Medical Specialties Commons^™

Difference In Clinical Presentation And Surgical Outcomes In Pediatric And Adult Patients With Chiari Malformation Type 1: A Single Center Retrospective Study, Erik Öhlén, Victor Gabriel El-Hajj, Victor E. Staartjes, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Chiari malformation type 1 (CM1) is a common congenital disorder affecting both children and adults. Although pediatric and adult CM1 patients share many characteristics, the differences between the groups are not fully described.

METHOD: A comparative analysis was made of two previously defined cohorts of adult and pediatric non-syndromic CM1, surgically treated at the study center. Clinical outcomes were assessed using the Chicago Chiari outcome scale (CCOS) and radiological outcomes were measured as change in cerebellar tonsil and syringomyelia status.

RESULTS: A total of 209 patients (73 pediatric, 136 adults) were included, with median ages of 11 and 33 …

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Impact Of Age On Biology, Presentation And Outcomes In Marginal Zone Lymphoma: Results From A Multicenter Cohort Study, Pallawi Torka, Natalie S. Grover, Timothy J. Voorhees, Reem Karmali, Kaitlin Annunzio, Marcus P. Watkins, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Given the paucity of age-specific data about biology, presentation, and treatment outcomes in adults with MZL, we sought to evaluate differences between younger (≤ 70 years) and older (> 70 years) patients with MZL in a large retrospective cohort treated in the contemporary era (2010 onwards). The primary objective was progression-free survival (PFS), while secondary objectives included the evaluation of overall survival (OS) and the cumulative incidence of transformation between the 2 groups. A total of 598 patients were included in the analysis and among these 32% were > 70 years of age. There were no age-based differences in the prevalence …

5-Year Outcomes After Transcatheter Or Surgical Aortic Valve Replacement In Low-Risk Patients With Aortic Stenosis., John K Forrest, Steven J Yakubov, G Michael Deeb, Hemal Gada, Mubashir A Mumtaz, Basel Ramlawi, Tanvir Bajwa, John Crouch, William Merhi, Stephane Leung Wai Sang, Neal S Kleiman, George Petrossian, Newell B Robinson, Paul Sorajja, Ayman Iskander, Pierre Berthoumieu, Didier Tchétché, Christopher Feindel, Eric M Horlick, Shigeru Saito, Jae K Oh, Yoojin Jung, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: The Evolut Low Risk trial demonstrated that transcatheter aortic valve replacement (TAVR) was noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke at 2 years. Outcomes at 5 years have not been reported.

OBJECTIVES: This study sought to evaluate 5-year clinical and hemodynamic outcomes with TAVR vs surgery in patients from the Evolut Low Risk trial.

METHODS: We randomly assigned low-risk patients with severe aortic stenosis to TAVR or surgery. The primary endpoint was a composite of all-cause mortality or disabling stroke. Secondary endpoints included clinical, echocardiographic, and quality-of-life outcomes through 5 years.

RESULTS: A …

Unmet Supportive Care Needs In Patients With Advanced Cancer And Its Impact On Distress, Kayla W Miranda, Benjamin L Musher, Hoda J Badr

Faculty, Staff and Students Publications

Purpose: Patients with advanced cancer endure considerable physical and emotional distress without sufficient supportive care. This cross-sectional study examined the relationship between cancer-related symptoms, supportive care needs, and distress levels in patients with advanced lung, head and neck, or gastrointestinal cancers.

Methods: 158 patients were assessed for symptom burden and distress levels using the M.D. Anderson Symptom Inventory (MDASI) and unmet needs using the Supportive Care Needs Survey (SCNS-34) within one month of treatment initiation. Pearson correlations and multiple regression analyses were used to explore associations between supportive care needs and distress.

Results: Distress levels were moderate across the study …

Partnering With Social Media Influencers To Promote Hpv Vaccination In Diverse Communities, Amy Leader, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Preethi Selvan, Kayla Madden, Joshua Banks, Angela Sustaita-Ruiz

Department of Medical Oncology Faculty Papers

BACKGROUND: While human papillomavirus (HPV) vaccination is one of the most effective ways to prevent HPV-related cancers, many children and adolescents remain unvaccinated. Resistance often stems from parental vaccine hesitancy and mistrust of the health care system, both of which may be higher in communities of color. Partnering with social media influencers may be an effective method for disseminating health messages. We tested the impact of HPV social media posts developed by influencers on outcomes of knowledge, attitudes, and intentions to vaccinate.

METHODS: Ten social media influencers who identified as African American or Hispanic created posts about the HPV vaccine. …

Changes Of Eeg Beta Band Power And Functional Connectivity During Spaceflight: A Retrospective Study, Adrián Quivira-Lopesino, María Sevilla-García, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Ana Maria Cebolla, Guy Cheron, Michael Funke, Fernando Maestu

Faculty, Staff and Student Publications

Spaceflight exposes astronauts to unique conditions like microgravity, which may affect brain function, though it remains underexplored compared to other physiological systems. Astronauts often report temporary neurological symptoms, such as disorientation, visual disturbances, and motor issues, potentially linked to structural and electrophysiological brain changes. To investigate this, electroencephalography (EEG) is a reliable tool to study brain activity in space, measuring oscillatory activity and functional connectivity (FC). This study analyzed EEG data from five male astronauts during three stages: pre-flight, during low Earth orbit (LEO), and post-flight in a 2-min task-free eyes-closed (EC) condition followed by another 2-min of eyes-open (EO) …

Kras Mutation Detection By Liquid Biopsy For Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7-4.3, P <  0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.

Reduced Venetoclax Exposure To 7 Days Vs Standard Exposure With Hypomethylating Agents In Newly Diagnosed Aml Patients, Christophe Willekens, Alexandre Bazinet, Samy Chraibi, Alex Bataller, Justine Decroocq, Naszrin Arani, Benjamin Carpentier, Caitlin Rausch, Delphine Lebon, Abhishek Maiti, Nicolas Gauthier, Nicholas Short, Sarah Bonnet, Koji Sasaki, Sabine Khalife-Hachem, Mahesh Swaminathan, Jean-Baptiste Micol, Florence Pasquier, Christophe Marzac, Damien Roos-Weil, Laurent Pascal, Naval Daver, Tapan Kadia, Didier Bouscary, Farhad Ravandi, Arnaud Pages, Hagop Kantarjian, Stéphane De Botton, Courtney Dinardo

Faculty, Staff and Student Publications

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) …

A Screening Question To Assess Risk Of Using Antibiotics Without A Prescription: A Diagnostic Study, Ashley Collazo, Eva Amenta, Kiara Olmeda, Marissa Valentine-King, Lindsey Laytner, Azalia Mancera, Roger Zoorob, Michael K Paasche-Orlow, Richard L Street, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Objectives: Non-prescription antibiotic use (using antibiotics without medical advice) is potentially unsafe and promotes antimicrobial resistance. We studied predictors of prior non-prescription use and whether screening for prior non-prescription antibiotic use predicted intention of future non-prescription antibiotic use.

Methods: The survey was performed from January 2020 - June 2021 in six public primary care clinics and two private emergency departments. Prior non-prescription users were respondents who reported taking oral antibiotics for symptoms without contacting a clinician. Intended use was defined by answering yes to the question, "would you use antibiotics without contacting a doctor/nurse/dentist/clinic." We examined predictors for prior non-prescription …

Nitrate Ameliorates Alcohol-Induced Cognitive Impairment Via Oral Microbiota, Xiangxue Li, Zhaojun Ni, Weixiong Shi, Kangqing Zhao, Yanjie Zhang, Lina Liu, Zhong Wang, Jie Chen, Zhoulong Yu, Xuejiao Gao, Ying Qin, Jingwen Zhao, Wenjuan Peng, Jie Shi, Thomas R Kosten, Lin Lu, Lei Su, Yanxue Xue, Hongqiang Sun

Faculty, Staff and Students Publications

Alcohol use is associated with cognitive impairment and dysregulated inflammation. Oral nitrate may benefit cognitive impairment in aging through altering the oral microbiota. Similarly, the beneficial effects of nitrate on alcohol-induced cognitive decline and the roles of the oral microbiota merit investigation. Here we found that nitrate supplementation effectively mitigated cognitive impairment induced by chronic alcohol exposure in mice, reducing both systemic and neuroinflammation. Furthermore, nitrate restored the dysbiosis of the oral microbiota caused by alcohol consumption. Notably, removing the oral microbiota led to a subsequent loss of the beneficial effects of nitrate. Oral microbiota from donor alcohol use disordered …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Integrated Analysis Of Molecular And Clinical Features Associated With Overall Survival In Melanoma Patients With Brain Metastasis, Swaminathan Kumar, Meredith S Pelster, Merve Hasanov, Renato A Guerrieri, Courtney W Hudgens, Debora A Ledesma, Fuchenchu Wang, Grant M Fischer, Julie M Simon, Lauren E Haydu, Kalman V Katlowitz, Y N Vashisht Gopal, Jennifer L Mcquade, Lawrence N Kwong, Jason T Huse, Alexander J Lazar, Michael T Tetzlaff, Jeffrey E Gershenwald, Aron Y Joon, Ken Chen, Ziyi Li, Prahlad T Ram, Sherise D Ferguson, Michael A Davies

Faculty, Staff and Student Publications

Melanoma brain metastases (MBMs) are diagnosed in up to 60% of metastatic melanoma patients. Previous studies have identified clinical factors that correlate with overall survival (OS) after MBM diagnosis. However, molecular and immune features associated with OS are poorly understood. An improved understanding of the molecular and immune correlates of OS could provide insights into MBM patient outcomes and guide therapeutic development. Thus, we analyzed clinical features and outcomes of 74 melanoma patients who underwent surgical resection (via craniotomy) between 1991 and 2015 at our institution with RNA-seq data generated from their MBMs. The median post-operative OS was 8.6 months …

Single-Cell Analyses Reveal A Functionally Heterogeneous Exhausted Cd8+ T-Cell Subpopulation That Is Correlated With Response To Checkpoint Therapy In Melanoma, Kelly M Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M Haugh, Laura A Huppert, Lauren S Levine, Margaret M Lowe, Michael Alvarado, Markee Micu, Katy K Tsai, Melissa Chow, Meromit Singer, Jason M Schenkel, Arlene H Sharpe, Michael D Rosenblum, Kristen E Pauken, Adil I Daud

Faculty, Staff and Student Publications

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Germline Pathogenic Drosha Variants Are Linked To Pineoblastoma And Wilms Tumor Predisposition, Peter N Fiorica, Lisa Golmard, Jung Kim, Riyue Bao, Frank Y Lin, Angshumoy Roy, Allison Pribnow, Melissa R Perrino, Julien Masliah-Planchon, Sophie Michalak-Provost, Jennifer Wong, Mathilde Filser, Dominique Stoppa-Lyonnet, Franck Bourdeaut, Afane Brahimi, Olivier Ingster, Giselle Saulnier Sholler, Sarah A Jackson, Mark M Sasaki, Trent Fowler, Anita Ng, Ryan J Corbett, Rebecca S Kaufman, Jeremy S Haley, David J Carey, Kuan-Lin Huang, Sharon J Diskin, Jo Lynne Rokita, Hussam Al-Kateb, Rose B Mcgee, Joshua D Schiffman, Kenneth S Chen, Douglas R Stewart, D Williams Parsons, Sharon E Plon, Kris Ann P Schultz, Kenan Onel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts.

Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a …

An Uncharacteristic Case Presentation Of Functional Vision Disorder, Ramandeep Kaur Od, Theresa Zerilli-Zavgorodni Od, Nancy Shenouda-Awad Od

Optometric Clinical Practice

Background: Functional Vision Disorder (FVD), also commonly referred to as functional vision loss (FVL) or non-organic vision loss (NOVL), is defined as a visual acuity (VA) loss and/or visual field (VF) loss, without any identifiable ocular or cortical pathology. Many clinicians look at FVD as a diagnosis of exclusion and while it is imperative to rule out organic pathology, FVD diagnosis must be supported by clinical findings that prove normal visual function. Incorporating supplementary tests specific for demonstrating the integrity of the visual system and the non-organic nature of the symptoms will allow clinicians to be more confident when diagnosing …

A Space-Occupying Lesion Manifesting As Unilateral Optic Disc Edema, Len V. Koh Od, Phd, Anna Wells Od, Lindsay Jansen Od

Optometric Clinical Practice

Background: Primary and secondary orbital diseases can arise from different tissues in the periorbital regions as space-occupying lesion leading to ophthalmic symptoms. Therefore, eye care providers are often the first encounter for these patients.

Case report: A 54-year-old Caucasian male presented as a new patient at the eye clinic with an incidental finding of edema of the left optic disc. After a thorough optometric evaluation, a referral was made to a local ear-nose-throat (ENT) specialist who confirmed a diagnosis of cavernous hemangioma by further neuroimaging. Surgical removal eventuated in resolution of disc edema with restoration of vision.

Conclusion: An insidious …

An Open-Label Study Evaluating The Safety And Efficacy Of Amo-01 For The Treatment Of Seizures In Phelan-Mcdermid Syndrome, Tess Levy, J Lloyd Holder, Joseph P Horrigan, Michael F Snape, Alison Mcmorn, Christina Layton, Hailey Silver, Kate Friedman, Hannah Grosman, Slayton Underwood, Danielle Halpern, Jessica Zweifach, Paige M Siper, Alexander Kolevzon

Duncan NRI Faculty and Staff Publications

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene. Approximately 25% of individuals with PMS have epilepsy. Treatment of epilepsy in PMS may require multiple anticonvulsants, and in a minority of cases, seizures remain poorly controlled. Converging lines of evidence in different experimental models indicate that the Ras-ERK pathway is implicated in the pathophysiology of seizure generation and neurobehavioral symptoms in PMS. The goal of this study was to evaluate the safety, tolerability, and efficacy in treating seizures in adults and adolescents with PMS using AMO-01, a Ras-ERK pathway inhibitor. A single 6-hour intravenous infusion …

Effects Of Metformin Use On Aneurysmal Subarachnoid Hemorrhage Outcomes, Angel Bueno, Andrea Becerril-Gaitan, Collins Mokua, Kristina Ramirez-Garcia, Justin Nguyen, Faris Shaker, Tien Nguyen, Antonio Dono, Spiros Blackburn, Peng Roc Chen, Mark Dannenbaum, H Alex Choi, Arthur L Day, Jacques J Morcos, Ching-Jen Chen

Faculty, Staff and Student Publications

Background: Metformin is widely prescribed and has neuroprotective effects in animals, but its impact on brain injury after aneurysmal subarachnoid hemorrhage (aSAH) in humans is unclear.

Methods: This single-center retrospective review assessed patients with aSAH from 2009 to 2023, categorizing them based on pre-admission metformin use. The primary outcome was delayed cerebral ischemia (DCI), while secondary outcomes included in-hospital mortality, rebleeding, angiographic cerebral vasospasm (CVS), and favorable modified Rankin Scale (mRS) scores at discharge and the 3-month follow-up. Outcomes were analyzed using logistic regression. Sensitivity analysis was performed after excluding patients receiving comfort care.

Results: A total of 900 patients …

Her2-Selective Tyrosine Kinase Inhibitor, Zongertinib (Bi 1810631), In Patients With Advanced/Metastatic Solid Tumors With Her2 Alterations: A Phase Ia Dose-Escalation Study, John V Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto

Faculty, Staff and Student Publications

Purpose: Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors.

Materials and methods: Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); …

Cell Type-Specific Multi-Omics Analysis Of Cocaine Use Disorder In The Human Caudate Nucleus, Lea Zillich, Annasara Artioli, Veronika Pohořalá, Eric Zillich, Laura Stertz, Hanna Belschner, Ammar Jabali, Josef Frank, Fabian Streit, Diana Avetyan, Maja P Völker, Svenja Müller, Anita C Hansson, Thomas D Meyer, Marcella Rietschel, Julia Ladewig, Rainer Spanagel, Ana M M Oliveira, Consuelo Walss-Bass, Rick E Bernardi, Philipp Koch, Stephanie H Witt

Faculty, Staff and Student Publications

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 30,030 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells. We observed 1485 differentially regulated genes and 10,342 differentially accessible peaks, with alterations in MSNs and astrocytes related to neurotransmitter activity and synapse organization. Gene regulatory network analysis identified transcription factors including ZEB1 as exhibiting distinct CocUD-specific subclusters, …

Impact Of Perioperative Organ Injury On Morbidity And Mortality In 28 Million Surgical Patients, Felix Kork, Yafen Liang, Adit A Ginde, Xiaoyi Yuan, Rolf Rossaint, Hongfang Liu, Alex S Evers, Holger K Eltzschig

Faculty, Staff and Student Publications

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases. In-hospital mortality was 1.4% (n = 393,157), and 4.4% of cases (n = 1,245,898) experienced perioperative organ injury. Perioperative organ injury was associated with 9-fold higher odds of death and prolonged hospital stay by 11.2 days. Acute kidney injury had the highest incidence (2.0%) and was associated with 25.0% mortality. While delirium had the second highest incidence (1.5%), it was associated …

Differential Antibody Response To Ebv Proteome Following Ebvst Immunotherapy In Ebv-Associated Lymphomas, Yomani D Sarathkumara, Nathan W Van Bibber, Zhiwei Liu, Helen E Heslop, Rayne H Rouce, Anna E Coghill, Cliona M Rooney, Carla Proietti, Denise L Doolan

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is associated with a diverse range of lymphomas. EBV-specific T-cell (EBVST) infusions have shown promise in safety and clinical effectiveness in treating EBV-associated lymphomas; however, not all patients respond to T-cell immunotherapies. To identify EBV antigen–specific antibody responses associated with clinical outcomes, we comprehensively characterized antibody responses to the complete EBV proteome using a custom protein microarray in 56 patients with EBV-associated lymphoma who received EBVST infusions in phase 1 clinical trials. Responders (nonprogressors) and nonresponders (progressors) had distinct antibody profiles against EBV. Twenty-five immunoglobulin G (IgG) antibodies were significantly elevated in higher levels in nonresponders than …

Phase 2 Trial Of Ibrutinib And Nivolumab In Patients With Relapsed Cns Lymphomas, Dai Chihara, Raphael E Steiner, Ranjit Nair, Lei Feng, Sairah Ahmed, Paolo Strati, Luis Malpica, Donna P Griffith, Shivon A Mathew, Wirt Montinez, Gita Masand, Felipe Samaniego, Maria A Rodriguez, Fredrick B Hagemeister, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Sattva S Neelapu, Christopher R Flowers, Jason R Westin

Faculty, Staff and Student Publications

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years …

Association Of Age, Sex And Education With Access To The Intravenous Thrombolysis For Acute Ischemic Stroke, Yoona Ko, Beom Joon Kim, Youngran Kim, Jong-Moo Park, Kyusik Kang, Jae Guk Kim, Jae-Kwan Cha, Tai Hwan Park, Kyungbok Lee, Jun Lee, Keun-Sik Hong, Byung-Chul Lee, Kyung-Ho Yu, Dong-Eog Kim, Joon-Tae Kim, Jay Chol Choi, Jee Hyun Kwon, Wook-Joo Kim, Kyu Sun Yum, Sung-Il Sohn, Hyungjong Park, Sang-Hwa Lee, Kwang-Yeol Park, Chi Kyung Kim, Sung Hyuk Heo, Moon-Ku Han, Anjail Z Sharrief, Sunil A Sheth, Hee-Joon Bae

Faculty, Staff and Student Publications

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients.

Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed …

A Phase Ii Trial Of Sitravatinib + Nivolumab After Progression On Immune Checkpoint Inhibitor In Patients With Metastatic Clear Cell Rcc, Andrew W Hahn, Nabil Adra, Ulka Vaishampayan, Lianchun Xiao, Nazli Dizman, Ying Yuan, Sagar S Mukhida, Matthew T Campbell, Jianjun Gao, Amado J Zurita, Eric Jonasch, Nizar M Tannir, Amishi Y Shah, Pavlos Msaouel

Faculty, Staff and Student Publications

Background: Sitravatinib, an oral multi-kinase inhibitor targeting VEGFR, TAM, and MET, has been shown to resensitize the tumor microenvironment to immune checkpoint inhibitors (ICI) by reducing immune-suppressive myeloid cells in metastatic clear cell RCC (ccRCC). ICI is the standard first-line (1L) treatment of metastatic ccRCC, and there is unmet need for improved treatment outcomes after progression on ICI. We hypothesized that sitravatinib plus nivolumab would revert an immunosuppressive tumor microenvironment (TME) to improve clinical outcomes.

Methods: In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into 3 …

Long-Term Patient-Reported Bowel And Urinary Quality Of Life In Patients Treated With Intensity-Modulated Radiotherapy Versus Intensity-Modulated Proton Therapy For Localized Prostate Cancer, Kimberly R Gergelis, Miao Bai, Jiasen Ma, David M Routman, Bradley J Stish, Brian J Davis, Thomas M Pisansky, Thomas J Whitaker, Richard Choo

Faculty, Staff and Student Publications

Purpose: This study aimed to compare long-term patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) for localized prostate cancer.

Methods and materials: Patients with clinical T1-T2 prostate cancer receiving IMRT or IMPT at a tertiary cancer center from 2015-2018 were analyzed to determine the changes in the prospectively collected bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26. The mean changes in EPIC-26 scores were evaluated from pretreatment to 24 months post-radiotherapy for each modality. A score change >50% of the baseline standard deviation was considered a …

A Prospective, Multicenter Analysis Of Recurrence-Free Survival After Sentinel Lymph Node Biopsy Decisions Influenced By The 31-Gep., J Michael Guenther, Andrew Ward, Brian J Martin, Mark Cripe, Timothy Beard, Oliver Wisco, Rohit Sharma, Stanley P Leong, Richard Essner, Joseph I Clark, John Hamner, Brenda Sickle-Santanello, Maki Yamamoto

Oncology Articles

BACKGROUND: Although most patients with cutaneous melanoma (CM) will have a negative sentinel lymph node biopsy (SLNB), up to 20%-30% of these patients will recur. The 31-gene expression profile (31-GEP) test has been prospectively validated to identify patients at low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) risk of SLN positivity and recurrence.

METHODS: DECIDE is a prospective, multicenter study to assess the effect of 31-GEP testing on SLNB performance rates in patients with T1-T2 tumors considering SLNB and to study long-term outcomes. Here, we assessed outcomes in patients with a Class 1A 31-GEP result (n = 130). …