Digital Commons Network^™

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

Targeting Steroid Receptor Coactivators For The Treatment Of Benign Female Reproductive Disorders, Yuri Park, Jaeyeong Jeong, Eunsu Kim, Nuri Sung, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of nuclear receptor signaling and play essential roles in female reproductive physiology. By integrating steroid hormone signaling with growth factors and metabolic pathways, SRC-1, SRC-2, and SRC-3 coordinate key processes such as decidualization, placental development, and ovarian function. Dysregulation of SRCs is strongly linked to the progression of benign gynecologic disorders, including polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids, largely through enhancing hormonal hypersensitivity and disrupting nuclear receptor-mediated cellular pathways. Emerging evidence further implicates specific SRC isoforms in disease pathogenesis, underscoring their potential as biomarkers and therapeutic targets. To inhibit SRC activity, …

Rising Burden Of Heart Failure: An Urgent Global Public Health Concern, Biykem Bozkurt

Faculty, Staff and Students Publications

No abstract provided.

Basal Cell Carcinoma Risk Prediction In Survivors Of Childhood Cancer, Cindy Im, Christina Boull, Zhe Lu, Kenneth Liao, Hasibul Hasan, Linwan Xu, Yadav Sapkota, Rebecca M Howell, Michael A Arnold, Miriam R Conces, Ashley J Housten, Judith Gebauer, Thorsten Langer, Jop C Teepen, Leontien C M Kremer, Louis S Constine, Yutaka Yasui, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Yan Yuan, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Survivors of childhood cancer face excess risk of developing basal cell carcinoma. Age-specific basal cell carcinoma risk prediction models for survivors may support targeted screening recommendations.

Methods: We developed models predicting basal cell carcinoma risk by ages 40 and 50 years featuring detailed cancer treatment predictors, utilizing statistical and machine-learning algorithms and data from 23 166 five-year survivors in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study. Selected models were externally validated in 5314 survivors in the St Jude Lifetime Cohort. Model discrimination and precision were evaluated using the area under the receiver operating characteristic curve (AUROC) …

Data-Driven Abdominal Phenotypes Of Type 2 Diabetes In Lean, Overweight, And Obese Cohorts From Computed Tomography, Lucas W Remedios, Chloe Cho, Trent M Schwartz, Dingjie Su, Gaurav Rudravaram, Chenyu Gao, Aravind R Krishnan, Adam M Saunders, Michael E Kim, Shunxing Bao, Alvin C Powers, Bennett A Landman, John Virostko

Faculty, Staff and Student Publications

Purpose: Although elevated body mass index (BMI) is a well-known risk factor for type 2 diabetes, the disease's presence in some lean adults and absence in others with obesity suggests that more detailed measurements of body composition may uncover abdominal phenotypes of type 2 diabetes. With artificial intelligence (AI) and computed tomography (CT), we can now leverage robust image segmentation to extract detailed measurements of size, shape, and tissue composition from abdominal organs, abdominal muscle, and abdominal fat depots in 3D clinical imaging at scale. This creates an opportunity to empirically define body composition signatures linked to type 2 diabetes …

Acute Kidney Injury Is Associated With Elevated Urinary Endotrophin, Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir M Parikh

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. Although serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI, nor has ETP been evaluated in a pediatric population. Urine samples were collected from a tertiary children's hospital. Medical records were reviewed, and patients who met criteria were sorted into three categories:

