Medical Specialties Commons^™

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Impacts Of The Conductive Networks On Solid-State Battery Operation, Shimao Deng, Yixian Wang, Tianxiao Sun, Wenlong Li, Mingyuan Ge, Jian Wang, Peter Cloetens, Piero Pianetta, David Mitlin, Yijin Liu

Faculty, Staff and Student Publications

The micromorphology of composite cathodes is known to play a vital role in determining all‐solid‐state battery (ASSB) performance. However, much of our current understanding is derived from empirical observations, lacking a deeper mechanistic foundation. The “rocking chair” concept of battery chemistry requires maintaining charge neutrality, emphasizing the necessity of examining electrode micromorphology from the perspective of conductive networks. This study systematically investigates the microscopic electrochemical impacts of conductive network micromorphology by varying the Li+‐to‐e− channel ratio in cathodes comprising LiNbO3‐coated LiNi0.8Co0.1Mn0.1O2, Li6PS5Cl, and carbon fibers. Utilizing multiscale synchrotron‐based spectro‐microscopy, we unravel that unbalanced Li+ and e− conducting channels intensify charge …

Trends And Disparities In Acute Coronary Syndrome-Related Mortality In The United States: Implications For Healthcare, Muhammad Khuzzaim Khan, Ibrahim Ahmed Khan, Abdul Moiz Javed, Arslan Wazir, Hira Saleem, Muhammad Zohaib, Faisal Rasheed, Priyanka Mohan Lal, Syeda Laiba Sherazi, Amiaz Karim, Nikhil Duseja, Hussam Al Hennawi

Abington Jefferson Health Papers

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States (US). However, the trends and disparities in ACS mortality are not well understood. This study aimed to analyze the ACS mortality in the US from 1999 to 2020 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. The age-adjusted mortality rates (AAMR) due to ACS were calculated for each year from 1999 to 2020, stratified by sex, race, urbanization, and state. The trends and disparities in AAMR were examined using descriptive statistics and graphical methods. The AAMR due …

Early Blood Pressure Targets In Acute Spinal Cord Injury: A Randomized Clinical Trial, Ruba Sajdeya, N. David Yanez, Michael Kampp, Michael D. Goodman, David Zonies, Brandon Togioka, Andrew Nunn, Robert D. Winfield, Niels D. Martin, Anirudh Kohli, Toan T. Huynh, David O. Okonkwo, Roy A. Poblete, Emily J. Gilmore, Randall M. Chesnut, Aaron E. Bunnell, Tetsu Ohnuma, Mona Hashemaghaie, Miriam M. Treggiari

Department of Surgery Faculty Papers

IMPORTANCE: Early blood pressure management is central to neurologic resuscitation of spinal cord injury; however, the role of augmented blood pressure is unclear.

OBJECTIVE: To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

INTERVENTIONS: Patients were equally randomized to augmented (>85-90 mm Hg) or conventional ( …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Performance Of 123i-Ioflupane Spect Striatal Binding In Dementia With Lewy Bodies, Emily F. Maly, Frank P. Difilippo, Brittany Lapin, Yadi Li, Sarah Berman, Andrea C. Bozoki, Jori E. Fleisher, James E. Galvin, David J. Irwin, Carol F. Lippa, Irene Litvan, Debby W. Tsuang, Cyrus P. Zabetian, Angela S. Taylor, Lynn M. Bekris, Oscar L. Lopez, Douglas Galasko, James B. Leverenz

Department of Neurology Faculty Papers

INTRODUCTION: We aimed to determine whether ¹²³I-ioflupane single-photon emission computed tomography (SPECT) striatal binding ratio (SBR) correlated with parkinsonian motor symptoms in dementia with Lewy bodies (DLB) and if SBR predicts worsening of parkinsonism over time.

METHODS: A retrospective cohort study of the U.S. Dementia with Lewy Bodies Consortium dataset including individuals with DLB with baseline ¹²³I-ioflupane SPECT analyzed with DaTQUANT and baseline and 24-month Movement Disorder Society Unified Parkinson's Disease Rating Scale–Part III (MDS-UPDRS-III). A subset had cerebrospinal fluid α-synuclein seed amplification assay (SAA) evaluation.

RESULTS: Baseline mean SBRs were significant predictors of baseline and 24-month MDS-UPDRS-III …

Association Between Climate Change Awareness And Depression & Anxiety: Findings From A U.S. Sample, Stanley Nkemjika, Colvette Brown, Henry Onyeaka, Srikanta Banerjee, Jennifer Oliphant

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Exploring the connection between climate change awareness and overall well-being is crucial, particularly in how it impacts both the environment and mental health. The mental health consequences of climate change and its awareness have not been thoroughly examined, especially in the U.S. In this study, the relationship between awareness of climate change and depression or anxiety among U.S. adults was explored. Similarly, the role of climate change awareness has not been explored in relation to mental health concerns.

METHODS: Based on the HINTS-6 dataset, a nationally representative, cross-sectional survey conducted by the National Cancer Institute, a variety of statistical …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Fares Qeadan, Amanda D Henderson, Andrew R Harrison, Giovanni Defazio, Mark Hallett, Gamze Kilic-Berkmen, Laura Wright, Samantha Pentecost, Paul Reyes, Anna Tingin, Joseph Jankovic, Jane Boyd, Charlene Hudgins, Janet Hieshetter, Joel S Perlmutter, Hyder A Jinnah, Sarah Pirio Richardson

Faculty, Staff and Students Publications

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

A Phase 2 Study Of Obinutuzumab Combined With Lenalidomide In Previously Untreated High Tumor Burden Follicular Lymphoma, Neha Akkad, Lei Feng, Jason R Westin, Fredrick B Hagemeister, Hun Ju Lee, Luis Fayad, Sairah Ahmed, Ranjit Nair, Maria Alma Rodriguez, Paolo Strati, Dai Chihara, Christopher R Flowers, Linda Claret, Karina Ibanez, Michael Wang, Nathan H Fowler, Jared Henderson, R Eric Davis, Sattva S Neelapu, Michael Green, Loretta J Nastoupil

Faculty, Staff and Student Publications

Follicular lymphoma (FL) has a clinical course that is often characterized by high response rates to first-line therapy, followed by multiple relapses over a prolonged natural history. Currently, there are multiple possible approaches to frontline therapy for untreated advanced-stage FL, but there is an ongoing debate around what is the preferred approach. Based on the benefits seen with combining lenalidomide, an immunomodulatory agent, with rituximab, an anti-CD20 antibody, we aimed to evaluate the safety and efficacy of lenalidomide in combination with obinuzutumab, an anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity. The eligibility criteria included a diagnosis of FL, grade 1 …

Fruquintinib In Less Pretreated Patients: Multivariate Profile-Matching Analysis Of Fresco-2 To Fresco, Arvind Dasari, Cathy Eng, Sara Lonardi, Rocio Garcia-Carbonero, Toshiki Masuishi, Chiara Cremolini, François Ghiringhelli, Joleen Hubbard, Tanios Bekaii-Saab, Jeremy Jones, Rui-Hua Xu, Lin Shen, Jianming Xu, Yuxian Bai, Yanhong Deng, Ying Yuan, Wei Wei, Jianchang Lin, Lucy Chen, Zhao Yang, William R Schelman, Shukui Qin, Jin Li

Faculty, Staff and Student Publications

Background: In the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, fruquintinib vs placebo, plus best supportive care, significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). These studies were conducted in temporally and geographically diverse populations that received distinct prior therapies; FRESCO patients were less pretreated than FRESCO-2 patients. This analysis assessed the efficacy and safety of fruquintinib in a less pretreated global population than the FRESCO-2 intention-to-treat (ITT) population.

Methods: In FRESCO and FRESCO-2, patients were randomized 2:1 to receive oral fruquintinib 5 mg or matched placebo. Profile matching was undertaken …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …

Detection Of Cancers Three Years Prior To Diagnosis Using Plasma Cell-Free Dna, Yuxuan Wang, Corinne E Joshu, Samuel D Curtis, Christopher Douville, Vernon A Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W Kinzler, Nickolas Papadopoulos, Elizabeth A Platz, Bert Vogelstein

Faculty, Staff and Student Publications

To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …

Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.

METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

Bone Quality Response To Lifestyle Intervention In Older Adults With Obesity (Limb-Q Trial): A Randomised Controlled Trial, Giulia Gregori, Sanjay Mediwala, Michael Liebschner, Daeseung Kim, Mon S Bryant, Nina Klonis, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Lifestyle interventions for weight loss might exacerbate age-related bone loss and osteoporosis. However, there is limited knowledge about their effects on bone quality. We examined whether lifestyle intervention can preserve or enhance bone quality, despite reductions in bone mineral density.

