Medical Specialties Commons^™

History Of Childhood Physical Abuse Is Associated With Gut Microbiota Diversity Among Adult Psychiatric Inpatients, Jessica C Rohr, Katelynn A Bourassa, Dominique S Thompson, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Alok Madan

Faculty, Staff and Students Publications

BACKGROUND: Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients.

METHODS: 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community.

RESULTS: Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon …

Microbiome Alterations Driven By Trypanosoma Cruzi Infection In Two Disjunctive Murine Models, Sergio Castañeda, Marina Muñoz, Peter J Hotez, Maria Elena Bottazzi, Alberto E Paniz-Mondolfi, Kathryn M Jones, Rojelio Mejia, Cristina Poveda, Juan David Ramírez

Faculty, Staff and Students Publications

Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal …

Poly(A)-Binding Protein Is An Ataxin-2 Chaperone That Regulates Biomolecular Condensates, Steven Boeynaems, Yanniv Dorone, Yanrong Zhuang, Victoria Shabardina, Guozhong Huang, Anca Marian, Garam Kim, Anushka Sanyal, Nesli-Ece Şen, Daniel Griffith, Roberto Docampo, Keren Lasker, Iñaki Ruiz-Trillo, Georg Auburger, Alex S Holehouse, Edor Kabashi, Yi Lin, Aaron D Gitler

Duncan NRI Faculty and Staff Publications

Biomolecular condensation underlies the biogenesis of an expanding array of membraneless assemblies, including stress granules (SGs) which form under a variety of cellular stresses. Advances have been made in understanding the molecular grammar of a few scaffold proteins that make up these phases, but how the partitioning of hundreds of SG proteins is regulated remains largely unresolved. While investigating the rules that govern the condensation of ataxin-2, a SG protein implicated in neurodegenerative disease, we unexpectedly identified a short 14aa sequence that acts as a condensation switch and is conserved across the eukaryote lineage. We identify poly(A)-binding proteins as unconventional …

Complement C3ar Depletion Reverses Hif-1Α-Induced Metabolic Impairment And Enhances Microglial Response To Aβ Pathology, Manasee Gedam, Michele M Comerota, Nicholas E Propson, Tao Chen, Feng Jin, Meng C Wang, Hui Zheng

Faculty, Staff and Students Publications

Microglia are the major cell type expressing complement C3a receptor (C3aR) in the brain. Using a knockin mouse line in which a Td-tomato reporter is incorporated into the endogenous C3ar1 locus, we identified 2 major subpopulations of microglia with differential C3aR expression. Expressing the Td-tomato reporter on the APPNL-G-F-knockin (APP-KI) background revealed a significant shift of microglia to a high-C3aR-expressing subpopulation and they were enriched around amyloid β (Aβ) plaques. Transcriptomic analysis of C3aR-positive microglia documented dysfunctional metabolic signatures, including upregulation of hypoxia-inducible factor 1 (HIF-1) signaling and abnormal lipid metabolism in APP-KI mice compared with wild-type controls. Using primary …

Snx3 Is Important For Mammalian Neural Tube Closure Via Its Role In Canonical And Non-Canonical Wnt Signaling, Lei Dong, Mengchuan Xu, Yang Li, Wanting Xu, Chengwei Wu, Hanfei Zheng, Zhenyu Xiao, Guochen Sun, Lei Ding, Xiaobo Li, Wenming Li, Liying Zhou, Qin Xia

Faculty, Staff and Student Publications

Cancer cells consistently utilize the unfolded protein response (UPR) to encounter the abnormal endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins. Extreme activation of the UPR could also provoke maladaptive cell death. Previous reports have shown that NRF2 antioxidant signaling is activated by UPR and serves as noncanonical pathway to defense and reduce excessive ROS levels during ER stress. However, the mechanisms of regulating NRF2 signaling upon ER stress in glioblastoma have not been fully elucidated. Here we identify that SMURF1 protects against ER stress and facilitates glioblastoma cell survival by rewiring KEAP1-NRF2 pathway. We show that …

Her3-Targeted Therapeutic Antibodies And Antibody–Drug Conjugates In Non-Small Cell Lung Cancer Refractory To Egfr-Tyrosine Kinase Inhibitors, Margaret E. Larsen, Hui Lyu, Bolin Liu

