Medicine and Health Sciences Commons^™

It Is Time To Define An Organizational Model For The Prevention And Management Of Infections Along The Surgical Pathway: A Worldwide Cross-Sectional Survey, Massimo Sartellli, John E. Mazuski, Et Al.

2020-Current year OA Pubs

No abstract provided.

Job-Exposure Matrix: A Useful Tool For Incorporating Workplace Exposure Data Into Population Health Research And Practice, Alexis Descatha, Marc Fadel, Grace Sembajwe, Susan Peters, Bradley A Evanoff

2020-Current year OA Pubs

Workplace exposures to physical, chemical, and psychosocial factors account for a large burden of chronic diseases. Obtaining useful estimates of current and past workplace exposures is challenging, particularly in large general population studies. Job-exposure matrices (JEMs) are a useful tool for exposure assessment, particularly when no individual level exposure data are available. A JEM provides a cross-tabulation of job titles (sometimes combined with industry) and estimated exposures to workers carrying out these jobs during different time periods. The major limitation of JEMs is that they do not account for individual variation in exposures within the same job. This limitation is …

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

Differentiating Amyloid Beta Spread In Autosomal Dominant And Sporadic Alzheimer's Disease, Elizabeth Levitis, Jacob W Vogel, Thomas Funck, Vladimir Hachinski, Serge Gauthier, Jonathan Vöglein, Johannes Levin, Brian A Gordon, Tammie Benzinger, Yasser Iturria-Medina, Alan C Evans, Dominantly Inherited Alzheimer Network, Alzheimer’S Disease Neuroimaging Initiative

2020-Current year OA Pubs

Amyloid-beta deposition is one of the hallmark pathologies in both sporadic Alzheimer's disease and autosomal-dominant Alzheimer's disease, the latter of which is caused by mutations in genes involved in amyloid-beta processing. Despite amyloid-beta deposition being a centrepiece to both sporadic Alzheimer's disease and autosomal-dominant Alzheimer's disease, some differences between these Alzheimer's disease subtypes have been observed with respect to the spatial pattern of amyloid-beta. Previous work has shown that the spatial pattern of amyloid-beta in individuals spanning the sporadic Alzheimer's disease spectrum can be reproduced with high accuracy using an epidemic spreading model which simulates the diffusion of amyloid-beta across …

A Framework For Extension Studies Using Real-World Data To Examine Long-Term Safety And Effectiveness, Mehmet Burcu, Cyntia B Manzano-Salgado, Anne M Butler, Jennifer B Christian

2020-Current year OA Pubs

Understanding the long-term benefits and risks of treatments, devices, and vaccines is critically important for individual- and population-level healthcare decision-making. Extension studies, or 'roll-over studies,' are studies that allow for patients participating in a parent clinical trial to 'roll-over' into a subsequent related study to continue to observe and measure long-term safety, tolerability, and/or effectiveness. These designs are not new and are often used as an approach to satisfy regulatory post-approval safety requirements. However, designs using traditional clinical trial infrastructure can be expensive and burdensome to conduct, particularly, when following patients for many years post trial completion. Given the increasing …

Il-1 Reprogramming Of Adult Neural Stem Cells Limits Neurocognitive Recovery After Viral Encephalitis By Maintaining A Proinflammatory State, Allison L Soung, Veronica A Davé, Charise Garber, Eric D Tycksen, Lauren L Vollmer, Robyn S Klein

2020-Current year OA Pubs

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting …

Sustainability Of Breastfeeding Interventions To Reduce Child Mortality Rates In Low, Middle-Income Countries: A Systematic Review Of Randomized Controlled Trials, Alexis Engelhart, Stacey Mason, Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Victoria Carter, Thembekile Shato, Titilola Gbaja-Biamila, David Oladele, Juliet Iwelunmor

2020-Current year OA Pubs

Child mortality is the lowest it has ever been, but the burden of death in low- and middle-income countries (LMICs) is still prevalent, and the numbers average above the global mean. Breastfeeding contributes to the reduction of child mortality by improving chance of survival beyond childhood. Therefore, it is essential to examine how evidence-based breastfeeding interventions are being maintained in resource-constrained settings. Guided by Scheirer and Dearing's sustainability framework, the aim of this systematic review was to explore how evidence-based breastfeeding interventions implemented to address child mortality in LMICs are sustained. The literature search included randomized controlled trials (RCTs) of …

Theta-Gamma Coupling As A Cortical Biomarker Of Brain-Computer Interface-Mediated Motor Recovery In Chronic Stroke, Nabi Rustamov, Joseph Humphries, Alexandre Carter, Eric C Leuthardt

2020-Current year OA Pubs

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain-computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain-computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain-computer interface. This study …

Psychiatric Diagnoses And Medications In Wolfram Syndrome, Angela M Reiersen, Jacob S Noel, Tasha Doty, Richa A Sinkre, Anagha Narayanan, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the

OBJECTIVE: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

METHOD: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

RESULTS: Study participants with Wolfram …

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Increased Virus Dissemination Leads To Enhanced Lung Injury But Not Inflammation During Influenza-Associated Secondary Bacterial Infection, Amanda P Smith, Lindey C Lane, Ivan Ramirez Zuniga, David M Moquin, Peter Vogel, Amber M Smith

2020-Current year OA Pubs

Secondary bacterial infections increase influenza-related morbidity and mortality, particularly if acquired after 5-7 d from the viral onset. Synergistic host responses and direct pathogen-pathogen interactions are thought to lead to a state of hyperinflammation, but the kinetics of the lung pathology have not yet been detailed, and identifying the contribution of different mechanisms to disease is difficult because these may change over time. To address this gap, we examined host-pathogen and lung pathology dynamics following a secondary bacterial infection initiated at different time points after influenza within a murine model. We then used a mathematical approach to quantify the increased …

Yoga Therapy During Chemotherapy For Early-Stage And Locally Advanced Breast Cancer, Samantha K Greaney, Neha Amin, Bethany C Prudner, Maggie Compernolle, Linda J Sandell, Susan C Tebb, Katherine N Weilbaecher, Peri Abeln, Jingqin Luo, Yu Tao, Angela C Hirbe, Lindsay L Peterson

2020-Current year OA Pubs

BACKGROUND: Chemotherapy is associated with decreased quality of life (QOL), fatigue, depression, and weight gain in patients with breast cancer. Weight gain is associated with poorer prognosis. Yoga improves QOL, fatigue, and mood in women with breast cancer but its effect on treatment-related weight gain has not been studied. The aim of this trial was to determine the feasibility of personalized yoga therapy in women receiving treatment for early-stage or locally advanced breast cancer and assess its impact on weight gain.

METHODS: Thirty women were randomized 1:1 to receive yoga therapy by a certified yoga therapist during treatment or a …

The Enigma Stroke Recovery Working Group: Big Data Neuroimaging To Study Brain-Behavior Relationships After Stroke, Sook-Lei Liew, Catherine E Lang, Anup K Bhattacharya, Et Al.

2020-Current year OA Pubs

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data …

Actin Capping Protein Regulates Postsynaptic Spine Development Through Cpi-Motif Interactions, Kenneth R Myers, Yanjie Fan, Patrick Mcconnell, John A Cooper, James Q Zheng

2020-Current year OA Pubs

Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to …

Bridging The Technological Divide: Stigmas And Challenges With Technology In Digital Brain Health Studies Of Older Adults, Jessica Nicosia, Andrew J Aschenbrenner, Sarah L Adams, Marisol Tahan, Sarah H Stout, Hannah Wilks, Joyce E Balls-Berry, John C Morris, Jason Hassenstab

2020-Current year OA Pubs

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults' technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment (

Advances In Our Clinical Understanding Of Autonomic Regulation Therapy Using Vagal Nerve Stimulation In Patients Living With Heart Failure, Marvin A Konstam, Douglas L Mann, John James E Udelson, Jeffrey L Ardell, Gaetano M De Ferrari, Martin R Cowie, Helmut U Klein, Douglas D Gregory, Joseph M Massaro, Imad Libbus, Lorenzo A Dicarlo, Javed Butler, John D Parker, John R Teerlink

2020-Current year OA Pubs

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to …

Association Of Pretreatment Hippocampal Volume With Neurocognitive Function In Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy For Brain Metastases: Secondary Analysis Of Nrg Oncology/Rtog 0933, Christopher D. Abraham, Stephanie L. Pugh, Joseph A. Bovi, Vinai Gondi, Minesh P. Mehta, Tammie Benzinger, Christopher J. Owen, Simon S. Lo, Vijayananda Kundapur, Paul D. Brown, Alexander Y. Sun, Steven P. Howard, Albert S Denittis, Clifford G. Robinson, Lisa A. Kachnic

2020-Current year OA Pubs

PURPOSE: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933.

METHODS AND MATERIALS: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test-Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Variation In Ampicillin Dosing For Lower Respiratory Tract Infections And Neonatal Bacterial Infections In Us Children's Hospitals, Elizabeth A Daniels, Christopher C Mcpherson, Jason G Newland, Brian R Lee

2020-Current year OA Pubs

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications.

DESIGN: Retrospective cohort study.

SETTING: The study included data from 32 children's hospitals in the United States.

METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, …

Chronic Neuropsychiatric Sequelae Of Sars-Cov-2: Protocol And Methods From The Alzheimer's Association Global Consortium, Gabriel A De Erausquin, Carlos Cruchaga, Igor Zwir, Et Al

2020-Current year OA Pubs

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity …

The Future Of Ad Clinical Trials With The Advent Of Anti-Amyloid Therapies: An Ctad Task Force Report, J Delrieu, R J Bateman, J Touchon, M Sabbagh, J Cummings

2020-Current year OA Pubs

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer's disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. …

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

Combination Laser Interstitial Thermal Therapy Plus Stereotactic Radiotherapy Increases Time To Progression For Biopsy-Proven Recurrent Brain Metastases, Matthew M Grabowski, Alex Scott, Michael Olufawo, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases.

METHODS: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression …

Voting Behavior During Fda Medical Device Advisory Committee Panel Meetings, Amanda Maisel-Campbell, Daniel I Schlessinger, Arianna F. Yanes, Emir Veledar, Kelly A. Reynolds, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, Emily Poon, Murad Alam

2020-Current year OA Pubs

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations.

METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to …

The Association Of Prescription Opioid Use With Suicide Attempts: An Analysis Of Statewide Medical Claims Data, Chongliang Luo, Kun Chen, Riddhi Doshi, Nathaniel Rickles, Yong Chen, Harold Schwartz, Robert H. Aseltine

2020-Current year OA Pubs

BACKGROUND: Suicides and opioid overdose deaths are among the most pressing public health concerns in the US. However direct evidence for the association between opioid use and suicidal behavior is limited. The objective of this article is to examine the association between frequency and dose of prescription opioid use and subsequent suicide attempts.

METHODS AND FINDINGS: This retrospective cohort study analyzed 4 years of statewide medical claims data from the Connecticut All-Payer Claims Database. Commercially insured adult patients in Connecticut (n = 842,773) who had any medical claims beginning in January 2012 were followed through December 2015. The primary outcome …

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

Cognitive And Brain Reserve Predict Decline In Adverse Driving Behaviors Among Cognitively Normal Older Adults, Samantha A Murphy, Ling Chen, Jason M Doherty, Prerana Acharyya, Noah Riley, Ann M Johnson, Alexis Walker, Hailee Domash, Maren Jorgensen, Sayeh Bayat, David B Carr, Beau M Ances, Ganesh M Babulal

2020-Current year OA Pubs

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain's adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer's …

Infantile-Onset Pompe Disease Complicated By Sickle Cell Anemia: Case Report And Management Considerations, Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C Schroeder, Jamie N Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L Hulbert, Hoanh Thi Nguyen

2020-Current year OA Pubs

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two

Case Report: Real-World Experience Using A Personalized Cancer-Specific Circulating Tumor Dna Assay In Different Metastatic Melanoma Scenarios, Karam Khaddour, Alice Zhou, Omar H Butt, Griffin Budde, Allyson Koyen Malashevich, George Ansstas

2020-Current year OA Pubs

Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and prognostication in metastatic melanoma. However, several challenges exist, including the reduced shedding of ctDNA into the bloodstream in the metastatic setting, differences in sensitivity among various ctDNA assays, and the inherent inability to distinguish tumor-specific mutations from other mutations that are not related to the cancer of interest. Using a ctDNA assay that is designed to detect multiple single-nucleotide variants (SNVs) that are specific to …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

2020-Current year OA Pubs

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …