Medicine and Health Sciences Commons^™

Voxel-Based Dosimetry Predicting Treatment Response And Related Toxicity In Hcc Patients Treated With Resin-Based Y90 Radioembolization: A Prospective, Single-Arm Study, Nima Kokabi, Linzi Arndt-Webster, Bernard Chen, David Brandon, Ila Sethi, Amir Davarpanahfakhr, James Galt, Mohammad Elsayed, Zachary Bercu, Mircea Cristescu, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC).

PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization.

MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral …

Therapeutic Potential Of Tumor Treating Fields For Malignant Brain Tumors, Youyou Zhou, Xiaoqing Xing, Jinyun Zhou, Han Jiang, Peili Cen, Chentao Jin, Yan Zhong, Rui Zhou, Jing Wang, Mei Tian, Hong Zhang

Faculty, Staff and Student Publications

BACKGROUND: Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field and can lead to the development of novel therapeutic options.

RECENT FINDINGS: A series of biological processes induced by TTFields to exert anti-cancer effects have been identified. Recent studies have shown that TTFields can alter the bioelectrical state of macromolecules and organelles involved in cancer biology. Massive alterations in cancer cell proteomics and transcriptomics caused by TTFields …

Enhancing Oral Delivery Of Plant-Derived Vesicles For Colitis, Yuan Liu, Adrian Lankenau Ahumada, Emine Bayraktar, Paul Schwartz, Mamur Chowdhury, Sixiang Shi, Manu M Sebastian, Htet Khant, Natalia De Val, Nazende Nur Bayram, Guodong Zhang, Thanh Chung Vu, Zuliang Jie, Nicholas B Jennings, Cristian Rodriguez-Aguayo, Jody Swain, Elaine Stur, Lingegowda S Mangala, Yutuan Wu, Supriya Nagaraju, Brooke Ermias, Chun Li, Gabriel Lopez-Berestein, Janet Braam, Anil K Sood

Faculty, Staff and Student Publications

Plant-derived vesicles (PDVs) are attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs did not have an appreciable impact on PDV structure, number, or therapeutic effect. Additionally, packaging the lyophilized Eudragit S100-coated PDVs into capsules allowed them to pass through the …

Predictors Of Perceived Functional Status In Early Systemic Sclerosis: A Prospective Longitudinal Study Of An Early Disease Cohort, Julia Chernis, Maryam Buni, Sarah Kazzaz, Jun Ying, Marka Lyons, Shervin Assassi, Maureen Mayes

Faculty, Staff and Student Publications

OBJECTIVE: The modified Health Assessment Questionnaire (M-HAQ) is a well-established patient-reported outcome measure in systemic sclerosis (SSc) studies that reflects how a patient functions in several categories of activities of daily living. This study analyzed clinical, demographic, and socioeconomic factors that predict M-HAQ scores over time.

METHODS: This study included 388 patients with baseline M-HAQ scores from the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) early disease cohort with a mean disease duration of 2.5 years, mean follow-up time of 3.9 years, and median follow-up of 7.2 years. A total of 1,950 M-HAQ measurements were analyzed. Baseline disease characteristics …

The Kynurenine Pathway In Major Depressive Disorder, Bipolar Disorder, And Schizophrenia: A Systematic Review And Meta-Analysis Of Cerebrospinal Fluid Studies, Mehmet Enes Inam, Brisa S Fernandes, Estela Salagre, Iria Grande, Eduard Vieta, João Quevedo, Zhongming Zhao

Faculty, Staff and Student Publications

INTRODUCTION: The kynurenine pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of the kynurenine pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD.

METHODS: PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies until April 2022 that assessed kynurenine metabolites, namely, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), and 3- hydroxykynurenine (3-HK) in SZ, BD, or MDD subjects compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses …

Gwas And Meta-Analysis Identifies 49 Genetic Variants Underlying Critical Covid-19, Erola Pairo-Castineira, Konrad Rawlik, Andrew D Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A Mcconkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny Mcauley, Hugh Montgomery, Peter J M Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Genomicc Investigators, Scourge Consortium, Isaricc Investigators, 23andme Covid-19 Team, Jian Yang, Chris P Ponting, James F Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D Luchessi, Esteban J Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J Kenneth Baillie

Faculty, Staff and Student Publications

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a …

Characterizing The Interplay Of Treatment Parameters And Complexity And Their Impact On Performance On An Iroc Imrt Phantom Using Machine Learning, Hunter Mehrens, Andrea Molineu, Nadia Hernandez, Laurence Court, Rebecca Howell, David Jaffray, Christine B Peterson, Julianne Pollard-Larkin, Stephen F Kry

Faculty, Staff and Student Publications

AIM OF THE STUDY: To elucidate the important factors and their interplay that drive performance on IMRT phantoms from the Imaging and Radiation Oncology Core (IROC).

METHODS: IROC's IMRT head and neck phantom contains two targets and an organ at risk. Point and 2D dose are measured by TLDs and film, respectively. 1,542 irradiations between 2012-2020 were retrospectively analyzed based on output parameters, complexity metrics, and treatment parameters. Univariate analysis compared parameters based on pass/fail, and random forest modeling was used to predict output parameters and determine the underlying importance of the variables.

RESULTS: The average phantom pass rate was …

Quantitative Dual-Energy Ct Image Guidance For Thermochemical Ablation: In Vivo Results In The Rabbit Vx2 Model, Emily A Thompson, Natalie W Fowlkes, Megan C Jacobsen, Rick R Layman, Erik N K Cressman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the feasibility of using dual-energy computed tomography (CT) and theranostic cesium hydroxide (CsOH) for image guidance of thermochemical ablation (TCA) in a rabbit VX2 tumor model.

MATERIALS AND METHODS: In vivo experiments were performed on New Zealand white rabbits, where VX2 tumor fragments (0.3 mL) were inoculated into the right and left flanks (n = 16 rabbits, 32 tumors). Catheters were placed in the approximate center of 1- to 2-cm diameter tumors under ultrasound guidance. TCA was delivered in 1 of 3 treatment groups: untreated control, 5-M TCA, or 10-M TCA. The TCA base reagent was doped …

Applicability And Usage Of Dose Mapping/Accumulation In Radiotherapy, Martina Murr, Kristy K Brock, Marco Fusella, Nicholas Hardcastle, Mohammad Hussein, Michael G Jameson, Isak Wahlstedt, Johnson Yuen, Jamie R Mcclelland, Eliana Vasquez Osorio

Faculty, Staff and Student Publications

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of …

Critical Review Of Oncologic Medical Malpractice Claims Against Orthopaedic Surgeons, William Davis, Shravya Kichena, Michael D Eckhoff, Benjamin R Childs, Rajiv Rajani, Matthew E Wells, Sean P Kelly

Faculty, Staff and Student Publications

INTRODUCTION: The purpose of this study was to determine the most common allegations for malpractice litigation brought against orthopaedic surgeons for oncologic matters and the resulting verdicts.

METHODS: The Westlaw Legal research database was queried for malpractice cases filed against orthopaedic surgeons for oncologic matters in the United States after 1980. Plaintiff demographics, state of filing, allegations, and outcomes of lawsuits were recorded and reported accordingly.

RESULTS: A total of 36 cases met the inclusion and exclusion criteria and were subsequently included in the final analysis. The overall rate of cases filed remained consistent through the past four decades and …

Heterogeneity Of Treatment Effects Of Hydrocortisone By Risk Of Bronchopulmonary Dysplasia Or Death Among Extremely Preterm Infants In The National Institute Of Child Health And Human Development Neonatal Research Network Trial: A Secondary Analysis Of A Randomized Clinical Trial, Samuel J Gentle, Matthew A Rysavy, Lei Li, Matthew M Laughon, Ravi M Patel, Erik A Jensen, Susan Hintz, Namasivayam Ambalavanan, Waldemar A Carlo, Kristi Watterberg, National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

IMPORTANCE: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.

OBJECTIVE: To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.

DESIGN, SETTING, AND PARTICIPANTS: …

Sarcoidosis And Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study And Review Of The Literature, Felipe Soto, Luis F Torre-Sada, Frank E Mott, Sang T Kim, Roza Nurieva, Vickie R Shannon, Saadia A Faiz, Roberto F Casal, Mehmet Altan, Julie Lin, Ajay Sheshadri

Faculty, Staff and Student Publications

Pulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis. This is the first case showing that anti-IL-5 inhibition may be safe in patients who develop eosinophilic asthma after ICI therapy. We further show that sarcoidosis does not necessarily require treatment cessation. This case …

Brain Engagement During A Cognitive Flexibility Task Relates To Academic Performance In English Learners, Tehila Nugiel, Mackenzie E Mitchell, Damion V Demeter, Annacarolina Garza, Paul T Cirino, Arturo E Hernandez, Jenifer Juranek, Jessica A Church

Faculty, Staff and Student Publications

English Learners (ELs), students from non-English-speaking backgrounds, are a fast-growing, understudied, group of students in the U.S. with unique learning challenges. Cognitive flexibility—the ability to switch between task demands with ease—may be an important factor in learning for ELs as they have to manage learning in their non-dominant language and access knowledge in multiple languages. We used functional MRI to measure cognitive flexibility brain activity in a group of Hispanic middle school ELs (N = 63) and related it to their academic skills. We found that brain engagement during the cognitive flexibility task was related to both out-of-scanner reading …

Alendronate Conjugate For Targeted Delivery To Bone-Forming Prostate Cancer, Jossana A Damasco, Guoyu Yu, Ajay Kumar, Joy Perez, Rio Carlo M Lirag, Elizabeth M Whitley, Sue-Hwa Lin, Marites P Melancon

Faculty, Staff and Student Publications

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, …

Comparative Tumor Microenvironment Analysis Of Primary And Recurrent Ovarian Granulosa Cell Tumors, Eleonora Khlebus, Veena K Vuttaradhi, Thomas Welte, Namrata Khurana, Joseph Celestino, Hannah C Beird, Curtis Gumbs, Latasha Little, Alejandra Flores Legarreta, Bryan M Fellman, Tri Nguyen, Barrett Lawson, Sammy Ferri-Borgogno, Samuel C Mok, Russell R Broaddus, David M Gershenson, P Andrew Futreal, R Tyler Hillman

Faculty, Staff and Student Publications

Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using “clusterProfiler” and “GSVA” R packages. TME …

A Model For Gastrointestinal Tract Motility In A 4d Imaging Phantom Of Human Anatomy, Ergys Subashi, Paul Segars, Harini Veeraraghavan, Joseph Deasy, Neelam Tyagi

Faculty, Staff and Student Publications

BACKGROUND: Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms.

PURPOSE: To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy.

MATERIALS AND METHODS: Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on …

Barriers To Colonoscopy In Uk Colorectal Cancer Screening Programmes: Qualitative Interviews With Ethnic Minority Groups, Robert S Kerrison, Natalie Gil, Elizabeth Travis, Robyn Jones, Katriina L Whitaker, Colin Rees, Stephen Duffy, Christian Von Wagner

Faculty, Staff and Student Publications

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom.

METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had …

Accuracy Of Administrative Claim Data For Gastric Adenoma After Endoscopic Resection, Ga-Yeong Shin, Hyun Ho Choi, Jae Myung Park, Sang Yoon Kim, Jun Young Park, Donghoon Kang, Yu Kyung Cho, Sung Soo Kim, Myung-Gyu Choi

Faculty, Staff and Student Publications

BACKGROUND/AIMS: Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas.

METHODS: Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen.