School of Medicine Faculty Publications

Human epidermal growth factor receptor 3 (HER3) is a unique member of the human epidermal growth factor receptor (HER/EGFR) family, since it has negligible kinase activity. Therefore, HER3 must interact with a kinase-proficient receptor to form a heterodimer, leading to the activation of signaling cascades. Overexpression of HER3 is observed in various human cancers, including non-small cell lung cancer (NSCLC), and correlates with poor clinical outcomes in patients. Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers. Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase …

An Agenda To Advance Research In Myelodysplastic Syndromes: A Top 10 Priority List From The First International Workshop In Mds, Maximilian Stahl, Omar Abdel-Wahab, Andrew H. Wei, Michael R. Savona, Mina L. Xu, Zhuoer Xie, Justin Taylor, Daniel Starczynowski, Guillermo F. Sanz, David A. Sallman, Valeria Santini, Gail J. Roboz, Mrinal M. Patnaik, Eric Padron, Olatoyosi Odenike, Aziz Nazha, Stephen D. Nimer, Ravindra Majeti, Richard F. Little, Steven Gore, Alan F. List, Vijay Kutchroo, Rami S. Komrokji, Tae Kon Kim, Nina Kim, Christopher S. Hourigan, Robert P. Hasserjian, Stephanie Halene, Elizabeth A. Griffiths, Peter L. Greenberg, Maria Figueroa, Pierre Fenaux, Fabio Efficace, Amy E. Dezern, Matteo G. Della Porta, Naval G. Daver, Jane E. Churpek, Hetty E. Carraway, Andrew M. Brunner, Uma Borate, John M. Bennett, Rafael Bejar, Jacqueline Boultwood, Sanam Loghavi, Jan Philipp Bewersdorf, Uwe Platzbecker, David P. Steensma, Mikkael A. Sekeres, Rena J. Buckstein, Amer M. Zeidan

Department of Medical Oncology Faculty Papers

No abstract provided.

Radiofrequency Ablation As A Treatment Modality For Primary Hyperparathyroidism: A Systematic Literature Review, Peter P. Issa, Emad Kandil, Grace S. Lee

School of Medicine Faculty Publications

Background: Primary hyperparathyroidism (pHPT) is an endocrine disorder typically characterized by elevated serum calcium and elevated parathyroid hormone (PTH). While parathyroidectomy is the standard treatment, non-operative intervention such as radiofrequency ablation (RFA) has been adopted as an alternative for the management of pHPT, as it has been utilized in other endocrine glands such as thyroid and adrenal. In this literature review, we aim to evaluate the current practice of RFA for pHPT. Methods: A systematic literature search using PubMed, Web of Science, and Embase through June 2022 was conducted. Studies included in the review consisted of patient cohorts who had …

Editorial: Developments In Sickle Cell Disease Therapy And Potentials For Gene Therapy, Robert W. Maitta, Hollie M. Reeves

Faculty Scholarship

No abstract provided.

Exenatide As An Adjunct To Nicotine Patch For Smoking Cessation And Prevention Of Postcessation Weight Gain Among Treatment-Seeking Smokers With Pre-Diabetes And/Or Overweight: Study Protocol For A Randomised, Placebo-Controlled Clinical Trial, Luba Yammine, Christopher D Verrico, Francesco Versace, Heather E Webber, Robert Suchting, Michael F Weaver, Thomas R Kosten, Husein Alibhai, Paul M Cinciripini, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

INTRODUCTION: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have …

Advances And Emerging Medical Applications Of Direct Mass Spectrometry Technologies For Tissue Analysis, Mary E King, Monica Lin, Meredith Spradlin, Livia S Eberlin

Faculty, Staff and Students Publications

Offering superb speed, chemical specificity, and analytical sensitivity, direct mass spectrometry (MS) technologies are highly amenable for the molecular analysis of complex tissues to aid in disease characterization and help identify new diagnostic, prognostic, and predictive markers. By enabling detection of clinically actionable molecular profiles from tissues and cells, direct MS technologies have the potential to guide treatment decisions and transform sample analysis within clinical workflows. In this review, we highlight recent health-related developments and applications of direct MS technologies that exhibit tangible potential to accelerate clinical research and disease diagnosis, including oncological and neurodegenerative diseases and microbial infections. We …

A Multi-Omics Atlas Of The Human Retina At Single-Cell Resolution, Qingnan Liang, Xuesen Cheng, Jun Wang, Leah Owen, Akbar Shakoor, John L Lillvis, Charles Zhang, Michael Farkas, Ivana K Kim, Yumei Li, Margaret Deangelis, Rui Chen

