Medicine and Health Sciences Commons^™

Poems Syndrome: Real World Experience In Diagnosis And Systemic Therapy - 108 Patients Multicenter Analysis, Artur Jurczyszyn, Mark Fiala, Ravi Vij, Et Al.

2020-Current year OA Pubs

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present …

Ex Vivo Propagation In A Novel 3d High-Throughput Co-Culture System For Multiple Myeloma, Johannes M Waldschmidt, Stefan J Fruttiger, Dagmar Wider, Johannes Jung, Andreas R Thomsen, Tanja N Hartmann, Justus Duyster, Martin J Hug, Kareem A Azab, Manfred Jung, Ralph Wäsch, Monika Engelhardt

2020-Current year OA Pubs

PURPOSE: Multiple myeloma (MM) remains an incurable hematologic malignancy which ultimately develops drug resistance and evades treatment. Despite substantial therapeutic advances over the past years, the clinical failure rate of preclinically promising anti-MM drugs remains substantial. More realistic in vitro models are thus required to better predict clinical efficacy of a preclinically active compound.

METHODS: Here, we report on the establishment of a conical agarose 3D co-culture platform for the preclinical propagation of primary MM cells ex vivo. Cell growth was compared to yet established 2D and liquid overlay systems. MM cell lines (MMCL: RPMI-8226, U266, OPM-2) and primary patient …

How Risky Are Risk Factors? An Analysis Of Prenatal Risk Factors In Patients Participating In The Congenital Upper Limb Differences Registry, Tyler Schaeffer, Maria F Canizares, Lindley B Wall, Deborah Bohn, Suzanne Steinman, Julie Samora, Mary Claire Manske, Douglas T Hutchinson, Apurva S Shah, Andrea S Bauer, Could Study Group

2020-Current year OA Pubs

PURPOSE: Risk factors for congenital upper limb differences (CoULDs) are often studied at the general population level. The CoULD registry provides a unique opportunity to study prenatal risk factors within a large patient sample.

METHODS: All patients enrolled between June 2014 and March 2020 in the prospective CoULD registry, a national multicenter database of patients diagnosed with a CoULD, were included in the analysis. We analyzed self-reported, prenatal risk factors, including maternal smoking, alcohol use, recreational drug use, prescription drug use, gestational diabetes mellitus (GDM), and gestational hypertension. The outcome measures included comorbid medical conditions, proximal involvement of limb difference, …

Efficacy And Safety Of Bempedoic Acid In Patients Not Receiving Statins In Phase 3 Clinical Trials, Ulrich Laufs, Christie M Ballantyne, Maciej Banach, Harold Bays, Alberico L Catapano, P Barton Duell, Anne C Goldberg, Antonio M Gotto, Lawrence A Leiter, Kausik K Ray, Leanne T Bloedon, Diane Macdougall, Yang Zhang, G B John Mancini

2020-Current year OA Pubs

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.

OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.

METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for …

Optimization Of Care For Patients With Hereditary Angioedema Living In Rural Areas, Marc A Riedl, Douglas T Johnston, John Anderson, J Allen Meadows, Daniel Soteres, Stephen B Leblanc, H James Wedner, David M Lang

2020-Current year OA Pubs

BACKGROUND: People living in rural areas of the United States experience greater health inequality than individuals residing in urban or suburban locations and encounter several barriers to obtaining optimal health care. Health disparities are compounded for patients with rare diseases such as hereditary angioedema (HAE), an autosomal dominant genetic disorder characterized by recurrent, severe abdominal pain and life-threatening oropharyngeal or laryngeal swelling.

OBJECTIVE: To explore the challenges of managing patients with HAE in rural areas and suggest possible improvements for optimizing care.

DATA SOURCES: PubMed was searched for articles on patient care management, treatment challenges, rural health, and HAE.

STUDY …

Sars-Cov-2 Infection And Covid-19 Outcomes In Rheumatic Diseases: A Systematic Literature Review And Meta-Analysis, Richard Conway, Alfred H J Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients.

METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality …

An Alternate Technique For Goniotomy: Description Of Procedure And Preliminary Results, Thomas Shute, Wesley Green, James Liu, Arsham Sheybani

2020-Current year OA Pubs

PURPOSE: Multiple glaucoma treatment modalities seek to lower IOP by bypassing or removing a portion of the juxtacanalicular trabecular meshwork. These procedures often require expensive implants or specialized surgical instruments. The authors developed a technique for ab interno goniectomy utilizing a standard disposable 25-gauge hypodermic needle. The surgical procedure-termed bent ab interno needle goniectomy (BANG)-and preliminary results are presented here.

METHODS: A retrospective chart review was performed for all patients who underwent goniotomy using a modified hypodermic needle by one of the three authors between July 2017 and June 2018. The mean and standard deviation pre- and postoperative IOP and …

Vaccine Protection Against The Sars-Cov-2 Omicron Variant In Macaques, Abishek Chandrashekar, Adrianus C. M. Boon, Et Al.

2020-Current year OA Pubs

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers …

Silencing Alanine Transaminase 2 In Diabetic Liver Attenuates Hyperglycemia By Reducing Gluconeogenesis From Amino Acids, Michael R. Martino, Manuel Gutiérrez-Aguilar, Nicole K. H. Yiew, Andrew J. Lutkewitte, Jason M. Singer, Kyle S. Mccommis, Daniel Ferguson, Kim H. H. Liss, Jun Yoshino, M. Katie Renkemeyer, Gordon I. Smith, Kevin Cho, Justin A. Fletcher, Samuel Klein, Gary J. Patti, Shawn C. Burgess, Brian N. Finck

2020-Current year OA Pubs

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation of

Ptsd Is Associated With Impaired Event Processing And Memory For Everyday Events, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks

2020-Current year OA Pubs

Current theories of posttraumatic stress disorder (PTSD) propose that memory abnormalities are central to the development and persistence of symptoms. While the most notable memory disturbances in PTSD involve memory for the trauma itself, individuals often have trouble remembering aspects of everyday life. Further, people with PTSD may have difficulty segmenting ongoing activity into discrete units, which is important for our perception and later memory of the activity. The current study investigated whether PTSD diagnosis and symptom severity predicted event segmentation and memory for everyday activities. To do so, 63 people with PTSD and 64 controls with a trauma history …

Directed Mutational Scanning Reveals A Balance Between Acidic And Hydrophobic Residues In Strong Human Activation Domains, Max V Staller, Eddie Ramirez, Sanjana R Kotha, Alex S Holehouse, Rohit V Pappu, Barak A Cohen

2020-Current year OA Pubs

Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of …

Calgb 40603 (Alliance): Long-Term Outcomes And Genomic Correlates Of Response And Survival After Neoadjuvant Chemotherapy With Or Without Carboplatin And Bevacizumab In Triple-Negative Breast Cancer, Jonathan H Shepherd, Cynthia Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: CALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.

PATIENTS AND METHODS: The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose …

Centrosome-Dependent Microtubule Modifications Set The Conditions For Axon Formation, Durga Praveen Meka, Ewelina Betleja, Tao Cheng, Moe R Mahjoub, Et Al.

2020-Current year OA Pubs

Microtubule (MT) modifications are critical during axon development, with stable MTs populating the axon. How these modifications are spatially coordinated is unclear. Here, via high-resolution microscopy, we show that early developing neurons have fewer somatic acetylated MTs restricted near the centrosome. At later stages, however, acetylated MTs spread out in soma and concentrate in growing axon. Live imaging in early plated neurons of the MT plus-end protein, EB3, show increased displacement and growth rate near the MTOC, suggesting local differences that might support axon selection. Moreover, F-actin disruption in early developing neurons, which show fewer somatic acetylated MTs, does not …

Comprehensive Cross-Sectional And Longitudinal Analyses Of Plasma Neurofilament Light Across Ftd Spectrum Disorders, Tania F. Gendron, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with …

Somatic Dnmt3a Inactivation Leads To Slow, Canonical Dna Methylation Loss In Murine Hematopoietic Cells, Amanda M. Smith, Angela M. Verdoni, Haley J. Abel, David Y. Chen, Shamika Ketkar, Elizabeth R. Leight, Christopher A. Miller, Timothy J. Ley

2020-Current year OA Pubs

Mutations in the gene encoding DNA methyltransferase 3A (

Anatomical Variability, Multi-Modal Coordinate Systems, And Precision Targeting In The Marmoset Brain, Takayuki Ose, David C Van Essen, Matthew F Glasser, Et Al.

2020-Current year OA Pubs

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and …

An International Survey On Nasal Nitric Oxide Measurement Practices For The Diagnosis Of Primary Ciliary Dyskinesia, Nicole Beydon, Thomas Ferkol, Et Al.

2020-Current year OA Pubs

Nasal nitric oxide (nNO) measurements are used in the assessment of patients suspected of having primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurement in children, an international online survey was conducted to better understand current measurement practices among providers involved in PCD diagnostics. 78 professionals responded, representing 65 centres across 18 countries, mainly in Europe and North America. Nearly all centres measured nNO in children and more than half performed measurements before …

When Reboa Grows Wings: Resuscitative Endovascular Balloon Occlusion Of The Aorta To Facilitate Aeromedical Transport, Jason A Snyder, Douglas J E Schuerer, Grant V Bochicchio, Mark H Hoofnagle

2020-Current year OA Pubs

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a helpful adjunct in the control of non-compressible truncal hemorrhage. Concerns regarding ischemia time limits its applicability in transfer. We describe the first reported case of civilian transfer via aeromedical transport to a higher level of care with a zone 3 REBOA catheter deployed.

CASE REPORT: We present the case of a patient in hemorrhagic shock with a complex pelvic fracture exceeding the capability of a rural level-two trauma center requiring the use of REBOA catheter to permit aeromedical transport to a level-one trauma center for definitive embolization.

CONCLUSION: Deployment …

Enhancing Discovery Of Genetic Variants For Posttraumatic Stress Disorder Through Integration Of Quantitative Phenotypes And Trauma Exposure Information, Adam X. Maihofer, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs).

METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. …

Clinical Validation Of Guardant360 Cdx As A Blood-Based Companion Diagnostic For Sotorasib, Joshua M Bauml, Bob T Li, Vamsidhar Velcheti, Ramaswamy Govindan, Alessandra Curioni-Fontecedro, Christophe Dooms, Toshiaki Takahashi, Andrew W Duda, Justin I Odegaard, Fernando Cruz-Guilloty, Liming Jin, Ying Zhang, Abraham Anderson, Ferdinandos Skoulidis

2020-Current year OA Pubs

OBJECTIVES: Effective therapy for non-small-cell lung cancer (NSCLC) depends on morphological and genomic classification, with comprehensive screening for guideline-recommended biomarkers critical to guide treatment. Companion diagnostics, which provide robust genotyping results, represent an important component of personalized oncology. We evaluated the clinical validity of Guardant360 CDx as a companion diagnostic for sotorasib for detection of KRAS p.G12C, an important oncogenic NSCLC driver mutation.

MATERIALS AND METHODS: KRAS p.G12C was tested in NSCLC patients from CodeBreaK100 (NCT03600833) in pretreatment plasma samples using Guardant360 CDx liquid biopsy and archival tissue samples using therascreen® KRAS RGQ polymerase chain reaction (PCR) kit tissue testing. …

Soluble Trem2 In Csf And Its Association With Other Biomarkers And Cognition In Autosomal-Dominant Alzheimer's Disease: A Longitudinal Observational Study, Estrella Morenas-Rodríguez, Yan Li, Chengjie Xiong, Anne M. Fagan, Stephanie Schultz, Brian A. Gordon, Tammie L. S. Benzinger, Jason Hassenstab, Eric Mcdade, Celeste M. Karch, John C. Morris, Randall J. Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease.

METHODS: We did a longitudinal analysis of data from the Dominantly Inherited …

Suppressing Fatty Acid Synthase By Type I Interferon And Chemical Inhibitors As A Broad Spectrum Anti-Viral Strategy Against Sars-Cov-2, Saba R. Aliyari, Xiaochao Wei, Clay F. Semenkovich, Et Al.

2020-Current year OA Pubs

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased …

Clinical Outcomes From The Assessing Donor-Derived Cell-Free Dna Monitoring Insights Of Kidney Allografts With Longitudinal Surveillance (Admiral) Study, Lihong Bu, Haris Murad, Tarek Alhamad, Et Al.

2020-Current year OA Pubs

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) …

A Bayesian Spatiotemporal Model For Prevalence Estimation Of A Vre Outbreak In A Tertiary Care Hospital, A. Atkinson, B. Ellenberger, V. Piezzi, T. Kaspar, O. Endrich, A. B. Leichtle, M. Zwahlen, J. Marschall

2020-Current year OA Pubs

BACKGROUND: There was a nosocomial outbreak of vancomycin-resistant enterococci (VRE) at the hospital between 1

METHODS: A room-centric analysis of 12 floors (243 rooms) of the main hospital building was undertaken, including data on 37,558 patients over 22,072 person-weeks for the first 2 years of the outbreak (2018-2019). Poisson Bayesian hierarchical models were fitted to estimate prevalence per room and per week, including both spatial and temporal random effects terms.

RESULTS: Exploratory data analysis revealed significant variability in prevalence between departments and floors, along with sporadic spatial and temporal clustering during colonization 'flare-ups'. The oncology department experienced slightly higher prevalence …

Soluble Trem2: Innocent Bystander Or Active Player In Neurological Diseases?, Fabia Filipello, Claire Goldsbury, Shih Feng You, Alberto Locca, Celeste M Karch, Laura Piccio

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by macrophages and microglia in the central nervous system (CNS). TREM2 has attracted a lot of interest in the past decade for its critical role in modulating microglia functions under homeostatic conditions and in neurodegenerative diseases. Genetic variation in TREM2 is sufficient to cause Nasu-Hakola disease, a rare pre-senile dementia with bone cysts, and to increase risk for Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders. Beyond the role played by TREM2 genetic variants in these diseases, TREM2 engagement is a key step in microglia activation …

High-Throughput Methodology To Identify Crispr-Generated Danio Rerio Mutants Using Fragment Analysis With Unmodified Pcr Products, Sarah Colijn, Ying Yin, Amber N Stratman

2020-Current year OA Pubs

Targeted mutagenesis in zebrafish, fruit flies, and C. elegans has been significantly improved over the years through CRISPR technology. CRISPR enables researchers to efficiently examine cellular pathways by inducing small, targeted mutations in vivo. Though these mutations are commonly random insertions or deletions (indels), they often result in functionally disrupted alleles of a target gene if the CRISPR components are appropriately designed. However, current protocols used to identify the presence of CRISPR-generated indels are often labor intensive, time-consuming, or expensive. Here, we describe a straightforward, high-throughput method for identifying the presence of mutations by using a fragment analyzer platform which …

Joanne Knight Breast Health Cohort At Siteman Cancer Center, Graham A Colditz, Debbie L Bennett, Jennifer Tappenden, Courtney Beers, Nicole Ackermann, Ningying Wu, Jingqin Luo, Sarah Humble, Erin Linnenbringer, Kia Davis, Shu Jiang, Adetunji T Toriola

2020-Current year OA Pubs

PURPOSE: The Joanne Knight Breast Health Cohort was established to link breast cancer risk factors, mammographic breast density, benign breast biopsies and associated tissue markers, and blood markers in a diverse population of women undergoing routine mammographic screening to study risk factors and validate models for breast cancer risk prediction.

METHODS: Women were recruited from November 2008 to April 2012 through the mammography service at the Joanne Knight Breast Health Center at Washington University in St. Louis, Missouri. Baseline questionnaire risk factors, blood, and screening mammograms were collected from 12,153 women. Of these, 1,672 were excluded for prior history of …

Phase 1b Trial Of Anti-Vegf/Pdgfr Vorolanib Combined With Immune Checkpoint Inhibitors In Patients With Advanced Solid Tumors, Nusayba A Bagegni, Haeseong Park, Katlyn Kraft, Maura O-Toole, Feng Gao, Saiama N Waqar, Lee Ratner, Daniel Morgensztern, Siddhartha Devarakonda, Manik Amin, Maria Q Baggstrom, Chris Liang, Giovanni Selvaggi, Andrea Wang-Gillam

2020-Current year OA Pubs

PURPOSE: Vorolanib is a multi-target tyrosine kinase inhibitor with anti-angiogenic properties. This study aimed to evaluate the tolerability, safety and efficacy of vorolanib when added to checkpoint inhibitors (CPIs) in patients with advanced solid tumors.

METHODS: We conducted a phase 1b study of vorolanib (300 or 400 mg orally once daily) plus pembrolizumab or nivolumab using a standard 3 + 3 design to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The endpoints included safety, toxicity and objective response rate, according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

RESULTS: …

Implementation And Early Experience Of A Pediatric Electrophysiology Telehealth Program, Jonathan Schweber, Lisa Roelle, Juliana Ocasio, Aarti S Dalal, Nathan Miller, George F Van Hare, Jennifer N Avari Silva

2020-Current year OA Pubs

BACKGROUND: Telehealth (TH) visits have been growing with exponential increased utilization during the COVID-19 pandemic. The aim of this manuscript is to describe the implementation and early experience of a pediatric electrophysiology (EP) TH program implemented during the pandemic, assessing patient satisfaction, patient equity and inclusion (measured by geographical outreach), and sustainability.

METHODS: A retrospective chart review study was performed and data were collected from the medical record, including demographic, testing, and billing data from scheduled TH encounters between March and August 2020 of a single pediatric EP group in the Midwest. Patients were called to complete satisfaction surveys.

RESULTS: …

Deglutarylation Of Glutaryl-Coa Dehydrogenase By Deacylating Enzyme Sirt5 Promotes Lysine Oxidation In Mice, Dhaval P Bhatt, C Allie Mills, Kristin A Anderson, Bárbara J Henriques, Tânia G Lucas, Sara Francisco, Juan Liu, Olga R Ilkayeva, Alexander E Adams, Shreyas R Kulkarni, Donald S Backos, Michael B Major, Paul A Grimsrud, Cláudio M Gomes, Matthew D Hirschey

2020-Current year OA Pubs

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show …