Digital Commons Network^™

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

The Upfront Project: Tailored Implementation And Evaluation Of A Patient Decision Aid To Support Shared Decision-Making About Management Of Symptomatic Uterine Fibroids, Rachel C Forcino, Mary Politi, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States.

METHODS: We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level …

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Alan Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

METHODS AND RESULTS: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ

CONCLUSIONS: Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor-β pathway genes, particularly

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica Ryu, Yoshina Gautam, Diana Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David Relman, Ahmed Shibl, Jeevan Bahadur Sherchand, Aashish Jha, Emily Davenport

SKMC Student Presentations and Publications

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Patient-Reported Convenience And Effectiveness Of Telehealth For Breast Cancer Management, Akshara Singareeka Raghavendra, Kristofer Jennings, Gil Guerra, Debu Tripathy, Meghan S Karuturi

Faculty, Staff and Student Publications

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, telehealth was rarely used for breast cancer management at tertiary care centers. We sought to examine patient satisfaction, experiences, preferences, and perceived effectiveness and technical quality of telehealth visits in follow-up patients receiving routine outpatient care in the breast medical oncology practice at The University of Texas MD Anderson Cancer Center.

Methods: We administered a survey to 60 follow-up patients for a duration of 9 months (January 5, 2021 to October 27, 2021) who had at least one telehealth consultation during the COVID-19 pandemic, from April 10, 2020 to October 21, 2021. …

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy In High-Grade Epithelial Ovarian Cancer: A Lance Randomized Clinical Trial, J Alejandro Rauh-Hain, Alexander Melamed, René Pareja, Taymaa May, Abdulrahman Sinno, Leah Mcnally, Neil S Horowitz, Pierandrea De Iaco, Chad M Michener, Luc Van Lonkhuijzen, Maria D Iniesta, Ying Yuan, Pedro T Ramirez, Anna Fagotti

Faculty, Staff and Student Publications

Importance: Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC).

Objective: To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT).

Design, setting, and participants: This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was …

Differences In Brain Volume In Military Service Members And Veterans After Blast-Related Mild Tbi: A Limbic-Cenc Study, Emily L Dennis, Jared A Rowland, Carrie Esopenko, Nicholas J Tustison, Mary R Newsome, Elizabeth S Hovenden, Brian B Avants, Jessica Gill, Sidney R Hinds, Kimbra Kenney, Hannah M Lindsey, Sarah L Martindale, Mary Jo Pugh, Randall S Scheibel, Pashtun-Poh Shahim, Robert Shih, James R Stone, Maya Troyanskaya, William C Walker, Kent Werner, Gerald E York, David X Cifu, David F Tate, Elisabeth A Wilde

Faculty, Staff and Students Publications

Importance: Blast-related mild traumatic brain injuries (TBIs), the "signature injury" of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear.

Objective: To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members.

Design, setting, and participants: Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in …

Age-Related Decline In Blood-Brain Barrier Function Is More Pronounced In Males Than Females In Parietal And Temporal Regions, Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial …

Race, Gender, And Faculty Retention In Academic Medicine, Taneisha S Scheuermann, Lauren Clark, Nasrin Sultana, Nathalia Machado, Elena Shergina, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: Poor retention may be associated with lack of faculty diversity in academic medicine.

OBJECTIVE: To examine differences in faculty retention by gender, degree type, and race and ethnicity using data from US medical schools.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from 155 medical schools for 1978 to 2021, which were obtained from the Association of American Medical Colleges. Retention rates were calculated by gender, race and ethnicity, and degree type. Time to attrition was estimated using Kaplan-Meier curves and adjusted Cox proportional hazards models were used to examine the differences in retention by gender and race. …

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation For Depression: A Randomized Clinical Trial, Dongsheng Zhou, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Junyao Liu, Shen Li, Wenhao Zhuang, Yanli Li, Ruichenxi Luo, Zhiwang Liu, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Raymond Y Cho, Thomas R Kosten, Xiang-Yang Zhang

Staff and Researcher Publications

IMPORTANCE: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD).

