Digital Commons Network^™

Variability In Treatment Of Utis In Children With Genitourinary Anomalies In Children's Hospitals, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Sanyukta Desai, Pearl W Chang, Michael J Tchou, John M Morrison, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Cynthia Abou Zeid, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

Objective: In children with urinary tract anomalies, febrile urinary tract infections (UTIs) are associated with increased risks of sepsis, hospitalization, and kidney injury. However, the best treatment strategies are unknown. We aimed to describe antibiotic treatment practices and outcomes for UTIs in children with urinary tract anomalies and evaluate whether variability in UTI treatment exists between hospitals.

Methods: We conducted a multicenter retrospective cohort study of children seen in emergency departments (EDs) in 6 free-standing US children's hospitals from January 1, 2017, through December 31, 2018. We included children aged 0-17 years with an anatomic or functional urinary tract anomaly …

Comparing Rituximab And Cyclophosphamide In Induction Therapy For Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An Archive Registry Cohort Study, Samuel J Gagne, Vidya Sivaraman, Else S Bosman, Brett Klamer, Kimberly A Morishita, Adam Huber, Alvaro Orjuela, Barbara Eberhard, Charlotte Myrup, Dana Gerstbacher, Dirk Foell, Eslam Al-Abadi, Flora Mcerlane, Kathryn Cook, Linda Wagner-Weiner, Melissa Elder, L Nandini Moorthy, Paul Dancey, Rae Yeung, Raju Khubchandani, Samundeeswari Deepak, Sirirat Charuvanij, Stacey Tarvin, Susan Shenoi, Tamara Tanner, Kelly Brown, David A Cabral, Archive Investigators Network Within The Pedvas Initiative

Faculty, Staff and Students Publications

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index …

Complete, Sustained Resolution Of Pain With Pseudoarthrectomy For Bertolotti Syndrome: A Case Report, Emanuel Narcis Husu, Nirav Parekh, Jeremy I Simon

Faculty, Staff and Students Publications

Background: Bertolotti syndrome, characterized by lumbar pain due to a lumbosacral (LS) transitional vertebra, is a known but still controversial and overlooked pain generator despite an explosion of information on the condition in the last decade. Current management includes plain radiography, advanced imaging, minimally invasive interventions, and LS fusion.

Case report: We present a unique case of a middle-aged man with Castellvi IIa Bertolotti syndrome consisting of a unilateral enlarged, dysplastic L5 transverse process forming a pseudoarticulation (PA) with the ilium and normal anatomy contralaterally. He was diagnosed on a plain radiograph and following a diagnostic injection of the PA, …

Destructive And Protective Effects And Therapeutic Targets Of Il-36 Family Cytokines In Dry Eye Disease, Xin Chen, Na Lin, Haixia Liu, Jing Lin, Ning Gao, Zhao Liu, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

Purpose: To explore the destructive and protective effects and therapeutic targets of IL-36 cytokines in dry eye disease using a murine dry eye model.

Methods: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls. A topical challenge model was performed in normal mice with exogenous rmIL-36α, rhIL-38 and 2 % ectoine, or PBS vehicle. IL-36 cytokine expression was assessed by RT-qPCR and immunofluorescent (IF) staining. Corneal epithelial damage was evaluated by corneal smoothness score, Oregon Green Dextran (OGD) fluorescent staining, and tight junction barrier.

Results: All members of the IL-36 …

Warm-Ischemia And Cold Storage Induced Modulation Of Ferroptosis Observed In Human Hearts Donated After Circulatory Death And Brain Death, Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

We investigated ferroptosis, a type of programmed cell death mechanism, in human hearts donated after brain death (DBD) and those donated after circulatory death (DCD), focusing on warm ischemia time (WIT) and cold storage. A total of 24 hearts were procured, with six from the DBD group and 18 from the DCD group. The DCD group was divided into three subgroups, each containing six hearts, based on different WITs of 20, 40, and 60 min. All procured hearts were placed in cold storage for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h. …

Learning Tracheal Intubation With A Hyperangulated Videolaryngoscopy Blade: Sub-Analysis Of A Randomised Controlled Trial, Sascha Ott, Lukas M Müller-Wirtz, Sergio Bustamante, Julian Rössler, Nikolaos J Skubas, Karan Shah, Daniel I Sessler, Alparslan Turan, Kurt Ruetzler

Faculty, Staff and Student Publications

Introduction: The number of tracheal intubation attempts required to reach proficiency in videolaryngoscopy with hyperangulated blades is unknown. Understanding this training requirement might guide training for clinicians who perform laryngoscopy. We therefore performed a planned sub-analysis of a randomised controlled trial comparing tracheal intubation success with videolaryngoscopy vs. direct laryngoscopy to determine the number of tracheal intubations with a hyperangulated videolaryngoscope blade needed to provide an acceptable first-attempt success rate.

Methods: We included clinicians from a randomised controlled trial who were familiar with direct laryngoscopy and Macintosh-blade videolaryngoscopy but inexperienced with hyperangulated videolaryngoscopy. Cumulative sum statistics were used to generate …

"When The Bills Keep On Coming:" The Experiences Of Seafood Processors During The Covid-19 Pandemic, Shannon Guillot-Wright, Laura Porterfield, Brenda Wilson, Lacy Davis

Faculty, Staff and Student Publications

Essential workers were at increased risk during the COVID-19 pandemic, including seafood processors who are often rendered invisible within the public sphere. To examine the health and safety concerns of seafood processors, many who are low income or im/migrant workers on H-2B visas, our team conducted qualitative research with 44 participants. We found that in addition to high occupational health hazards that existed before the pandemic, COVID-19 increased workers' financial risks, which put them in more dangerous health and safety positions, since they needed to work through physical and mental health illness. These financial risks can be seen through the …

Genome-Wide Association Study Meta-Analysis Provides Insights Into The Etiology Of Heart Failure And Its Subtypes, Albert Henry, Xiaodong Mo, Chris Finan, Mark D Chaffin, Doug Speed, Hanane Issa, Spiros Denaxas, James S Ware, Sean L Zheng, Anders Malarstig, Jasmine Gratton, Isabelle Bond, Carolina Roselli, David Miller, Sandesh Chopade, A Floriaan Schmidt, Erik Abner, Lance Adams, Charlotte Andersson, Krishna G Aragam, Johan Ärnlöv, Geraldine Asselin, Anna Axelsson Raja, Joshua D Backman, Traci M Bartz, Kiran J Biddinger, Mary L Biggs, Heather L Bloom, Eric Boersma, Jeffrey Brandimarto, Michael R Brown, Søren Brunak, Mie Topholm Bruun, Leonard Buckbinder, Henning Bundgaard, David J Carey, Daniel I Chasman, Xing Chen, James P Cook, Tomasz Czuba, Simon De Denus, Abbas Dehghan, Graciela E Delgado, Alexander S Doney, Marcus Dörr, Joseph Dowsett, Samuel C Dudley, Gunnar Engström, Christian Erikstrup, Tõnu Esko, Eric H Farber-Eger, Stephan B Felix, Sarah Finer, Ian Ford, Mohsen Ghanbari, Sahar Ghasemi, Jonas Ghouse, Vilmantas Giedraitis, Franco Giulianini, John S Gottdiener, Stefan Gross, Daníel F Guðbjartsson, Hongsheng Gui, Rebecca Gutmann, Sara Hägg, Christopher M Haggerty, Åsa K Hedman, Anna Helgadottir, Harry Hemingway, Hans Hillege, Craig L Hyde, Bitten Aagaard Jensen, J Wouter Jukema, Isabella Kardys, Ravi Karra, Maryam Kavousi, Jorge R Kizer, Marcus E Kleber, Lars Køber, Andrea Koekemoer, Karoline Kuchenbaecker, Yi-Pin Lai, David Lanfear, Claudia Langenberg, Honghuang Lin, Lars Lind, Cecilia M Lindgren, Peter P Liu, Barry London, Brandon D Lowery, Jian'an Luan, Steven A Lubitz, Patrik Magnusson, Kenneth B Margulies, Nicholas A Marston, Hilary Martin, Winfried März, Olle Melander, Ify R Mordi, Michael P Morley, Andrew P Morris, Alanna C Morrison, Lori Morton, Michael W Nagle, Christopher P Nelson, Alexander Niessner, Teemu Niiranen, Raymond Noordam, Christoph Nowak, Michelle L O'Donoghue, Sisse Rye Ostrowski, Anjali T Owens, Colin N A Palmer, Guillaume Paré, Ole Birger Pedersen, Markus Perola, Marie Pigeyre, Bruce M Psaty, Kenneth M Rice, Paul M Ridker, Simon P R Romaine, Jerome I Rotter, Christian T Ruff, Marc S Sabatine, Neneh Sallah, Veikko Salomaa, Naveed Sattar, Alaa A Shalaby, Akshay Shekhar, Diane T Smelser, Nicholas L Smith, Erik Sørensen, Sundararajan Srinivasan, Kari Stefansson, Garðar Sveinbjörnsson, Per Svensson, Mari-Liis Tammesoo, Jean-Claude Tardif, Maris Teder-Laving, Alexander Teumer, Guðmundur Thorgeirsson, Unnur Thorsteinsdottir, Christian Torp-Pedersen, Vinicius Tragante, Stella Trompet, Andre G Uitterlinden, Henrik Ullum, Pim Van Der Harst, David Van Heel, Jessica Van Setten, Marion Van Vugt, Abirami Veluchamy, Monique Verschuuren, Niek Verweij, Christoffer Rasmus Vissing, Uwe Völker, Adriaan A Voors, Lars Wallentin, Yunzhang Wang, Peter E Weeke, Kerri L Wiggins, L Keoki Williams, Yifan Yang, Bing Yu, Faiez Zannad, Chaoqun Zheng, Folkert W Asselbergs, Thomas P Cappola, Marie-Pierre Dubé, Michael E Dunn, Chim C Lang, Nilesh J Samani, Svati Shah, Ramachandran S Vasan, J Gustav Smith, Hilma Holm, Sonia Shah, Patrick T Ellinor, Aroon D Hingorani, Quinn Wells, R Thomas Lumbers

Faculty, Staff and Student Publications

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. …

Environmental Health Disparities In Pediatric Cancer: A Report From The Fourth Symposium On Childhood Cancer Health Disparities, Thanh T Hoang, Zdenko Herceg, Don W Coulter, Adam De Smith, Manish Arora, William E Funk, David Haynes, Stephen H Linder, Leticia M Nogueira, Amy E Hughes, Lindsay A Williams, Jeremy M Schraw, Michael E Scheurer, Philip J Lupo

Faculty, Staff and Student Publications

The 4th Symposium on Childhood Cancer Health Disparities was held at Texas Children's Hospital in Houston, Texas, on September 26, 2023. The symposium registered 94 attendees from different backgrounds (e.g. clinicians, epidemiologists, exposure assessment scientists, geospatial experts) with an interest in environmental health disparities of pediatric cancer susceptibility and treatment outcomes. The focus of the symposium was to provide an overview of the role of environmental risk factors in studies of pediatric cancer, introduce novel exposure assessment tools that can be applied to the field, and highlight opportunities to study the impact of environmental health disparities in pediatric cancer susceptibility …

Epigenome-Wide Association Study Of Incident Type 2 Diabetes In Black And White Participants From The Atherosclerosis Risk In Communities Study, Sowmya Venkataraghavan, James S Pankow, Eric Boerwinkle, Myriam Fornage, Elizabeth Selvin, Debashree Ray

The Brown Foundation: Institute of Molecular Medicine

Aims/hypothesis: DNA methylation studies of incident type 2 diabetes in US populations are limited and to our knowledge none include individuals of African descent. We aimed to fill this gap by identifying methylation sites (CpG sites) and regions likely influencing the development of type 2 diabetes using data from Black and White individuals from the USA.

Methods: We prospectively followed 2091 Black and 1029 White individuals without type 2 diabetes from the Atherosclerosis Risk in Communities study over a median follow-up period of 17 years, and performed an epigenome-wide association analysis of blood-based methylation levels with incident type 2 diabetes …

Individualized Blood Pressure Regulation And Acute Kidney Injury In Older Patients Having Major Abdominal Surgery: A Pilot Randomized Trial, Zhaohua Pang, Shuang Liang, Nannan Zhou, Xiaoyan Zhu, Qulian Guo, Daniel I Sessler, Wangyuan Zou

Faculty, Staff and Student Publications

Background: Acute kidney injury (AKI) is a common postoperative complication, and hypotension may contribute. We therefore tested the primary hypothesis that individualized intraoperative blood pressure regulation reduces postoperative AKI in older surgical patients.

Methods: We enrolled patients ≥60 years old scheduled for elective major abdominal surgery with invasive arterial pressure monitoring. All had goal-directed fluid management based on stroke volume variation cardiac output, and administration of a starch. Participants were randomly assigned to: (1) individualized blood pressure management targeting a systolic blood pressure (SBP) within -20% and +10% if baseline SBP was ≥130 mmHg or diastolic blood pressure was ≥80 …

A Phase I Study Of The Pharmacokinetics, Pharmacodynamics, And Safety Of Liposomal Bupivacaine For Sciatic Nerve Block In The Popliteal Fossa For Bunionectomy, Daniel I Sessler, Xiaodong Bao, David Leiman, Jia Song, Jason Chittenden, Alexander Voelkner, Alparslan Turan, Jeffrey Gadsden

Faculty, Staff and Student Publications

This trial assessed the pharmacokinetics, pharmacodynamics, and safety of liposomal bupivacaine given via ultrasound-guided popliteal sciatic nerve block with or without immediate-release bupivacaine hydrochloride in adults having bunionectomies. Forty-five adults were enrolled into four sequential cohorts: (1) liposomal bupivacaine 266 mg with bupivacaine hydrochloride 50 mg; (2) liposomal bupivacaine 133 mg with bupivacaine hydrochloride 50 mg; (3) liposomal bupivacaine 266 mg; or (4) bupivacaine hydrochloride 100 mg. Outcomes included pharmacokinetics (e.g., bupivacaine maximum plasma concentration [C

Apoe And Alzheimer’S Disease And Related Dementias Risk Among 12,221 Hispanics/Latinos, Sandra Barral, Zikun Yang, Nicole Phillips, Robert C Barber, Adam M Brickman, Lawrence S Honig, Basilio Cieza, Dolly Reyes-Dumeyer, Richard Mayeux, Farid Rajabli, Michael L Cuccaro, Jeffery M Vance, Silvia Mejia Arango, Rafael Samper-Ternent, Alejandra Michaels Obregon, Rosa Montesinos, Marcio Soto-Añari, Juan Carlos Duran, Maria Cusicanqui, Ivonne Z Jimenez Velazquez, Victoria Marca, Maryenela Illanes-Manrique, Mario Cornejo-Olivas, Margaret Pericak-Vance, Rebeca Wong, Sid O'Bryant, Nilton Custodio, Giuseppe Tosto

Faculty, Staff and Student Publications

Background: Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos.

Methods: APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.

Results: APOE ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71-13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58-11.74), Mexican-Americans …

Development And Evaluation Of An Automated Multimodal Mobile Detection Of Oral Cancer Imaging System To Aid In Risk-Based Management Of Oral Mucosal Lesions, Ruchika Mitbander, David Brenes, Jackson B Coole, Alex Kortum, Imran S Vohra, Jennifer Carns, Richard A Schwarz, Ida Varghese, Safia Durab, Sean Anderson, Nancy E Bass, Ashlee D Clayton, Hawraa Badaoui, Loganayaki Anandasivam, Rachel A Giese, Ann M Gillenwater, Nadarajah Vigneswaran, Rebecca Richards-Kortum

Faculty, Staff and Student Publications

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage, although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders, which are associated with an increased risk of oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile detection of oral cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC …

Daratumumab/Lenalidomide/Dexamethasone In Transplant-Ineligible Newly Diagnosed Myeloma: Maia Long-Term Outcomes, Thierry Facon, Philippe Moreau, Katja Weisel, Hartmut Goldschmidt, Saad Z Usmani, Ajai Chari, Torben Plesner, Robert Z Orlowski, Nizar Bahlis, Supratik Basu, Cyrille Hulin, Hang Quach, Michael O'Dwyer, Aurore Perrot, Caroline Jacquet, Christopher P Venner, Noopur Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Gordon Cook, George Wang, Huiling Pei, Maria Krevvata, Robin Carson, Fredrik Borgsten, Shaji K Kumar

Faculty, Staff and Student Publications

In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months), including a subgroup analysis by patient age (< 70, ≥70 to < 75, ≥75, and ≥80 years). Overall, 737 transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint, PFS, was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45-0.67; P <  0.0001). Median OS was not reached in the D-Rd group versus 65.5 months in the Rd group (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003); estimated 60-month OS rates were 66.6% and 53.6%, respectively. D-Rd achieved higher rates of complete response or better (≥CR; 51.1% vs 30.1%), minimal residual disease (MRD) negativity (32.1% vs 11.1%), and sustained MRD negativity (≥18 months: 16.8% vs 3.3%) versus Rd (all P <  0.0001). D-Rd demonstrated clinically meaningful efficacy benefits across age groups. No new safety concerns were observed. Updated results (median follow-up, >5 years) continue to support frontline use of D-Rd in transplant-ineligible patients with NDMM.

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Micah J Marshall, Chelsea Caspell-Garcia, Michael C Brumm, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Frozen Section Mohs: A Hybrid Technique And One Plastic Surgeon's Experience With 1714 Consecutive Skin Cancer Removals, Michael L. Chang, Steven L. Chang, Fady Gerges, Matthew M. Delancy, Amanda C. Yang, Lawrence D. Chang

Student Papers, Posters & Projects

While US nonmelanoma skin cancer (NMSC) mortality rate has decreased in the past decade, its incidence is rising. Traditional surgical treatments include wide local excision, intraoperative frozen section analysis (IFSA), and Mohs micrographic surgery (MMS). IFSA and MMS are techniques that provide intraoperative analysis allowing the surgeon to confirm margins clear of malignancy and minimize tissue damage, especially in cosmetically sensitive subunits. MMS, with cure rates up to 99%-100%, is considered the gold standard but is limited geographically and financially because of specialized training. We report a hybrid surgical technique that effectively excises cutaneous malignancy but can be utilized by …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Symptom Documentation In Unstructured Palliative Care Notes Of Children And Adolescents With Cancer., Katherine Bernier Carney, Jacob Wilkes, Tumilara Aderibigbe, Kristin Stegenga, Holly Spraker-Perlman, Lauri A. Linder

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support.

OBJECTIVE: To explore the documentation of symptom prevalence and characteristics in unstructured clinical notes by pediatric palliative care clinicians caring for children and adolescents with cancer.

METHODS: We reviewed unstructured clinical notes documented by the pediatric palliative care team for 115 children and adolescents with cancer. Symptom-related data were abstracted and evaluated using content analysis based on the …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Pediatric Myeloid Neoplasms With Ubtf Tandem Duplications: Morphologic, Immunophenotypic, And Clinical Characterization, Mahsa Khanlari, Wei Wang, Yonghui Ni, Paul E Mead, Masayuki Umeda, Tami Westover, Jing Ma, Jeffrey E Rubnitz, Juan M Barajas, Stanley Pounds, Jeffery M Klco

Faculty, Staff and Student Publications

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts …

Receptor Tyrosine Kinase Fusion-Mediated Resistance To Egfr Tki In Egfr-Mutant Nsclc: A Multi-Center Analysis And Literature Review, Yang Xia, Kaiwen Wang, Jing Zhao, Zhaohui Arter, Yongchang Zhang, Jiaqi Zhou, Yuefei Lu, Liang Zeng, Robyn Du, Jennifer A Owens, Yasir Y Elamin, Carl M Gay, Ferdinandos Skoulidis, Anne S Tsao, Charles Lu, Tina Cascone, Don L Gibbons, Jianjun Zhang, Olivia Chen, Kevin K S Mok, Misako Nagasaka, Wen Li, John V Heymach, Sai-Hong Ignatius Ou, Molly Li, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Drug resistance remains a major clinical challenge in EGFR-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition.

Methods: We queried clinical databases from multiple institutions to identify patients who had RTK fusions detected on next-generation sequencing testing results from …

Efficacy And Safety Of Denileukin Diftitox-Cxdl, An Improved Purity Formulation Of Denileukin Diftitox, In Patients With Relapsed Or Refractory Cutaneous T-Cell Lymphoma, Francine M Foss, Youn H Kim, H Miles Prince, Oleg E Akilov, Christiane Querfeld, Lucia Seminario-Vidal, David C Fisher, Timothy M Kuzel, Costas K Yannakou, Larisa J Geskin, Tatyana Feldman, Lubomir Sokol, Pamela Blair Allen, Nam Hoang Dang, Fernando Cabanillas, Henry K Wong, Chean Eng Ooi, Dongyuan Xing, Nicholas Sauter, Preeti Singh, Myron Czuczman, Madeleine Duvic

Faculty, Staff and Student Publications

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Real-World Effectiveness Of Chemoimmunotherapy And Novel Therapies For Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma, Loretta J Nastoupil, Clark R Andersen, Amy Ayers, Yucai Wang, Thomas M Habermann, Dai Chihara, Brad S Kahl, Brian K Link, Jean L Koff, Jonathon B Cohen, Peter Martin, Izidore S Lossos, Michele Stanchina, Sara Haddadi, Carla Casulo, Sabarish Ayyappan, Ruitao Lin, Ziyi Li, Melissa A Larson, Matthew J Maurer, Lynn Huynh, Chi Gao, Ramya Ramasubramanian, Mei Sheng Duh, Alex Mutebi, Tongsheng Wang, Monika Jun, Anthony Wang, Rajesh Kamalakar, Anupama Kalsekar, James R Cerhan, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L+).

Materials and methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Manual Therapy For Fibrosis-Related Late Effect Dysphagia In Head And Neck Cancer Survivors: The Mantle Nonrandomized Clinical Trial, Holly Mcmillan, Carla L Warneke, Sheila Buoy, Christine Porsche, Kiara Savage, Stephen Y Lai, Clifton D Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

Importance: Late radiation-associated dysphagia (RAD) after head and neck cancer (HNC) treatment is challenging and commonly treatment refractory, with fibrosis stiffening connective tissues and compressing peripheral nerve tracts, contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT), while common for cancer-related pain and other indications, remains largely unstudied for fibrosis-related late RAD.

Objective: To determine the feasibility and safety of MT, estimate effect size and durability of MT for associated improvements in cervical range of motion (CROM), and examine functional outcomes after MT in survivors of HNC with fibrosis-related late RAD.

Design, setting, and participants: This …