Medical Specialties Commons^™

A Phase Ia Study Of A Novel Anti-Her2 Antibody-Drug Conjugate Gq1001 In Patients With Previously Treated Her2 Positive Advanced Solid Tumors, Chenfei Zhou, Bin Wang, Christina Teng, Hui Yang, Sarina A Piha-Paul, Gary Richardson, Ashanya Malalasekera, Yajun Sun, Wei Wang, Jieqiong Liu, Yan Shi, Xianbao Zhan, Charlotte Lemech

Faculty, Staff and Student Publications

Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.

Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary …

Prdm16 Enhances Osteoblastogenic Runx2 Via Canonical Wnt10b/Β-Catenin Pathway In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Mia Prado, Virginia Fuenmayor Lopez, Georgia Colleluori, Lina Aguirre, Rui Chen, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

We previously reported that PRDM16 mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that Prdm16 regulates Runx2, an important osteoblastic transcription factor, expression and activity. However, the changes in PRDM16, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling …

Clinical And Imaging Features Of Head And Neck Metastasis Of High-Grade Glioma: A Single-Center Case Series, Rami W Eldaya, Diana Kaya, Michelle Williams, Susana Calle, Dawid Schellingerhout

Faculty, Staff and Student Publications

High-grade gliomas are the most frequent primary brain tumors, yet extraneural metastasis is exceedingly rare. This is in part secondary to the relatively poor survival of these patients and likely the shielding effect of the blood-brain barrier. Given the rarity of extraneural metastasis, the pathophysiology and imaging appearance of extraneural metastasis is under-reported and poorly understood. In this case series we present 6 patients with pathology-confirmed high-grade glioma and extraneural head and neck metastasis. We highlight imaging features of metastasis on CT, MRI, and PET/CT. We also explore potential correlations and pathophysiology of high-grade glioma metastasis to the head and …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

Faculty, Staff and Student Publications

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Early Treatment Discontinuation In Patients With Deficient Mismatch Repair Or Microsatellite Instability High Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD).

Methods: To assess whether ETD is associated with similar outcomes compared …

A Prospective, Multicenter Analysis Of The Integrated 31-Gene Expression Profile Test For Sentinel Lymph Node Biopsy (I31-Gep For Slnb) Test Demonstrates Reduced Number Of Unnecessary Slnbs In Patients With Cutaneous Melanoma., J Michael Guenther, Andrew Ward, Brian J Martin, Mark Cripe, Rohit Sharma, Stanley P Leong, Joseph I Clark, John Hamner, Timothy Beard

Oncology Articles

BACKGROUND: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with <  5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

METHODS: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322). To determine if incorporating the i31-GEP into decision-making resulted in fewer SLNBs performed, propensity score-matching was performed to a non-overlapping cohort for whom the 31-GEP was not used for SLNB decision-making.

RESULTS: No patients with <  5% i31-GEP predicted risk had a positive SLNB (0/35). Propensity matching demonstrated an 18.5% reduction in SLNBs performed (43.7% vs. 62.2%. p <  0.001). The i31-GEP could have reduced the number of unnecessary biopsies by 25.0% (35/140).

CONCLUSIONS: This prospective study confirmed the performance and clinical utility of the i31-GEP for …

Rethinking The Rise Of Early-Onset Gastrointestinal Cancers: A Call To Action, Benjamin A Weinberg, Caitlin C Murphy, David R Freyer, K Leigh Greathouse, Jan K Blancato, Elena M Stoffel, Julia L Drewes, Anne Blaes, John M Salsman, Y Nancy You, Hannah Arem, Reetu Mukherji, Priyanka Kanth, Xin Hu, Anne Fabrizio, Marion L Hartley, Marios Giannakis, John L Marshall

Faculty, Staff and Student Publications

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship …

Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski

Faculty, Staff and Student Publications

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned …

Adverse Prehospital Events And Outcomes After Traumatic Brain Injury, Amelia W Maiga, Hsing-Hua Sylvia Lin, Stephen R Wisniewski, Joshua B Brown, Ernest E Moore, Martin A Schreiber, Bellal Joseph, Chad T Wilson, Bryan A Cotton, Daniel G Ostermayer, Brian G Harbrecht, Mayur B Patel, Jason L Sperry, Francis X Guyette, Henry E Wang

Faculty, Staff and Student Publications

Importance: While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes.

Objective: To validate the associations of prehospital hypoxia, hypotension, and hypocarbia with TBI outcomes in a US national trauma network.

Design, setting, and participants: This cohort study examined data from 8 level I trauma centers and their affiliated ground and air emergency medical services (EMS) agencies in the Linking Investigations in Trauma and Emergency Services (LITES) Network from January 1, 2017, to June 30, 2021. Adult patients …

The Role Of Iowa Gambling Task Performance In Response To Citalopram Treatment For Cocaine Use Disorder, Constanza De Dios, Robert Suchting, Charles E Green, Heather E Webber, F Gerard Moeller, Scott D Lane, Joy Schmitz

Faculty, Staff and Student Publications

Background:

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use.

