Digital Commons Network^™

Management Of Pediatric Appendicitis During The Covid-19 Pandemic: A Nationwide Multicenter Cohort Study, Brittany Hegde, Elisa Garcia, Andrew Hu, Mehul Raval, Sanyu Takirambudde, Derek Wakeman, Ruth Lewit, Ankush Gosain, Raphael H Parrado, Robert A Cina, Krista Stephenson, Melvin S Dassinger, Daniel Zhang, Moiz M Mustafa, Donna Koo, Aaron M Lipskar, Katherine Scheidler, Kyle J Van Arendonk, Patrick Berg, Raquel Gonzalez, Daniel Scheese, Jeffrey Haynes, Alexander Mina, Irving J Zamora, Monica E Lopez, Steven C Mehl, Elizabeth Gilliam, Katrina Lofberg, Brianna Spencer, Afif N Kulaylat, Brian C Gulack, Matthew Johnson, Matthew Laskovy, Pavan Brahmamdam, Aoi Shimomura, Therese Blanch, Kuojen Tsao, Bethany J Slater

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has impacted timely access to care for children, including patients with appendicitis. This study aimed to evaluate the effect of the COVID-19 pandemic on management of appendicitis and patient outcomes.

METHODS: A multicenter retrospective study was performed including 19 children's hospitals from April 2019-October 2020 of children (age≤18 years) diagnosed with appendicitis. Groups were defined by each hospital's city/state stay-at-home orders (SAHO), designating patients as Pre-COVID (Pre-SAHO) or COVID (Post-SAHO). Demographic, treatment, and outcome data were obtained, and univariate and multivariable analysis was performed.

RESULTS: Of 6,014 patients, 2,413 (40.1%) presented during the COVID-19 pandemic. More …

Extracorporeal Carbon Dioxide Removal With The Hemolung In Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study, Ravindranath Tiruvoipati, Bindu Akkanti, Kha Dinh, Nicholas Barrett, Alexandra May, Jeremy Kimmel, Steven A Conrad

Faculty, Staff and Student Publications

Objectives: Extracorporeal carbon dioxide removal (ECCO 2 R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO 2 R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research.

Design: Multicenter, multinational, retrospective review.

Setting: Data from the Hemolung Registry between April 2013 and June …

Steroids For The Treatment Of Viral Encephalitis: A Systematic Literature Review And Meta-Analysis, Emira Hodzic, Rodrigo Hasbun, Alejandro Granillo, Anna R Tröscher, Helga Wagner, Tim J Von Oertzen, Judith N Wagner

Faculty, Staff and Student Publications

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE.

Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1.

Results: We screened 378 studies and included 50. 155 patients were …

Are There Sex Differences In Interactive Associations Of Environmental Exposure To Lead (Pb), Mercury (Hg), And Manganese (Mn) With Gst Genes (Gstp1, Gstt1, And Gstm1) In Relation To Asd In Jamaican Children?, Hiba T Zwiya, Maureen Samms-Vaughan, Jan Bressler, Minjae Lee, Courtney Byrd-Williams, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

Background: Male preponderance is well-established in children with autism spectrum disorder (ASD). Glutathione S-transferase (GST) genes play a crucial role in suppressing oxidative stress triggered by environmental stressors.

Objective: To determine whether the association between metals and ASD differs by sex and by GST genes.

Methods: Using data from 344 pairs of sex-and age-matched cases and controls, we assessed the association of each metal with ASD or ASD severity, by applying conditional logistic regression (CLR) or general linear models (GLM). Sex was assessed as an effect modifier in separate GST genetic models.

Results: For Pb exposure, using a recessive model …

Bystanders Or Not? Microglia And Lymphocytes In Aging And Stroke, Justin N Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

As the average age of the world population increases, more people will face debilitating aging-associated conditions, including dementia and stroke. Not only does the incidence of these conditions increase with age, but the recovery afterward is often worse in older patients. Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients. Aging causes profound changes in the immune system including the activation of microglia in the brain. Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation, white matter damage, and cognitive impairment in both older humans and …

The Effects Of Obesity And Metabolic Abnormalities On Severe Covid-19-Related Outcomes After Vaccination: A Population-Based Study, Rebeca Kelly, Diego Aviles, Catriona Krisulevicz, Krystal Hunter, Lauren Krill, David Warshal, Olga Ostrovsky

Faculty, Staff and Student Publications

High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in …

Postoperative Complications Of True Dropless Cataract Surgery Versus Standard Topical Drops, Evan K Wotipka, Alex J Wright, James Z Fan, David Fuhriman, Alice Z Chuang, Grace C Lindhorst, Robert M Feldman, Eric L Crowell

Faculty, Staff and Student Publications

Purpose  Compare postoperative outcomes in cataract surgery between eyes with standard drop regimen versus dropless protocol by residents.

Design  Retrospective cohort study between April 1, 2018 and March 31, 2020.

Methods  The study was performed at Lyndon B. Johnson General Hospital in Houston, Harris County, Texas. A total of 547 eyes (234 dropless vs. 313 standard) with phacoemulsification cataract surgery and minimum of 1-month follow-up with best-corrected visual acuity (BCVA) were included. Dropless received 40 mg sub-Tenon's triamcinolone and intracameral moxifloxacin. Patients were followed at postoperative day 1 (POD1), week 1 (POW1), and month 1 (POM1). Postoperative rate of BCVA …

Non-Canonical Wnt Signaling In The Eye, Ruchi Shah, Cynthia Amador, Steven T Chun, Sean Ghiam, Mehrnoosh Saghizadeh, Andrei A Kramerov, Alexander V Ljubimov

Faculty, Staff and Student Publications

Wnt signaling comprises a group of complex signal transduction pathways that play critical roles in cell proliferation, differentiation, and apoptosis during development, as well as in stem cell maintenance and adult tissue homeostasis. Wnt pathways are classified into two major groups, canonical (β-catenin-dependent) or non-canonical (β-catenin-independent). Most previous studies in the eye have focused on canonical Wnt signaling, and the role of non-canonical signaling remains poorly understood. Additionally, the crosstalk between canonical and non-canonical Wnt signaling in the eye has hardly been explored. In this review, we present an overview of available data on ocular non-canonical Wnt signaling, including developmental …

Endovascular Versus Medical Management Of Posterior Cerebral Artery Occlusion Stroke: The Plato Study, Thanh N Nguyen, Muhammad M Qureshi, Davide Strambo, Daniel Strbian, Silja Räty, Christian Herweh, Mohamad Abdalkader, Marta Olive-Gadea, Marc Ribo, Marios Psychogios, Urs Fischer, Anh Nguyen, Joji B Kuramatsu, David Haupenthal, Martin Köhrmann, Cornelius Deuschl, Jordi Kühne Escola, Shadi Yaghi, Liqi Shu, Volker Puetz, Daniel P O Kaiser, Johannes Kaesmacher, Adnan Mujanovic, Dominique Cornelius Marterstock, Tobias Engelhorn, Piers Klein, Diogo C Haussen, Mahmoud H Mohammaden, Hend Abdelhamid, Lorena Souza Viana, Bruno Cunha, Isabel Fragata, Michele Romoli, Francesco Diana, Pekka Virtanen, Kimmo Lappalainen, Judith Clark, Stavros Matsoukas, Johanna T Fifi, Sunil A Sheth, Sergio Salazar-Marioni, João Pedro Marto, João Nuno Ramos, Milena Miszczuk, Christoph Riegler, Ashutosh P Jadhav, Shashvat M Desai, Volker Maus, Maximilian Kaeder, Adnan H Siddiqui, Andre Monteiro, Hesham E Masoud, Neil Suryadevara, Maxim Mokin, Shail Thanki, James E Siegler, Jane Khalife, Italo Linfante, Guilherme Dabus, Negar Asdaghi, Vasu Saini, Christian H Nolte, Eberhard Siebert, Thomas R Meinel, Stefanos Finitsis, Markus A Möhlenbruch, Peter A Ringleb, Anne Berberich, Raul G Nogueira, Uta Hanning, Lukas Meyer, Patrik Michel, Simon Nagel

Faculty, Staff and Student Publications

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion.

Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift …

Spontaneous Resolution Of 2 High Flow Cervical Vertebral Arteriovenous Fistulas, Hussein A Zeineddine, Bryden H Dawes, Matthew P Mullarkey, Juan Carlos Martinez-Gutierrez, Peng Roc Chen

Faculty, Staff and Student Publications

Cervical vertebral arteriovenous fistula is a rare entity that is typically managed with endovascular techniques. We describe 2 consecutive cases of spontaneous obliteration of high flow cervical vertebral arteriovenous fistulas following angiography. Our cases pose an interesting natural history course, and we review the role of angiography in the unusual phenomenon of spontaneous obliteration of vascular malformations. These 2 cases bring forward the possibility of conservative management in such lesions.

Mird Pamphlet No 28, Part 1: Mirdcalc—A Software Tool For Medical Internal Radiation Dosimetry, Adam L Kesner, Lukas M Carter, Juan C Ocampo Ramos, Daniel Lafontaine, Edmond A Olguin, Justin L Brown, Bonnie President, Derek W Jokisch, Darrell R Fisher, Wesley E Bolch

Faculty, Staff and Student Publications

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, …

Association Of Trauma Molecular Endotypes With Differential Response To Transfusion Resuscitation Strategies, Matthew R Thau, Ted Liu, Neha A Sathe, Grant E O'Keefe, Bryce R H Robinson, Eileen Bulger, Charles E Wade, Erin E Fox, John B Holcomb, W Conrad Liles, Ian B Stanaway, Carmen Mikacenic, Mark M Wurfel, Pavan K Bhatraju, Eric D Morrell

Faculty, Staff and Student Publications

IMPORTANCE: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies.

OBJECTIVE: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe …

Immunometabolism At The Heart Of Cardiovascular Disease, Matthew Deberge, Rajesh Chaudhary, Samantha Schroth, Edward B Thorp

Faculty, Staff and Student Publications

Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. …

Difficult Or Impossible Facemask Ventilation In Children With Difficult Tracheal Intubation: A Retrospective Analysis Of The Pedi Registry, Annery G Garcia-Marcinkiewicz, Lisa K Lee, Bishr Haydar, John E Fiadjoe, Clyde T Matava, Pete G Kovatsis, James Peyton, Mary L Stein, Raymond Park, Brad M Taicher, Thomas W Templeton

Faculty, Staff and Student Publications

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a …

Thiazolidinedione Use And Retinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Glenn Jaffe, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

BACKGROUND: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

METHODS: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium …

Functional Assessment Of The Dural Lymphatic Vessels Using Dynamic Contrast Mri In Multiple Sclerosis, Refaat E Gabr, John A Lincoln, Khader M Hasan, Larry A Kramer

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance.

METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T …

The Genetics Of Primary Ciliary Dyskinesia In Puerto Rico, Paolo Zanoni, Katharina Steindl, Heinrich Sticht, Beatrice Oneda, Pascal Joset, Ivan Ivanovski, Anselm H C Horn, Elena M Cabello, Julia Laube, Markus Zweier, Alessandra Baumer, Anita Rauch, Nadia Khan

Faculty, Staff and Student Publications

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Transplantation Referral Patterns For Patients With Newly Diagnosed Higher-Risk Myelodysplastic Syndromes And Acute Myeloid Leukemia At Academic And Community Sites In The Connect® Myeloid Disease Registry: Potential Barriers To Care, Benjamin Tomlinson, Marcos De Lima, Christopher R Cogle, Michael A Thompson, David L Grinblatt, Daniel A Pollyea, Rami S Komrokji, Gail J Roboz, Michael R Savona, Mikkael A Sekeres, Mehrdad Abedi, Guillermo Garcia-Manero, Sandra E Kurtin, Jaroslaw P Maciejewski, Jay L Patel, Dennis A Revicki, Tracy I George, E Dawn Flick, Pavel Kiselev, Chrystal U Louis, Irene S Degutis, Melissa Nifenecker, Harry P Erba, David P Steensma, Bart L Scott

Faculty, Staff and Student Publications

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to …

Nivolumab And Ipilimumab With Concurrent Stereotactic Radiosurgery For Intracranial Metastases From Non-Small Cell Lung Cancer: Analysis Of The Safety Cohort For Non-Randomized, Open-Label, Phase I/Ii Trial, Mehmet Altan, Yan Wang, Juhee Song, James Welsh, Chad Tang, Nandita Guha-Thakurta, George R Blumenschein, Brett W Carter, Jeffrey S Wefel, Amol J Ghia, Debra N Yeboa, Mary Frances Mcaleer, Caroline Chung, Kristina D Woodhouse, Susan L Mcgovern, Chenyang Wang, Betty Y S Kim, Jeffrey S Weinberg, Tina M Briere, Yasir Y Elamin, Xiuning Le, Tina Cascone, Marcelo V Negrao, Ferdinandos Skoulidis, Renata Ferrarotto, John V Heymach, Jing Li

Faculty, Staff and Student Publications

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.

PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered …

Therapeutic Potential Of Salicylamide Derivatives For Combating Viral Infections, Jimin Xu, Yu Xue, Andrew A Bolinger, Jun Li, Mingxiang Zhou, Haiying Chen, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. …

Sox11 Is An Effective Discriminatory Marker, When Used In Conjunction With Ck20 And Ttf1, For Merkel Cell Carcinoma: Comparative Analysis Of Sox11, Ck20, Pax5, And Ttf1 Expression In Merkel Cell Carcinoma And Pulmonary Small Cell Carcinoma, Woo Cheal Cho, Kaitlin Vanderbeck, Priyadharsini Nagarajan, Denái R Milton, Pavandeep Gill, Wei-Lien Wang, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Phyu P Aung

Faculty, Staff and Student Publications

Context.—: Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1- in MCC and CK20-/TTF1+ in PSmCC).

Objective.—: To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC.

Design.—: SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. …

Venetoclax Consolidation In High-Risk Cll Treated With Ibrutinib For ≥1 Year Achieves A High Rate Of Undetectable Mrd, Philip A Thompson, Michael J Keating, Alessandra Ferrajoli, Nitin Jain, Christine B Peterson, Naveen Garg, Sa A Wang, Jeffrey L Jorgensen, Tapan M Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J Short, William G Wierda

Faculty, Staff and Student Publications

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10−4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were …

Cisplatin Decreases Voluntary Wheel-Running Activity But Does Not Impair Food-Motivated Behavior In Mice, Kiersten S Scott, Brandon Chelette, Chinenye Chidomere, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less …

Addressing The Global Expertise Gap In Radiation Oncology: The Radiation Planning Assistant, Laurence Court, Ajay Aggarwal, Hester Burger, Carlos Cardenas, Christine Chung, Raphael Douglas, Monique Du Toit, David Jaffray, Anuja Jhingran, Michael Mejia, Raymond Mumme, Sikudhani Muya, Komeela Naidoo, Jerry Ndumbalo, Kelly Nealon, Tucker Netherton, Callistus Nguyen, Niki Olanrewaju, Jeannette Parkes, Willie Shaw, Christoph Trauernicht, Melody Xu, Jinzhong Yang, Lifei Zhang, Hannah Simonds, Beth M Beadle

Faculty, Staff and Student Publications

PURPOSE: Automation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).

DESIGN: In this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and …

Transcriptional Profiling And Consensus Molecular Subtype Assignment To Understand Response And Resistance To Anti-Epidermal Growth Factor Receptor Therapy In Colorectal Cancer, Saikat Chowdhury, Ria Gupta, Joshua Millstein, Kangyu Lin, Valsala Haridas, Mohammad A Zeineddine, Christine Parseghian, Heinz-Josef Lenz, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Activating mutations in KRAS, NRAS, and BRAF are known to cause resistance to anti–epidermal growth factor receptor (EGFR) therapy; however, only approximately 40% of patients with colorectal cancer (CRC) with RASWT tumors respond to anti-EGFR treatment. We sought to discover novel biomarkers to predict response to anti-EGFR antibody treatment in CRC and to understand mechanisms of resistance to anti-EGFR therapy.

MATERIALS AND METHODS: Transcriptomic profiles from three clinical and two preclinical cohorts treated with cetuximab were used to assign consensus molecular subtypes (CMS) to each sample and correlated with outcomes.

RESULTS: Restricting to RASWT patients, …

Plasma Cell Myeloma With Ras/Braf Mutations Is Frequently Associated With A Complex Karyotype, Advanced Stage Disease, And Poorer Prognosis, Nianyi Li, Pei Lin, Zhuang Zuo, M James You, Wen Shuai, Robert Orlowski, Elisabet E Manasanch, Shaoying Li, Jie Xu, Sofia Garces, Fatima Zahra Jelloul, Zhenya Tang, Wei Wang, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

BACKGROUND: Mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high-risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results.

METHODS: We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF-mutated myeloma, and compare with 79 patients without any mutations.

RESULTS: We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF-mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and …

First-In-Human Study Of Oleclumab, A Potent, Selective Anti-Cd73 Monoclonal Antibody, Alone Or In Combination With Durvalumab In Patients With Advanced Solid Tumors, Johanna Bendell, Patricia Lorusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison, Minal Barve, Manik Amin, Jayesh Desai, Trisha Wise-Draper, Steven Eck, Yu Jiang, Anis A Khan, Yuling Wu, Philip Martin, Zachary A Cooper, Nairouz Elgeioushi, Nancy Mueller, Rakesh Kumar, Sandip Pravin Patel

Faculty, Staff and Student Publications

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy …

Emerging Signaling Regulation Of Sinoatrial Node Dysfunction, Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND.

RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), …

Factors Affecting Treatment Adherence Among Leprosy Patients: Perceptions Of Healthcare Providers, Veincent Christian F Pepito, Arianna Maever Loreche, Rae Erica D Samontina, Sarah Jane A Abdon, David Norman L Fuentes, Ofelia P Saniel

Faculty, Staff and Student Publications

BACKGROUND: Treatment adherence is a vital aspect in the management of chronic diseases like leprosy; however, most studies on treatment adherence focus on patients. This study aims to examine the perceptions of healthcare providers on factors that can promote or prevent patients from adhering to treatment.

METHODS: We conducted three focus group discussions (FGDs) with healthcare providers who have at least one year experience in managing leprosy in three large leprosy case-holding hospitals in Metro Manila, Philippines. We audio-recorded, transcribed, translated the FGD proceedings, and analyzed the transcripts thematically to identify patient-intrinsic and patient-extrinsic enablers and barriers to treatment adherence …