Medicine and Health Sciences Commons^™

Late Cardiac Events After Allogeneic Stem Cell Transplant: Incidence, Risk Factors, And Impact On Overall Survival, Christine Auberle, Daniel Lenihan, Feng Gao, Amanda Cashen

2020-Current year OA Pubs

BACKGROUND: There is limited data on the impact of cardiac disease on long term outcomes of allogeneic stem cell transplant (alloSCT). Our study aims to describe the incidence of late cardiac events after alloSCT, identify risk factors for developing a late cardiac event, and illustrate the impact of late cardiac events on overall survival.

METHODS: Patients who underwent alloSCT from 2007 to 2017 and survived more than 1 year after transplant (N = 804) were included. Gray's sub-distribution methods, while accounting for death as a competing risk, were used to calculate the cumulative incidence of late cardiac events. Univariate regression …

Intraocular Pressure And Medication Changes Associated With Xen Gel Stent: A Systematic Review Of The Literature, Joseph F Panarelli, Vanessa Vera, Arsham Sheybani, Nathan Radcliffe, Richard Fiscella, Brian A Francis, Oluwatosin U Smith, Robert J Noecker

2020-Current year OA Pubs

The Xen gel stent (Allergan Inc, an AbbVie company; Dublin, Ireland) was conceived as an option for patients requiring modest IOP reduction but for whom trabeculectomy was not yet indicated. As with any glaucoma surgery, establishing criteria for patient selection and identifying factors that contribute to a high likelihood of success are important. To help guide clinical decision-making, a systematic review of published studies on the gel stent was performed, with the goal of understanding postoperative outcomes based on clinical and patient factors. Results were organized around a series of pertinent clinical questions based on scenarios encountered in clinical practice. …

Alcohol Consumption And Epigenetic Age Acceleration In Young Adults, Drew R Nannini, Lei Liu, Et Al.

2020-Current year OA Pubs

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (

Olutasidenib (Ft-2102) In Patients With Relapsed Or Refractory Idh1-Mutant Glioma: A Multicenter, Open-Label, Phase Ib/Ii Trial, Macarena I De La Fuente, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation.

METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety …

Lecanemab In Early Alzheimer's Disease, Christopher H Van Dyck, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease.

METHODS: We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab …

Individual Differences In Naturalistic Learning Link Negative Emotionality To The Development Of Anxiety, William J Villano, Noah I Kraus, Travis R Reneau, Brittany A Jaso, A Ross Otto, Aaron S Heller

2020-Current year OA Pubs

Organisms learn from prediction errors (PEs) to predict the future. Laboratory studies using small financial outcomes find that humans use PEs to update expectations and link individual differences in PE-based learning to internalizing disorders. Because of the low-stakes outcomes in most tasks, it is unclear whether PE learning emerges in naturalistic, high-stakes contexts and whether individual differences in PE learning predict psychopathology risk. Using experience sampling to assess 625 college students' expected exam grades, we found evidence of PE-based learning and a general tendency to discount negative PEs, an "optimism bias." However, individuals with elevated negative emotionality, a personality trait …

Preclinical Studies In Krabbe Disease: A Model For The Investigation Of Novel Combination Therapies For Lysosomal Storage Diseases, Gregory Heller, Allison M Bradbury, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will …

Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni

2020-Current year OA Pubs

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.

Arginine Methylation Of The Pgc-1Α C-Terminus Is Temperature-Dependent, Meryl Mendoza, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia I. Zurita-Lopez

2020-Current year OA Pubs

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed

Association Of State Insurance Mandates For Fertility Treatment With Multiple Embryo Transfer After Preimplantation Genetic Testing For Aneuploidy, Bronwyn S Bedrick, Katelin B Nickel, Joan K Riley, Tarun Jain, Emily S Jungheim

2020-Current year OA Pubs

IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A).

OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Andrea Wang-Gillam, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Large Variations In The Prices Of Urologic Procedures At Academic Medical Centers 1 Year After Implementation Of The Price Transparency Final Rule, Zeynep G Gul, Danielle R Sharbaugh, Cailey J Guercio, Daniel L Pelzman, Cameron A Jones, Emily C Hacker, Vivian I Anyaeche, Levi Bowers, Ashti M Shah, Michael G Stencel, Jonathan G Yabes, Bruce L Jacobs, Benjamin J Davies

2020-Current year OA Pubs

IMPORTANCE: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs.

OBJECTIVE: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study that determined the prices of 5 common urologic …

Magnify Is A Universal Molecular Anchoring Strategy For Expansion Microscopy, Aleksandra Klimas, Brendan R Gallagher, Piyumi Wijesekara, Sinda Fekir, Emma F Dibernardo, Zhangyu Cheng, Donna B Stolz, Franca Cambi, Simon C Watkins, Steven L Brody, Amjad Horani, Alison L Barth, Christopher I Moore, Xi Ren, Yongxin Zhao

2020-Current year OA Pubs

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional …

Chronic Trem2 Activation Exacerbates Aβ-Associated Tau Seeding And Spreading, Nimansha Jain, Caroline A Lewis, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD. Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the …

Hydrogen Deuterium Exchange And Other Mass Spectrometry-Based Approaches For Epitope Mapping, Prashant N Jethva, Michael L Gross

2020-Current year OA Pubs

Antigen-antibody interactions are a fundamental subset of protein-protein interactions responsible for the "survival of the fittest". Determining the interacting interface of the antigen, called an epitope, and that on the antibody, called a paratope, is crucial to antibody development. Because each antigen presents multiple epitopes (unique footprints), sophisticated approaches are required to determine the target region for a given antibody. Although X-ray crystallography, Cryo-EM, and nuclear magnetic resonance can provide atomic details of an epitope, they are often laborious, poor in throughput, and insensitive. Mass spectrometry-based approaches offer rapid turnaround, intermediate structural resolution, and virtually no size limit for the …

Testing Of A Novel Questionnaire Of Household Exposure To Wood Smoke, Paula M. Meek, Sarah J. Schmiege, Akshay Sood, Hans Petersen, Rodrigo Vazquez-Guillamet, Hammad Irshad, Jacob Mcdonald, Yohannes Tesfaigzi

2020-Current year OA Pubs

Household air pollution from wood smoke (WS), contributes to adverse health effects in both low- and high-income countries. However, measurement of WS exposure has been limited to expensive in-home monitoring and lengthy face-to-face interviews. This paper reports on the development and testing of a novel, self-report nine-item measure of WS exposure, called the Household Exposure to Wood Smoke (HEWS). A sample of 149 individuals using household wood stoves for heating from western states in the U.S., completed the HEWS during the winter months (November to March) of 2013 through 2016 with 30 subjects having in-home particle monitoring. Hard copy or …

Genetic Variation In Environmental Enteropathy And Stunting In Zambian Children: A Pilot Genome Wide Association Study Using The H3africa Chip, Monica N. Mweetwa, Talin Haritunians, Shishir Dube, Kanta Chandwe, Beatrice Amadi, Kanekwa Zyambo, Ta-Chiang Liu, Dermot Mcgovern, Paul Kelly

2020-Current year OA Pubs

PURPOSE: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy.

METHOD: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array.

RESULTS: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Quality Improvements In Radiation Oncology Clinical Trials, Koren Smith, Jeff Michalski, Et Al.

2020-Current year OA Pubs

Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use …

Psychosocial Work Environment Stressors For School Staff During The Covid-19 Pandemic: Barriers And Facilitators For Supporting Wellbeing, Liz R Rolf, Liz Vestal, Ashley C Moore, Nikole Lobb Dougherty, Nancy Mueller, Jason G Newland

2020-Current year OA Pubs

INTRODUCTION: After periods of remote and/or hybrid learning as a result of the COVID-19 global pandemic, the return to in-person learning has been beneficial for both students and teachers, but it has not been without challenges. This study was designed to assess the impact of the return to in-person learning on the school experience, and efforts made to ease the transition in furthering a positive in-person learning environment.

MATERIALS AND METHODS: We conducted a series of listening sessions with 4 stakeholder groups: students (

RESULTS: Three main themes emerged around school staff experiences: (1) increased levels of stress and anxiety …

Exploring The Villalta Scale To Capture Postthrombotic Syndrome Using Alternative Approaches: A Subanalysis Of The Attract Trial, Cristina T Pop, Chu-Shu Gu, Suresh Vedantham, Jean-Philippe Galanaud, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use.

OBJECTIVES: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial.

METHODS: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their …

Abundance Of Acvr1b Transcript Is Elevated During Septic Conditions: Perspectives Obtained From A Hands-On Reductionist Investigation, Anucha Preechanukul, Thatcha Yimthin, Sarunporn Tandhavanant, Tobias Brummaier, Chalita Chomkatekaew, Sukanta Das, Basirudeen Syed Ahamed Kabeer, Mohammed Toufiq, Darawan Rinchai, T Eoin West, Damien Chaussabel, Narisara Chantratita, Mathieu Garand

2020-Current year OA Pubs

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Aromatic Amino Acid Metabolites Alter Interferon Signaling And Influenza Pathogenesis, Gautam Anand, Colin Clark-Dinovo, Alexandra M Perry, Victoria M Goodwin, Emma St Raymond, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

The ability of gut microbial metabolites to influence the host is increasingly recognized. The microbiota extensively metabolizes the three aromatic amino acids, tryptophan, tyrosine, and phenylalanine. Previously we have found that a metabolite of tyrosine, 4-OH-phenylpropionic acid, can enhance type I interferon (IFN) signaling and protect from influenza pathogenesis in a murine model. Herein we screened 17 related aromatic amino acid metabolites for effects on IFN signaling in human lung epithelial cells and monocytes alone and in the presence of IFN-β, influenza, and LPS. While the tryptophan family metabolites reduced IFN signaling in both cell types, the tyrosine and phenylalanine …

Transferrin Receptor In Primary And Metastatic Breast Cancer: Evaluation Of Expression And Experimental Modulation To Improve Molecular Targeting, Francesca Fontana, Alison K. Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S. Allen, Yalin Xu, Jennifer L. Davis, Ariel Gabay, Jingyu Xiang, Kristin A. Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher

2020-Current year OA Pubs

BACKGROUND: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.

METHODS: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were …

The Oral Selective Estrogen Receptor Degrader Gdc-0810 (Arn-810) In Postmenopausal Women With Hormone Receptor-Positive Her2-Negative (Hr + /Her2 -) Advanced/Metastatic Breast Cancer, Aditya Bardia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

METHODS: A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

RESULTS: Patients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose …

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Association Of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension Of Survival Among Patients With Newly Diagnosed And Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial, Linda M Liau, Jian L Campian, George Ansstas, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.

OBJECTIVE: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to …

Eliminating Central Line Associated Bloodstream Infections In Pediatric Oncology Patients: A Quality Improvement Effort, Daniel N. Willis, Karen Looper, Rema A. Malone, Barbara Ricken, Ashley Slater, Amanda Fuller, Meagan Mccaughey, Angela Niesen, Joan R. Smith, Beverly Brozanski

2020-Current year OA Pubs

UNLABELLED: Central Line-Associated Bloodstream Infections (CLABSI) are the largest contributor to harm across the Children's Hospital's Solutions for Patient Safety network. Pediatric hematology/oncology (PHO) patients are at increased risk for CLABSI due to multiple factors. Consequently, traditional CLABSI prevention strategies are insufficient to eliminate CLABSI in this high-risk population.

METHODS: Our SMART aim was to reduce the CLABSI rate by 50% from a baseline of 1.89/1000 central line days to less than 0.9/1000 central line days by December 31, 2021. We created a multidisciplinary team being mindful to identify roles and responsibilities upfront. We developed a key driver diagram and …