 1:1 propensity score matching, 146 patients who were …

Physical Activity, Telomere Length, And Cardiometabolic Syndrome In Older Women: The Cardiovascular Health Study, Jeni Page, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Michelle C Odden, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background: Cardiometabolic syndrome (CMS) affects approximately 39% of US women and increases risk for cardiovascular disease, diabetes, and stroke. Telomere length, a biomarker of cellular aging, is associated with CMS and may be influenced by physical activity (PA), potentially mitigating telomere shortening. Black women have higher CMS prevalence compared to white women and may exhibit distinct telomere length dynamics influenced by interactions between CMS and PA.

Methods: Data were drawn from the Cardiovascular Health Study and included black and white women who provided data on PA, CMS risk factors, and telomere length (N = 417). Linear regression models examined the …

Application Of The Lancet Commission Criteria For The Diagnosis Of Obesity To A Clinical Trials Population: The Leap Trial, Faith Anne N Heeren, Kathleen R Ruddiman, Courtney Simmons, Brian N White, Byron C Jaeger, Nicholas M Pajewski, Stephanie A Hooker, Deborah B Horn, Katy Martin-Fernandez, Kimberly A Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis

Faculty, Staff and Student Publications

Objective: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity."

Results: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD …

Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno

Faculty, Staff and Student Publications

The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is …

Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder

Faculty, Staff and Student Publications

Purpose: The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined.

Methods: We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS).

Results: Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin

Faculty, Staff and Student Publications

This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …

Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail

Faculty, Staff and Student Publications

Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …

The Crucial Role Of Machine Learning Models In Predicting Current Childhood Asthma: Model Comparison, Calibration, And Shap-Based Interpretation, Aditya Chakraborty, A. K.M. Raquibul Bashar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background: Asthma is one of the most prominent chronic diseases in children and one of the most challenging ailments to diagnose in infants and preschoolers in the United States. Predictive models can be instrumental in improving early diagnosis, personalized treatment strategies, and disease progression. By utilizing nationalized data, this study focuses on building and comparing high-performing analytical predictive models based on the relevant risk factors and identifying the most influential predictors.

Methods: We analyzed cross-sectional BRFSS Asthma Call-Back Survey data (2011-2020; N = 9,813) and randomly split participants into training and testing sets. An XGBoost model (hyperparameters tuned via grid …

Intratracheal Interleukin-10 Administration Reduces Acute Lung Injury Induced By Sulfur Dioxide Exposure In Mice, Amy J. Nelson, Todd A. Wyatt, Bradley W. Richmond, Belinda Diaz, Angela Gleason, Michael J. Duryee, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of reducing acute high-consequence airborne chemical exposure-induced lung disease are lacking. This study seeks to determine the therapeutic potential of interleukin (IL)-10 administered following acute sulfur dioxide (SO₂) exposure in mice. C57BL/6 male and female mice were exposed to SO₂ gas at 125 ppm for 4 h and subsequently treated 2-3 h later with IL-10 (1 μg) or vehicle control by intratracheal instillation for a total of 3 doses over 2 days with comparisons to sham-treated mice (N = 20 mice/group). IL-10 treatment reduced SO₂-induced weight loss with corresponding reductions in SO_{2 …}

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Genomic Determinants Of Response And Resistance To Pirtobrutinib In Relapsed/Refractory Chronic Lymphocytic Leukemia, Jennifer R Brown, Bastien Nguyen, Sai Prasad Desikan, Helen Won, Shady I Tantawy, Samuel C Mcneely, Narasimha Marella, Hetal S Randeria, Lauren M Hanson, Andrew Parker, Salomé Calado Botelho, Jennifer A Woyach, Krish Patel, Constantine S Tam, Toby A Eyre, Chan Y Cheah, Nirav N Shah, Paolo Ghia, Wojciech Jurczak, Minna Balbas, Binoj Nair, Paolo Abada, Chunxiao Wang, Denise Wang, Lindsey E Roeker, Varsha Gandhi, William G Wierda

Faculty, Staff and Student Publications

Pirtobrutinib, a noncovalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). We analyzed genomic correlations with response and resistance to pirtobrutinib in relapsed/refractory (R/R) patients with CLL pretreated with cBTKi enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on peripheral blood mononuclear cells at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%), and 17p deletion (28%). Common baseline BTK mutations included C481S …