OBJECTIVE: To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo …

Performance Of Risk Models For Antimicrobial Resistance In Adult Patients With Sepsis, M Cristina Vazquez Guillamet, Hanyang Liu, Andrew Atkinson, Victoria J Fraser, Chenyang Lu, Marin H Kollef

2020-Current year OA Pubs

IMPORTANCE: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

OBJECTIVE: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. …

Race And Ethnicity, Gender, And Promotion Of Physicians In Academic Medicine, Lauren Clark, Elena Shergina, Nathalia Machado, Taneisha S Scheuermann, Nasrin Sultana, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: The ranks of academic physicians do not reflect the diversity of the US population. To create a diverse and effective medical workforce, it is important to know the extent to which gender, race and ethnicity, and the intersection of these factors are associated with career advancement.

OBJECTIVE: To assess whether race and ethnicity and gender are associated with appointment to or promotion within academic medicine.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Association of American Medical Colleges data on graduates of all US MD-granting medical schools from 1979 to 2019 merged with faculty appointment data since 2000. Data …

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Position- And Sex-Related Differences In Sagittal And Frontal Plane Concentric Isokinetic Hip Muscle Peak Torques And Agonist-Antagonist Ratios, Lisa T. Hoglund, Matthew C. Schiffino, James E. Freels, Isabella G. Romano

Department of Physical Therapy Faculty Papers

BACKGROUND: Hip muscle weakness is associated with many musculoskeletal conditions and athletic injuries. Isokinetic testing is often performed to measure a patient's strength or to assess treatment response. Patient sex and positioning during isokinetic strength testing may influence peak torque production and the agonist-antagonist peak torque ratios. However, different test positions are used clinically and in research to measure hip muscle strength. It is unknown how patient test position or sex impacts test results.

HYPOTHESIS/PURPOSE: The purpose of this study was to determine whether concentric isokinetic peak torques of sagittal and frontal plane hip muscles differ when tested in recumbent …

Distinct Escherichia Coli Transcriptional Profiles In The Guts Of Recurrent Uti Sufferers Revealed By Pangenome Hybrid Selection, Mark G Young, Jesús Bazan Villicana, Philippe Azimzadeh, Andrew Kau, Karen W Dodson, Henry L Schreiber 4th, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E. coli, we develop E. coli PanSelect, which uses probes designed to specifically capture E. coli's broad pangenome. We demonstrate its ability to enrich diverse E. coli by orders of magnitude, in a mock community and in human stool from a study investigating recurrent UTI (rUTI). Comparisons of transcriptomes between gut E. coli of women with and without history of rUTI suggest rUTI gut E. coli are responding to increased oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of in vivo E. coli biology in other low-abundance environments, and the framework described here has broad applicability to other diverse, low-abundance organisms.

Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

METHODS: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of …

Genetic Alterations In Chromatin Regulatory Genes In Upper Tract Urothelial Carcinoma And Urothelial Bladder Cancer., Shuo Wang, Xuzhi Yan, Weihua Lan, Yapeng Wang, Ze Wang, Dali Tong, Yao Zhang, Qiang Ran, Haoyang Li, Junhao Jin, Haiyang Xiao, Jing Xu, Qian Yan, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Jun Qin, Luofu Wang, Jun Jiang, Qiuli Liu

PCOM Scholarly Works

PURPOSE: Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T-cell receptor (TCR) diversity in UTUC and UCB.

MATERIALS AND METHODS: Targeted next-generation sequencing or whole-exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle-invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes …

Association Between E-Scooter Temporal Usage Patterns With Injuries Resulting In Admission To A Level One Trauma Center, Kevin C Rix, Andrew E Springer, Katelyn Jetelina, Nalini Ranjit, Catherine C Mcdonald, Douglas J Wiebe, Thomas B Coopwood

Faculty, Staff and Student Publications

Background: As e-scooters have become common modes of transportations in urban environments, riding e-scooters has become a common mechanism of injury. This study examines the relationship between when riders are using these devices (i.e. day of week, and time of the day) and injury incidence based on data from a large U.S. city.

Methods: This study is a retrospective cohort study of patients in the trauma registry at a level one trauma center. Registry data were combined with a publicly available dataset of all e-scooter trips that occurred during the study period. Frequency of injuries and trips were analyzed using …

Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk

Faculty, Staff and Student Publications

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, setting, and participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic …

Mean Arterial Pressure (Map) Augmentation In Traumatic Spinal Cord Injuries: Early Hyperperfusion Treatment Influences Neurologic Outcomes., Aimee K Lariccia, Kimberly Sperwer, Michael L Lieber, M Chance Spalding

Trauma and Acute Care Articles

Context: Hyperperfusion therapy, mean arterial blood pressure (MAP) > 85 mmHg, is a recommended treatment of blunt traumatic spinal cord injury (SCI). We hypothesized the first 24 h of MAP augmentation would be most influential on neurological outcomes.Design: This retrospective study from a level 1 urban trauma center dating 1/2017 to 12/2019 included all blunt traumatic spinal cord injured patients receiving hyperperfusion therapy. Patients were grouped as "No improvement" vs "Improvement" measured by change in American Spinal Injury Association (ASIA) score during their hospitalization. MAP values for the first 12, first 24 and last 72 h were compared between the …

The Phenotypic And Genotypic Spectrum Of Individuals With Mono- Or Biallelic Ank3 Variants., Francesca Furia, Amanda M. Levy, Miel Theunis, Michael J. Bamshad, Meghan N. Bartos, Emilia K. Bijlsma, Francesco Brancati, Lucile Cejudo, Jessica X. Chong, Chiara De Luca, Sarah Joy Dean, Alena Egense, Himanshu Goel, Adam J. Guenzel, Ulrike Hüffmeier, Eric Legius, Grazia M S Mancini, Iñigo Marcos-Alcalde, Tanguy Niclass, Marc Planes, Sylvia Redon, David Ros-Pardo, Karen Rouault, Rachel Schot, Sarah Schuhmann, Joseph J. Shen, Alice M. Tao, Isabelle Thiffault, Hilde Van Esch, Ingrid M. Wentzensen, Tahsin Stefan Barakat, Rikke S. Møller, Paulino Gomez-Puertas, Wendy K. Chung, Elena Gardella, Zeynep Tümer

Manuscripts, Articles, Book Chapters and Other Papers

ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism …

Adverse Childhood Experiences And Psychological Correlates Of Substance Use Disorders Among Black Sexual Minority Women, Shemeka Thorpe, Kaylee A Palomino, Natalie Malone, Danelle Stevens-Watkins

Kinesiology and Health Promotion Faculty Publications

This study examined the influence of adverse childhood experiences (ACEs) on Black sexual minority women's mental health and substance use disorders in adulthood. Secondary data analysis was conducted using N = 149 Black sexual minority women's reports from the Generations Study. Study variables included psychological distress, chronic strains, stressful life events, ACEs, and substance use disorders, including alcohol use disorder and drug use disorder. Quantitative data analysis consisted of descriptives and bivariate correlations. Participants' total ACE scores were positively significantly correlated with increased alcohol misuse, chronic life strains, and stressful life events. Exposure to household interpersonal violence and household mental …

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

Dosimetric Predictors Of Acute And Late Gastrointestinal Toxicities In Stereotactic Online Adaptive Magnetic Resonance-Guided Radiotherapy (Smart) For Locally Advanced Pancreatic Adenocarcinoma, Alden D'Souza, Hayley B Stowe, Olga L Green, Joshua Schiff, Geoffrey D Hugo, John Ginn, Borna Maraghechi, Kylie H Kang, Hyun Kim, Shahed N Badiyan, Pamela Samson, Clifford G Robinson, Alex Price, Lauren E Henke

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: A retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART).

MATERIALS AND METHODS: 147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR …

Family Lore, A Variant Of Uncertain Significance, And Cadasil, Rhys Duarte, Liesbeth Vossaert, Sandra A Darilek, Chelsi Rose, Evan Schauer, Christian Parobek, Emily Bland, Keren Machol, Elizabeth Mizerik, Chaya N Murali

Faculty, Staff and Students Publications

An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in NOTCH3, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his …

Antiseizure Medication-Induced Hypersensitivity Reactions: Data From A Large Healthcare System, Benjamin Cadle, Feride Un Candan, Zulfi Haneef, Christopher Ryan Barton, Dylan Brock, Irfan Ali, Jaime Shoup, Cemal Karakas

Faculty, Staff and Students Publications

Background and objectives: Data on hypersensitivity reactions (HR) to individual anti-seizure medications (ASMs), and reactions to additional ASMs, is often limited by sample size. This data is vital in helping clinicians identify initial and subsequent ASMs to use in treating persons with epilepsy (PWE). Using a very large dataset, our study attempts to quantify the occurrence of HR across 31 different ASMs. We also attempt to investigate whether certain pairs of ASMs are associated with a higher frequency of HR.

Methods: The Slicer-Dicer tool in the Epic electronic medical records system was used to analyze patients seen between 2012 and …

An Artificial Intelligence-Generated Model Predicts 90-Day Survival In Alcohol-Associated Hepatitis: A Global Cohort Study, Winston Dunn, Yanming Li, Ashwani K Singal, Douglas A Simonetto, Luis A Díaz, Francisco Idalsoaga, Gustavo Ayares, Jorge Arnold, María Ayala-Valverde, Diego Perez, Jaime Gomez, Rodrigo Escarate, Eduardo Fuentes-López, Carolina Ramirez-Cadiz, Dalia Morales-Arraez, Wei Zhang, Steve Qian, Joseph C Ahn, Seth Buryska, Heer Mehta, Nicholas Dunn, Muhammad Waleed, Horia Stefanescu, Andreea Bumbu, Adelina Horhat, Bashar Attar, Rohit Agrawal, Joaquín Cabezas, Victor Echavaría, Berta Cuyàs, Maria Poca, German Soriano, Shiv K Sarin, Rakhi Maiwall, Prasun K Jalal, Fátima Higuera-De-La-Tijera, Anand V Kulkarni, P Nagaraja Rao, Patricia Guerra-Salazar, Lubomir Skladaný, Natália Kubánek, Veronica Prado, Ana Clemente-Sanchez, Diego Rincon, Tehseen Haider, Kristina R Chacko, Gustavo A Romero, Florencia D Pollarsky, Juan C Restrepo, Luis G Toro, Pamela Yaquich, Manuel Mendizabal, Maria L Garrido, Sebastián Marciano, Melisa Dirchwolf, Victor Vargas, César Jiménez, David Hudson, Guadalupe García-Tsao, Guillermo Ortiz, Juan G Abraldes, Patrick S Kamath, Marco Arrese, Vijay H Shah, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Background and aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model.

Approach and results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) …

Trends In The Use Of Biologic Disease-Modifying Antirheumatic Drugs In Patients With Rheumatoid Arthritis And Recently Diagnosed Colorectal, Lung, Or Prostate Cancer, Maria E Suarez-Almazor, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Suja S Rajan, Sharon H Giordano

Faculty, Staff and Student Publications

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer.

METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic …

A Phase I Dose Escalation Study Of The Lrp5 Antagonist Bi 905681 In Patients With Advanced And Metastatic Solid Tumors, D. R. Spigel, J. S. Wang, L. Pronk, B. Muskens, M. Teufel, Babar Bashir, H. Burris

Department of Medical Oncology Faculty Papers

BACKGROUND: The Wnt pathway is involved in proliferation and tissue homeostasis. Aberrant activation promotes cancer cell proliferation and survival. Inhibition of the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) coreceptors that regulate Wnt signaling could prevent cancer cell proliferation. BI 905681 is a novel LRP5 antagonist that has demonstrated potent in vivo antitumor activity.

PATIENTS AND METHODS: This was a phase I, dose escalation study (NCT04147247) evaluating BI 905681 in patients with advanced solid tumors over two dosing schedules (schedule A: every 3 weeks, 3-week cycles and schedule B: every 2 weeks, 4-week cycles). The primary endpoint was the maximum tolerated …