Microbial Signals In Primary And Metastatic Brain Tumors, Golnaz Morad, Ashish V Damania, Brenda Melendez, Bharat B Singh, Fabiana J Veguilla, Rebecca A Soto, Yasmine M Hoballah, Pranoti V Sahasrabhojane, Matthew C Wong, Mona M Ahmed, Rene N Rico, Kaitlyn N Lewis, Khalida Wani, Diana D Shamsutdinova, Rossana N Lazcano Segura, Davis R Ingram, Eric A Goethe, Abderrahman Day, Ivonne I Flores, Lauren K Mcdaniel, Manoj Chelvanambi, Sarah B Johnson, Florentia Dimitriou, Pravesh Gupta, Shivangi Oberai, M Anna Zal, Phoebe Doss, Mohamed A Jamal, Eiko Hayase, Chetna Wathoo, Lisa M Norberg, Stephanie L Jenkins, Sara Nass, Joy Gumin, Lihong Long, Jing Yang, Gina R Bradley, Mahesh Prasad Bekal, Antonio G Dono, Pavel S Pichardo-Rojas, Samuel W Andrewes, Leomar Y Ballester, Jillian S Losh, Jiyong Liang, Longfei Huo, Douglas C Nielsen, Brittany C Parker Kerrigan, Priscilla K Brastianos, Natalie Wall Fowlkes, Chia-Chi Chang, Robert R Jenq, Candelaria Gomez-Manzano, Jason T Huse, Michael A Davies, Alexander J Lazar, Krishna P Bhat, Nitin Tandon, Yoshua Esquenazi, Christine B Peterson, Vinay K Puduvalli, Frederick F Lang, Christopher D Johnston, Susan Bullman, Nadim J Ajami, Sherise D Ferguson, Jennifer A Wargo

Faculty, Staff and Student Publications

Gliomas and brain metastases are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. Although our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intratumoral microbiota emphasize the importance of rigorous, orthogonal validation. This prospective, multi-institutional study included a total of 243 samples from 221 patients, comprising 168 glioma and brain metastases samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescence in situ hybridization, immunohistochemistry and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and brain metastases …

Diffuse Cutaneous Alk-Immunoreactive Histiocytosis With Mef2c::Flt3 Fusion, Sanjana Likki, Kevin Lee, Fiorinda Muhaj, Wei Wang, Pei Lin, Woo Cheal Cho, Doina Ivan, Carlos A Torres-Cabala, Luis Fayad, Jonathan L Curry

Faculty, Staff and Student Publications

No abstract provided.

Perceived Prejudice Or Discrimination In Medical Care Among Us Adults, Inimfon Jackson, Robert Yu, Joël Fokom Domgue, Sanjay Shete

Faculty, Staff and Student Publications

No abstract provided.

An Analysis Of How Autistic Burnout Relates To Posttraumatic Stress In Autistic Adults, Antonio F Pagán, Madeline J Bruce, Juliana L Vanderburg, Grace Sattem, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

This study investigated the relationship between autistic burnout and posttraumatic stress symptoms (PTSS) in trauma-exposed autistic adults without intellectual disability (n = 91). Cross-sectional relationships between autistic burnout (measured by the ABSI), PTSS (PCL-5), depression (PHQ-9), and anxiety (GAD-7) were assessed using Pearson correlations. To examine the distinctiveness of autistic burnout from posttraumatic stress, an exploratory factor analysis was conducted on ABSI and PCL-5 data. A strong correlation was found between autistic burnout and PTSS (r = .70, p < .001), an exploratory factor analysis suggested shared underlying factors. These findings indicate a close relationship between autistic burnout and …

Analysis Of Content Related To Retrograde Cricopharyngeal Dysfunction On Tiktok: Opportunities For Patient Education And Advocacy, Aidan Wright, Nathaniel Hunter, Vivian Jin, Andrew Tritter

Faculty, Staff and Student Publications

Objective: TikTok has experienced exponential growth as a social media platform, with over 1 billion active users. Concurrently, retrograde cricopharyngeal dysfunction (RCPD) has seen a surge in awareness among patients and on social media. Our objective was to characterize the most popular RCPD-related content on TikTok.

Methods: The top 50 videos associated with the following hashtags were analyzed: "RCPD," "noburp," "retrograde cricopharyngeal dysfunction," and "noburpsyndrome." Recorded metrics included views, likes, and comments, along with information regarding the creator's identity, gender, geographical location, and the video's purpose.

Results: One hundred and three videos were included in the final analysis, with a …

Delayed Presentation Of A Retained Colonic Segment In A Child With Intestinal Failure On Teduglutide, Rachel C Bordelon, Sarah J Varalla, Varaha S Tammisetti, Mohamed M Shahin, Amanda Tchakarov, Essam Imseis, Allison L Speer

Faculty, Staff and Student Publications

Teduglutide is a glucagon-like peptide 2 (GLP-2) analogue that was approved by the United States Food and Drug Administration for the treatment of pediatric (>1 year) intestinal failure due to short bowel syndrome in 2019. GLP-2 analogues promote rapid intestinal adaptation, increasing the absorptive capacity of residual intestine after surgical resection to aid the achievement of enteral autonomy or reduce parenteral nutrition requirements. Despite relatively few reported side effects, there is a theoretical risk of proliferative complications. Here we present an intriguing case of a pediatric patient found to have a decade-long retained, discontinuous segment of colon from a …

The Mythology Of Polymyositis, Suur Biliciler, Tahseen Mozaffar

Faculty, Staff and Student Publications

Polymyositis (PM) has been in the diagnostic armamentarium in medicine since the mid-nineteenth century. Medicine training puts a heavy emphasis on this diagnosis, and anyone with proximal muscle weakness with elevated serum creatinine kinase is assumed to be PM and a number of patients were rendered this diagnosis without additional testing. This article addresses the historical aspects of the diagnosis of PM and its evolution. We review this literature that addresses the rarity of this diagnosis and rightly puts in perspective in terms of its occurrence in relation to other inflammatory myositides.

Innovations In Thrombectomy Training: A Systematic Review And Expert Recommendations From The Society Of Vascular And Interventional Neurology-Mission Thrombectomy Initiative, Fawaz Al-Mufti, Mohamed Elfil, Abdallah Abbas, Haneen Sabet, Hazem S Ghaith, Ariel Sacknovitz, Ankita Jain, Victor Urrutia, Nabeel Herial, Gabor Toth, Mohamad El-Ghanem, Krishna Amuluru, Viktor C Szeder, Jonathan Crowe, Karol Budohoski, Zurab Nadareishvili, Kaustubh Limaye, Fazeel Siddiqui, Boris Pabon, Ossama Yassin Mansour, Atilla Ozcan Ozdemir, Houman Khosravani, Hamza Shaikh, Nishita Singh, Hesham Masoud, Sushanth R Aroor, Shashvat Desai, Santiago Ortega-Gutierrez, Fredrick Echols, Thanh N Nguyen, Pankajavalli Ramakrishnan, Priyank Khandelwal, Dileep R Yavagal, Kaiz Asif

Faculty, Staff and Student Publications

Background: Mechanical thrombectomy is a critical intervention for patients with acute ischemic stroke with large vessel occlusion. However, significant barriers remain in its widespread implementation, particularly in low- to middle-income countries, including a shortage of trained physicians and limited access to advanced medical technologies. This systematic review and meta-analysis aimed to comprehensively evaluate current mechanical thrombectomy training methodologies and assess their effectiveness in improving procedural skills among neurointerventional teams.

Methods: We conducted a systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, searching PubMed, Scopus, and Web of Science. Eight studies were included, with 3 studies eligible …

Multiomics Reveal Plasma Constituents Associated With Thrombosis Among Trauma Patients Who Do Not Respond To Enoxaparin, Ian S Lacroix, Monika Dzieciatkowska, Francesca Cendali, Kelly Sanders, Charles E Wade, Bryan A Cotton, Mitchell J Cohen, Angelo D'Alessandro, Kirk Hansen, Jessica C Cardenas

Faculty, Staff and Student Publications

Venous thromboembolism (VTE) is among the most common complications affecting patients with severe injuries. Although enoxaparin resistance is common, predicting which patients among this subgroup will develop VTE remains a clinical challenge. The goal of this study was to use multiomics to identify plasma constituents associated with VTE development among trauma patients exhibiting poor responses to enoxaparin. We conducted a secondary analysis of trauma patients at high risk of VTE based on injury characteristics. Plasma was collected daily for the first 8 hospital days. Patients who never responded to enoxaparin were defined as not achieving an anti-factor Xa (FXa) level …

Sweet Syndrome Successfully Treated With Upadacitinib, Valeria Duque-Clavijo, Hung Q Doan, John A Das, Stephen K Tyring

Faculty, Staff and Student Publications

No abstract provided.

Depression Polygenicity And Disease Activity And Disability Worsening In Multiple Sclerosis, Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla Mckay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec

Faculty, Staff and Student Publications

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and …

Characteristics And Outcomes Associated With Multiple Triage Visits Among Patients With Suspected Preterm Labor Or Preterm Premature Rupture Of Membranes, Jameaka L Hamilton, Paula L Mcgee, George R Saade, Rebecca G Clifton, Michael W Varner, Alan T N Tita, Monica Longo, Edward F Bell, Barbara J Stoll, Donna Allard, Ashley Salazar, John M Thorp, Uma M Reddy, Maged M Costantine, Emily S Miller, Dwight J Rouse, Hyagriv N Simhan, Jennifer L Bailit, Lorraine Dugoff, George A Macones, Baha M Sibai

Faculty, Staff and Student Publications

Background: Hospital-based obstetrical triage units frequently serve as an extension to outpatient care. Evaluation of the burden of preterm birth (PTB) typically focuses on the delivery and neonatal periods, while antepartum health care utilization related to risk of PTB is seldom reported.

Objective: To identify the characteristics and outcomes associated with multiple triage visits among patients with suspected preterm labor (PTL) or preterm premature rupture of membranes (pPROM).

Study design: Secondary analysis of a retrospective cohort study of all triage visits from 20 0/7 through 34 6/7 weeks gestation on randomly selected dates in 2019 at 34 hospitals across the …

Transforming Preterm Care: The Power Of Small Baby Guidelines In Enhancing Outcomes, Leeann Pavlek, Debra Armbruster, Cecilie Halling, Kaitlyn Hipp, Maria Jebbia, Susan Lopata, Matthew Rysavy, Rebecca Saliga, Sheria Wilson, Claire Beaullieu

Faculty, Staff and Student Publications

As survival rates of extremely preterm (EPT) infants continue to improve, focus has shifted to reduce morbidity and complications in these vulnerable patients. Management of EPT infants presents significant clinical, logistical, and sometimes ethical challenges. Outcomes across centers are highly variable and strongly influenced by the care provided in the early neonatal period. Standardized guidelines, based on published literature and center-specific experiences, play an important role in improving outcomes for EPT infants. Multidisciplinary guidelines provide a framework for clinical management and support a consistent care approach. Guidelines can improve care throughout the entire neonatal intensive care unit (NICU) course, beginning …

The Distal Acromial Tip Fusion: A Novel Procedure To Mitigate Acromial Stress Fractures In High-Risk Patients Undergoing Reverse Shoulder Arthroplasty, Trevor G Simcox, Jeffrey Dela Cruz, Gennaro Dellicarpini, Wojciech K Dzieza, Itaru Kawashima, Kevin W Farmer, Jonathan O Wright, Thomas W Wright, Joseph J King

Faculty, Staff and Student Publications

Acromion and scapular spine fractures (ASFs) pose significant challenges in the management of patients undergoing reverse total shoulder arthroplasty and there is a pressing need for effective preventive measures. Current predictive factors for ASF include female sex, osteoporosis, older age, and anatomical considerations such as glenoid medialization and acromial morphology. However, surgical options to mitigate ASF risk are limited. In this study, we propose a novel technique: incorporation of distal acromial tip fusion (DATF) during primary reverse total shoulder arthroplasty procedures. DATF involves bony fusion between the undersurface of the anterolateral acromion and the region where the superior rim of …

Prevalence Of Obesity With Confirmed Excess Adiposity In Us Children And Adolescents, Alexandra B Palmer, Kyung Hyun Lee, Rashedeh Roshani, Elizabeth Frankel, Miryoung Lee, Mohammad Y Anwar, Heather M Highland, Kristin L Young, Mariaelisa Graff, Joseph B Mccormick, Susan P Fisher-Hoch, Joyce P Samuel, Jennifer E Below, Kari E North, Penny Gordon-Larsen

Faculty, Staff and Student Publications

No abstract provided.

Functional Ability Profiles In Beta-Propeller Protein-Associated Neurodegeneration (Bpan), Francesco Gavazzi, Samuel R Pierce, Vanessa Smith, Eric Yang, Julie Skorup, Kristy Pucci, Emma Kotes, Allan M Glanzman, Stacy V Cusack, Todd Levy, Holly Dubbs, Emma Wiener, Sarah Woidill, Joseph Vithayathil, Abbas Jawad, Nivedita Thakur, Laura A Adang

Faculty, Staff and Student Publications

Background: Beta-propeller Protein-Associated Neurodegeneration (BPAN) is a rare neurodevelopmental degenerative disorder caused by pathogenic variants in WDR45 leading to brain iron accumulation. Its rarity and complex clinical course make it difficult to select appropriate clinical outcome assessments (COAs). This study evaluates established COAs for feasibility and effectiveness in capturing BPAN's functional ability profiles exploring cognitive, motor, and behavioral features.

Methods: We performed an observational study. Children were recruited as part of the Myelin Disorders Biorepository Project at the Children's Hospital of Philadelphia. We administered the Gross Motor Function Measure-88 (GMFM-88), the Leiter International Performance Scale (Leiter-3), and the Vineland Adaptive …

Priming With Transcutaneous Spinal Direct Current Stimulation Followed By Robotic Exoskeleton Gait Training In Individuals With Spinal Cord Injury: A Case Series, Marcie Kern, Catherine Velasquez-Ignacio, Taimoor Afzal, Shih-Chiao Tseng, Gerard E Francisco, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

Objectives: To investigate the safety and feasibility of repeated transcutaneous spinal direct current stimulation (tsDCS) as priming strategy during exoskeleton-assisted locomotor training in individuals with SCI and evaluate potential neurophysiologic and functional gait changes.

Study design: Case series experimental design.

Setting: Research laboratory at a post-acute rehabilitation hospital.

Participants: Four participants with chronic incomplete SCI.

Interventions: Four participants with chronic incomplete SCI received three weeks of training consisting of two types of interventions after baseline (A): 20-minute tsDCS (anode or cathode) applied over the spinous processes of T10 followed by 20-minute exoskeleton-assisted locomotor training (B, B1, B2) and 20-minute exoskeleton-assisted …

From Reflex Reaction To Rational Action-Personalizing Surgical Antibiotic Prophylaxis, Renee W Green, William D Rieger, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Missing The Target: A Scoping Review Of The Use Of Percent Weight Loss For Obesity Management, Diana Sherifali, Megan Racey, Donna Fitzpatrick-Lewis, Michelle Greenway, Sanjeev Sockalingam, Jun Wada, Soo Huat Teoh, Ian Patton, David Macklin, Elizabeth F C Van Rossum, Luca Busetto, Deborah Bade Horn, J D Patricia Nece, Morgan Emile Gabriel Salmon Leguede, Nicole Pearce, Carel Le Roux, Jamy Ard, Angela S Alberga, Lee Kaplan, Arya M Sharma, Sean Wharton

Faculty, Staff and Student Publications

Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.

Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted …

Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis In Ectopic Cushing Syndrome, Raghavendra Pandit, Chethan Yamichannaiah, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Tushar Bandgar

Faculty, Staff and Student Publications

A woman in her fourth decade of life with metastatic ectopic Cushing syndrome due to a thymic neuroendocrine tumor developed an acute adrenocorticotropin (ACTH)-mediated hypercortisolemic crisis 5 days after initiating lutetium-177-labeled DOTA-[Tyr3]-octreotate (177Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). She presented with hypertension, rapid weight gain (8 kg in a week), psychosis, and biochemical evidence of severe hypercortisolism: serum cortisol: 141 µg/dL (SI: 3889.7 nmol/L) (reference range, 5-25 µg/dL [SI: 137.9-689.7 nmol/L]), plasma ACTH greater than 2000 pg/mL (SI >440.4 pmol/L) (reference range, 10-60 pg/mL [SI: 2.2-13.3 pmol/L]), potassium: 3.4 mEq/L (reference range, 3.5-5.0 mEq/L). Low-dose intravenous etomidate (0.02 mg/kg/h) was …