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Mepolizumab Improves Outcomes In Patients With Crswnp With One Or More Prior Nasal Polyp Surgeries, Joseph K. Han, Joaquim Mullol, Martin Wagenmann, Laura Walrave, Lingjiao Zhang, Ana R. Sousa, Peter Howarth, Claire Hopkins

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often undergo multiple nasal surgeries. The Phase III SYNAPSE study (GSK ID:205687; NCT0308579) demonstrated that mepolizumab reduces the need for repeat surgery. We explored whether outcomes differed based on the number of prior surgeries. METHODOLOGY: This post hoc analysis of SYNAPSE stratified patients by history of 1 or more than 1 prior surgery. Patients were randomised to receive mepolizumab or placebo every 4 weeks, alongside standard of care, for 52 weeks. Outcomes included change from baseline in endoscopic nasal polyp (NP) score, visual analogue scale (VAS) scores for nasal obstruction, loss …

Characteristics Of Cerebral Palsy In The Midwestern Us, Susie Kim, Kelsey Steffen, Lauren Gottschalk-Henneberry, Jennifer Miros, Amy Robichaux-Viehoever, Karen Taca, Bhooma R Aravamuthan

2020-Current year OA Pubs

OBJECTIVE: Cerebral palsy (CP) is the most common lifelong motor disability worldwide. Yet, data is limited on how CP manifests in the US. Our objective was to characterize and determine factors affecting functional outcomes in a large population of young people with CP in the Midwestern US.

METHODS: We integrated caregiver and clinician-facing standardized data entry into routine clinical care at a tertiary care CP center (https://bit.ly/CP-Intake-Methodology). We extracted this data for people with an ICD10 diagnosis of CP seen between March 22, 2023 and December 28, 2023 and used it to describe CP characteristics and determine factors affecting the …

A Single-Cell Atlas Characterizes Dysregulation Of The Bone Marrow Immune Microenvironment Associated With Outcomes In Multiple Myeloma, William C Pilcher, Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, Mark A Fiala, Chiang I-Ling, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, John F Dipersio, Shaji Kumar, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune …

Clinical Outcomes Following Mechanical Thrombectomy In Pulmonary Embolism Response Team-Consulted Patients: A Retrospective Analysis, Ryan Nolan, Maanasi Samant, Suresh Vedantham, Westley Ohman, Nathan Droz, Kristen Sanfilippo, Pavan Kavali

2020-Current year OA Pubs

PURPOSE: To determine if use of mechanical thrombectomy (MT) impacts survival and additional outcomes in patients with acute intermediate-high-risk and high-risk pulmonary embolism (PE) who were evaluated by a Pulmonary Embolism Response Team (PERT).

METHODS: This retrospective, single-center study included patients with intermediate-high-risk and high-risk PE who received PERT evaluation over 3.5 years and were treated with anticoagulation (AC) alone or MT + AC. The primary outcome was 30-day all-cause mortality, measured with inverse probability of treatment weighting. Exploratory outcomes included survival during the study period, PE-associated/caused mortality, hospital length of stay (LOS), supplemental oxygen at discharge, and MT-related metrics. …

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …

Common And Recurrent Dysregulated Molecular Network Of Placental Hypoxia And Associated Vasculogenesis And Angiogenesis In Fetal Growth Restriction, Wei Li, Xiaoyi Bai, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes

Once-Weekly Navepegritide In Children With Achondroplasia: The Approach Randomized Clinical Trial, Ravi Savarirayan, Ciara Mcdonnell, Carlos A Bacino, Daniel G Hoernschemeyer, Janet M Legare, M Jennifer Abuzzahab, Paul L Hofman, Philippe M Campeau, Josep Maria De Bergua Domingo, Leanne M Ward, Kevin Smit, Alden Smith, Meng Mao, Michael S Ominsky, Lærke C Freiberg, Aimee D Shu, Hanne B Hove

Faculty, Staff and Students Publications

Importance: Historically considered a skeletal dysplasia characterized by disproportionate short stature, achondroplasia is a condition with multisystemic effects due to the widespread expression of the fibroblast growth factor receptor 3 variant throughout the body, impacting muscle, neurological function, cardiorespiratory health, and health-related quality of life.

Objective: To evaluate the efficacy, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide, while assessing benefits beyond growth that may have important implications for complications and health-related quality of life in children with achondroplasia.

Design, setting, and participants: Enrollment for this pivotal phase 2b, randomized, double-blind, placebo-controlled trial (APPROACH) was …

Case Series Of Nizon-Isidor Syndrome By Heterozygous Variants In Med12l With Further Evidence Of Mitotic Instability In One Case With Diploid-Triploid Mosaicism, Russell Stewart, Kimberly M Ezell, Deanna S Bell, Brian Corner, Ashley Mcminn, Joy D Cogan, Rizwan Hamid, Lynette Rives, John A Phillips, Nina Paddu, Gitanjali Srivastava, Ronit Marom, Farah A Ladha, Claudia Soler-Alfonso, Rachel Franciskovich, Mary Koziura, Sumit Pruthi, Gabriele Richard, Christina B Sheedy, Undiagnosed Diseases Network, Thomas Cassini

Faculty, Staff and Students Publications

Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing …

A Survey-Based Assessment Of Treatment Preferences For Distal Radius Fractures In Participants Aged 65 Years And Older, Zayd Al Rawi, Elizabeth Graesser, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: The management of distal radius fractures (DRF) in patients aged ≥65 years is debated because there is evidence that operative and nonsurgical treatment yield similar outcomes 1 year after injury. When more than one reasonable treatment option exists, shared decision-making between the patient and physician should be used. This study elicited preferences for the treatment of DRF using a survey of participants aged ≥65 years.

METHODS: A survey for participants ≥65 years was administered using Amazon Mechanical Turk. Participants were presented with a theoretical scenario in which they sustained a DRF, followed by two treatment options (surgery or casting) …

Steroid Hormone Metabolites And Mammographic Breast Density In Premenopausal Women, Ghazaleh Pourali, Kayode A Matthew, Myung Sik Jeon, Chongliang Luo, Gary J Patti, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Steroid hormones influence breast morphology and cellular proliferation and are associated with breast carcinogenesis. However, their associations with mammographic breast density (MBD) are less studied, particularly in premenopausal women. We, therefore, investigated the associations of steroid hormone metabolites with MBD in premenopausal women.

METHODS: Our study included 700 premenopausal women scheduled for screening mammograms. We analyzed 54 steroid hormone metabolites (Metabolon®) and assessed volumetric measures of MBD including volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV) using Volpara. We investigated associations using linear regression modeling to estimate the covariate-adjusted means of VPD, NDV, and DV, corresponding …

Psychometric Properties Of A Novel Affective Bias Task And Its Application In Clinical And Nonclinical Populations, Prathik Kalva, Kourtney Kanja, Brian A Metzger, Xiaoxu Fan, Brian Cui, Bailey Pascuzzi, John Magnotti, Madaline Mocchi, Raissa Mathura, Kelly R Bijanki

Faculty, Staff and Students Publications

To mitigate limitations in self-reported mood assessments, we introduce a novel affective bias task (ABT). The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and non-clinical populations. Initial assessment in a large non-clinical sample established normative ratings. Depressive symptoms were tracked relative to task performance in a non-clinical sample, as well as in a clinical cohort undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger …

Clinical Factors And Diagnoses Associated With Inappropriate Urine Culture Ordering In Primary Care, Marissa Valentine-King, Barbara W Trautner, Michael A Hansen, Roger Zoorob, Lisa C K Danek, Kenneth Muldrew, Forrest Hudson, Robert L Atmar, Larissa Grigoryan

Faculty, Staff and Students Publications

Objective: Evaluate the prevalence and risk factors for inappropriately ordered urine cultures in primary care.

Design: Cross-sectional study using chart reviews.

Setting: Two primary care, safety-net clinics in Houston, Texas.

Patients: Non-pregnant adults without a urinary catheter who had a urine culture and a primary care visit between 11/2018 and 3/2020.

Methods: We classified patients lacking physician documentation of the following symptoms as having an inappropriately ordered urine culture: dysuria, frequency, urgency, hematuria, fever, chills, costovertebral angle tenderness, nephrolithiasis, and pain (suprapubic, pelvic, or flank). We extracted patient demographics, visit-related diagnostic codes, past medical history, and urine culture results. Diagnostic …