RESULTS: Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in …

Two Stacked Coins Mimicking An Esophageal Button Battery: A Case Presentation And Review Of The Literature, Nicholas Rossi, Devin Reddy, John Coggins, Duncan C Whatley, Harold S Pine, Shiva Daram

Faculty, Staff and Student Publications

As button battery (BB) ingestion has become a popular topic with growing public awareness in recent years, pediatric otolaryngologists maintain a high index of suspicion for this diagnosis. Several recent reports have revealed the possibility for benign objects to masquerade as BBs, such as two coins stacked together or a coin with different metals in concentric rings. A 4-year-old female presented to the ED after unwitnessed ingestion of a foreign body. The child was reportedly seen playing with her sister's coin collection prior to the acute onset of drooling and dysphagia. She was vitally stable and without any shortness of …

Current Treatment Strategies And Risk Stratification For Oral Carcinoma, Issa Mohamad, Mica D E Glaun, Kumar Prabhash, Ahmed Busheri, Stephen Y Lai, Vanita Noronha, Ali Hosni

Faculty, Staff and Student Publications

Management of oral cavity squamous cell carcinoma (OSCC) involves a multidisciplinary team approach. Surgery is ideally the primary treatment option for nonmetastatic OSCC, and less invasive curative surgical approaches are preferred in early-stage disease to minimize surgical-related morbidity. For patients at high risk of recurrence, adjuvant treatment using radiation therapy or chemoradiation is often used. Systemic therapy may also be used in the neoadjuvant setting (for advanced-stage disease with the intent of mandibular preservation) or in the palliative setting (for nonsalvageable locoregional recurrence and/or distant metastases). Patient involvement in treatment decision is the key for patient-driven management, particularly in clinical …

Pirtobrutinib And Venetoclax Combination Overcomes Resistance To Targeted And Chimeric Antigen Receptor T-Cell Therapy In Aggressive Mantle Cell Lymphoma, Yang Liu, Fangfang Yan, Vivian Changying Jiang, Yijing Li, Yuxuan Che, Joseph Mcintosh, Alexa Jordan, Ian Hou, Lei Nie, Jingling Jin, Wei Wang, Heng-Huan Lee, Yixin Yao, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

Utilization Of Indoor Tanning: A Cross-Sectional Study Using Mobile Device Data, Mackenzie R Wehner, Yao Li, Ashna A Sethi, Candice L Hinkston, Nasim Khalfe, Carly F Stender, Malgorzata K Nowakowska, Olivia G Cohen, Sharon H Giordano, Eleni Linos

Faculty, Staff and Student Publications

No abstract provided.

Understanding Cardiac Senescence One Cell Type At A Time, Payel Sen, Priyatansh Gurha

Faculty, Staff and Student Publications

No abstract provided.

Association Of Cumulative Colorectal Surgery Hospital Costs, Readmissions, And Emergency Department/Observation Stays With Insurance Type, Michael A Jacobs, Jasmine C Tetley, Jeongsoo Kim, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Background/purpose: Medicare's Hospital Readmission Reduction Program disproportionately penalizes safety-net hospitals (SNH) caring for vulnerable populations. This study assessed the association of insurance type with 30-day emergency department visits/observation stays (EDOS), readmissions, and cumulative costs in colorectal surgery patients.

Methods: Retrospective inpatient cohort study using the National Surgical Quality Improvement Program (2013-2019) with cost data in a SNH. The odds of EDOS and readmissions and cumulative variable (index hospitalization and all 30-day EDOS and readmissions) costs were modeled adjusting for frailty, case status, presence of a stoma, and open versus laparoscopic surgery.

Results: The cohort had 245 private, 195 Medicare, and …

Molecular Identity Changes Of Tumor-Associated Macrophages And Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Mouse Glioblastoma Model, Yanrong Zhang, Jing Wang, Sara Natasha Ghobadi, Haiyan Zhou, Ai Huang, Marco Gerosa, Qingyi Hou, Olivier Keunen, Anna Golebiewska, Frezghi G Habte, Gerald A Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark

Faculty, Staff and Student Publications

An orthotopically allografted mouse GL26 glioma model (Ccr2^RFP/wt-Cx3cr1^GFP/wt) was used to evaluate the effect of transient, focal opening of the Blood Brain Barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB Opening was induced by Magnetic Resonance Imaging (MRI)-guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not show significant changes in cell numbers when compared to tumors in animals not receiving FUS. However, tumors that received two or three sessions …

Towards A Better Mucolytic, Burton F Dickey, Christopher M Evans

Faculty, Staff and Student Publications

No abstract provided.

The Efficacy Of Selinexor (Kpt-330), An Xpo1 Inhibitor, On Non-Hematologic Cancers: A Comprehensive Review, Jennifer R Landes, Stephen A Moore, Brooke R Bartley, Hung Q Doan, Peter L Rady, Stephen K Tyring

Faculty, Staff and Student Publications

Purpose: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors.

Methods: Pertinent literature searches in PubMed and the Karyopharm Therapeutics …

Pathway-Driven Rare Germline Variants Associated With Transplant-Associated Thrombotic Microangiopathy (Ta-Tma), Zhihui Zhang, Wei Hong, Qian Wu, Spiridon Tsavachidis, Jian-Rong Li, Christopher I Amos, Chao Cheng, Sarah E Sartain, Vahid Afshar-Kharghan, Jing-Fei Dong, Pavan Bhatraju, Paul J Martin, Robert S Makar, Pavan K Bendapudi, Ang Li

Faculty, Staff and Student Publications

The significance of rare germline mutations in transplant-associated thrombotic microangiopathy (TA-TMA) is not well studied. We performed a genetic association study in 100 adult TA-TMA patients vs. 98 post-transplant controls after matching by race, sex, and year. We focused on 5 pathways in complement, von Willebrand factor (VWF) function and related proteins, VWF clearance, ADAMTS13 function and related proteins, and endothelial activation (3641variants in 52 genes). In the primary analysis focused on 189 functional rare variants, no differential variant enrichment was observed in any of the pathways; specifically, 29 % TA-TMA and 33 % controls had at least 1 rare …

Biallelic Variants In Adamts15 Cause A Novel Form Of Distal Arthrogryposis, Felix Boschann, Ozgur Cogulu, Davut Pehlivan, Saranya Balachandran, Pedro Vallecillo-Garcia, Christopher M Grochowski, Nils R Hansmeier, Zeynep H Coban Akdemir, Cesar A Prada-Medina, Ayca Aykut, Björn Fischer-Zirnsak, Simon Badura, Burak Durmaz, Ferda Ozkinay, René Hägerling, Jennifer E Posey, Sigmar Stricker, Gabriele Gillessen-Kaesbach, Malte Spielmann, Denise Horn, Knut Brockmann, James R Lupski, Uwe Kornak, Julia Schmidt

Faculty, Staff and Student Publications

No abstract provided.

Incidence Of Primary End Point Changes Among Active Cancer Phase 3 Randomized Clinical Trials, Marcus A Florez, Joseph Abi Jaoude, Roshal R Patel, Ramez Kouzy, Timothy A Lin, Brian De, Esther J Beck, Cullen M Taniguchi, Bruce D Minsky, Clifton D Fuller, J Jack Lee, Michael Kupferman, Kanwal P Raghav, Michael J Overman, Charles R Thomas, Ethan B Ludmir

Faculty, Staff and Student Publications

IMPORTANCE: Primary end point (PEP) changes to an active clinical trial raise questions regarding trial quality and the risk of outcome reporting bias. It is unknown how the frequency and transparency of the reported changes depend on reporting method and whether the PEP changes are associated with trial positivity (ie, the trial met the prespecified statistical threshold for PEP positivity).

OBJECTIVES: To assess the frequency of reported PEP changes in oncology randomized clinical trials (RCTs) and whether these changes are associated with trial positivity.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used publicly available data for complete oncology phase 3 …