Methods: The Lifestyle Intervention to Improve Bone Quality (LIMB-Q) study was a randomised controlled trial conducted at Baylor College of Medicine and the Michael E DeBakey VA Medical Center (Houston, TX, USA) including older adults (aged 65-85 years) with obesity (BMI ≥30 kg/m2). Participants were randomly assigned to receive either an intensive lifestyle intervention (intensive lifestyle group, consisting of …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Mucinous Cystic Neoplasms Of The Pancreas And Liver Share A Similar Dna Methylation Profile With Mucinous Ovarian Tumors, Zoe Leoni, Teodor G Calina, Tobias Janik, Elena Grafenhorst, Eliane T Taube, Christopher Cm Neumann, Baoqing Chen, Elena I Braicu, Jalid Sehouli, Thomas Malinka, Wenzel Schöning, Johann Pratschke, George A Calin, David S Klimstra, Jamal K Benhamida, Irene Esposito, Markus Möbs, David Horst, Simon Schallenberg, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian-like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and six hepatic MCNs (MCN-L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

One-Year Outcomes From The Pivotal Trial Of A Four-Branch Off-The-Shelf Solution To Treat Pararenal And Extent Iv Thoracoabdominal Aortic Aneurysms, Mark A Farber, Sukgu Han, Michel S Makaroun, Jon S Matsumura, Bernardo C Mendes, Gustavo S Oderich, Luis A Sanchez, Bjoern D Suckow, Carlos H Timaran

Faculty, Staff and Students Publications

Objective: To report 1-year primary-arm outcomes of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis pivotal trial.

Methods: The multicenter, nonrandomized, prospective study included patients with extent IV thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). All-cause and adjudicated lesion-related mortality were assessed at 12 months. Core-lab-reported, imaging-dependent outcomes included aneurysm size, endoleaks assessed through 1-year follow-up window, and target vessel instability (defined as occlusion, stenosis, type Ic/IIIc endoleak, or reintervention) at 1 year.

Results: One hundred two patients were treated; 59 patients had an extent IV TAAA and 43 had a PRAA. The mean maximum aneurysm diameter was 59.4 ± …

Five-Year Pivotal Trial Outcomes Of The Gore Excluder Conformable Endoprosthesis Implanted In Abdominal Aortic Aneurysms With Short Non-Angulated Infrarenal Seal Zones, Bjoern D Suckow, Gustavo S Oderich, Mahmoud W Almadani, Dai Yamanouchi, Alyssa J Pyun, Erin Moore, Patrick E Muck, Robert Y Rhee

Faculty, Staff and Students Publications

Objective: The GORE EXCLUDER Conformable Abdominal Aortic Aneurysm Endoprosthesis with Active Control System (EXCC) is approved in the United States (U.S.) for treatment of AAAs and highly angulated (≤90°) and short (≥10 mm) infrarenal aortic proximal seal zones (necks). Reported here are the 5-year outcomes of the EXCC U.S. pivotal clinical trial in the short, non-angulated cohort (SNA).

Methods: The EXCC investigational device exemption prospective pivotal trial short neck sub-study across 31 sites included patients with infrarenal necks measuring ≥10 mm length and ≤60° angulation. Five-year outcomes assessed by Core lab and adjudicated by independent review committee included patient safety …

Leveraging Existing Cohort Studies Of Mexican Women To Better Understand Hispanic Health And Cancer Risk, Dalia Stern, Liliana Gomez-Flores-Ramos, Britton Trabert, V Wendy Setiawan, Loïc Le Marchand, Henry Gomez, Paul A Scheet, Humberto Parada, Amber Pirzada, Martin Lajous, Leslie V Farland

Faculty, Staff and Student Publications

Background: Hispanics have been historically underrepresented in epidemiologic cancer research. Existing cohort studies focused on recruiting Hispanic participants have been relatively small, making studying cancer outcomes challenging. Therefore, we aimed to compare the distribution of cancer risk factors among Hispanic women of Mexican heritage (HWMH) participating in existing cohorts to explore the possibility of future data pooling efforts.

Methods: We used baseline data of HWMH from three US-based studies, the Mexican American Cohort (MAC; n = 19,797; 2001-2017), the Multiethnic Cohort (MEC; n = 18,007; 1993-1996), and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 4,022; 2008-2011), and …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

Baseline Α-Synuclein Seeding Activity And Disease Progression In Sporadic And Genetic Parkinson’S Disease In The Ppmi Cohort, Jackson G Schumacher, Xinyuan Zhang, Eric A Macklin, Jian Wang, Armin Bayati, Johannes M Dijkstra, Hirohisa Watanabe, Michael A Schwarzschild, Marianna Cortese, Xuehong Zhang, Xiqun Chen

Faculty, Staff and Student Publications

Background: α-Synuclein (α-syn) seed amplification assays (SAAs) have shown remarkable potential in diagnosing Parkinson's disease (PD). Using data from the Parkinson's Progression Markers Initiative (PPMI) cohort, we aimed to test whether baseline α-syn seeding activity and α-syn SAA kinetic parameters are associated with disease progression in sporadic PD, LRRK2-associated PD (LRRK2 PD), and GBA-associated PD (GBA PD).

Methods: We analysed 7 years of motor, non-motor, and cognitive assessments and 5 years of dopamine transporter imaging along with baseline α-syn SAA results from 564 PPMI participants (n = 332 sporadic PD, 162 LRRK2 PD, and 70 GBA PD) using linear mixed-effects …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …