Medical Specialties Commons^™

Clinical Profile Of Patients With Monocular Elevation Deficiency Undergoing Strabismus Surgery, Mohamad Reza Akbari, Babak Masoomian, Elham Azizi, Mohammed Omer Mahmood, Arash Mirmohammadsadeghi, Ali Majdi, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To provide a comprehensive evaluation of the visual, refractive, and strabismic characteristics of patients with monocular elevation deficiency (MED) undergoing strabismus surgery.

METHODS: The medical records of patients at a single institution who were diagnosed with and underwent surgery for MED were reviewed retrospectively. Visual acuity, refractive error, angle of deviation, abnormal head posture (AHP), presence of ptosis, prevalence of amblyopia and strabismic patterns were analyzed, with MED eyes compared with fellow eyes.

RESULTS: A total of 105 patients were included. Mean cylindrical refractive error was significantly higher in MED eyes compared with fellow eyes (-1.40 ± 1.70 D …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Ranran Wu, Rahmah Ejaz, Hamid K Rudsari, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Azacitidine, Venetoclax, And Magrolimab In Newly Diagnosed And Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/Ii Study And Correlative Analysis, Naval Daver, Jayastu Senapati, Hagop M Kantarjian, Bofei Wang, Patrick K Reville, Sanam Loghavi, Musa Yilmaz, Courtney D Dinardo, Tapan M Kadia, Mhd Yousuf Yassouf, Abhishek Maiti, Sankalp Arora, Guillermo Montalban Bravo, Guilin Tang, Gautam Borthakur, Koji Sasaki, Naveen Pemmaraju, Joie Alvarez, Graciela M Nogueras Gonzalez, Jing Ning, Ghayas C Issa, Marina Konopleva, Michael Andreeff, Farhad Ravandi, Guillermo Garcia-Manero, Hussein A Abbas

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody directed against the macrophage checkpoint CD47 on myeloid leukemia cells that was preclinically synergistic with azacitidine-venetoclax, warranting further clinical evaluation.

Patients and methods: In this phase Ib/II study, the triplet combination of azacitidine, venetoclax, and magrolimab was evaluated in adult patients with first-line (ineligible for intensive chemotherapy) and relapsed/refractory acute myeloid leukemia. Azacitidine was dosed at 75 mg/m2 for 7 days, venetoclax at 400 mg/day for 28 days, and magrolimab (recommended phase II dose) as follows: 1 mg/kg dose on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days …

Time Dependency For Human Papillomavirus Circulating Tumor Dna Detection After Chemoradiation As A Prognostic Biomarker For Localized Anal Cancer, Van K Morris, Weihong Xiao, Kangyu Lin, Chi Wut Wong, Michael T Wotman, Emma B Holliday, Ryan W Huey, Sonal S Noticewala, Ethan B Ludmir, Alisha H Bent, Kaysia Ludford, Craig Messick, Eugene J Koay, Grace Smith, Tsuyoshi Konishi, Brian Bednarski, George J Chang, Albert C Koong, Y Nancy You, Prajnan Das, Maura L Gillison

Faculty, Staff and Student Publications

Purpose: Although detection of ctDNA weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Experimental design: Patients with stages I to III anal cancer treated with chemoradiation between December 2020 and March 2024 were evaluated for human papillomavirus (HPV) ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay, targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was …

Risk And Protective Factors Associated With Teenage Pregnancy And Intergenerational Interventions: A Scoping Review Protocol, Zamasomi Luvuno, Wilbroda Hlolosile Chiya, Silingene Joyce Ngcobo, Deshini Naidoo, Serwaa Omowale, Tracy Zhandire, Elizabeth Musili Joseph-Shehu, Busisiwe Purity Ncama, Sinegugu E Duma

Faculty, Staff and Student Publications

Introduction: Teenage pregnancy remains a critical global health issue, particularly in low- and middle-income countries. The intergenerational transmission of teenage pregnancy underscores the need for targeted interventions. Existing research on intergenerational approaches is fragmented, with varying methodologies and outcomes. This scoping review seeks to address this gap by answering the following research questions: What are the available intergenerational interventions for teenage pregnancy, and what are the associated risks and protective factors for early and late teenage pregnancy?

Methods and analysis: This study does not involve primary data collection and therefore does not require ethical approval. The review will be conducted …

Hematopoietic Stem Cell Transplantation Outcomes For High-Risk Aml: A Report From The Children's Oncology Group., Benjamin J. Huang, Lauren K. Meyer, Todd A. Alonzo, Yi-Cheng Wang, Adam J. Lamble, Rhonda E. Ries, Weijie Wang, Betsy Hirsch, Gordana Raca, Xiaotu Ma, Alan S. Gamis, Richard Aplenc, E Anders Kolb, Todd M. Cooper, Katherine Tarlock, Michael R. Loken, Soheil Meshinchi, Joseph H. Chewning, William G. Woods, John T. Horan

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Hematopoietic stem cell transplantation (HSCT) is used as consolidation for pediatric patients with high-risk AML in first complete remission (CR1). The definition of high-risk AML has evolved considerably over the past two decades with the successive identification of new unfavorable risk factors. We conducted a cross-study analysis to determine whether HSCT improves the outcomes of patients with contemporarily defined high-risk AML.

METHODS: We combined data from AAML0531 and AAML1031, the last two phase III clinical trials completed by the Children's Oncology Group (COG). These two trials established the prognostic importance of measurable residual disease (MRD) and several high-risk cryptic …

Real-World Outcomes For Young Adult Patients Receiving Cd19 Car T-Cell Therapy., Hannah Lust, Liora M. Schultz, Soyang Kwon, Gregory W. Roloff, Ibrahim Aldoss, Christina Baggott, Samuel John, Jenna E. Rossoff, Kevin O. Mcnerney, Vanessa A. Fabrizio, Julie-An Talano, Amy Moskop, Kevin J. Curran, Christine L. Phillips, Nicole Karras, Susanne H C Baumeister, Stacy L. Cooper, Michelle Hermiston, Prakash Satwani, Muna Qayed, Sunil S. Raikar, Margaret Macmillan, Erin Hall, Khanh Nguyen, Ryan D. Cassaday, Noam E. Kopmar, Vamsi K. Kota, John Mathews, Paul Shaughnessy, Marc S. Schwartz, Abdullah Ladha, George Yaghmour, Muthu V. Kumaran, Veronika Bachanova, Sean Tracy, Tamer Othman, Marlise R. Luskin, Evan C. Chen, Anjani S. Advani, Nikeshan Jeyakumar, Katharine Miller, Amy Zhang, Katherine C. Sutherland, Bijal D. Shah, Lori Muffly, Rawan Faramand

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 chimeric antigen receptor T-cell therapy (CAR T) products for young adults (YA) with relapsed/refractory B-cell acute lymphoblastic leukemia. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Using retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe the efficacy and safety of tisa-cel and brexu-cel in 70 YAs (18-26 years; tisa-cel, n = 50; brexu-cel, n = 20). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed more frequently …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Fluorescence-Guided Ureteral Identification In Robotic Surgery For Advanced Endometriosis: A Comparison Of Junior Versus Senior Surgeons, Linda A Alpuing Radilla, Qiannan Yang, Daniel Y Lovell, Tamisa Koythong, Brooke Thigpen, Luis E Delgadillo Chabolla, Qianqing Wang, Xiaoming Guan

Faculty, Staff and Students Publications

Identifying the ureters in patients with advanced endometriosis and severe pelvic adhesive disease can be challenging. Adhesiolysis along the deformed pelvic sidewall may increase the risk of prolonged operative time and incidental ureteral injury. This study aimed to evaluate the safety and surgical outcomes of using Indocyanine Green (ICG) under near-infrared fluorescence for intraoperative ureteral localization and preservation during robot-assisted laparoscopic surgery (RALS) for advanced endometriosis, comparing procedures performed by two junior surgeons to those performed by one senior surgeon. This was a retrospective observational case series conducted by three minimally invasive gynecologic surgeons (X.G., T.K., B.T.) at a single …