Faculty, Staff and Students Publications

Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including more than 250,000 nuclei for single-nuclei RNA-seq and 137,000 nuclei for single-nuclei ATAC-seq. Cross-species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared with that of rodent and chicken retina. Through integrative analysis, we identified 35,000 distal cis-element-gene pairs, constructed transcription factor (TF)-target regulons for more than 200 …

Rare Event Of Intraoral Kinking Of Endotracheal Tube Upon Prone Positioning In A Patient Undergoing Posterior Fossa Surgery, Sonali Turki, Amiya K. Barik, Amit Sharma, Abhishek Arya

International Journal of Health and Allied Sciences

Prone position is commonly employed for many surgical procedures including neurosurgeries, spine surgeries, urological procedures, and in refractory ARDS patients. An endotracheal tube is a conduit to provide a secured airway to the patient. But in case of any equipment failure, it can cause catastrophic events. Intra-oral kinking is a rarer event. It can pose a major troubleshooting standstill owing to the inaccessible view of the kinked portion and the rarity of its occurrence to cross the clinician’s mind in the emergency scenario. We thus report this as the first such case of intraoral kinking against the soft palate in …

Noninvasive Continuous Monitoring To Improve Outcome Of Preeclamptic Women Undergoing Spinal Anesthesia For Cesarean Section, Andrea M. Regan, Molly Amin, Josue Brainin Md

Department of Health Sciences Faculty Proceedings, Presentations, Posters, Speeches, Lectures, etc.

Spinal induced hypotension is a common side effect and occurs in up to 33% of patients. Preeclamptic women have a high risk of severe hypotension related to spinal anesthesia while undergoing cesarean section Hypotension, short or cumulative episodes, increase nausea and vomiting in parturient and can potentially result in fetal acidosis, hypoxic-ischemic encephalopathy(HIE), and lower Apgar scores. The recommend standard of care is a minimum of five-minute interval blood pressure monitoring which risks late detection and treatment of hypotension. ClearSight® noninvasive continuous hemodynamic monitoring decreases the risk of hypotension-associated complications in mother and fetus and improves maternal nausea and vomiting …

Obstetric Treatment Of Post Dural Puncture Headaches (Pdph): Less Invasive Alternatives To Epidural Blood Patches (Ebp), Andrea M. Regan, Molly Amin, Josue Brainin Md, Sanjeev Patel Md

Department of Health Sciences Faculty Proceedings, Presentations, Posters, Speeches, Lectures, etc.

Neuraxial labor analgesia for vaginal delivery or cesarean section is performed in more than 71% of women in the United States. Postdural puncture headache(PDPH) is a relatively common complication of neuraxial anesthesia. Epidural blood patch (EBP) is considered the gold standard treatment, and although EBP is a highly effective intervention, it is not without risk. There is growing evidence that less invasive alternative treatments, such as combined use of atropine and neostigmine have effectively relieved PDPH where traditional, conservative methods have failed. The goal is to discover the best method in preventing PDPH and less invasive treatment alternatives compared to …

Reasons For Transfer And Subsequent Outcomes Among Patients Undergoing Elective Spine Surgery At An Orthopedic Specialty Hospital, Tristan B. Fried, Yunsoo Lee, Jeremy C. Heard, Nicholas S. Siegel, Tariq Z. Issa, Mark J. Lambrechts, Caroline Zaworski, Jasmine Wang, Taylor D'Amore, Amit Syal, Charles Lawall, John J. Mangan, Jose A. Canseco, Barrett I. Woods, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder

Rothman Institute Papers

Objective:

To evaluate the reasons for transfer as well as the 90-day outcomes of patients who were transferred from a high-volume orthopedic specialty hospital (OSH) following elective spine surgery.

Materials and Methods:

All patients admitted to a single OSH for elective spine surgery from 2014 to 2021 were retrospectively identified. Ninety-day complications, readmissions, revisions, and mortality events were collected and a 3:1 propensity match was conducted.

