Medicine and Health Sciences Commons^™

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Faculty, Staff and Student Publications

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

Dockopathies: A Systematic Review Of The Clinical Pathologies Associated With Human Dock Pathogenic Variants, Adrienne Samani, Katherine G English, Michael A Lopez, Camille L Birch, Donna M Brown, Gurpreet Kaur, Elizabeth A Worthey, Matthew S Alexander

Faculty, Staff and Student Publications

The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

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The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

The Effect Of Body Mass Index On Therapeutic Response To Bacterial Vaginosis In Pregnancy, Kevin P Lee, Misha V Koshelev, D3code Team, Omar Pacha

Faculty, Staff and Student Publications

No abstract provided.

A Case Of Perifollicular Macular Amyloidosis, Imran T Baig, Jamael L Thomas, Misha V Koshelev

Faculty, Staff and Student Publications

Macular amyloidosis is a common type of primary localized cutaneous amyloidosis. We present a case report of a 74-year-old patient with no significant past medical history who was evaluated for dark macules and pruritus for over a year. On exam, follicular-based brown macules on the upper and lower back, bilateral shoulders, and bilateral dorsal upper arms were noted. The morphology and distribution of follicular-based macules was unusual, so the differential included follicular lichen planus, follicular eczema, and macular amyloidosis. Punch biopsy showed deposits of eosinophilic fibrillary material along with pigmentary incontinence in the papillary dermis, consistent with macular amyloidosis. Additionally, …

Severe Radiation-Induced Lymphopenia Attenuates The Benefit Of Durvalumab After Concurrent Chemoradiotherapy For Nsclc, Wang Jing, Ting Xu, Lirong Wu, Pablo B Lopez, Clemens Grassberger, Susannah G Ellsworth, Radhe Mohan, Brian P Hobbs, George R Blumenschein, Janet Tu, Mehmet Altan, Percy Lee, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

Introduction: Durvalumab after concurrent chemoradiation (CCRT) for NSCLC improves survival, but only in a subset of patients. We investigated the effect of severe radiation-induced lymphopenia (sRIL) on survival in these patients.

Methods: Outcomes after CCRT (2010-2019) or CCRT followed by durvalumab (2018-2019) were reviewed. RIL was defined by absolute lymphocyte count (ALC) nadir in samples collected at end of CCRT; sRIL was defined as nadir ALC less than 0.23 × 109/L (the lowest tertile). Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Cox proportional hazard modeling evaluated associations between clinical variables and survival.

Results: Of …

Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Matthew Fiala, Abana Azariah, Jean Woo, Ahmed Kamel Abdel Aal, Alexa Levey

Faculty, Staff and Student Publications

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Repeatability And Reproducibility Assessment Of The Apparent Diffusion Coefficient In The Prostate: A Trial Of The Ecog-Acrin Research Group (Acrin 6701), Michael A Boss, Bradley S Snyder, Eunhee Kim, Dena Flamini, Sarah Englander, Karthik M Sundaram, Naveen Gumpeni, Suzanne L Palmer, Haesun Choi, Adam T Froemming, Thorsten Persigehl, Matthew S Davenport, Dariya Malyarenko, Thomas L Chenevert, Mark A Rosen

Faculty, Staff and Student Publications

Background: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.

Purpose: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting.

Study type: Prospective multi-institutional.

Subjects: Twenty-nine males, ages 53 to 80 (median 63) …

Predominantly Persistent Intraretinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Maxwell Pistilli, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Cynthia A Toth, Glenn J Jaffe, Daniel F Martin, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration.

DESIGN: Cohort within a randomized clinical trial.

PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment.

METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the …

Patient-Reported Bowel And Urinary Function In Long-Term Survivors Of Squamous Cell Carcinoma Of The Anus Treated With Definitive Intensity Modulated Radiation Therapy And Concurrent Chemotherapy, Brian De, Kelsey L Corrigan, Michael K Rooney, Ethan B Ludmir, Prajnan Das, Grace L Smith, Cullen M Taniguchi, Bruce D Minsky, Eugene J Koay, Albert Koong, Van K Morris, Craig A Messick, Y Nancy You, George J Chang, O Lenaine Westney, Graciela M Nogueras Gonzalez, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs).