Rewired M6a Of Promoter Antisense Rnas In Alzheimer’S Disease Regulates Neuronal Genes In 3d Nucleome, Benxia Hu, Yuqiang Shi, Feng Xiong, Yi-Ting Chen, Xiaoyu Zhu, Elisa Carrillo, Xingzhao Wen, Nathan Drolet, Chetan Singh Rajpurohit, Xiangmin Xu, Dung-Fang Lee, Claudio Soto, Sheng Zhong, Vasanthi Jayaraman, Hui Zheng, Wenbo Li

Faculty, Staff and Student Publications

N6-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs. Notably, many promoter-antisense RNAs (paRNAs) displayed cell-type-specific expression and changes in AD, including one produced adjacent to MAPT that encodes the Tau protein. MAPT-paRNA is highly expressed …

The Effect Of Birthweight And Gestational Age On Cognitive Function In Midlife: The Bogalusa Heart Study, Eunsun Gill, David J Libon, Soo Jung Kang, Ileana De Anda-Duran, Lydia A Bazzano, Wei Chen, Camilo Fernandez-Alonso, Emily W Harville

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Although the relationships between birthweight, gestational age (GA), and cognitive function (CF) before midlife have been demonstrated, the relationships after midlife and potential racial disparities remain inconclusive. This study examined the association between birthweight, GA, and midlife CF stratified by race.

METHOD: 1,032 subjects from the Bogalusa Heart Study (67% Whites, 33% Blacks, mean age 48.1 ± 5.3 years) were studied. Cognition was assessed with tests measuring verbal episodic memory, working memory, attention, graphomotor information processing speed, and global CF. Each test was standardized by sex and age, then averaged. The global CF was computed by averaging all cognitive …

Variants In Bsn, Encoding The Presynaptic Protein Bassoon, Result In A Distinct Neurodevelopmental Disorder With A Broad Phenotypic Range, Stacy G Guzman, Sarah M Ruggiero, Shiva Ganesan, Colin A Ellis, Alicia G Harrison, Katie R Sullivan, Zornitza Stark, Natasha J Brown, Sajel L Kana, Anabelle Tuttle, Jair Tenorio, Pablo Lapunzina, Julián Nevado, Marie T Mcdonald, Courtney Jensen, Patricia G Wheeler, Lila Stange, Jennifer Morrison, Boris Keren, Solveig Heide, Meg W Keating, Kameryn M Butler, Mike A Lyons, Shailly Jain, Mehdi Yeganeh, Michelle L Thompson, Molly Schroeder, Hoanh Nguyen, Jorge Granadillo, Kari M Johnston, Chaya N Murali, Katie Bosanko, T Andrew Burrow, Chop Birth Defects Biorepository, Penn Medicine Biobank, Syreeta Morgan, Deborah J Watson, Hakon Hakonarson, Ingo Helbig

Faculty, Staff and Students Publications

Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders (NDDs) and epilepsy. Here, we describe 14 individuals with de novo disruptive variants in BSN, which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks. Clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29, 45%), febrile seizures (7/29, 25%), generalized tonic-clonic seizures (5/29, 17%), and focal-onset seizures (3/29, 10%). Behavioral phenotypes were present in almost half of all individuals (14/29, 48%), …

Loss Of Function Of The Zinc Finger Homeobox 4 Gene, Zfhx4, Underlies A Neurodevelopmental Disorder, María Del Rocío Pérez Baca, María Palomares-Bralo, Michiel Vanhooydonck, Lisa Hamerlinck, Eva D'Haene, Sebastian Leimbacher, Eva Z Jacobs, Laurenz De Cock, Erika D'Haenens, Annelies Dheedene, Zoë Malfait, Lies Vantomme, Ananilia Silva, Kathleen Rooney, Xiaonan Zhao, Amir Hossein Saeidian, Nichole Marie Owen, Fernando Santos-Simarro, Roser Lleuger-Pujol, Sixto García-Miñaúr, Itsaso Losantos-García, Björn Menten, Gaia Gestri, Nicola Ragge, Bekim Sadikovic, Elke Bogaert, Kris Vleminckx, Thomas Naert, Delfien Syx, Bert Callewaert, Sarah Vergult

Faculty, Staff and Students Publications

8q21.11 microdeletions involving ZFHX4 have previously been associated with a syndromic form of intellectual disability, hypotonia, unstable gait, and hearing loss. We report on 63 individuals-57 probands and 6 affected family members-with protein-truncating variants (n = 41), (micro)deletions (n = 21), or an inversion (n = 1) affecting ZFHX4. Probands display variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis. The phenotypes associated with 8q21.11 microdeletions and ZFHX4 intragenic loss-of-function (LoF) variants largely overlap, although leukocyte-derived DNA shows a mild …

Swi/Snf Atpase Silenced Hlf Potentiates Lung Metastasis In Solid Cancers, Jin Zhou, Austin Hepperla, Jeremy M Simon, Kangsan Kim, Qing Hu, Chuanhai Zhang, Lei Dong, Lianxin Hu, Cheng Zhang, Chengheng Liao, Alice Fang, Yayoi Adachi, Haoyong Fu, Tao Wang, Qian Liang, Fangzhou Zhao, Hongyi Liu, Masashi Takeda, Jun Fang, Hua Zhong, Peter Ly, Lu Wang, Payal Kapur, Lin Xu, Liwei Jia, Srinivas Malladi, James Brugarolas, M Celeste Simon, Bo Li, Qing Zhang

Faculty, Staff and Student Publications

Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Here, using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conduct an in vivo genome-wide CRISPR-Cas9 screen and identify HLF as a potent suppressor of lung metastasis. HLF depletion enhances ccRCC cell migration and lung metastasis, whereas HLF overexpression abrogates these effects. In ccRCC patients, HLF expression is reduced at metastatic sites and associates with epigenetic silencing mediated by the SWI/SNF ATPase subunit BRG1. HLF levels negatively correlate with migration potential in collagen. Mechanistically, HLF regulates LPXN expression, modulating the …

Senescence Caused By Telomerase Inactivation In Myeloid, Mesenchymal, And Endothelial Cells Has Distinct Effects On Cancer Progression, Joseph Rupert, Zhanguo Gao, Yongmei Yu, Mikhail G Kolonin

Faculty, Staff and Student Publications

The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We generated genetic Tert knockout (KO) mice driven by the LysM promoter in myeloid cells, by the Pdgfra or Pdgfrb promoter in mesenchymal cells, and by the Tie2e promoter in endothelial cells. We compared the effect of the Tert KOs in syngeneic models of orthotopically grafted E0771 breast adenocarcinoma, RM1 prostate adenocarcinoma, and KPC pancreatic adenocarcinoma. Tumors in LysM-Tert …

Omitting Regional Nodal Irradiation After Response To Neoadjuvant Chemotherapy, Eleftherios P Mamounas, Hanna Bandos, Julia R White, Thomas B Julian, Atif J Khan, Simona F Shaitelman, Mylin A Torres, Frank A Vicini, Patricia A Ganz, Susan A Mccloskey, Peter C Lucas, Nilendu Gupta, X Allen Li, Beryl Mccormick, Benjamin Smith, Rahul D Tendulkar, Vivek S Kavadi, Koji Matsumoto, Samantha Andrews Seaward, William J Irvin, Jolinta Y Lin, Robert W Mutter, Thierry M Muanza, Jannifer Stromberg, Reshma Jagsi, Anna C Weiss, Walter J Curran, Norman Wolmark

Faculty, Staff and Student Publications

Background: The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

Methods: We evaluated whether regional nodal irradiation improves outcomes in patients with biopsy-proven, node-positive breast cancer who reach ypN0 status after neoadjuvant chemotherapy. Patients with breast cancer with a clinical stage of T1 to T3 (tumor size, ≤2 cm to >5 cm), N1, and M0 (indicating spread to one to three axillary lymph nodes but no distant …

Cross-Sectional Analysis Of Wound-Associated Soluble Factors In Early, Established, And Chronic Wounds Of Recessive Dystrophic Epidermolysis Bullosa Patients, Vitali Alexeev, Leonie Huitema, Taylor Phillips, Paras Patel, Mauricio Garza, Franziska Ringpfeil, Julio Salas-Alanis, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds represent the primary health-related burden for hereditary recessive dystrophic epidermolysis bullosa (RDEB) patients. Contribution of wound-associated soluble constituents to wound progression remains not well defined.

OBJECTIVE: To conduct cross-sectional analysis of cytokine, chemokine, and growth factor in exudates from RDEB wounds and define changes associated with wound progression.

METHODS: Concentrations of selected cytokines, chemokines, and growth factors were evaluated by multiplex ELISA in eight blister fluids and 66 exudates from early, established, and chronic RDEB and five chronic venous ulcers (VU). A cross-sectional analysis was performed.

RESULTS: Our data demonstrated that proinflammatory CXCL8 and IL-1β tend …

Prediction Of Methotrexate Neurotoxicity Using Clinical, Sociodemographic, And Area-Based Information In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, Maria Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Center for Medical Ethics and Health Policy Staff Publications

Background: Methotrexate is a critical component of pediatric acute lymphoblastic leukemia (ALL) therapy that can result in neurotoxicity which has been associated with an increased risk of relapse. We leveraged machine learning to develop a neurotoxicity risk prediction model in a diverse cohort of children with ALL.

Methods: We included children (age 2-20 years) diagnosed with ALL (2005-2019) and treated in Texas without pre-existing neurologic disease. Clinical information was obtained by medical record review. Neurotoxicity occurring post-induction and prior to maintenance therapy was defined as neurologic episodes occurring within 21 days of methotrexate. Suspected cases were independently confirmed by 2 …

Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma

Faculty, Staff and Student Publications

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA …

Career Impact Of The National Interprofessional Fellowship In Patient Safety: An Alumni Evaluation, Bradley V Watts, Kathleen Carluzzo, Blake F Webb, Kelley Arredondo

Faculty, Staff and Students Publications

Background: There has been a proliferation of health professions training programmes focused on quality and patient safety, but little information regarding the outcomes of these programmes. The purpose of this study was to examine the impact of an interprofessional quality and patient safety curriculum on career outcomes of interprofessional healthcare learners for the Veterans Affairs Patient Safety Fellowship.

Method: We conducted a survey-based assessment of 117 alumni of the Interprofessional Fellowship in Patient Safety assessing their satisfaction with the training program and career impacts.

Results: 84 of 117 alumni were located and participated in the assessment. Fellows entered the training …

Impact Of Sociodemographic Determinants On Enrollment Into Contemporary Lymphoma Clinical Trials: A Systematic Review, Jun Yang Jiang, Ang Li, Alexis Romero, Christopher R Flowers, Chijioke Nze

Faculty, Staff and Students Publications

While the incidence and survival associated with lymphoma have improved in recent years, outcome disparities related to sociodemographic factors such as age, sex, race, ethnicity, socioeconomic status (SES), and other social determinants of health (SDOH) remain prevalent in the modern era. Clinical trials are crucial for further improving outcomes, yet not all sociodemographic groups are equally represented in contemporary lymphoma trials. We conducted a systematic review of the literature evaluating the impact of SDOH on enrollment into clinical trials in the United States and identified 21 relevant studies. We confirmed that Black and Hispanic individuals are underrepresented in lymphoma clinical …

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

Center for Medical Ethics and Health Policy Staff Publications

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

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …

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

Department of Surgery Faculty Papers

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

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

Manuscripts, Articles, Book Chapters and Other Papers

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

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

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Students Publications

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

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

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

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

Faculty, Staff and Students Publications

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

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

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

Exposure: Epinephrine administration route: IO or IV route.

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

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

Trauma and Acute Care Articles

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