Results:

Thirty-five (1.5%) of 2351 spine patients were transferred, most commonly for arrhythmia (n = 7; 20%). Thirty-three transferred patients were matched to 99 who were not transferred, and groups had similar rates …

Neighbourhood‐Level Social Deprivation And The Risk Of Recurrent Heart Failure Hospitalizations In Type 2 Diabetes, Salil V. Deo, Sadeer Al-Kindi, Yakov Elgudin, Eiran Gorodeski, Sanjay Rajagopalan

Faculty Scholarship

Background: The importance of type 2 diabetes mellitus (T2D) in heart failure hospitalizations (HFH) is acknowledged. As information on the prevalence and influence of social deprivation on HFH is limited, we studied this issue in a racially diverse cohort. Methods: Linking data from US Veterans with stable T2D (without prevalent HF) with a zip-code derived population-level social deprivation index (SDI), we grouped them according to increasing SDI as follows: SDI: group I: ≤20; II: 21-40; III: 41-60; IV: 61-80; and V (most deprived) 81-100. Over a 10-year follow-up period, we identified the total (first and recurrent) number of HFH episodes …

Troponin In Acute Chest Pain To Risk Stratify And Guide Effective Use Of Computed Tomography Coronary Angiography (Target-Ctca): A Randomised Controlled Trial, Kuan Ken Lee, David Lowe, Rachel O'Brien, Ryan Wereski, Anda Bularga, Caelan Taggart, Matthew T H Lowry, Amy V Ferry, Michelle C Williams, Giles Roditi, John Byrne, Chris Tuck, Denise Cranley, Praveen Thokala, Steve Goodacre, Catriona Keerie, John Norrie, David E Newby, Alasdair J Gray, Nicholas L Mills

Faculty, Staff and Student Publications

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.

METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. …

Impact Of An Integrated Classifier Using Biomarkers, Clinical And Imaging Factors On Clinical Decisions Making For Lung Nodules, Fayez Kheir, Juan P. Uribe, Juan Cedeno, Gustavo Munera, Harsh Patel, Ramsy Abdelghani, Atul Matta, Sadia Benzaquen, Regina Villalobos, Adnan Majid

Einstein Health Papers

BACKGROUND: An integrated classifier that utilizes plasma proteomic biomarker along with five clinical and imaging factors was previously shown to be potentially useful in lung nodule evaluation. This study evaluated the impact of the integrated proteomic classifier on management decisions in patients with a pretest probability of cancer (pCA) ≤50% in "real-world" clinical setting.

METHODS: Retrospective study examining patients with lung nodules who were evaluated using the integrated classifier as compared to standard clinical care during the same period, with at least 1-year follow-up.

RESULTS: A total of 995 patients were evaluated for lung nodules over 1 year following the …

Top 10 Things To Know About Falls In Older Adults, Alexander W. Zirulnik, Shan Liu

Journal of Geriatric Emergency Medicine

No abstract provided.

A Novel Comorbidity Score For Older Adults With Non-Hodgkin Lymphoma: The 3-Factor Risk Estimate Scale, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Alessandra Ferrajoli, Alexey V Danilov, Sharon H Giordano

Faculty, Staff and Student Publications

For patients with non-Hodgkin lymphoma (NHL), formal comorbidity assessment is recommended but is rarely conducted in routine practice. A simple, validated measure of comorbidities that standardizes their assessment could improve adherence to guidelines. We previously constructed the 3-factor risk estimate scale (TRES) among patients with chronic lymphocytic leukemia (CLL). Here, we investigated TRES in multiple NHL subtypes. In the surveillance, epidemiology, and end results-Medicare database, patients with NHL diagnosed from 2008 to 2017 were included. Upper gastrointestinal, endocrine, and vascular comorbidities were identified using ICD-9/ICD-10 codes to assign TRES scores. Patient characteristic distributions were compared using χ2 or t test. …

