Digital Commons Network^™

Opioid Prescribing Patterns And The Effect Of Chronic Kidney Disease In Pediatric Urology Population: A Retrospective Cohort Analysis., Kristen M. Meier, Darren Ha, Carter Sevick, Eliza D. Blanchette, Megan A. Brockel, Vijaya M. Vemulakonda, Kyle O. Rove

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Significant efforts have been undertaken to decrease opioid prescribing, but there is little research into patient-specific factors presenting as barriers in the pediatric surgical population. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be a safe and effective alternative to opioids for pain control, however, concerns about their impact on renal function limit their use in patients with chronic kidney disease (CKD). Data is limited on the interplay of CKD on opioid prescribing.

OBJECTIVE: We hypothesized that opioid reduction efforts were successful, but patients with CKD would be more likely to receive an opioid prescription than those without CKD. …

Methylated Arginine Metabolites As Biomarkers For Clinical Status And Response To Type 5 Phosphodiesterase Inhibition In Patients With Fontan Circulation., Ari Cedars, Cedric Manlhiot, Bhargava Kumar Chinni, Alexander R. Opotowsky, Kristian Becker, Anne Le, Pratik Khare, Jong Love Ko, Allen Everett, Shelby Kutty, Mark W. Russell, R Mark Payne, Andrew M. Atz, Brian W. Mccrindle, Rahul H. Rathod, Matthew Lewis, David Goldberg, Kevin Hill, Michelle Ploutz, Jon Detterich, Kurt Schumacher, Robert Whitehill, Daniel J. Penny, Mark Cartoski, Rachel Sullivan, Matthew Files, Ruchira Garg, Jonathan B. Wagner, Roni Jacobsen, Todd Nowlen, Scott Fletcher, Jennifer Conway, Gi Boem Kim, Fred Wu, Victor Zak

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is significant interest in NO pathway modulators, specifically type 5 phosphodiesterase inhibitors (PDE5is), to treat patients with a Fontan circulation. Trials, however, have had mixed results. The relationship between the NO pathway and clinical status in patients with Fontan circulation is a significant knowledge gap.

METHODS AND RESULTS: We performed targeted metabolomic analysis using liquid chromatography coupled to mass spectrometry to quantify plasma NO pathway metabolite concentrations from 2 well-characterized populations of patients with Fontan circulation: the Boston Adult Congenital Heart Disease Biobank and Fontan Udenafil Exercise Longitudinal studies. We investigated associations between NO metabolite concentrations and clinical …

Methylation Patterns Of The Nasal Epigenome Of Hospitalized Sars-Cov-2 Positive Patients Reveal Insights Into Molecular Mechanisms Of Covid-19., Benjamin L. Spector, Boryana Koseva, Rebecca Mclennan, Dithi Banerjee, Kamani Lankachandra, Todd Bradley, Rangaraj Selvarangan, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts to identify factors responsible for differential COVID-19 severity include but are not limited to genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links to disease severity. However, whole epigenome analysis of the respiratory tract, the target tissue of SARS-CoV-2, remains ill-defined.

RESULTS: We interrogated the nasal methylome to identify pathophysiologic drivers in COVID-19 severity through whole genome bisulfite sequencing (WGBS) of nasal samples from COVID-19 positive individuals …

Genetic Testing Utilization In The U.S. Registry For Childhood Interstitial And Diffuse Lung Diseases., Laura A. Voss, Rebekah J. Nevel, Jennifer A. Wambach, Lawrence M. Nogee, Robin R. Deterding, Alicia M. Casey, Michael G. O'Connor, Daniel I. Craven, Jane B. Taylor, Gail H. Deutsch, Jade B. Tam-Williams, Lea C. Steffes, Steven K. Brennan, Maria T. Santiago, Sara C. Sadreameli, Andrea F. Heras, Michael R. Powers, Antonia P. Popova, Manvi Bansal, Aaron Hamvas, William A. Gower, Fernando Urrego, Lisa R. Young, Child Registry Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Childhood interstitial and diffuse lung diseases (chILD) comprise a diverse group of rare disorders. Identifying the underlying cause is crucial for treatment, prognosis, and estimating recurrence risk. The objective of this study was to assess the utilization of genetic testing for subjects enrolled in the United States National Registry for ChILD, a multicenter observational study.

METHODS: Genetic data from participating sites were reviewed and analyzed in relationship to clinical characteristics.

RESULTS: Of 609 children enrolled from 22 centers, genetic testing was performed for 55.5% (n = 338). Genetic testing results were positive (diagnostic) for 22.8% (n = 77), negative …

Factors Associated With Shock At Presentation In Kawasaki Disease Versus Multisystem Inflammatory Syndrome In Children Associated With Covid-19., Supriya S. Jain, Ashraf S. Harahsheh, Simon Lee, Geetha Raghuveer, Nagib Dahdah, Michael Khoury, Michael A. Portman, Melissa Wehrmann, Arash A. Sabati, Marianna Fabi, Deepika Thacker, Nilanjana Misra, Mark D. Hicar, Nadine F. Choueiter, Matthew D. Elias, Audrey Dionne, William B. Orr, Jacqueline R. Szmuszkovicz, Seda Selamet Tierney, Luis Martin Garrido-Garcia, Frederic Dallaire, Balasubramanian Sundaram, Deepa Prasad, Tyler H. Harris, Elizabeth Braunlin, Elisa Fernandez Cooke, Cedric Manlhiot, Pedrom Farid, Brian W. Mccrindle, International Kawasaki Disease Registry

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: While clinical overlap between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) has been evident, information regarding those presenting with shock has been limited. We sought to determine associations with shock within and between diagnosis groups.

METHODS: The International KD Registry enrolled contemporaneous patients with either KD or MIS-C from 39 sites in 7 countries from January 1, 2020, to January 1, 2023. Demographics, clinical features and presentation, management, laboratory values, and outcomes were compared between the diagnosis and shock groups.

RESULTS: Shock at presentation was noted for 19 of 672 KD patients (2.8%) and 653 of …

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …

Hbv Transmission Knowledge Among Korean-American Chronic Hepatitis B Patients In The United States, Giyoung Lee, Hee-Soon Juon, Eunji Kim, Katherine C Smith, Hie-Won Hann, Mimi Chang, Ann C. Klassen

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B (CHB) is a condition that disproportionately affects Asian Americans in the United States. Knowledge of transmission is crucial for CHB patients to practice prevention methods to limit the spread of the hepatitis B virus (HBV), but also live their lives free from unwarranted fears or restrictions. Among Asian CHB patients, several misperceptions about HBV transmission have been identified. This analysis aims to assess the current state of HBV knowledge among a cohort of Korean-American CHB patients. This mixed-methods study includes 363 respondents who completed a survey in either Korean (N = 298) or English (N = 65) …

Frequency Of Variants In Mendelian Alzheimer’S Disease Genes Within The Alzheimer’S Disease Sequencing Project, Dongyu Wang, Alexandra Scalici, Yanbing Wang, Honghuang Lin, Achilleas Pitsillides, Nancy Heard-Costa, Carlos Cruchaga, Ellen Ziegemeier, Joshua C Bis, Myriam Fornage, Eric Boerwinkle, Philip L De Jager, Ellen Wijsman, Josée Dupuis, Alan E Renton, Sudha Seshadri, Alison M Goate, Alzheimer's Disease Neuroimaging Initiative (Adni), The Alzheimer's Disease Sequencing Project, Anita L Destefano, Gina M Peloso

Faculty, Staff and Student Publications

Background:

Prior studies examined variants within presenilin-2 (PSEN2), presenilin-1 (PSEN1), and amyloid precursor protein (APP) genes. However, previously-reported clinically-relevant variants and other predicted damaging missense (DM) variants have not been characterized in a newer release of the Alzheimer’s Disease Sequencing Project (ADSP).

Objective:

To characterize previously-reported clinically-relevant variants and DM variants in PSEN2, PSEN1, APP within the participants from the ADSP.

Methods:

We identified rare variants (MAF< 1%) in PSEN2, PSEN1, and APP in 14,641 individuals with whole genome sequencing and 16,849 individuals with whole exome sequencing available (Ntotal = 31,490). We additionally curated …

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 …

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Rachel A Keuls, Scott A Ochsner, Mary B O'Neill, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

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 …

Diet And Survival After A Diagnosis Of Ovarian Cancer: A Pooled Analysis From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Renhua Na, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice Lee, Valerie Mcguire, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Joellen M Schildkraut, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm C Pike, Celeste Leigh Pearce, Penelope M Webb, Multidisciplinary Ovarian Cancer Outcomes Group And Ovarian Cancer Association Consortium

Faculty, Staff and Student Publications

Background: Prognosis after a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent.

Objectives: This study aims to pool data from studies conducted around the world to evaluate the relationships among dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer.

Methods: This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their prediagnosis diet. Adjusted hazard ratios (aHRs) …

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 …

In Vivo Antibody Labeling Route And Fluorophore Dictate Labeling Efficiency, Sensitivity, And Longevity, Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel

Faculty, Staff and Student Publications

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while …

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 …