Methods and materials: We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). …

Lif-Ting Ferroptosis To Improve Liver Cancer Therapy, Fan Yao, Yang Zhao, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Pure Erythroid Leukemia Is Characterized By Biallelic Tp53 Inactivation And Abnormal P53 Expression Patterns In De Novo And Secondary Cases, Hong Fang, Sa A Wang, Joseph D Khoury, Siba El Hussein, Do Hwan Kim, Mehrnoosh Tashakori, Zhenya Tang, Shaoying Li, Zhihong Hu, Fatima Zahra Jelloul, Keyur P Patel, Timothy J Mcdonnell, Tapan Kadia, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

International Expert Consensus On Immunotherapy For Early-Stage Non-Small Cell Lung Cancer, Wenhua Liang, Kaican Cai, Qingdong Cao, Chun Chen, Haiquan Chen, Jun Chen, Ke-Neng Chen, Qixun Chen, Tianqing Chu, Yuchao Dong, Jiang Fan, Wentao Fang, Junke Fu, Xiangning Fu, Shugeng Gao, Di Ge, Guojun Geng, Qing Geng, Jie He, Jian Hu, Jie Hu, Wei-Dong Hu, Feng Jiang, Tao Jiang, Wenjie Jiao, He-Cheng Li, Qiang Li, Shanqing Li, Shuben Li, Xiangnan Li, Yong-De Liao, Changhong Liu, Hongxu Liu, Yang Liu, Zhuming Lu, Qingquan Luo, Haitao Ma, Xiaojie Pan, Guibin Qiao, Shengxiang Ren, Weiyu Shen, Yong Song, Daqiang Sun, Guangsuo Wang, Jie Wang, Mengzhao Wang, Qiwen Wang, Wen-Xiang Wang, Li Wei, Ming Wu, Nan Wu, Hui Xia, Shi-Dong Xu, Fan Yang, Kang Yang, Yue Yang, Fenglei Yu, Zhen-Tao Yu, Dong-Sheng Yue, Lanjun Zhang, Weidong Zhang, Zhenfa Zhang, Guofang Zhao, Jian Zhao, Xiaojing Zhao, Chengzhi Zhou, Qinghua Zhou, Kunshou Zhu, Yuming Zhu, Toyoaki Hida, Wolfram C M Dempke, Antonio Rossi, Marc De Perrot, Robert A Ramirez, Mariano Provencio, Jay M Lee, Antonio Passaro, Lorenzo Spaggiari, Jonathan Spicer, Nicolas Girard, Patrick M Forde, Tony S K Mok, Tina Cascone, Jianxing He

Faculty, Staff and Student Publications

No abstract provided.

Covid-19 And Blood Clots: A Report Of Massive Pulmonary Embolism In Covid-19 Patient Supported On Veno-Venous Ecmo And The Utility Of Thrombolysis, Bindu Akkanti, Joseph Zwischenberger, Mark T Warner, Kha Dinh, Rahat Hussain, Farah Kazzaz, Pascal Kingah, Lisa M Janowiak, Biswajit Kar, Igor D Gregoric

Faculty, Staff and Student Publications

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our …

Primary Sjögren's Syndrome Presenting As Cerebral Venous Thrombosis: A Rare Case, Mohan Sonu Chandra, Monisha G A, Ravi Kiran M

Faculty, Staff and Student Publications

Sjogren's syndrome is a late-onset, slowly progressing autoimmune disease characterized by the destruction of the exocrine glands by lymphocytic infiltration, resulting in dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Sjögren's syndrome may be associated with various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. We report a case of a 34-year-old female who delivered a live baby 20 days ago. She presented in a postictal state after two episodes of tonic-clonic movements of limbs with altered sensorium with a history of headache for seven days. Further evaluation revealed that the subject had a history of multiple …

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

Intermediary Role Of Lung Alveolar Type 1 Cells In Epithelial Repair Upon Sendai Virus Infection, Belinda J Hernandez, Margo P Cain, Anne M Lynch, Jose R Flores, Michael J Tuvim, Burton F Dickey, Jichao Chen

Faculty, Staff and Student Publications

The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+ (Sry-box 2+) clusters without differentiating into AT1 or AT2 cells. Large AT2 cell-depleted areas remain covered by …

Cisplatin And Gemcitabine Exert Opposite Effects On Immunotherapy With Pd-1 Antibody In K-Ras-Driven Cancer, Christophe Glorieux, Xiaojun Xia, Xin You, Zining Wang, Yi Han, Jing Yang, Gauthier Noppe, Christophe De Meester, Jianhua Ling, Annie Robert, Hui Zhang, Sheng-Ping Li, Huamin Wang, Paul J Chiao, Li Zhang, Xiaobing Li, Peng Huang

Faculty, Staff and Student Publications

INTRODUCTION: Immunochemotherapy using PD-1/PD-L1 antibodies in combination with chemotherapeutic agents has become a mainstream treatment for cancer patients, but it remains unclear which drug combinations would produce best therapeutic outcome.

OBJECTIVES: The purpose of this study was to investigate two common chemotherapeutic drugs, gemcitabine and cisplatin, for their impacts on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers known to overexpress PD-L1.

METHODS: Both in vitro assays and syngeneic mouse tumor models were used in this study. Biochemical and molecular assays were used to determine the effects of drugs on T cell functions in cell culture models and in …

Dynamic S-Acylation Of The Er-Resident Protein Stromal Interaction Molecule 1 (Stim1) Is Required For Store-Operated Ca2+ Entry, Goutham Kodakandla, Savannah J West, Qiaochu Wang, Ritika Tewari, Michael X Zhu, Askar M Akimzhanov, Darren Boehning

Faculty, Staff and Student Publications

Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein stromal interaction molecule 1 (STIM1) physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long-chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a …

A Decade's Experience In Pediatric Chromosomal Microarray Reveals Distinct Characteristics Across Ordering Specialties, Mariam T Mathew, Austin Antoniou, Naveen Ramesh, Min Hu, Jeffrey Gaither, Danielle Mouhlas, Sayaka Hashimoto, Maggie Humphrey, Theodora Matthews, Jesse M Hunter, Shalini Reshmi, Matthew Schultz, Kristy Lee, Ruthann Pfau, Catherine Cottrell, Kim L Mcbride, Nicholas E Navin, Bimal P Chaudhari, Marco L Leung

Faculty, Staff and Student Publications

Chromosomal microarray (CMA) is a testing modality frequently used in pediatric patients; however, published data on its utilization are limited to the genetic setting. We performed a database search for all CMA testing performed from 2010 to 2020, and delineated the diagnostic yield based on patient characteristics, including sex, age, clinical specialty of providers, indication of testing, and pathogenic finding. The indications for testing were further categorized into Human Phenotype Ontology categories for analysis. This study included a cohort of 14,541 patients from 29 different medical specialties, of whom 30% were from the genetics clinic. The clinical indications for testing …

Car Treg Cells: Prime Suspects In Therapeutic Resistance, Neeraj Saini, Sattva S Neelapu

Faculty, Staff and Student Publications

Using comprehensive single-cell profiling, two studies reveal the molecular phenotypes of CAR T cells associated with durable response in patients with lymphoma, and highlight the role of CAR regulatory T cells in mediating resistance.

Quantifying The Risk And Dosimetric Variables Of Symptomatic Brainstem Injury After Proton Beam Radiation In Pediatric Brain Tumors, Rituraj Upadhyay, Kaiping Liao, David R Grosshans, Susan L Mcgovern, Mary Frances Mcaleer, Wafik Zaky, Murali M Chintagumpala, Anita Mahajan, Debra Nana Yeboa, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT.

Methods: All patients < 21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem.

Results: A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT …

Health Care Utilization And Costs Associated With Functional Status In Patients With Psoriatic Arthritis, Alexis Ogdie, Mark Hwang, Phani Veeranki, Alexandria Portelli, Steven Sison, Jason Shafrin, Sofia Pedro, Steven Hass, Peter Hur, Nina Kim, Esther Yi, Kaleb Michaud

Faculty, Staff and Student Publications

BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) has been validated and widely used in psoriatic arthritis (PsA) clinical trials for the assessment of patient functional status. Significant improvements in the HAQ-DI have been reported in response to therapeutic interventions; however, few US studies have evaluated the economic impact of functional disability in patients with PsA.

OBJECTIVE: To evaluate the association of functional status with health care resource utilization (HCRU) and total health care costs in US patients diagnosed with PsA.

METHODS: This retrospective study included adult patients with PsA enrolled in FORWARD between July 2009 and June 2019 who …

Development Of A Novel Pharmacophore Model To Screen Specific Inhibitors For The Serine-Threonine Protein Phosphatase Calcineurin, Abhisek Mukherjee, Karina Cuanalo-Contreras, Abha Sood, Claudio Soto

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Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required …

Tumor Immune Contexture Is A Determinant Of Anti-Cd19 Car T Cell Efficacy In Large B Cell Lymphoma, Nathalie Scholler, Regis Perbost, Frederick L Locke, Michael D Jain, Sarah Turcan, Corinne Danan, Edmund C Chang, Sattva S Neelapu, David B Miklos, Caron A Jacobson, Lazaros J Lekakis, Yi Lin, Armin Ghobadi, Jenny J Kim, Justin Chou, Vicki Plaks, Zixing Wang, Allen Xue, Mike Mattie, John M Rossi, Adrian Bot, Jérôme Galon

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell …

Oligometastatic Disease In The Liver: The Role Of Interventional Oncology, Ather Adnan, Rahul Anil Sheth, Alda Tam

Faculty, Staff and Student Publications

Oligometastatic disease represents a clinically discrete intermediate stage of cancer progression and is an expanding area of research. While surgical metastatectomy has been recognized for decades as an effective treatment option in select patients, options for metastasis-directed therapy have broadened in scope with advancements in the armamentarium of non- and minimally invasive modalities. Recent preclinical studies investigating the immunology surrounding liver metastases demonstrate treatment resistance to immunotherapy in affected patients and show how locoregional therapy has the ability to overcome this resistance. In this paper, we review advancements in our understanding of oligometastatic disease, metastasis-directed therapy, effect of liver metastasis …

An Empirical Model Of Proton Rbe Based On The Linear Correlation Between X-Ray And Proton Radiosensitivity, David B Flint, Chase E Ruff, Scott J Bright, Pablo Yepes, Qianxia Wang, Mandira Manandhar, Mariam Ben Kacem, Broderick X Turner, David K J Martinus, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Background: Proton relative biological effectiveness (RBE) is known to depend on physical factors of the proton beam, such as its linear energy transfer (LET), as well as on cell-line specific biological factors, such as their ability to repair DNA damage. However, in a clinical setting, proton RBE is still considered to have a fixed value of 1.1 despite the existence of several empirical models that can predict proton RBE based on how a cell's survival curve (linear-quadratic model [LQM]) parameters α and β vary with the LET of the proton beam. Part of the hesitation to incorporate variable RBE models …

Lmo2 Expression Is Frequent In T-Lymphoblastic Leukemia And Correlates With Survival, Regardless Of T-Cell Stage, Kerri-Ann Latchmansingh, Xiaoqiong Wang, Ramiro E Verdun, Mario L Marques-Piubelli, Francisco Vega, M James You, Jennifer Chapman, Izidore S Lossos

Faculty, Staff and Student Publications

T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 …

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy.

Results: The …

An Interdisciplinary Consensus On The Management Of Brain Metastases In Patients With Renal Cell Carcinoma, Elshad Hasanov, Debra Nana Yeboa, Mathew D Tucker, Todd A Swanson, Thomas Hendrix Beckham, Brian Rini, Chibawanye I Ene, Merve Hasanov, Sophie Derks, Marion Smits, Shaan Dudani, Daniel Y C Heng, Priscilla K Brastianos, Axel Bex, Sahin Hanalioglu, Jeffrey S Weinberg, Laure Hirsch, Maria I Carlo, Ayal Aizer, Paul David Brown, Mehmet Asim Bilen, Eric Lin Chang, Jerry Jaboin, James Brugarolas, Toni K Choueiri, Michael B Atkins, Bradley A Mcgregor, Lia M Halasz, Toral R Patel, Scott G Soltys, David F Mcdermott, James Bradley Elder, Mustafa K Baskaya, James B Yu, Robert Timmerman, Michelle Miran Kim, Melike Mut, James Markert, Kathryn Beal, Nizar M Tannir, George Samandouras, Frederick F Lang, Rachel Giles, Eric Jonasch

Faculty, Staff and Student Publications

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of …