Development Of A Definition Of Postacute Sequelae Of Sars-Cov-2 Infection, Tanayott Thaweethai, Sarah E Jolley, Elizabeth W Karlson, Emily B Levitan, Bruce Levy, Grace A Mccomsey, Lisa Mccorkell, Girish N Nadkarni, Sairam Parthasarathy, Upinder Singh, Tiffany A Walker, Caitlin A Selvaggi, Daniel J Shinnick, Carolin C M Schulte, Rachel Atchley-Challenner, George A Alba, Radica Alicic, Natasha Altman, Khamal Anglin, Urania Argueta, Hassan Ashktorab, Gaston Baslet, Ingrid V Bassett, Lucinda Bateman, Brahmchetna Bedi, Shamik Bhattacharyya, Marie-Abele Bind, Andra L Blomkalns, Hector Bonilla, Hassan Brim, Patricia A Bush, Mario Castro, James Chan, Alexander W Charney, Peter Chen, Lori B Chibnik, Helen Y Chu, Rebecca G Clifton, Maged M Costantine, Sushma K Cribbs, Sylvia I Davila Nieves, Steven G Deeks, Alexandria Duven, Ivette F Emery, Nathan Erdmann, Kristine M Erlandson, Kacey C Ernst, Rachael Farah-Abraham, Cheryl E Farner, Elen M Feuerriegel, Judes Fleurimont, Vivian Fonseca, Nicholas Franko, Vivian Gainer, Jennifer C Gander, Edward M Gardner, Linda N Geng, Kelly S Gibson, Minjoung Go, Jason D Goldman, Halle Grebe, Frank L Greenway, Mounira Habli, John Hafner, Jenny E Han, Keith A Hanson, James Heath, Carla Hernandez, Rachel Hess, Sally L Hodder, Matthew K Hoffman, Susan E Hoover, Beatrice Huang, Brenna L Hughes, Prasanna Jagannathan, Janice John, Michael R Jordan, Stuart D Katz, Elizabeth S Kaufman, John D Kelly, Sara W Kelly, Megan M Kemp, John P Kirwan, Jonathan D Klein, Kenneth S Knox, Jerry A Krishnan, Andre Kumar, Adeyinka O Laiyemo, Allison A Lambert, Margaret Lanca, Joyce K Lee-Iannotti, Brian P Logarbo, Michele T Longo, Carlos A Luciano, Karen Lutrick, Jason H Maley, Gail Mallett, Jai G Marathe, Vincent Marconi, Gailen D Marshall, Christopher F Martin, Yuri Matusov, Alem Mehari, Hector Mendez-Figueroa, Robin Mermelstein, Torri D Metz, Richard Morse, Jarrod Mosier, Christian Mouchati, Janet Mullington, Shawn N Murphy, Robert B Neuman, Janko Z Nikolich, Ighovwerha Ofotokun, Elizabeth Ojemakinde, Anna Palatnik, Kristy Palomares, Tanyalak Parimon, Samuel Parry, Jan E Patterson, Thomas F Patterson, Rachel E Patzer, Michael J Peluso, Priscilla Pemu, Christian M Pettker, Beth A Plunkett, Kristen Pogreba-Brown, Athena Poppas, John G Quigley, Uma Reddy, Rebecca Reece, Harrison Reeder, W B Reeves, Eric M Reiman, Franz Rischard, Jonathan Rosand, Dwight J Rouse, Adam Ruff, George Saade, Grecio J Sandoval, Jorge L Santana, Shannon M Schlater, Frank C Sciurba, Fitzgerald Shepherd, Zaki A Sherif, Hyagriv Simhan, Nora G Singer, Daniel W Skupski, Amber Sowles, Jeffrey A Sparks, Fatima I Sukhera, Barbara S Taylor, Larissa Teunis, Robert J Thomas, John M Thorp, Paul Thuluvath, Amberly Ticotsky, Alan T Tita, Katherine R Tuttle, Alfredo E Urdaneta, Daisy Valdivieso, Timothy M Vanwagoner, Andrew Vasey, Monica Verduzco-Gutierrez, Zachary S Wallace, Honorine D Ward, David E Warren, Steven J Weiner, Shelley Welch, Sidney W Whiteheart, Zanthia Wiley, Juan P Wisnivesky, Lynn M Yee, Sokratis Zisis, Leora I Horwitz, Andrea S Foulkes

Faculty, Staff and Student Publications

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, …

Eganelisib, A First-In-Class Pi3kγ Inhibitor, In Patients With Advanced Solid Tumors: Results Of The Phase 1/1b Mario-1 Trial, David S Hong, Michael Postow, Bartosz Chmielowski, Ryan Sullivan, Amita Patnaik, Ezra E W Cohen, Geoffrey Shapiro, Conor Steuer, Martin Gutierrez, Heather Yeckes-Rodin, Robert Ilaria, Brenda O'Connell, Joanna Peng, Guangbin Peng, Nora Zizlsperger, Anthony Tolcher, Jedd D Wolchok

Faculty, Staff and Student Publications

Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.

Patients and methods: Dose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE).

Results: …

Correction: Dual Inhibition Of Igf-Ir And Alk As An Effective Strategy To Eradicate Npm-Alk+ T-Cell Lymphoma, Bhawana George, Suraj Konnath George, Wenyu Shi, Abedul Haque, Ping Shi, Ghazaleh Eskandari, Magnus Axelson, Olle Larsson, Ahmed O Kaseb, Hesham M Amin

Faculty, Staff and Student Publications

No abstract provided.