Continuous Androgen Deprivation Therapy With Or Without Metastasis-Directed Therapy For Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized Extend Trial, Alexander D Sherry, Bilal A Siddiqui, Cara Haymaker, Bryan M Fellman, Marina N Medina-Rosales, Tharakeswara K Bathala, Shuqi Wang, Suyu Liu, Aaron Seo, Kieko Hara, Hsinyi Lu, Patricia Troncoso, Stephen G Chun, Chul S Ha, Lauren L Mayo, Henry Mok, Ryan J Park, Brian F Chapin, Ryan M Phillips, Matthew P Deek, Craig A Kovitz, Ana Aparicio, Amado J Zurita, Patrick G Pilie, Lorenzo Cohen, Seungtaek L Choi, Alexandre Reuben, Phuoc T Tran, Paul G Corn, Sumit K Subudhi, Chad Tang

Faculty, Staff and Student Publications

Background and objective: Oligometastatic prostate cancer (omPC) is characterized by limited metastases. We hypothesized that metastasis-directed therapy (MDT) to all sites of omPC combined with androgen deprivation therapy (ADT) would improve clinical outcomes.

Methods: In the multicenter phase 2 EXTEND trial, patients with omPC were randomized 1:1 to ADT versus MDT + ADT in two independently powered and randomized baskets, one using intermittent ADT and one using continuous ADT. The primary endpoint was progression-free survival (PFS). The secondary endpoints included radiologic PFS (rPFS) and castration resistance-free survival (CRFS). Here, the primary results of the continuous ADT basket, the combined analysis …

Rank-Based Learning: A Novel High-Throughput Algorithm Resilient To Missing Data And Effective For Datasets With Small Sample Size, Lulu Song, Hamid Khoshfekr Rudsari, Johannes F Fahrmann, Jody Vykoukal, Sam Hanash, James P Long, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

High-throughput omics data present challenges for binary classification due to platform variability, batch effects, missing values, and high dimensionality. This study presents a novel Rank-Based Learning (RBL) method that leverages relative feature rankings to improve robustness and generalizability. We evaluated RBL against established methods like Logistic Regression (LR) and Random Forest (RF) using simulated data and two real-world plasma proteomics datasets: early-stage small cell lung cancer (SCLC) and duodenopancreatic neuroendocrine tumors (dpNET) in patients with Multiple Endocrine Neoplasia type 1 (MEN1). In simulation experiments, RBL outperformed LR under conditions involving batch effects, missing data, and varying numbers of true differential …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …

Phase 2 Study Of Monotherapy With Pembrolizumab For Advanced Adrenocortical Carcinoma, Brenda Chahla, Bettzy Stephen, Juhee Song, Vania Balderrama-Brondani, Feyza Yaylaci, Matthew T Campbell, Aung Naing, Mouhammed Amir Habra

Faculty, Staff and Student Publications

Introduction: Adrenocortical carcinoma (ACC) is a rare cancer with suboptimal response to chemotherapy. The role of immunotherapy in ACC management is evolving.

Methods: An investigator-initiated, open-label, phase 2 clinical trial was performed to ascertain the activity and safety of monotherapy with pembrolizumab (a humanized monoclonal anti-programmed cell death protein 1 antibody) in patients with advanced ACC. This study was part of a basket clinical trial (ClinicalTrials.gov ID: NCT02721732). Study participants were enrolled from August 15, 2016, until December 7, 2020. Pembrolizumab (200 mg) was administered intravenously every 3 weeks. All other lines of therapy, including mitotane, were stopped before …