Medical Specialties Commons^™

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …

Cytarabine Pharmacogenomics And Outcomes Among Children And Young Adults With Acute Myeloid Leukemia., Richard J. Marrero, Vivek M. Shastri, Deedra Nicolet, Krzysztof Mrózek, Christopher J. Walker, William G. Blum, Bayard L. Powell, Jonathan E. Kolitz, Joseph O. Moore, Geoffrey L. Uy, Wendy Stock, Andrew J. Carroll, John C. Byrd, Richard Aplenc, Todd M. Cooper, Alan S. Gamis, Huiyun Wu, Stanley Pounds, Yi-Cheng Wang, Todd A. Alonzo, Soheil Meshinchi, Ann-Kathrin Eisfeld, Edward A. Kolb, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Therapeutic responses in acute myeloid leukemia (AML) demonstrate considerable variability both across and within established risk stratifications and age groups. Moreover, significant racial disparities persist, with Black patients experiencing inferior survival outcomes compared with their White counterparts.

OBJECTIVE: To validate the association of the previously reported 10 single nucleotide variant (SNV)-based ara-C pharmacogenomics score (ACS10) with survival outcomes in a large cohort of pediatric AML patients; to evaluate whether ACS10 remains relevant in an adolescent and young adult (AYA) population of patients with AML treated with similar intensive induction chemotherapy protocols; and to assess the association of ACS10 with …

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …

Iron Deficiency Without Anemia And Reduced Basal Ganglia Iron Content In Youths, Dimitri Fiani, Joo-Won Kim, Mianzhi Hu, Ramiro Salas, Sarah Heilbronner, Jacquelyn Powers, Muhammad Haque, Stephanie Dinh, Xiaofan Huang, Darrell Worthy, Sridevi Devaraj, Junqian Xu, Chadi Calarge

Faculty, Staff and Students Publications

Importance: Although brain iron is necessary for neurogenesis, myelination, and neurotransmitter synthesis, iron deficiency (ID) is defined solely based on hematological outcomes.

Objective: To examine the association of ID without anemia with basal ganglia (BG) iron content and its structural and functional sequelae in adolescents.

Design, setting, and participants: This cross-sectional study enrolled participants using the electronic medical record system from a large network of pediatrics clinics between December 2020 and April 2024. Otherwise healthy, unmedicated participants aged 10 to 17 years with a depressive or anxiety disorder or with no psychopathology were consecutively enrolled. Anemia and acute inflammation led …

Intraosseous Vs Intravenous Access For Epinephrine In Pediatric Out-Of-Hospital Cardiac Arrest, Masashi Okubo, Sho Komukai, Junichi Izawa, Sunhee Chung, Cameron Dezfulian, Francis X Guyette, Joshua R Lupton, Christian Martin-Gill, Sylvia Owusu-Ansah, Sriram Ramgopal, Clifton W Callaway

Faculty, Staff and Students Publications

Importance: While epinephrine is commonly administered in children with out-of-hospital cardiac arrest (OHCA) via an intraosseous (IO) or intravenous (IV) route, the optimal route of epinephrine delivery is unclear.

Objective: To evaluate the association between the route of epinephrine administration (IO or IV) and patient outcomes after pediatric OHCA.

Design, setting, and participants: Retrospective cohort study of pediatric patients (aged < 18 years) with nontraumatic OHCA treated by emergency medical services who received prehospital epinephrine either via an IO or IV route. Patients were included in the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective OHCA registry at 10 sites in the US and Canada from April 2011 to June 2015. Data analysis was performed from May 2024 to April 2025.

Exposure: Epinephrine administration route: IO or IV route.

Main outcomes and measures: The primary outcome was survival to hospital discharge. The secondary outcome was return of spontaneous circulation (ROSC) before hospital arrival. Propensity scores were calculated and inverse probability of …

Surgical Management Of An Intracranial Injury Caused By A Handcrafted Arrow In Sub-Saharan Africa: A Global Neurosurgical Relevance., Allie L Heineman, Quinn Jackson, Chris Karas, Robert Galler, Victor Awuor, Hiren Patel

Trauma and Acute Care Articles

This case report and literature review describe an intracranial injury resulting from a handcrafted arrow that required emergent surgical management in a patient treated at a public hospital in Sub-Saharan Africa. The authors are members of the non-profit organizations Chunilal Initiative and Kisumu Intuitive, which deliver charitable neurosurgical care to the region on a quarterly basis. This unique neurotrauma case, involving a penetrating, contaminated, metallic object, highlights the surgical and antibacterial management of intracranial arrow injuries and emphasizes the importance of neurosurgical missions to underserved regions globally. The patient is a 16-year-old male tribal member with no known or reported …

Long-Term Non-Conditional And Conditional Metastasis Of Uveal Melanoma By Tumor Size Category In 8034 Patients, Rolika Bansal, Hidayet Sener, Jerry A. Shields, Carol L. Shields

Wills Eye Hospital Papers

PURPOSE: To estimate metastasis of patients with uveal melanoma (UM) based on tumor size categories classified by ultrasonographic thickness as small (0.0-3.0 mm), medium (3.1-8.0 mm), or large (≥8.1 mm) using both non-conditional and conditional analyses.

DESIGN: Retrospective analysis.

METHODS: A retrospective study of 8034 cases over 35-years at a single ocular oncology referral center evaluated the primary endpoint of cumulative incidence of metastasis at 5-, 10-, 15-, 20-, 25- and 30-years using non-conditional and conditional analysis at 3-years, 5-years, and 10-years of metastasis-free survival.

RESULTS: The mean thicknesses for small, medium, and large UMs were 2.5 mm, 5.0 mm, …

A Rare Sequela Of Untreated Streptococcus Pharyngitis: A Case Report., Meredith Hiltbrand Lehoe, Emily Cushing

Ambulatory and Primary Care Articles

Pharyngitis is commonly caused by the gram positive bacteria, streptococcus. Given the potential morbid complications of untreated streptococcal pharyngitis, antibiotics are critical. One of the rarer complications is pulmonary-renal syndrome (PRS), defined as rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. PRS is associated with high rates of morbidity and mortality, making swift diagnosis and treatment imperative for survival. More common causes of PRS are tied to autoimmune diseases. This case describes a novel progression of PRS caused by streptococcus. A 26-year-old male with no significant medical history presented to our emergency department with streptococcal group A-positive sore throat. After discontinuing …

Diabetes-Related Distress Over Time And Its Associations With Glucose Levels In School-Aged Children., Susana R. Patton, Nicole Kahhan, Amy Milkes, Ryan J. Mcdonough, Matthew Benson, Mark A. Clements, Jessica S. Pierce

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: In a cohort of families of school-age children (8-12.99 years old) with type 1 diabetes, we examined the stability of parent and child diabetes-related distress (DRD) over 6 months and the associations between parent and child DRD and child glycated hemoglobin (HbA1c) over time.

RESEARCH DESIGN AND METHODS: We recruited families from two large pediatric hospital systems in the USA and used validated measures of parent (Parent Problem Areas in Diabetes-Child, PPAID-C) and child (Problem Areas in Diabetes-Child, PAID-C) DRD and children's HbA1c. We collected data at baseline and 6 months. We calculated minimal clinically important differences in PPAID-C …

Changes In The Fxr-Cistrome And Alterations In Bile Acid Physiology In Wilson Disease, Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore

Children’s Nutrition Research Center Staff Publications

Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.

Methods: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.

Results: FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. …

Facilitators And Barriers To Neurologist Referral Of Patients For Epilepsy Surgery Evaluation., Chloé E Hill, Daniel Hochster, Jessica E Baker, Alison L Herman, Nishad Shaheid, Susanna S O'Kula, Jack M Parent, Darin B Zahuranec, Lesli E Skolarus

Neuroscience Articles

OBJECTIVE: Epilepsy surgery offers a potential cure for drug-resistant epilepsy (DRE), yet surgery is underutilized. An estimated 5% of patients with DRE undergo long-term EEG monitoring (LTM) annually, the requisite first step of evaluation for surgical candidacy. Much of the variation in LTM referral may be attributable to individual neurologist practice rather than patient characteristics. We explored neurologist behaviors and practices in epilepsy surgery referral to guide future interventions to expand patient access to surgery.

METHODS: This qualitative interview study recruited neurologists who treated adults with epilepsy. Interviews were grounded in the Theoretical Domains Framework (TDF) of behavior change to …

Reliability Of Physician Estimation Of Pelvic Free Fluid Volume On The Pediatric Focused Assessment With Sonography For Trauma., Ashkon Shaahinfar, Jennifer Rosin Wiebelhaus, Newton Addo, Ronald A. Cohen, Pinar Karakas-Rothey, Aaron E. Kornblith

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To evaluate the reliability of physician gestalt estimation of pelvic free fluid volume on pediatric Focused Assessment with Sonography for Trauma (FAST). To determine a reliable cut-off volume and characteristics associated with small pelvic free fluid.

METHODS: Our study assessed the ability of 2 ultrasound-trained pediatric emergency medicine (PEM) physicians and 2 pediatric radiologists to characterize pelvic free fluid in a retrospective convenience sample of archived FAST from a Level 1 pediatric trauma center, April 2018-June 2020. Inter- and intra-rater reliability were measured to determine the most reliable volume cut-off. Chi-squared and Fisher's exact tests determined characteristics associated with …

Validity And Reliability Of The Tampa Scale For Kinesiophobia For Adolescents With Heart Disease., David A. White, William R. Black, Emily Cramer, Lindsey Malloy-Walton, Mollie Walton, Laura Martis, Brandy Enneking, Kelli M. Teson, Jessica S. Watson, Jami Gross-Toalson

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To assess the validity and reliability of a newly adapted Tampa Scale for KP for adolescents with HD (TSK-Heart-A).

METHODS: The TSK-Heart-A survey consists of 17 Likert scale items, producing a summary score (SS) ranging from 17 (low KP) to 68 (high KP). Following content and face validity, adolescents (age 12-18 yr) with arrhythmia disorders or Fontan palliation were recruited. The PROMIS pediatric anxiety and depression short forms, Pediatric Quality of Life Inventory (PedsQL) generic core and cardiac module, and a PA questionnaire for adolescents (PAQ-A) were used for criterion validity. The TSK-Heart-A was completed twice (20.4 ± 6.3 …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Psychometric Properties Of The Spanish Yale-Brown Obsessive-Compulsive Scale - Second Edition, Eric A Storch, Jessica Sc Cheng, Miranda Higham, Josselyn S Muñoz, Vanessa Zavala Cruz, Dayan Berrones, Diana P Obando, Jacey L Anderberg, Renee M Frederick, Vissente Tapia-Cuevas, Macarena Churruca Muñoz, Constanza Uribe Villar, Pablo R Moya, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Andrew D Wiese, Caitlin M Pinciotti, Melisa N Sagarnaga, Joseph F Mcguire, Ogechi C Onyeka, María B Moyano, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), Wayne K Goodman, James J Crowley

Faculty, Staff and Students Publications

The Yale-Brown Obsessive-Compulsive Scale, Second Edition (Y-BOCS-II) is an evidence-based clinician-rated measure for assessing the presence and severity of obsessive-compulsive symptoms. The Spanish version of the Y-BOCS-II has not yet been validated. The present study examines the psychometric properties of the Spanish Y-BOCS-II (Spanish-Y-BOCS-II) in adults with obsessive-compulsive disorder (OCD) who are of Hispanic/Latino ancestry. The Spanish-Y-BOCS-II was administered to 1805 adults with OCD. Participants also completed a battery of measures assessing OCD, depression, and anxiety symptoms. The internal consistency for the Symptom Checklist (Kuder-Richardson-20=0.92), Obsession Severity (α=0.87), Compulsion Severity (α=0.86), and Total Severity (α=0.92) were high. The inter-rater reliability …

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques, Jumah G Ahmad, Alexander J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

Postoperative Caregiver Decision Regret Following Velopharyngeal Dysfunction Surgery., Rohit Nallani, Nathan Farrokhian, Meghan Tracy, Kevin J. Sykes, Jill M. Arganbright

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Decision regret (DR) is a powerful factor in medical decision-making, particularly for surgical decisions which carry multiple risks, impact quality of life (QOL), and have uncertain outcomes. While prior studies have investigated caregiver DR after tonsillectomy and otologic surgery, there is a paucity of data assessing DR following pediatric otolaryngology procedures. The aim of this study is to measure DR following velopharyngeal dysfunction (VPD) surgery.

METHODS: A cross-sectional survey study with chart review was performed of caregivers of children who had VPD surgery performed by a single surgeon at a tertiary children's hospital. Demographic, medical, and surgical history were …

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

Novel Treatment-Specific Causal Biomarkers For Colorectal Cancer By Omics Integration, Akram Yazdani, Azam Yazdani, Raul Mendez-Giraldez, Gianluigi Pillonetto, Esmat Samiei, Reza Hadi, Heinz-Josef Lenz, Alan P Venook, Ahmad Samiei, Andrew B Nixon, Joseph A Lucci, Scott Kopetz, Monica M Bertagnolli, Federico Innocenti

Faculty, Staff and Student Publications

While monoclonal antibody-based targeted therapies have substantially improved progression-free survival in cancer patients, the variability in individual responses poses a significant challenge in patient care. Therefore, identifying cancer subtypes and their associated biomarkers is required for assigning effective treatment. In this study, we integrated genotype and pre-treatment tissue RNA-seq data and identified biomarkers causally associated with the overall survival (OS) of colorectal cancer (CRC) patients treated with either cetuximab or bevacizumab. We performed enrichment analysis for specific consensus molecular subtypes (CMS) of CRC and evaluated differential expression of identified genes using paired tumor and normal tissue from an external cohort. …

Impact Of Screening For Human Papillomavirus-Positive Oropharyngeal Cancers: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

Background: We estimated the impact of screening on morbidity and mortality of human papillomavirus (HPV)16-positive oropharyngeal cancer among US men aged 45-79 years.

Methods: We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed 4 progression speeds across cancer stages (very slow, slow, fast, and very fast) and 4 screening frequencies.

Results: Among US men aged 45-79 years in 2021 (n = 54 …

Association Of Sirt6 Expression With Risk Of Pneumonitis Induced By Radiotherapy In Cancer Patients, Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

Faculty, Staff and Student Publications

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Functional Vs Structural Cortical Deficit Pattern Biomarkers For Major Depressive Disorder, Peter Kochunov, Bhim M Adhikari, David Keator, Daniel Amen, Si Gao, Nicole R Karcher, Demetrio Labate, Robert Azencott, Yewen Huang, Hussain Syed, Hongjie Ke, Paul M Thompson, Danny J J Wang, Braxton D Mitchell, Jessica A Turner, Theo G M Van Erp, Neda Jahanshad, Yizhou Ma, Xiaoming Du, William Burroughs, Shuo Chen, Tianzhou Ma, Jair C Soares, L Elliot Hong

Faculty, Staff and Student Publications

Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

Objective: To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus …

Home-Based Transcranial Direct Current Stimulation For Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial And Open-Label Treatment Phases, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

Faculty, Staff and Student Publications

Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were …

The Burden Of Burnout: Understanding Its Prevalence And Organizational Drivers In Medical Physics, Deborah Schofield, C Lynn Chevalier, Laurence Court, William Harmsen, Akiva Turner

Faculty, Staff and Student Publications

Background: Burnout is a work-related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care.

Purpose: The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined.

Methods: The anonymous survey was distributed to 1962 full members of the American …