Need For Risk Adjustment In Comparative Effectiveness And Cost-Effectiveness Studies In R/R Follicular Lymphoma, John Gribben, M Lia Palomba, Anik R Patel, Myrna Nahas, Sattva S Neelapu

Faculty, Staff and Student Publications

No abstract provided.

Application Of Natural Polysaccharides And Their Novel Dosage Forms In Gynecological Cancers: Therapeutic Implications From The Diversity Potential Of Natural Compounds, Yi Li, Chuanlong Zhang, Lu Feng, Qian Shen, Fudong Liu, Xiaochen Jiang, Bo Pang

Faculty, Staff and Student Publications

Cancer is one of the most lethal diseases. Globally, the number of cancers is nearly 10 million per year. Gynecological cancers (for instance, ovarian, cervical, and endometrial), relying on hidden diseases, misdiagnoses, and high recurrence rates, have seriously affected women's health. Traditional chemotherapy, hormone therapy, targeted therapy, and immunotherapy effectively improve the prognosis of gynecological cancer patients. However, with the emergence of adverse reactions and drug resistance, leading to the occurrence of complications and poor compliance of patients, we have to focus on the new treatment direction of gynecological cancers. Because of the potential effects of natural drugs in regulating …

Asct Vs Cart For Patients With Relapsed Lbcl In Pr: Role Of Tmtv, Paolo Strati, Oren Pasvolsky, Lei Feng, Guofan Xu, Sanjit O Tewari, Jaimole Varghese, Karla Ow, Minifrida Santiago, Ajlan Al Zaki, Andrew Jallouk, Sattva S Neelapu, Partow Kebriaei, Elizabeth J Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

No abstract provided.

Antitumor Efficacy Of Dual Blockade With Encorafenib + Cetuximab In Combination With Chemotherapy In Human Brafv600e-Mutant Colorectal Cancer, Stefania Napolitano, Melanie Woods, Hey Min Lee, Vincenzo De Falco, Giulia Martini, Carminia Maria Della Corte, Erika Martinelli, Vincenzo Famiglietti, Davide Ciardiello, Amanda Anderson, Natalie Wall Fowlkes, Oscar Eduardo Villareal, Alexey Sorokin, Preeti Kanikarla, Olu Coker, Van Morris, Lucia Altucci, Josep Tabernero, Teresa Troiani, Fortunato Ciardiello, Scott Kopetz

Faculty, Staff and Student Publications

PURPOSE: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC.

EXPERIMENTAL DESIGN: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts. Mice were randomized to receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin regimens (FOLFIRI or FOLFOX), (E+C) or the combination. Patients received long-term treatment until disease progression, with deescalation strategies used to mimic maintenance therapy. Transcriptomic changes after progression on cytotoxic chemotherapy or targeted therapy were …

Targeted Therapy With The Mutant Idh2 Inhibitor Enasidenib For High-Risk Idh2-Mutant Myelodysplastic Syndrome, Courtney D Dinardo, Sangeetha Venugopal, Curtis Lachowiez, Koichi Takahashi, Sanam Loghavi, Guillermo Montalban-Bravo, Xuemei Wang, Hetty Carraway, Mikkael Sekeres, Ameenah Sukkur, Danielle Hammond, Kelly Chien, Abhishek Maiti, Lucia Masarova, Koji Sasaki, Yesid Alvarado, Tapan Kadia, Nicholas J Short, Naval Daver, Gautam Borthakur, Farhad Ravandi, Hagop M Kantarjian, Bhumika Patel, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

The isocitrate dehydrogenase enzyme 2 (IDH2) gene is mutated in ∼5% of patients with myelodysplastic syndrome (MDS). Enasidenib is an oral, selective, mutant IDH2 inhibitor approved for IDH2-mutated (mIDH2) relapsed/refractory acute myeloid leukemia. We designed a 2-arm multicenter study to evaluate safety and efficacy of (A) the combination of enasidenib with azacitidine for newly diagnosed mIDH2 MDS, and (B) enasidenib monotherapy for mIDH2 MDS after prior hypomethylating agent (HMA) therapy. Fifty patients with mIDH2 MDS enrolled: 27 in arm A and 23 in arm B. Median age of patients was 73 years. The most common adverse events were neutropenia (40%), …

Biological Mechanism Of Sex Difference In Stroke Manifestation And Outcomes, Wi-Sun Ryu, Jinyong Chung, Dawid Schellingerhout, Sang-Wuk Jeong, Hang-Rai Kim, Jung E Park, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Man Seok Park, Kang-Ho Choi, Juneyoung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location.

METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 >days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods …