Digital Commons Network^™

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

A Multicenter Open-Label Randomized Phase Ii Study Of Osimertinib With And Without Ramucirumab In Tyrosine Kinase Inhibitor–Naïve Egfr-Mutant Metastatic Non–Small Cell Lung Cancer (Ramose Trial), Xiuning Le, Jyoti D Patel, Elaine Shum, Christina Baik, Rachel E Sanborn, Catherine A Shu, Chul Kim, Mary Jo Fidler, Richard Hall, Yasir Y Elamin, Janet Tu, George Blumenschein, Jianjun Zhang, Don Gibbons, Carl Gay, Nisha A Mohindra, Young Chae, Yanis Boumber, Joshua Sabari, Rafael Santana-Davila, Shane Rogosin, Benjamin Herzberg, Ben Creelan, Bruna Pellini, Tawee Tanvetyanon, Simon Heeke, Mike Hernandez, Jhanelle E Gray, Andreas Saltos, John V Heymach

Faculty, Staff and Student Publications

Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).

Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for …

Real-World Neoadjuvant And Adjuvant Trastuzumab-Containing Regimen Patterns And Their Association With Survival Among Patients With Operable Her2-Positive Breast Cancer From 2007 To 2021, Hui Zhao, Chan Shen, Jaime J Laureano, Xiudong Lei, Jiangong Niu, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Chemotherapy in combination with trastuzumab is the standard neoadjuvant and adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Assessing the regimens administered to patients with HER2-positive BC in the real world is lacking. We evaluated neoadjuvant and adjuvant regimen patterns among HER2-positive BC patients (2007 to 2021) identified in a health insurance claims database.

Methods: Female BC patients ≥ 18 years who received chemotherapy, surgery, and trastuzumab were chosen from Optum's de-identified Clinformatics® Data Mart database. Summary statistics, Joinpoint models, Kaplan-Meier survival curves, and Cox regression models were used to analyze the data.

Results: …

Pexidartinib And Standard Neoadjuvant Therapy In The Adaptively Randomized I-Spy2 Trial For Early Breast Cancer, Hope S Rugo, Mike Campbell, Christina Yau, A Jo Chien, Anne M Wallace, Claudine Isaacs, Judy C Boughey, Hyo S Han, Meredith Buxton, Julia L Clennell, Smita M Asare, Katherine Steeg, Amy Wilson, Ruby Singhrao, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Nola M Hylton, Angela M Demichele, Douglas Yee, Laura J Van't Veer, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.

Results: A total of 9 participants were randomized to receive pexidartinib …

Decoding Cancer Etiology With Cellular Reprogramming, Mo-Fan Huang, Megan E Fisher, Trinh T T Phan, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

Cancer research remains clinically unmet in many areas due to limited access to patient samples and the lack of reliable model systems that truly reflect human cancer biology. The emergence of patient-derived induced pluripotent stem cells and engineered human pluripotent stem cells (hPSCs) has helped overcome these challenges, offering a versatile alternative platform for advancing cancer research. These hPSCs are already proving to be valuable models for studying specific cancer driver mutations, offering insights into cancer origins, pathogenesis, tumor heterogeneity, clonal evolution, and facilitating drug discovery and testing. This article reviews recent progress in utilizing hPSCs for clinically relevant cancer …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Selinexor (Kpt-330) In Combination With Immune Checkpoint Inhibition In Uveal Melanoma: A Phase 1b Trial, Mohamed A Gouda, Abdulrazzak Zarifa, Yali Yang, Bettzy Stephen, Serdar A Gurses, Ashabari Sprenger, Yanyan Tian, Mohamed H Derbala, Isabella Glitza Oliva, Funda Meric-Bernstam, Sapna P Patel

Faculty, Staff and Student Publications

Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.

Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma. Patients received selinexor 60 mg PO twice weekly with standard of care, commercially available immune checkpoint inhibitor of the investigator's choice. In …

Imaging Lung Tumor Motion Using Integrated-Mode Proton Radiography-A Phantom Study Towards Tumor Tracking In Proton Radiotherapy, Ryan Fullarton, Mikaël Simard, Lennart Volz, Allison Toltz, Savanna Chung, Christoph Schuy, Daniel G Robertson, Gary Royle, Sam Beddar, Colin Baker, Christian Graeff, Charles-Antoine Collins-Fekete

Faculty, Staff and Student Publications

BACKGROUND: Motion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.

