Medical Specialties Commons^™

Cervical Necrotizing Fasciitis And Shock In The Post-Operative Pediatric Patient., Paul Bryan Hankey, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Cervical necrotizing fasciitis (CNF) is a rare infection that can quickly lead to devastating patient outcomes. Considering the vital importance of surrounding neck structures, rapid control of the infection is essential. Infection is most frequently polymicrobial and occurs in the adult patient in the context of certain medical comorbidities. Complications are typically limited to tissue destruction in the form of necrosis. There are no current reports describing CNF complicated by acute shock in the post-operative pediatric patient. Here, we present a pediatric case of CNF complicated by acute shock following Sistrunk procedure for removal of a supposed thyroglossal duct cyst. …

Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong

Faculty, Staff and Student Publications

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Methods: Human serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1KO) mice were fed a 45% high-fat diet, with serum samples collected every 2 weeks to monitor LRG1 and insulin levels throughout diet-induced obesity. MIN6 beta cells were used to investigate the effects …

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …

Prevention And Management Of Infectious Complications In Pediatric Patients With Cancer: A Survey Assessment Of Current Practices Across Children's Oncology Group Institutions., Leonora R. Slatnick, David Hoogstra, Brian T. Fisher, Joshua Wolf, Etan Orgel, C Nathan Nessle, Pratik A. Patel, Tamara P. Miller, Jennifer Wilkes, L Lee Dupuis, Erin Goode, Kasey Jackson, Daniel N. Willis, Caitlin Elgarten, Catherine Aftandilian, Joel Thompson, Sarah Alexander, Melissa P. Beauchemin, Jennifer A. Belsky, Jennifer Hess, Zachary D. Prudowsky, Terri Guinipero, Jenna Rossoff, Jenna Demedis, Alexandra M. Walsh, Rebecca Richards, Daniel K. Choi, Christopher C. Dvorak, Adam J. Esbenshade

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

METHODS: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

RESULTS: The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most …

Temperature-Controlled Radiofrequency Treatment Of The Nasal Valve In Nasal Airway Obstruction Patients With Septal Deviation, Dennis M Tang, Philip G Chen, Arthur W Wu, William C Yao

Faculty, Staff and Student Publications

Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.

Outcomes Of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Zhongya Wang, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Naureen Syed, Yosra Aljawai, Hans C Lee, Krina K Patel, Melody R Becnel, Christine Ye, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM …

The Associations Of Sensory Impairment With 10-Year Risk Of Dementia And Alzheimer's Disease: The Health And Retirement Study, 2010-2020, Kun Li, Rahul Ghosal, Donglan Zhang, Yike Li, Matthew C Lohman, Monique J Brown, Anwar T Merchant, Chih-Hsiang Yang, Jean Neils-Strunjas, Daniela B Friedman, Jingkai Wei

Faculty, Staff and Student Publications

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. …

Elder Mistreatment Within Stroke Family Caregiving, Carina Katigbak, Wesley R Browning, Sean Savitz, Carolyn E Z Pickering

Faculty, Staff and Student Publications

This secondary data analysis sought to identify characteristics associated with mistreatment among chronic stroke survivors who transition to dementia. We examined baseline data from a multi-time series survey study (n = 453; where caregivers of those with stroke n = 107, and those without stroke, n = 346) on caregiving experiences influencing dementia family caregivers’ abusive or neglectful behaviors. Inferential statistical analysis indicated that baseline mistreatment rates were similar across stroke and non-stroke subgroups, though this finding was not significant. Caregiver depression was significantly associated with mistreatment. Multi-morbidity, prescription medication use, and limited mobility were more common among stroke …

Difference-Makers For Collecting Sexual Orientation And Gender Identity Data In Oncology Settings, Mandi L Pratt-Chapman, Edward J Miech, Megan A Mullins, Shine Chang, Gwendolyn P Quinn, Shail Maingi, Matthew B Schabath, Charles Kamen

Faculty, Staff and Student Publications

Purpose: The purpose of this analysis was to identify key difference-making conditions that distinguish oncology institutions that collect sexual orientation and gender identity (SOGI) data across a sample of American Society of Clinical Oncology (ASCO) members.

Methods: From October to November 2020, an anonymous 54-item web-based survey was distributed to ASCO members. Coincidence analysis was used to identify difference-making conditions for the collection of SOGI data.

Results: ASCO members' responses to just three items consistently distinguished practices that reported collecting both SO and GI data (n = 25) from those who did not (n = 20): (1)."Do you ask your …

An Automated Treatment Planning Portfolio For Whole Breast Radiotherapy, Hana Baroudi, Leonard Che Fru, Deborah Schofield, Dominique L Roniger, Callistus Nguyen, Donald Hancock, Christine Chung, Beth M Beadle, Kent A Gifford, Tucker Netherton, Joshua S Niedzielski, Adam Melancon, Manickam Muruganandham, Meena Khan, Simona F Shaitelman, Sanjay Shete, Patricia Murina, Daniel Venencia, Sheeba Thengumpallil, Conny Vrieling, Joy Zhang, Melissa P Mitchell, Laurence E Court

Faculty, Staff and Student Publications

Background: Automation in radiotherapy presents a promising solution to the increasing cancer burden and workforce shortages. However, existing automated methods for breast radiotherapy lack a comprehensive, end-to-end solution that meets varying standards of care.

Purpose: This study aims to develop a complete portfolio of automated radiotherapy treatment planning for intact breasts, tailored to individual patient factors, clinical approaches, and available resources.

Methods: We developed five automated conventional treatment approaches and utilized an established RapidPlan model for volumetric arc therapy. These approaches include conventional tangents for whole breast treatment, two variants for supraclavicular nodes (SCLV) treatment with/without axillary nodes, and two …

Rhabdoid Tumor Of The Kidney And Soft Tissues: Results From National Wilms Tumor Study-5 And Children's Oncology Group Study Aren0321, James I Geller, Lindsay A Renfro, Paul E Grundy, Elizabeth J Perlman, John A Kalapurakal, Peter F Ehrlich, Jackie Biegel, Vicki Huff, Anne B Warwick, Arnold Paulino, Elizabeth A Mullen, Najat C Daw, Fredric A Hoffer, Zelig Tochner, Kenneth Gow, Eric Gratias, Deborah A Ward, James R Anderson, Conrad V Fernandez, Jeffrey S Dome

Faculty, Staff and Student Publications

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients and methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1). We report event-free survival (EFS) and overall survival (OS) from each study.

Results: Thirty patients received Regimen RTK on NWTS-5; …

An Antibody-Toxin Conjugate Targeting Cd47 Linked To The Bacterial Toxin Listeriolysin O For Cancer Immunotherapy, Benjamin R Schrank, Yifan Wang, Annette Wu, Nhat Tran, Daeyong Lee, Jared Edwards, Kristin Huntoon, Shiyan Dong, Jonghoon Ha, Yifan Ma, Adam J Grippin, Seong Dong Jeong, Abin Antony, Mengyu Chang, Minjeong Kang, Thomas D Gallup, Albert C Koong, Jing Li, Kyuson Yun, Betty Y S Kim, Wen Jiang

Faculty, Staff and Student Publications

Antigen-presenting cells phagocytose tumor cells and subsequently cross-present tumor-derived antigens. However, these processes are impeded by phagocytosis checkpoints and inefficient cytosolic transport of antigenic peptides from phagolysosomes. Here, using a microbial-inspired strategy, we engineered an antibody-toxin conjugate (ATC) that targets the 'don't eat me' signal CD47 linked to the bacterial toxin listeriolysin O from the intracellular bacterium Listeria monocytogenes via a cleavable linker (CD47-LLO). CD47-LLO promotes cancer cell phagocytosis by macrophages followed by LLO release and activation to form pores on phagolysosomal membranes that enhance antigen cross-presentation of tumor-derived peptides and activate cytosolic immune sensors. CD47-LLO treatment in vivo significantly …

Wmh Contributions To Cognitive Impairment: Rationale And Design Of The Diverse Vcid Study, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason Hinman, David K Johnson, Danielle Harvey, Myriam Fornage

Faculty, Staff and Student Publications

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter …

American Association Of Physicists In Medicine (Aapm) Chapter Climate Check: Mixed Methods Analysis Of Survey Responses, Ashley J Cetnar, Ghada Aldosary, Meghan C Koo, Holly Lincoln, Angélica Pérez-Andújar, Surendra Prajapati, Samantha J Simiele, Kristi R G Hendrickson

Faculty, Staff and Student Publications

Introduction: The American Association of Physicists in Medicine (AAPM) recently shared results and recommendations from its first Equity, Diversity, and Inclusion (EDI) Climate Survey, which was designed to assess the climate at the workplace, the AAPM organization, and the AAPM regional chapter level. This work further explores the status of EDI at the regional chapter level.

Methods: AAPM's EDI Survey was distributed to 5500 members and had a response rate of 25%. In the survey, three open-ended comment boxes were provided for feedback, including one for regional AAPM members. Sixty-four percent of respondents indicated they were part of a regional …

Psychometric Evaluation Of The Scleroderma Skin Questionnaire: A Novel Patient-Reported Outcome For Skin Disease In Patients With Systemic Sclerosis, Jeong Min Yu, John M Vanburen, Angela Child, Jessica S Alvey, Lisa A Mandl, Laura C Pinheiro, Shervin Assassi, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Brian Skaug, Virginia D Steen, Elizabeth R Volkmann, Jessica K Gordon

Faculty, Staff and Student Publications

Objective: We aimed to evaluate the psychometric properties of the Scleroderma Skin Questionnaire (SSQ), a novel patient-reported outcome (PRO) to assess systemic sclerosis (SSc)-related skin symptoms.

Methods: Participants were recruited from the SSc Collaborative National Quality and Efficacy Registry (CONQUER). Internal consistency was determined using Cronbach α and McDonald ω total (ωt). The correlation of the SSQ was assessed with the modified Rodnan skin score (mRSS), physician global assessment (PGA), Scleroderma Health Assessment Questionnaire, 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and patient global assessment to assess criterion, convergent, and divergent validity. Correlations were also assessed between patients' self-reported recall …

An Inducible Foxl2-Dependent Mouse Model Of Ovarian Adult Type Granulosa Cell Tumor, Jian Li, Thomas Welte, Katherine Calzoncinth, Veena K Vuttaradhi, Allison L Brodsky, Kwong-Kwok Wong, Manu M Sebastian, Barrett Lawson, Charles V Kingsley, R Tyler Hillman

Faculty, Staff and Student Publications

Background: Adult-type granulosa cell tumors (AGCTs) are rare ovarian sex cord/stromal tumors with near-universal hotspot mutations in FOXL2 (c.C402G; p.Cys134Trp). Progress in the treatment of relapsed AGCT has been hindered by the lack of high-fidelity FOXL2-based mouse models. To address this critical unmet need, we created and validated a genetically engineered inducible mouse model of the human FOXL2 mutation that recapitulates the key features of the human disease.

Methods: Gene targeting in embryonic stem cells was used to introduce a Cre-inducible Foxl2C130W allele (mouse equivalent of the human oncogenic mutation) into the endogenous mouse Foxl2 locus. Animals with the Foxl2C130W-FLEx …

Loncastuximab In High-Risk And Heavily Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Realworld Analysis From 21 Us Centers, Viktoriya Zelikson, Ashwath Gurumurthi, Yazeed Sawalha, Kaitlin Annunzio, Aditi Saha, Ning Dong, David Qualls, Behzad Amoozgar, Brad Kahl, John Baird, Pavan Challa, Scott F Huntington, Jennifer Santos, Steven Bair, Mayur Narkhede, Shuning Li, Zachary Frosch, Carrie Ho, Stephen D Smith, Allison Winter, Daniel Landsburg, Fateeha Furqan, Mehdi Hamadani, Katelin Baird, Jason Romancik, Hanan Alharthy, Jennie Law, Leyla Bojanini, Ranjana Advani, Boyu Hu, Patrick Connor Johnson, Natalie S Grover, Mwanasha Merril, Jennifer L Crombie, Nazila Shafagati, Cole Sterling, Loretta J Nastoupil, Narendranath Epperla, Emily C Ayers

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the …

A Phase 1 Study Of Durvalumab As Monotherapy Or Combined With Tremelimumab With Or Without Azacitidine In Patients With Myelodysplastic Syndrome, Guillermo Garcia-Manero, Manila Gaddh, Uwe Platzbecker, R Coleman Lindsley, Sarah M Larson, Timothy Chevassut, Pierre Fenaux, Rami Komrokji, Roger Lyons, Aref Al-Kali, Yu Jiang, John Bothos, Danielle M Townsley, Amer M Zeidan

Faculty, Staff and Student Publications

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status). Primary safety endpoints included dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). …

Encorafenib, Cetuximab And Chemotherapy In Braf-Mutant Colorectal Cancer: A Randomized Phase 3 Trial, Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero

Faculty, Staff and Student Publications

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, …

Reducing Igg Accumulation Via Neonatal Fc Receptor (Fcrn) Blockade Relieves Neuropathic Pain, Nathan T Fiore, Kendal F Willcox, Dorsa Dayani, Younus A Zuberi, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Preclinical and clinical studies have established that autoreactive immunoglobulin G (IgG) can drive neuropathic pain. We recently demonstrated that sciatic nerve chronic constriction injury (CCI) in male and female mice results in the production of pronociceptive IgG, which accumulates around the lumbar region, including within the dorsal root ganglia (DRG) and spinal cord, facilitating the development of neuropathic pain. These data raise the intriguing possibility that neuropathic pain may be alleviated by reducing the accumulation of IgG. To this end, we tested whether biologic inhibition or genetic deletion of the neonatal Fc receptor (FcRn) would attenuate mechanical hypersensitivity (allodynia) and …

Imgn853 Induces Autophagic Cell Death In Combination Therapy For Ovarian Cancer, Anca Chelariu-Raicu, Thanh Chung Vu, Sujanitha Umamaheswaran, Elaine Stur, Pahul Hanjra, Yunah Han, Min Hu, Jerome Lin, Barrett C Lawson, Jinsong Liu, Anil K Sood, Yunfei Wen

Faculty, Staff and Student Publications

FOLR1 is heterogeneously overexpressed in epithelial ovarian cancer. We examined the combined effects of the anti-FOLR1 antibody-drug conjugate (IMGN853) with other drugs, including topotecan, anti-VEGF-A antibody, and olaparib. These findings could contribute to the continued development of IMGN853 in the treatment of ovarian cancer.

Safety And Antitumor Activity Of A Novel Acd25 Treg Depleter Rg6292 As A Single Agent And In Combination With Atezolizumab In Patients With Solid Tumors, Valentina Gambardella, Michael Ong, Maria E Rodriguez-Ruiz, Jean-Pascal Machiels, Miguel F Sanmamed, Vladimir Galvao, Anna Spreafico, Daniel J Renouf, Stephen J Luen, Rachel Galot, Bernard Doger De Spéville, Emiliano Calvo, Aung Naing, Samira Curdt, Theresa Maria Kolben, Eva Rossmann, Tamara Tanos, Kevin Smart, Maria Amann, Yuying Xie, Linxinyu Xu, Enrique Gomez Alcaide, Nicolas Städler, Nicole Justies, Christophe Boetsch, Vaios Karanikas, Gabriel Schnetzler, Kristoffer S Rohrberg

Faculty, Staff and Student Publications

Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab were evaluated in two phase I studies.

Patients and methods: Adult patients with advanced solid tumors were administered intravenous RG6292, given every 3 weeks alone (study 1: NCT04158583, n = 76) or with 1,200 mg atezolizumab every 3 weeks (study 2: NCT04642365, n = 49). …

Rationale And Design Of The Defiance Study: A Randomized Controlled Trial Of Mechanical Thrombectomy Versus Anticoagulation Alone For Iliofemoral Deep Vein Thrombosis., Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black

Heart and Vascular Articles

BACKGROUND: Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.

METHODS: The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, …

Bevacizumab Beyond Progression: Impact Of Subsequent Bevacizumab Re-Treatment In Patients With Ovarian, Fallopian Tube, And Peritoneal Cancer After Progression, Amma Asare, Rebecca Ann Previs, Daniel Spinosa, Bryan Fellman, Amelia L Scott, Isabelle Mulder, May Mahmoud, Ahmed Enbaya, Jean Hansen Siedel, Lauren Cobb, Pamela T Soliman, Anil K Sood, Robert L Coleman, Angeles Alvarez Secord, Shannon N Westin

Faculty, Staff and Student Publications

Background: This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.

Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results: Among 226 patients with OC …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Exome Sequencing Identifies Helb As A Novel Susceptibility Gene For Non-Mucinous, Non-High-Grade-Serous Epithelial Ovarian Cancer, Ed M Dicks, Jonthan P Tyrer, Suzana Ezquina, Michelle Jones, John Baierl, Pei-Chen Peng, Michael Diaz, Ellen Goode, Stacey J Winham, Thilo Dörk, Toon Van Gorp, Anna De Fazio, David D L Bowtell, Dale W Garsed, Kunle Odunsi, Kirsten Moysich, Marina Pavanello, Florentia Fostira, Penelope M Webb, Jana Soukupová, Paul A Cohen, Weiva Sieh, Renée Turzanski Fortner, Charite Ricker, Beth Karlan, Ian Campbell, James D Brenton, Susan J Ramus, Simon A Gayther, Paul D P Pharoah

Faculty, Staff and Student Publications

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which …

Immunelens Characterizes Systemic Immune Dysregulation In Aging And Cancer, Robert Bentham, Thomas P Jones, James R M Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas B K Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, Genomics England Consortium, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower …

The Vivid Trial 12-Month Outcomes Of The Venous Stent For The Iliofemoral Vein Using The Duo Venous Stent System., Mahmood Razavi, Michael Lichtenberg, Kush Desai, David Dexter, Peter Soukas, Nicolas Shammas, Ankur Lodha, Paul Gagne, Anna Nordell, Raghu Kolluri, Mark Garcia

Heart and Vascular Articles

OBJECTIVE: There are varying anatomical and mechanical demands of stent placement in the iliofemoral venous segment; the Duo Venous Stent System is designed to address these issues. The purpose of the VIVID (Venous stent for the Iliofemoral Vein Investigational clinical trial using the Duo Venous Stent System) study was to investigate the safety and efficacy of the Duo Venous Stent System for the treatment of patients with nonmalignant iliofemoral venous obstructive disease.

METHODS: This was an international, prospective, multicenter, single-arm study that enrolled patients with symptomatic nonthrombotic (NT), post-thrombotic (PTS), or acute deep vein thrombotic (aDVT) iliofemoral venous outflow obstruction. …

Ethnoracial Disparities In Gray Matter Atrophy Are Mediated By Structural Disconnectivity In Multiple Sclerosis, Ahmed Bayoumi, Joseph A Thomas, Breanna R Alonzo, Juan Jimenez, Christopher M Orlando, Carlos A Pérez, Khader M Hasan, Jerry S Wolinsky, John A Lincoln

Faculty, Staff and Student Publications

Objective: To investigate ethnoracial disparities in gray matter (GM) atrophy, the contribution of white matter lesions and consequent structural disconnectivity among patients with multiple sclerosis (MS).

Methods: This retrospective study included 297 patients with MS (pwMS), 98 Hispanic/Latinx (H-MS), 82 non-Hispanic Black (B-MS), and 117 non-Hispanic White (W-MS). GM atrophy was assessed using univariate, voxel-based morphometry, and multivariate techniques, source-based morphometry. Structural disconnectivity secondary to white matter lesions was evaluated using the network modification tool. Mediation analyses explored relationships between ethnoracial groups, white matter lesions, structural disconnectivity, and gray matter atrophy.

Results: B-MS and H-MS generally exhibited greater gray matter …

Trends In Kidney Allograft Failure Among First-Time Transplant Recipients In The United States, Pascale Khairallah, Elizabeth C Lorenz, Amy Waterman, Nidhi Aggarwal, Akshta Pai, Wolfgang C Winkelmayer, Jingbo Niu

Faculty, Staff and Students Publications

Rationale & objective: The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality.

Study design: Retrospective cohort study.

Setting & participants: Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019.

Exposure: The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019.

Outcome: (1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure.

Analytical approach: Competing risk …