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Efficacy And Safety Of Mechanical Thrombectomy In Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients On Low-Dose Aspirin, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and …

Effect Of The Cervical Lesion Severity On Procedural And Clinical Outcomes After Endovascular Treatment Of Acute Tandem Lesions: A Multicenter Study, Milagros Galecio-Castillo, Mudassir Farooqui, Ameer E Hassan, Mouhammad A Jumaa, Afshin A Divani, Marc Ribo, Michael Abraham, Nils H Petersen, Johanna T Fifi, Waldo R Guerrero, Amer M Malik, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Michael Dubinsky, Darko Quispe-Orozco, Wondwossen Tekle, Syed F Zaidi, Sara Y Sabbagh, Marta Olive-Gadea, Tiffany Barkley, Reade A De Leacy, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Charoskhon Turabova, Leonardo Cruz-Criollo, Piyush Kalakoti, Maxim Mokin, Dileep R Yavagal, Tudor G Jovin, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background: Tandem lesions pose unique challenges in the endovascular treatment of acute ischemic stroke. We aimed to compare the clinical and procedural outcomes of patients with tandem lesions and extracranial internal carotid artery (ICA) complete occlusion versus those with moderate to severe stenosis.

Methods: This is a subanalysis of a multicenter cohort of patients with acute anterior circulation tandem lesions treated with intracranial mechanical thrombectomy and carotid artery stenting, between January 2015 and December 2020. The patients were categorized into 2 groups: extracranial ICA stenosis >70% to 99% and complete occlusion. Outcomes included successful and excellent recanalization, functional independence, symptomatic …

Endovascular Therapy For Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis Of The Clear Study, Simon Winzer, Daniel P O Kaiser, Muhammad M Qureshi, Alicia C Castonguay, Daniel Strbian, Raul G Nogueira, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Hiroshi Yamagami, Kanta Tanaka, Sunil A Sheth, Anne Dusart, Patrik Michel, Marta Olive Gadea, Marc Ribo, Osama O Zaidat, Diogo C Haussen, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, James E Siegler, Ajit S Puri, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Milagros Galecio-Castillo, Sergio Salazar-Marioni, Pekka Virtanen, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Abiya Qureshi, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Mikko Sillanpää, Wei Hu, Eugene Lin, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Urs Fischer, Santiago Ortega-Gutierrez, Robin Lemmens, Peter A Ringleb, Thanh N Nguyen, Volker Puetz

Faculty, Staff and Student Publications

Background: There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The …

Hernia Recurrence Risk Matters More Than Mesh Type To Patients Undergoing Ventral Hernia Repair, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, Dalya M Ferguson, Jonah J Stulberg, Lillian S Kao, Julie L Holihan

Faculty, Staff and Student Publications

Introduction: Patients' perceptions about synthetic mesh for ventral hernia repair (VHR) may stem from a lack of knowledge of risks. We assessed patients' threshold for accepting the risk of hernia recurrence to avoid synthetic mesh.

Methods: Patients ≥18 y old with prior or upcoming VHR viewed a one-time video decision aid describing recurrence risk with biologic versus synthetic mesh. Patients chose between these options using a probability trade-off (PTO) technique, varying hernia recurrence rate with biologic mesh. Based on randomized trials, the recurrence rate using synthetic mesh was 9%. The PTO score was the recurrence rate (0%-100%) at which patients …

A Case Of Aqp4-Igg Neuromyelitis Optica Presenting With Orbital Inflammatory Syndrome, Lucy A Bailey, Roy F Riascos, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

A 45-year-old healthy African-American man experienced 2 months of right-eye soreness followed by acute onset of right painful vision loss with binocular, oblique diplopia. Visual acuity was count fingers OD and 20/20 OS. He had a partial, right, pupil-involving cranial nerve III palsy with a right relative afferent pupillary defect and optic disc edema with tortuous vessels. Magnetic resonance imaging showed increased T2 signal with tortuosity and thickening of the retrobulbar right optic nerve with associated restricted diffusion and enhancement, enhancement of orbital fat adjacent to the optic nerve sheath, and relative right proptosis. Workup was positive for aquaporin-4 antibody …

The Effect Of Anterior Closing Wedge Slope-Reducing Osteotomy On Coronal Alignment-Effect Of Osteotomy Technique, Starting Point, And Degree Of Correction., James Matthew Helm, Mark Coggins, Brian Crowley, Maile Curbo, Jacob Siahaan, Alexis Aboulafia, Alfred A Mansour

Faculty, Staff and Student Publications

Background: Techniques for anterior closing wedge slope-reducing osteotomy (ACW-SRO) remain variable regarding management of the tibial tubercle and osteotomy starting point. Moreover, the potential unintended effect on coronal alignment has not yet been determined.

Purpose: To determine the effect of the ACW-SRO technique and starting point on coronal alignment in knees with an elevated posterior tibial slope (PTS).

Study design: Descriptive laboratory study.

Methods: Full-length lower extremity computed tomography scans were retrospectively reviewed in patients presenting to our level 1 trauma center to identify patients with an elevated PTS of ≥12° without secondary trauma to the lower extremity. Materialise software …

A Recipe For Disaster - Sodium Bicarbonate Overdose

Faculty, Staff and Student Publications

Audience: Emergency medicine residents post-graduate years 1-4.

Introduction: Sodium bicarbonate is a compound found commonplace in many households and in many products. It lends itself to countless everyday uses including cooking and cleaning. Physicians prescribe sodium bicarbonate regularly both on- and off-label regularly for various ailments.1 Due to the ubiquitous way both emergency physicians and the general public use and are exposed to sodium bicarbonate, we wanted to prepare learners to identify and appropriately manage sodium bicarbonate toxicity.Obtaining a thorough history not just of medications prescribed but of significant ingestions or infusions is critical in diagnosing this toxicity. Furthermore, acute …

Ten Practical Tips For A Successful Presentation At An Infectious Disease Clinical Case Conference

Faculty, Staff and Student Publications

This mini-review provides 10 practical tips for infectious disease trainees presenting at clinical case conferences. These tips, grounded in principles from education theory, aim to enhance the effectiveness of case presentations.

Cdemapper: Enhancing National Institutes Of Health Common Data Element Use With Large Language Models, Yujia Zhou, Xubing Hao, Pritham Ram, Lingfei Qian, Qianqian Xie, Ruey-Ling Weng, Fongci Lin, Yan Hu, Licong Cui, Xiaoqian Jiang, Hua Xu, Na Hong

Faculty, Staff and Student Publications

Objective: Common Data Elements (CDEs) standardize data collection and sharing across studies, enhancing data interoperability and improving research reproducibility. However, implementing CDEs presents challenges due to the broad range and variety of data elements. This study aims to develop a CDE mapping tool to bridge the gap between local data elements and National Institutes of Health (NIH) CDEs.

Methods: We propose CDEMapper, a large language model (LLM)-powered mapping tool designed to assist in mapping local data elements to NIH CDEs. CDEMapper has 3 core modules: (1) CDE indexing and embeddings. NIH CDEs were indexed and embedded to support semantic search; …

Evaluating Large Language Model Performance To Support The Diagnosis And Management Of Patients With Primary Immune Disorders, Cullen Dutmer, Jocelyn R Farmer, Kirk Roberts, Guergana Savova, Mei-Sing Ong

Faculty, Staff and Student Publications

Background: Generative artificial intelligence (GAI) is transforming health care in a variety of ways; however, the present utility of GAI for supporting clinicians who treat rare disease such as primary immune disorders (PIs) is not well studied. We evaluated the ability of 6 state-of-the-art large language models (LLMs) for providing clinical guidance about PIs.

Objective: To quantitatively and qualitatively measure the utility of current, open-source LLMs for diagnosing and providing helpful clinical decision support about PIs.

Methods: Five expert clinical immunologists each provided 5 real-world, anonymized PI case vignettes via multi-turn prompting to 6 LLMs (OpenAI GPT-4o, Llama-3.1-8B-Instruct, Llama-3.1-70B-Instruct, Mistral-7B-Instruct-v0.3, …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Pancreatic Neuroendocrine Neoplasm (Pnen) Cohort, Sandip Pravin Patel, Jillian Fisher, Young Kwang Chae, Luisa Solis Soto, Anup Kasi, Mark Walshauser, Jiexin Zhang, Caroline Duault, Edgar Gonzalez-Kozlova, Ganiraju Manyam, Jianhua Zhang, Hong Chen, Dzifa Yawa Duose, Caddie Laberiano Fernandez, Raja Luthra, Gheath Al-Atrash, Seunghee Kim-Schulze, Holden T Maecker, Ignacio I Wistuba, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Christine M Magner, Helen X Chen, Elad Sharon, Megan Othus, Christopher W Ryan, Charles Blanke, Cara L Haymaker, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

Experimental design: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative …

Bayesian-Weighted Mendelian Randomization Reveals Sleep Apnea Syndrome Mediates The Bmi-Chronic Pain Link, Wenbao Shi, Jing Luo, Liu Yang, Dalin Chen, Yongqin Zhang, Kurt Ruetzler, Hua Jin

Faculty, Staff and Student Publications

Background: Body mass index (BMI) has a complex association with a variety of chronic pain conditions, which may be influenced by sleep apnea syndrome (SAS). However, the role of SAS within the causal pathway linking BMI to chronic pain remains unconfirmed. This study explored whether and to what extent SAS serves as a mediator between BMI and chronic pain using Bayesian-weighted Mendelian randomization (BWMR) techniques.

Methods: This study utilized genome-wide association study (GWAS) summary data for BMI (N=461,460) and SAS (N=476,853; based on ICD-10 code diagnostic registries) from the IEU OpenGWAS database, along with chronic pain GWAS data (ICD-10 code-based …

Letter Of Concern From The Association Of Academic Chairs Of Emergency Medicine Regarding Acgme Proposed Changes, Richard J Hamilton, Lance B Becker, Richard E Wolfe, D Adam Algren, Thomas Arnold, Ross P Berkeley, Chad M Cannon, Theodore J Corbin, Michael E Chansky, Harinder S Dhindsa, Charles L Emerman, David A Farcy, Chris Fox, Michael A Gibbs, Christopher S Goode, Steven Andy Godwin, Dietrich Jehle, David Johnson, Samuel M Keim, Babak Khazaeni, Barry J Knapp, Clint Hawthorne, John D Hoyle, Michael Christopher Kurz, Evan Leibner, Robert Mcnamara, Robert F Mccormack, Edward A Michelson, Chadwick Miller, Ashley Norse, Andrew Nugent, Brian J O'Neil, David T Overton, Edward A Panacek, William F Paolo, Denis R Pauzé, Amanda L Perez, Ralph J Riviello, Scott W Rodi, Peter S Pang, Juan A Gonzalez Sanchez, David Seaberg, Adam Schwartz, Stephen A Shiver, David P Sklar, Ben C Smith, Jeffrey R Stowell, Marc D Squillante, J Jeremy Thomas, Terry Vanden Hoek, Gregory A Volturo, E Lea Walters, Thomas E Wyatt, Donald M Yealy

Faculty, Staff and Student Publications

This letter, signed by over 50 academic chairs of emergency medicine, urges the ACGME to reconsider a proposed mandate requiring all emergency medicine residency programs to adopt a four-year training model. The authors argue that current three-year programs are supported by data demonstrating equivalent educational and clinical outcomes compared to four-year formats. They criticize the flawed survey methodology underpinning the proposal, note the loss of milestone-based training flexibility, and highlight the lack of added scholarly or clinical value in the fourth year. The letter also outlines negative consequences for fellowship participation, workforce development, trainee debt, and diversity. The signatories advocate …

Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Tae Won Kim, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators

Faculty, Staff and Student Publications

Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty, Staff and Student Publications

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …

A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, You Zhang

Faculty, Staff and Student Publications

Objective. Deformable liver motion tracking using a single x-ray projection enables real-time motion monitoring and treatment intervention. We introduce a conditional point cloud diffusion (PCD) model-based framework for accurate and robust liver motion tracking from arbitrarily angled single x-ray projections. Approach. We propose a conditional PCD model for liver motion tracking (PCD-Liver), which estimates volumetric liver motion by solving deformable vector fields (DVFs) of a prior liver surface point cloud, based on a single x-ray image. It is a patient-specific model of two main components: a rigid alignment model to estimate the liver’s overall shifts, and a conditional PCD …

Correction: Identification Of A Fusobacterial Rna-Binding Protein Involved In Host Small Rna-Mediated Growth Inhibition, Pu-Ting Dong, Mengdi Yang, Jie Hu, Lujia Cen, Peng Zhou, Difei Xu, Peng Xiong, Jiahe Li, Xuesong He

Faculty, Staff and Student Publications

No abstract provided.

Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Lauren Byers, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker

Faculty, Staff and Student Publications

Tumor-initiated emergency granulopoiesis results in expansion of the circulating neutrophil compartment and neutrophil recruitment into the tumor microenvironment (TME), which may in turn promote tumor progression. Although an elevated circulating neutrophil-to-lymphocyte ratio (cNLR) has repeatedly been demonstrated to be an adverse prognostic factor in patients with non-small cell lung cancer (NSCLC), whether this neutrophil expansion in circulation reflects a similar relative neutrophil abundance in the TME remains unclear. We sought to characterize the relationships between cNLR and the intratumoral neutrophil-to-lymphocyte ratio (tNLR), between tNLR and proteogenomic and immune features of NSCLC tumors, and between tNLR and prognosis.We analyzed tNLR (transcriptomic …

The Carsr Two-Component System Directly Controls Radd Expression As A Global Regulator That Senses Bacterial Coaggregation In Fusobacterium Nucleatum, Bibek G C, Chenggang Wu

Faculty, Staff and Student Publications

Two-component systems (TCS) enable bacteria to sense and respond to environmental signals, facilitating rapid adaptation. Fusobacterium nucleatum, a key oral pathobiont, employs the CarSR TCS to modulate coaggregation with various gram-positive partners by regulating the expression of radD, encoding a surface adhesion protein, as revealed by RNA-Seq analysis. However, the direct regulation of the radD-containing operon (radABCD) by the response regulator CarR, the broader CarR regulon, and the signals sensed by this system remain unclear. In this study, chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) identified approximately 161 CarR-enriched loci across the genome and …

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Giulia Maggioni, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …

Effect Of Perioperative Haemodynamic Management Based On Cerebral Autoregulation Monitored By Cerebral Oximetry Index During Carotid Endarterectomy: Protocol Of A Randomised Trial, Qixiao Yan, Daniel I Sessler, Rong Wang, Lei Zhao, Yuming Peng

Faculty, Staff and Student Publications

Introduction: Impaired cerebral autoregulation is associated with postoperative ischaemic brain injury and often occurs in patients with carotid artery stenosis. Adequate cerebral perfusion should therefore be maintained during carotid endarterectomies. Whether guiding intraoperative blood pressure to the Cerebral Oximetry Index (a measure of cerebral perfusion adequacy) reduces postoperative cerebral ischaemia remains unclear.

Methods and analysis: We plan a dual-centre randomised blinded trial. A total of 560 patients having elective carotid endarterectomy will be randomly assigned to guided versus routine haemodynamic management. In patients randomised to guided management, mean arterial pressure will be titrated to maintain a normal cerebral oximetry index. …

Education Improves Perceived Control But Not Risk Identification In Adolescents Regarding Fentanyl, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Background/objectives: In 2022, 2.2 million adolescents were diagnosed with substance use disorders, including 265,000 with opioid use disorder. The National Survey on Drug Use and Health revealed that 130,000 adolescents misused prescription pain medications, often obtaining them from friends or relatives. This age group perceives weekly heroin use as less risky than those younger or older.

Methods: A questionnaire was developed for 7th to 12th graders in a rural Texas school district as part of a fentanyl awareness curriculum. The questionnaire included Likert scale, multiple choice, and yes/no questions. The participants were categorized into younger (grades 7th and 8th) and …

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, María Hernández-Sánchez, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …

Blastemia Portrays A Poor Prognosis In Acute Leukemia Patients With Invasive Pulmonary Aspergillosis, Sung-Yeon Cho, Sebastian Wurster, Ying Jiang, Alexandre Bazinet, Yang Hui, Takahiro Matsuo, Guillermo Garcia-Manero, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Objectives: Severe and prolonged neutropenia is associated with poor outcomes of invasive pulmonary aspergillosis (IPA) in leukemia patients. Given the high frequency of IPA in patients with relapsed/refractory leukemia, we studied the association of peripheral blood blast burden (blastemia), IPA outcomes, and antifungal immune failure, even without neutropenia.

Methods: We retrospectively reviewed adult patients with acute leukemia (AL) or myelodysplastic syndrome and culture-positive proven/probable IPA (2011-2022). Blast and neutropenia indices were calculated and incorporated into multi-variable prognostic models. The impact of blasts on immune cell-mediated fungal clearance was studied in vitro.

Results: Among 74 patients, 69% had neutropenia and 57% …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Rahmah Ejaz, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Azacitidine, Venetoclax, And Magrolimab In Newly Diagnosed And Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/Ii Study And Correlative Analysis, Naval Daver, Jayastu Senapati, Hagop M Kantarjian, Bofei Wang, Patrick K Reville, Musa Yilmaz, Tapan M Kadia, Mhd Yousuf Yassouf, Abhishek Maiti, Sankalp Arora, Guillermo Montalban Bravo, Guilin Tang, Gautam Borthakur, Koji Sasaki, Naveen Pemmaraju, Joie Alvarez, Graciela M Nogueras Gonzalez, Jing Ning, Ghayas C Issa, Marina Konopleva, Michael Andreeff, Farhad Ravandi, Guillermo Garcia-Manero, Hussein A Abbas

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody directed against the macrophage checkpoint CD47 on myeloid leukemia cells that was preclinically synergistic with azacitidine-venetoclax, warranting further clinical evaluation.

Patients and methods: In this phase Ib/II study, the triplet combination of azacitidine, venetoclax, and magrolimab was evaluated in adult patients with first-line (ineligible for intensive chemotherapy) and relapsed/refractory acute myeloid leukemia. Azacitidine was dosed at 75 mg/m2 for 7 days, venetoclax at 400 mg/day for 28 days, and magrolimab (recommended phase II dose) as follows: 1 mg/kg dose on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days …

Risk And Protective Factors Associated With Teenage Pregnancy And Intergenerational Interventions: A Scoping Review Protocol, Serwaa Omowale, Busisiwe Purity Ncama, Sinegugu E Duma

Faculty, Staff and Student Publications

Introduction: Teenage pregnancy remains a critical global health issue, particularly in low- and middle-income countries. The intergenerational transmission of teenage pregnancy underscores the need for targeted interventions. Existing research on intergenerational approaches is fragmented, with varying methodologies and outcomes. This scoping review seeks to address this gap by answering the following research questions: What are the available intergenerational interventions for teenage pregnancy, and what are the associated risks and protective factors for early and late teenage pregnancy?

Methods and analysis: This study does not involve primary data collection and therefore does not require ethical approval. The review will be conducted …

Identification Of A Fusobacterial Rna-Binding Protein Involved In Host Small Rna-Mediated Growth Inhibition, Pu-Ting Dong, Mengdi Yang, Jie Hu, Lujia Cen, Peng Zhou, Difei Xu, Peng Xiong, Jiahe Li, Xuesong He

Faculty, Staff and Student Publications

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed …

Enhancing Dementia Classification For Diverse Demographic Groups: Using Vision Transformer-Based Continuous Scoring Of Clock Drawing Tests., Laura B Zahodne

Faculty, Staff and Student Publications

Objectives: Alzheimer's disease and related dementias significantly affect older adults' quality of life. The clock-drawing test (CDT) is a widely used dementia screening tool due to its ease of administration and effectiveness. However, manual CDT-coding in large-scale studies can be time-intensive and prone to coding errors and is typically limited to ordinal responses. In this study, we developed a continuous CDT score using a deep learning neural network (DLNN) and evaluated its ability to classify participants as having dementia or not.

Methods: Using a nationally representative sample of older adults from the National Health and Aging Trends Study (NHATS), we …

Structural Basis For The Substrate Specificity Of Helix Pomatia Amp Deaminase And A Chimeric Adgf Adenosine Deaminase, Gundeep Kaur, John R Horton, George Tzertzinis, Jujun Zhou, Ira Schildkraut

Faculty, Staff and Student Publications

Helix pomatia AMP deaminase (HPAMPD), an enzyme enriched in the foot muscle of the mollusk H. pomatia, exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is the first member of the adenosine deaminase-related growth factor (ADGF) family to prefer the nucleotide AMP over the nucleoside adenosine. To investigate the substrate selectivity of HPAMPD, we determined its structure in both the apo form and in complex with the adenosine analogs pentostatin and pentostatin-5'-monophosphate. Structurally, HPAMPD adopts a fold similar to human ADA2, an ADGF family member. HPAMPD has acquired the ability to interact with the 5'-monophosphate group of AMP through polar and …