PURPOSE: Proton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated-mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring …

Rapidbrachyivbt: A Dosimetry Software For Patient-Specific Intravascular Brachytherapy Dose Calculations On Optical Coherence Tomography Images, Maryam Rahbaran, Jonathan Kalinowski, Joseph M Decunha, Kevin J Croce, Brian A Bergmark, James M G Tsui, Phillip M Devlin, Shirin A Enger

Faculty, Staff and Student Publications

Background: Coronary artery disease is the most common form of cardiovascular disease. It is caused by excess plaque along the arterial wall, blocking blood flow to the heart (stenosis). A percutaneous coronary intervention widens the arterial wall with the inflation of a balloon inside the lesion area and leaves behind a metal stent to prevent re-narrowing of the artery (restenosis). However, in-stent restenosis may occur due to damage to the arterial wall tissue, triggering neointimal hyperplasia, producing fibrotic and calcified plaques and narrowing the artery again. Drug-eluting stents, which slowly release medication to inhibit neointimal hyperplasia, are used to prevent …

Open-Chest Cardiac Ultrasound-Mediated Imaging With A Vacuum Coupler, Nilesh Mathuria, Krithik Vishwanath, Giorgio Brero, Blake C Fallon, Antonio Martino, Richard C Willson, Carly S Filgueira, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods.

PURPOSE: To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches.

METHODS: The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the …

Incidence Of Heterotopic Ossification Without Additional Long-Term Nsaid Prophylaxis After Periacetabular Osteotomy And Concomitant Hip Arthroscopy, J Matthew Helm, Omar Stocks, Brian Crowley, Alexis Aboulafia, Jacob Siahaan, Alfred A Mansour

Faculty, Staff and Student Publications

Background: Periacetabular osteotomy (PAO) is an established treatment for hip dysplasia and has been increasingly combined with concomitant hip arthroscopy to address additional intra-articular hip pathology. Heterotopic ossification (HO) is a complication of arthroscopic and open hip procedures. Nonsteroidal anti-inflammatory drugs (NSAIDs) have become an established form of HO prophylaxis, but their use may delay bone healing.

Purpose: To examine the incidence of HO without NSAID prophylaxis in patients after PAO with concomitant hip arthroscopy and to evaluate the impact of other variables on the development of HO in these patients.

Study design: Case series; Level of evidence, 4.

Methods: …

American Society For Gastrointestinal Endoscopy Guideline On The Diagnosis And Management Of Gerd: Methodology And Review Of Evidence, Asge Standards Of Practice Committee, Madhav Desai, Wenly Ruan, Nirav C Thosani, Manuel Amaris, J Stephen Scott, Ahmed Saeed, Barham Abu Dayyeh, Marcia Irene Canto, Wasif Abidi, Omeed Alipour, Stuart K Amateau, Natalie Cosgrove, Sherif E Elhanafi, Nauzer Forbes, Divyanshoo R Kohli, Richard S Kwon, Larissa L Fujii-Lau, Jorge D Machicado, Neil B Marya, Saowanee Ngamruengphong, Swati Pawa, Sunil G Sheth, Nikhil R Thiruvengadam, Bashar J Qumseya

Faculty, Staff and Student Publications

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for strategies to diagnose and manage GERD. This document was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and serves as an update to the prior ASGE guideline on the role of endoscopy in the management of GERD (2014). The updated guideline addresses the indications for endoscopy in patients with GERD, including patients who have undergone sleeve gastrectomy (SG) and peroral endoscopic myotomy (POEM). It also discusses endoscopic evaluation of gastroesophageal junctional integrity comprehensively and uniformly. Important, this guideline discusses …

Patient Outcomes Following Parasagittal Interlaminar Epidural Steroid Injections For Bilateral Lumbar Radicular Symptoms: Correlation Of Contrast Spread With Symptom Relief, Jamal Hasoon, Omar Viswanath, Alan D Kaye, Alberto Pasqualucci, Giustino Varrassi

Faculty, Staff and Student Publications

Introduction Bilateral lumbar radicular symptoms are commonly treated with interlaminar epidural steroid injections (ILESIs). The parasagittal approach often results in unilateral contrast spread, which may influence the degree of bilateral symptom relief. This study evaluates whether unilateral contrast spread correlates with symptom improvement in both ipsilateral and contralateral symptoms. Methods A retrospective review of six patients with bilateral lumbar radiculopathy secondary to lumbar degenerative disc disease, spondylosis, or disc herniation was conducted. All patients underwent ILESIs using a parasagittal approach. The injectate consisted of bupivacaine, preservative-free normal saline, and triamcinolone. Contrast spread was assessed fluoroscopically, and symptom relief was evaluated …

All Three Supersystems-Nervous, Vascular, And Immune-Contribute To The Cortical Infarcts After Subarachnoid Hemorrhage, Jens P Dreier, Alexander Joerk, Hiroki Uchikawa, Viktor Horst, Coline L Lemale, Helena Radbruch, Devin W Mcbride, Peter Vajkoczy, Ulf C Schneider, Ran Xu

Faculty, Staff and Student Publications

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical …

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …

From Stable Teamwork To Dynamic Teaming In The Ambulatory Care Diagnostic Process, Scott I Tannenbaum, Eric J Thomas, Sigall K Bell, Eduardo Salas

Faculty, Staff and Student Publications

Dynamic teaming is required whenever people must coordinate with one another in a fluid context, particularly when the fundamental structures of a team, such as membership, priorities, tasks, modes of communication, and location are in near-constant flux. This is certainly the case in the contemporary ambulatory care diagnostic process, where circumstances and conditions require a shifting cast of individuals to coordinate dynamically to ensure patient safety. This article offers an updated perspective on dynamic teaming commonly required during the ambulatory diagnostic process. Drawing upon team science, it clarifies the characteristics of dynamic diagnostic teams, identifies common risk points in the …

Protein Arginine Methyltransferases As Regulators Of Cellular Stress, Julia Zaccarelli-Magalhães, Cristiane Teresinha Citadin, Julia Langman, Drew James Smith, Luiz Henrique Matuguma, Hung Wen Lin, Mariana Sayuri Berto Udo

Faculty, Staff and Student Publications

Arginine modification can be a "switch" to regulate DNA transcription and a post-translational modification via methylation of a variety of cellular targets involved in signal transduction, gene transcription, DNA repair, and mRNA alterations. This consequently can turn downstream biological effectors "on" and "off". Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs 1-9) in both the nucleus and cytoplasm, and is thought to be involved in many disease processes. However, PRMTs have not been well-documented in the brain and their function as it relates to metabolism, circulation, functional learning and memory are understudied. In this review, we provide a comprehensive …

Case Studies In Heritable Vascular Disease: Proceedings Of The Uthealth Houston Multidisciplinary Aortic Conference, Milan Jaiswal, Lucas Ribe, Rana O Afifi, Yuki Ikeno, Alana C Cecchi, Bihong Zhao, Akiko Tanaka, Gustavo S Oderich, L Maximilian Buja, Dianna M Milewicz, Siddharth K Prakash, Anthony L Estrera

Faculty, Staff and Student Publications

Heritable thoracic aortic disease is caused by dominantly inherited mutations in more than a dozen genes, including TGFB2 mutations that cause Loeys-Dietz syndrome. McGovern Medical School at UTHealth Houston convenes a regular conference that includes cardiothoracic and vascular surgeons, cardiologists, geneticists, radiologists, and pathologists to formulate multidisciplinary approaches for the management of complex heritable thoracic aortic disease cases. In this report, we highlight the unique management of individuals with distinct presentations of Loeys-Dietz syndrome owing to TGFB2 mutations.

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Toward A Biological Definition Of Neuronal And Glial Synucleinopathies, Claudio Soto, Brit Mollenhauer, Oskar Hansson, Un Jung Kang, Roy N Alcalay, David Standaert, Claudia Trenkwalder, Kenneth Marek, Douglas Galasko, Kathleen Poston

Faculty, Staff and Student Publications

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms. We underscore the utility of the αSyn seed amplification assay to detect aggregated αSyn in living …

Mutational And Co-Mutational Landscape Of Early Onset Colorectal Cancer, Jumanah Yousef Alshenaifi, Guglielmo Vetere, Giulia Maddalena, Mahmoud Yousef, Michael G White, John Paul Shen, Eduardo Vilar, Christine Parseghian, Arvind Dasari, Van Karlyle Morris, Ryan Huey, Michael J Overman, Robert Wolff, Kanwal P Raghav, Jason Willis, Kristin Alfaro, Andy Futreal, Y Nancy You, Scott Kopetz

Faculty, Staff and Student Publications

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations …

Refining Diagnostic Subtypes Of Peripheral T-Cell Lymphoma Using A Multiparameter Approach, Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Ab Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) …

Reperfused Myocardial Infarction: The Road To Ccs Classification Of Acute Mi And Beyond., Rohan Dharmakumar, Robert A Kloner, Michael Fishbein, Gerd Heusch, Keyur P Vora, Robert Gropler, Timothy Henry, Fai Shing-Chan, Dhirendra Singh, Nithya Jambunathan, Ramesh Subramanian, Rolf P Kreutz, Grant W Reed, Richard J Kovacs, Edward Fry, Ankur Kalra, Andreas Kumar, Subha V Raman

Heart and Vascular Articles

The Canadian Cardiovascular Society recently put forth a new classification of acute reperfused myocardial infarction (MI) based on stages of myocardial injury. Backed by more than 5 decades of intense investigation in the field, the key message of this new classification is that not all MIs are the same and that the type and extent of myocardial injury should be considered in diagnosing and treating MI. We review the literature with the goal of highlighting the progressive advances that enabled the synthesis of the Canadian Cardiovascular Society classification into 4 distinct stages of tissue injury. We emphasize the major breakthroughs …

Preclinical And Clinical-Scale Magnetic Particle Imaging Of Natural Killer Cells: In Vitro And Ex Vivo Demonstration Of Cellular Sensitivity, Resolution, And Quantification, Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) …

Phase Ii Study Of Copanlisib In Patients With Pten Loss: Results From Nci-Match Ecog-Acrin Trial (Eay131) Subprotocols Z1g And Z1h, Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.

Methods: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of PTEN mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the PTEN gene and retained expression of PTEN …

Outcomes Of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants An Independent Prognostic Designation, Jayastu Senapati, Hagop M Kantarjian, Fadi G Haddad, Nicholas J Short, Gautam Borthakur, Rashmi Kanagal-Shamanna, Guilin Tang, Elias Jabbour, Courtney D Dinardo, Naval Daver, Guillermo Montalban-Bravo, Vishrut Shah, Amin Alousi, Elizabeth Shpall, Uday Popat, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior …

Rescue Stenting For Failed Mechanical Thrombectomy In Acute Basilar Artery Occlusions: Analysis Of The Pc-Search Registry., Santiago Ortega-Gutierrez, Aaron Rodriguez-Calienes, Adam T Mierzwa, Milagros Galecio-Castillo, Mahmoud Dibas, Sami Al Kasab, Ashley Nelson, Ashutosh P Jadhav, Shashvat Desai, Gabor Toth, Anas Alrohimi, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Hisham Salahuddin, Aditya Pandey, Sravanthi Koduri, Nirav Vora, Nameer Aladamat, Khaled Gharaibeh, Ehad Afreen, Syed Zaidi, Mouhammad Jumaa

Neuroscience Articles

BACKGROUND: We aimed to investigate whether rescue stenting (RS) following failed mechanical thrombectomy (MT) for acute basilar artery occlusion results in superior functional outcomes and enhanced safety compared with the natural history of failed MT.

METHODS: This retrospective cohort study utilized data from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-Procedural Predictors for Mechanical Thrombectomy registry, encompassing 8 high-volume centers in the United States and covering the period from 2015 to 2021. Patients with basilar artery occlusion who experienced failed MT (modified Thrombolysis in Cerebral Infarction score of 0-2a after at least 1 attempt of clot retrieval) were …

Rapid Whole Genome Sequencing Uncovers A Triple Diagnosis: X-Linked Chondrodysplasia Punctata, Mecp2-Related Disorder, And Mosaic Jacobs Syndrome, Megan Samuels, Kathleen Shields, Paul Hillman, Laura Farach

Faculty, Staff and Student Publications

Background: Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences.

Methods and results: This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2-related …

Stealth Navigation With Ifuse-Torq Implant For Sacroiliac Joint Fusion Technique Guide., Jia Bao Lin, Bryan L Demyan, Logan M Bushnell, Morgan T Turnow, Benjamin C Taylor

Surgery Articles

INTRODUCTION: Dysfunction of the sacroiliac (SI) joint exists in nearly one-third of patients with lower back pain. There are nuances in diagnosing SI joint dysfunction with a combination of physical exam maneuvers and intra-articular injections. The management of patients with SI joint pain can include posterior pelvic fixation, which traditionally has been described using fluoroscopy to obtain safe placement of implants.

CASE REPORT: In this technique guide, we would like to introduce a novel technique of using Stealth navigation to facilitate SI fusion with the iFuse-TORQ implant.

CONCLUSION: SI dysfunction is a common cause of low back pain that can …