Objectives:

The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Methods:

We conducted a secondary analysis of a double-blind, placebo-controlled, randomized Bayesian adaptive trial investigating citalopram efficacy in CUD treatment-seeking adults. At baseline and mid-treatment, participants completed assessments of decision-making (Iowa Gambling Task; IGT), attention, response inhibition, and cognitive flexibility. Outcomes were longest duration of abstinence (LDA; count of consecutive …

Beyond The Numbers: A Qualitative Exploration Of Patient Perspectives On Postpartum Care And Maternal Mortality, Kristen A. Waters

Master of Public Health Program Student Publications

Introduction

Montgomery County faces one of Ohio's highest maternal mortality rates, with notable disparities by race. Despite their importance in reducing maternal deaths, up to 40% of women nationwide do not attend a postpartum care (PPC) visit. While well researched guidelines exist regarding the content and timing of PPC visits, there is a lack of patient perspective on this topic, specifically in the Black-identifying population in an area with a significant burden of maternal mortality.

Methods

Semi-structured interviews and focus group sessions were conducted with 31 participants of maternal health community events in Dayton, OH. Participants were asked their opinions …

Preferences And Feasibility Of Long-Acting Technologies For The Treatment Of Hepatitis C Virus: A Survey Of Patients In Diverse Low- And Middle-Income Countries, Renae Furl, Kimberly Scarsi, Harlan Sayles, Matt Anderson, Joelle Dountio Ofimboudem, Ethel D. Weld, Imam Waked, Asmaa Gomaa, Alzhraa Al-Khatib, Fatma Mohammed Elshobary, Hailemichael Desalegn, Henok Fisseha, Sunil Solomon, Shruti Mehta, Andrew Owen, Steve Rannard, David L. Thomas, Susan Swindells

Journal Articles: Infectious Diseases

Despite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low- and middle-income countries (LMICs). Long-acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA-HCV treatment across three LMICs: Egypt, Ethiopia and India. The survey focused on understanding barriers and facilitators to treatment, with emphasis on LA treatment preferences. Four-hundred respondents completed a survey including demographics, HCV treatment history and preferences for injections, implants and microarray patches (MAPs) compared to pills. Overall, 78% of respondents were willing to receive injections, 43% were willing to receive implants and …

Pregnancy Outcomes After Exposure To Tuberculosis Treatment In Phase 3 Clinical Trial, 2016-2020, Ekaterina V. Kurbatova, William C. Whitworth, Kia E. Bryant, Meredith G. Dixon, Kelly E. Dooley, Nigel A. Scott, Rosanna Boyd, Nicole E. Brown, Kimberley N. Chapman Hedges, Wendy Carr, Lakshmi P. Peddareddy, Grace Muzanyi, Rodney Dawson, Ziyad Waja, Neil Martinson, Jyoti S. V. Mathad, Payam Nahid, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Patrick P. J. Phillips, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We analyzed pregnancy outcomes of women who became pregnant during the study. Among 740 women, 97 (13.1%) became pregnant. Of 102 pregnancies (in 97 participants), 30 (29.4%) participants were exposed to study drugs. Fetal loss was reported for 3/13 (23.1%) in the control regimen, 1/9 (11.1%) in the rifapentine/moxifloxacin regimen, and 1/8 (12.5%) in the rifapentine regimen. Among 21 live births in exposed pregnancies (7 in each arm), 1 infant with a congenital anomaly was reported in a participant on the …

Time Of Urine Sampling May Influence The Association Between Urine Specific Gravity And Body Composition, Patrick B. Wilson, Brian K. Ferguson, Ian P. Winter

Exercise Science Faculty Publications

Urine specific gravity (USG) is frequently utilized in sports practice and research to assess hydration status. Prior research suggests that individuals with large amounts of fat-free mass (FFM) and muscle have elevated USG, but little is known about whether the time of collection (first-morning vs. spot sampling) and various nutritional factors influence these relationships. This cross-sectional, observational study assessed fasted first-morning (n = 55) and non-fasted spot USG (n = 51) samples in adults and evaluated relationships of USG with body composition and nutrition intake. The InBody 770 was used to estimate FFM, skeletal muscle mass (SMM), and total body …

Efficacy And Safety Of 4-Month Rifapentine-Based Tuberculosis Treatments In Persons With Diabetes., Ekaterina V. Kurbatova, William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P. J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and …

An Evaluation Of The Decline In Primary Care Physician Visits, 2010 To 2021, Anuradha Jetty, Marie Ezran, Alison Huffstetler, Yalda Jabbarpour

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Primary care is the backbone of the United States healthcare system, yet it continues to be underfunded and inaccessible to many. Previous studies explored primary care visit patterns until 2016, leaving gaps in our understanding of how recent factors like state Medicaid expansions, the Coronavirus Disease 2019 (COVID-19) pandemic, and population growth have influenced these patterns. Hence, the objective of the current study was to analyze the trends in primary care visits provided by outpatient clinicians over time and by visit type and contextualize study findings within the changing healthcare landscape.

METHODS: The Medical Expenditure Panel Survey data (2010-2021) …

Cochlear Implantation With Sporadic Inner Ear Schwannomas: Outcomes In 106 Patients From An International Multi-Institutional Study, John P. Marinelli, Torsten Rahne, James R. Dornhoffer, Christine M. Lohse, Justin Cottrell, J. Thomas Roland, Nicholas J. Thompson, Kevin D. Brown, Jacob C. Lucas, Seilesh C. Babu, Nathan R. Lindquist, Elizabeth L. Perkins, Donald Tan, John I. Lane, Jacob B. Hunter, Erin Harvey, Nicholas L. Deep, Samantha Y. Cerasiello, Matthew L. Kircher, Mana Espahbodi, Evan L. Tooker, Niels Cramer West, Per Caye-Thomasen, Matthew L. Carlson, Stefan K. Plontke

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To evaluate cochlear implant speech perception among patients with sporadic inner ear schwannoma who underwent ipsilateral implantation.

STUDY DESIGN: Retrospective multi-institutional cohort study.

SETTING: Eleven tertiary academic medical centers across Germany, Denmark, and the United States.

PATIENTS: One hundred six patients with sporadic inner ear schwannoma who received an ipsilateral cochlear implant from 2011 to 2022.

INTERVENTIONS: Ipsilateral cochlear implantation with observation, stereotactic radiosurgery, or microsurgery for tumor management.

MAIN OUTCOME MEASURES: Monosyllabic speech perception testing scores and rates of open-set speech perception.

RESULTS: Among 106 patients studied, 101 (95%) achieved open-set speech perception with a median of 24 …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

'I Did Not Know We Could Exercise This Small Premature Baby': Challenges Experienced By Parents While Implementing Early Intervention For Their Preterm Infants-A Qualitative Perspective, Manasa Kolibylu Raghupathy, Selim Jahangir, Sonia Khurana, Leslie Edward S. Lewis, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Background

Preterm birth is a highly stressful experience for both parents and infants. Parental participation in care enhances developmental outcomes, fosters parent-infant interactions and builds parental confidence. However, low parental adherence has always been a challenge in the successful implementation of intervention programs both in the NICU and at home. It is imperative to understand parents' perspectives and view the challenges that they experience through their lens while providing early intervention to their infants born preterm. This study is aimed at identifying new parents' challenges when implementing early intervention programs for their infants during the transition from hospital to home. …

Differential Plasma Carotenoid Profiles In Hypertensive Disorders Of Pregnancy, Colman Freel, Jonah Scheffler, Rebecca Drakowski, Elizabeth Lyden, Matthew Van Ormer, Melissa K. Thoene, Paras K. Mishra, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Background: Hypertensive disorders of pregnancy (HDP) affect one in six pregnancies globally. The etiology of HDP remains unclear but is known to involve oxidative stress. While the body produces endogenous antioxidants, antioxidative nutrients, like carotenoids, remain critical in modulating oxidative stress. The statuses of several carotenoids have been linked to hypertension in both pregnant and non-pregnant populations. However, their associations with the spectrum of HDP, including gestational hypertension (GH), chronic hypertension (CH), and preeclampsia (PE), remains unclear. Our objective was to quantify and compare carotenoid intake and plasma levels among HDP. Methods: We conducted a prospective cohort study …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

Placentas From Sars-Cov-2 Infection During Pregnancy Exhibit Foci Of Oxidative Stress And Dna Damage, Guilherme M Nobrega, Eliza R Mccoll, Arthur Antolini-Tavares, Renato T Souza, José Guilherme Cecatti, Maria Laura Costa, Indira U Mysorekar

Faculty, Staff and Students Publications

Problem: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.

Method of study: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …

Application Of A Digital Quality Measure For Cancer Diagnosis In Epic Cosmos, Andrew J Zimolzak, Sundas P Khan, Hardeep Singh, Jessica A Davila

Faculty, Staff and Students Publications

Objectives: Missed and delayed cancer diagnoses are common, harmful, and often preventable. We previously validated a digital quality measure (dQM) of emergency presentation (EP) of lung cancer in 2 US health systems. This study aimed to apply the dQM to a new national electronic health record (EHR) database and examine demographic associations.

Materials and methods: We applied the dQM (emergency encounter followed by new lung cancer diagnosis within 30 days) to Epic Cosmos, a deidentified database covering 184 million US patients. We examined dQM associations with sociodemographic factors.

Results: The overall EP rate was 19.6%. EP rate was higher in …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Maternal Rest Improves Growth In Small-For-Gestational-Age Fetuses (<10th Percentile), Greggory R Devore, Bardo Polanco, Wesley Lee, Jeffrey Brian Fowlkes, Emma E Peek, Manesha Putra, John C Hobbins

Faculty, Staff and Students Publications

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight ofHowever, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question.

OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus.

STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for …