tbuckley/cabot-search huggingface dataset:
INNV-07. TTFIELDS TREATMENT OF GLIOSARCOMA AND RECURRENT ANAPLASTIC OLIGODENDROGLIOMA
Authors: Nicholas Blondin, Robert Fulbright, Anita Huttner, Jennifer Moliterno-Gunel
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The Optune device delivers tumor treating fields (TTFields) and is considered as a standard of care for newly diagnosed and recurrent glioblastoma patients. The efficacy of Optune in other glioma subtypes, such as gliosarcoma and anaplastic oligodendroglioma, is still unclear. In this small case series, we present the clinical, pathologic and radiographic findings of two patients who utilized Optune and had improved outcomes compared to historical controls. CASE 1 A 49 year old woman underwent resection of a right temporal lobe gliosarcoma in November 2017. She received conventional radiation therapy with concurrent temozolomide, which was complicated by significant thrombocytopenia and leukopenia. She initiated Optune as monotherapy six weeks after completing radiation, and used the device for 24 months. She still has not had a recurrence, now 3.5 years since her initial diagnosis. CASE 2 A 46 year old woman underwent resection of a right frontal lobe oligodendroglioma, WHO Grade 2, in September 2011. She received one cycle of temozolomide in April 2014, complicated by thrombocytopenia, and no further chemotherapy was administered. In November 2017, she underwent resection of a new focus of enhancement at the margin of the resection cavity, which was confirmed to have transformed to WHO Grade 3. In August 2019, a radiographic progression of an enhancing nodule was observed. She initiated Optune as monotherapy in September 2019, and since that time, has had stable disease for 18 months. Optune treatment is still ongoing. CONCLUSIONS In a case of newly diagnosed gliosarcoma, Optune monotherapy has contributed to progression-free and overall survival of 3.5 years to date. In a case of recurrent anaplastic oligodendroglioma, Optune monotherapy has achieved stable disease for at least 18 months. These cases demonstrate that Optune can be safely utilized in these glioma subtypes and contributed to improved survival outcomes in these two patients.
Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
Authors: Stacey N. Reinke, Shama Naz, Romanas Chaleckis, Hector Gallart-Ayala, Johan Kolmert, Nazanin Z. Kermani, Angelica Tiotiu, David I. Broadhurst, Anders Lundqvist, Henric Olsson, Marika Ström, Åsa M. Wheelock, Cristina Gómez, Magnus Ericsson, Ana R. Sousa, John H. Riley, Stewart Bates, James Scholfield, Matthew Loza, Frédéric Baribaud, Per S. Bakke, Massimo Caruso, Pascal Chanez, Stephen J. Fowler, Thomas Geiser, Peter Howarth, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Annelie Behndig, Florian Singer, Jacek Musial, Dominick E. Shaw, Barbro Dahlén, Sile Hu, Jessica Lasky-Su, Peter J. Sterk, Kian Fan Chung, Ratko Djukanovic, Sven-Erik Dahlén, Ian M. Adcock, Craig E. Wheelock
Journal: European Respiratory Journal (2021)

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results A total of 90 metabolites were identified, with 40 significantly altered (p&lt;0.05, false discovery rate &lt;0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10 −20 ), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10 −4 ), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.
CTNI-13. MALIGNANT GLIOMA SUBSET FROM ACTUATE 1801 PHASE 1/2 STUDY OF 9-ING-41, A GLYCOGEN SYNTHASE KINASE 3 BETA (GSK-3β) INHIBITOR, AS A SINGLE AGENT AND COMBINED WITH CHEMOTHERAPY REFRACTORY
Authors: Yazmin Odia, Ludimila Cavalcante, Howard Safran, Steven Francis Powell, Pamela Munster, Wen Wee Ma, Benedito Carneiro, Bruno Bastos, Francis Giles, Solmaz Sahebjam
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND GSK3β serine/threonine kinase regulates metabolism and glycogen biosynthesis. GSK3β overexpression promotes tumor progression and resistance through NF-κB and p53 apoptotic pathways. GSK3β inhibits immunomodulation by downregulating checkpoints, e.g. PD-L1 and LAG-3, and increasing NK and T-cell mediated tumor killing. 9-ING-41 is a small-molecule, potent, selective GSK3β inhibitor with preclinical activity. In chemoresistant PDX glioblastoma models, 9-ING-41 enhanced lomustine antitumor effect. METHODS Patients with refractory malignancies were treated with 9-ING-41 monotherapy (n=65) or combined with 8 cytotoxic regimens after prior exposure (n=162) in the first-in-human study (NCT03678883). The recurrent gliomas subset was treated with 9-ING-41 monotherapy IV TIW q21day cycles at 3.3, 5, 9.3, 15mg/kg, or combined with lomustine 30 mg/m² PO weekly q84day cycles. Primary objective was safety and tolerability. RESULTS An RP2D of 15mg/kg IV TIW was confirmed across all 9 regimens, no accentuation of chemotherapy toxicity noted. Of 18 glioma patients enrolled, 13 were glioblastoma, 2 anaplastic astrocytomas, 1 anaplastic oligodendroglioma, and 1 diffuse astrocytoma; 6 female, 12 male; median age 52 (30-69) years; median ECOG was 1 (0-2). All received initial radiation and temozolomide (18/18), prior salvage therapies included nitrosoureas (15/18), bevacizumab (8/18), TTFields (6/18), checkpoint inhibitor (4/18). Median recurrences 3 (1-6). NGS alterations included: IDH/wildtype (11), IDH/mutation(3); 1p19q/codeletion(10); MGMT/unmethylated(11), MGMT/methylated(1); EGFR/amplification(6), EGFR/v3mutation(3), TERT/mutation(6), PTEN/loss(3), NF1/rearrangement(2), ATRX/loss (2), TP53/mutation(4), CDKN2A/deletion(2), RB1/loss(1), PALB2/mutation(10). Four patients received 9-ING-41 monotherapy, 14 concurrently treated with lomustine. No SAEs or grade 3/4 AEs attributed to 9-ING-41 noted, only G1/2 vision changes (9/18, 50%), infusion reactions (4/18, 22%). Lomustine-related toxicities included G3/4 thrombocytopenia (3/14, 21%), and G1/2 fatigue (4/14, 28%). Median therapy duration was 55 (4-305); 1 partial response ( &amp;gt;50%) noted with 9-ING-41/lomustine. Median PFS and OS were 1.9 (0.3-11.1) and 6.0 (1.6-16.6) months, respectively. CONCLUSIONS 9-ING-41 plus/minus lomustine is safe and warrants further study in glioma patients.
Abstract 10630: Perfusable Apparatus for Thick-Tissue Creation and Growth (patch) of Cardiac Tissue
Authors: Tyler Dunn, Katherine Nurminsky, Isaree Pitaktong, Yusheng Jason He, Sarah Koljaka, Olivia Dunne, Stephanie Ran, Wesley Shih, Anya Wang, Hiroshi Matsushita, Daniel Rodgers, Narutoshi Hibino
Journal: Circulation (2021)

Background: Cardiac tissue engineering has beendeveloped as apotential alternativetreatment for heart failure. However, current 3D tissues are limited insize and thickness due tothe lack of aneffective vascularizationmethod. We have developed anovel bioreactor systemtocreate viable vascularized cardiac tissue from multicellular spheroids using adigital lightprocessing (DLP)3D bioprinting system. Methods: Spheroids were created from induced pluripotent stem cells (iPSC)and cardiacfibroblasts (FB)using special dimple plates for mass production. One centimeter cubic tissueswere created from spheroids using aDLP 3D bioprinted mold with vascular channels. Thetissue was maintained inaperfusionchamber under regulated flow and pressure followingdifferentiationtocardiac tissue and endothelialization. Results: Mass productionof large spheroids (35,000/ tissue, diameter of 395.99um +/- 101.15um)was achieved from 170millioniPSCs and 50millionFBs for the creationof 1cm3cardiactissue inabioprinted mold with vascular channels. The cardiac tissues (n=5)were perfused for20days under stable pressure of 17.5+/- 3.05PSI and flow of 5000uL/min+/- 1116.42uL/min.Ondays 10and 20, Alamar blue assays showed viability for all five tissues (Alamar blueintensity: Day 101.57+/- 0.15. Day 202.21+/- 0.19). Conclusion: Thick and viable cardiac tissues were created and maintained using a3Dbioprinted vascularized mold and perfusionsystem for maturationand growth invitrofor 20days. This technology will opennew doors for viable invitrocardiac tissue creation.
Abstract 10769: Osteoprotegerin and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Daisuke Kamimura, Leo Buckley, Pranav Dorbala, Brian Claggett, Bing Yu, Josef Coresh, Kuni Matsushita, Patricia Chang, Ron C Hoogeveen, Christie M Ballantyne, Michael E Hall, Amil M Shah
Journal: Circulation (2021)

Background: Osteoprotegerin (OPG), a protein involved in bone metabolism, is associated with cardiac fibrosis and remodeling in animal models. Circulating OPG levels correlate with left ventricular mass index and plasma brain natriuretic peptide levels in humans, but the association with incident heart failure (HF) is not known. Methods: Among 10,261 participants in the community-based Atherosclerosis Risk in Communities (ARIC) Study free of prevalent HF at study Visit 3, we investigated the association of plasma OPG levels at Visit 3 with incident HF hospitalization post-Visit 3 using multivariable Cox proportional hazard models. OPG was measured using a high-throughput DNA aptamer-based proteomic platform (Somalogic, Boulder, CO), and relative fluorescence unit values were log2 transformed. All models adjusted for age, sex, race, study field center, body mass index, hypertension, diabetes, estimated glomerular filtration rate, smoking status, prevalent coronary artery disease, and atrial fibrillation. Results: Mean age was 60±6 years, 54% were women, and 20% of participants were Black. Higher OPG levels were associated with older age, female gender, Black race, and higher prevalence of hypertension, diabetes, and smoking (all p &lt;0.001). Over a median of 15.0 years follow-up (interquartile range: 13-15), there were 1301 incident HF hospitalizations. In multivariable models, higher serum OPG levels were associated with greater risk of incident HF (hazard ratio per 1 SD increase: 1.20 [95% confidence interval, 1.13-1.27]; Figure). This association persisted after further adjustment for NT-proBNP (HR 1.19 [95% CI 1.12-1.26], p&lt;.001). Conclusion: In this large community-based cohort, higher plasma OPG levels were significantly associated with incident HF hospitalization, independent of traditional cardiovascular risk factors and NT-proBNP. Further studies are warranted to clarify whether OPG could be a new therapeutic target for HF prevention.
Digital transformation could increase the burden of treatment on patients
Authors: Frances S Mair, Victor M Montori, Carl R May
Journal: BMJ (2021)

The burden of treatment refers to the demands that healthcare professionals and systems place on patients and their support community, and the implications this has on their quality of life. 1 It is an important barometer of quality of care.It includes the work involved in self-management of care such as: gaining an understanding of chronic conditions, their management and implications; engaging with health and social care professionals, family, and friends to access care and treatments; putting self-management recommendations into practice; taking multiple medications; enduring side effects; attending appointments and investigations; enacting lifestyle and behaviour changes; self-monitoring activities and reconfiguring treatments to make them workable; and navigating complex care systems.
Abstract 12928: The Impact of Medicaid Expansion on Black - White Disparities in Cardiovascular Disease Mortality
Authors: Brittany Brown-podgorski, Elizabeth A Jacobs, Catherine Cubbin
Journal: Circulation (2021)

Introduction: Cardiovascular disease (CVD) is a leading cause of mortality among US adults, especially low-income and uninsured adults. Non-Hispanic Black adults, who are overrepresented in these at-risk populations, are disproportionately burdened by poor cardiovascular health and CVD-related premature mortality. Medicaid expansion is associated with reduced CVD mortality overall, however research suggests that Medicaid expansion has had fewer impacts on health outcomes among non-Hispanic Black adults relative to non-Hispanic White adults. Therefore, it is unclear whether Medicaid expansion has lessened the disparate burden of CVD on this population. This study investigated the relationship between Medicaid expansion and Black-White disparities in CVD mortality. Methods: We estimated a difference-in-differences model using mortality data (2011 – 2019) from the Wide-Ranging Online Data for Epidemiologic Research (WONDER) system to compare changes in Black-White CVD mortality ratios between counties in expansion and non-expansion states. The age-adjusted mortality ratio (AAMR) was calculated by dividing the county-year age-adjusted mortality rate for non-Hispanic Black adults (ages 45 – 64) by the county-year age-adjusted mortality rate for non-Hispanic White adults. The final sample consisted of 1,720 county-year observations. Results: From 2011 – 2019, the AAMR was significantly higher among counties in expansion states ( p &lt;0.001). Controlling for county-level factors, Medicaid expansion was associated with a 2.01% decrease in the AAMR in CVD, but this relationship was not statistically significant (Figure 1). County-level rate of cardiologists per 100,000 and median household income were associated with a significant increase in the AAMR. Conclusion: Medicaid expansion may be associated with reduced CVD mortality overall; however, it is insufficient to counteract social and economic drivers of racial disparities in CVD mortality.
Spectrum of short-term inflammatory musculoskeletal manifestations after COVID-19 vaccine administration: a report of 66 cases
Authors: Francesco Ursini, Piero Ruscitti, Vincenzo Raimondo, Rossella De Angelis, Fabio Cacciapaglia, Erika Pigatto, Domenico Olivo, Ilenia Di Cola, Felice Galluccio, Francesca Francioso, Rosario Foti, Antonio Tavoni, Salvatore D'Angelo, Corrado Campochiaro, Francesca Motta, Maria De Santis, Silvia Bilia, Caterina Bruno, Giacomo De Luca, Marcella Visentini, Jacopo Ciaffi, Luana Mancarella, Veronica Brusi, Martina D’Onghia, Giovanna Cuomo, Enrico Fusaro, Lorenzo Dagna, Serena Guiducci, Riccardo Meliconi, Florenzo Iannone, Annamaria Iagnocco, Roberto Giacomelli, Clodoveo Ferri
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> <h3>Background</h3> In the last decade, integrative studies of microbiome and metabolome have experienced exponential growth in understanding their impact on human health and diseases. However, analyzing the resulting multi-omics data and their correlations remains a significant challenge in current studies due to the lack of a comprehensive computational tool to facilitate data integration and interpretation. In this study, we have developed a microbiome and metabolome integrative analysis pipeline (M<sup>2</sup>IA) to meet the urgent needs for tools that effectively integrate microbiome and metabolome data to derive biological insights. <h3>Results</h3> M<sup>2</sup>IA streamlines the integrative data analysis between metabolome and microbiome, including both univariate analysis and multivariate modeling methods. KEGG-based functional analysis of microbiome and metabolome are provided to explore their biological interactions within specific metabolic pathways. The functionality of M<sup>2</sup>IA was demonstrated using TwinsUK cohort data with 1116 fecal metabolites and 16s rRNA microbiome from 786 individuals. As a result, we identified two important pathways, i.e., the benzoate degradation and phosphotransferase system, were closely associated with obesity from both metabolome and microbiome. <h3>Conclusions</h3> M<sup>2</sup>IA is a public available web server (http://m2ia.met-bioinformatics.cn) with the capability to investigate the complex interplay between microbiome and metabolome, and help users to develop mechanistic hypothesis for nutritional and personalized therapies of diseases.
Abstract 10839: Two-year Follow-up Of Patients With Chronic Ischemic Heart Disease In A Specialized Center In Brazil
Authors: Henrique Trombini Pinesi, Eduardo M Moreira, Paula M Bolta, Eduardo B Martins, Fabio G Pitta, Paulo C Rezende, Eduardo G Lima, Whady Hueb, Cibele L Garzillo, Carlos V Serrano
Journal: Circulation (2021)

Introduction: Incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly between regions. Although populous, Brazil is often underrepresented in international registries. Objective: This study aimed to describe the quality of care and 2-year incidence of cardiovascular events and prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods: Patients with CIHD, denoted as previous revascularization, myocardial infarction (MI) or stenosis &gt; 50% in at least one epicardial coronary artery, were enrolled and followed for at least 2 years. Main endpoint was the composite of MI, stroke or death. We also evaluated prescription, symptoms and laboratory records. Results: 625 patients with mean age 65 (±9.6) years, 33.3% women, were included. Previous MI was present in 59.8%, CABG in 26.8%, and percutaneous coronary intervention in 40.6%. Diabetes was prevalent in 48.6%, high blood pressure in 83.1%, and chronic kidney disease (creatinine clearance &lt; 60 mL/min) in 34.7%. Residual coronary anatomy was known in 266 patients, of whom 29.3% had multivessel disease, and 11.7% had lesion in the left main artery. At a median follow-up (FU) of 881 days, we recorded 37 events of primary composite endpoint, with 2-year estimate event incidence of 7.05%. Age (HR per 10 years 1.61, 95%CI 1.32-1.97), stroke (3.65, 1.48-9.00) and LDL-cholesterol (1.23, 1.14-1.33) were the main prognostic factors in multivariate analysis. The participants experienced relief of angina symptoms based on Canadian Cardiovascular Society (CCS) scale (baseline vs. FU respectively): 65.7% vs. 81.7% were asymptomatic, 13 vs. 7.2% CCS1, 17.1 vs. 8.3% CCS2, 4.2 vs. 2.9% CCS3 or 4 (p &lt; 0.001). Analysis of therapeutic goals identified better quality of medication prescription, defined as the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker plus statin and any antithrombotic agent: 65.8% vs. 73.6% (p&lt;0.001) comparing baseline with FU. On the other hand, there was no improvement in LDL or blood pressure control. Conclusion: This study shows that CIHD patients had a 2-year incidence of the primary composite endpoint of 7.05%, LDL was the main modifiable risk factor of worse prognosis.
Abstract 6935: DOACs Use in Very Elderly AF Patients After TAVR Confers Significant Risk of Thromboembolic Events
Authors: Roberto C Cerrud-Rodriguez, Karlo A Wiley, isabella castillero, Ashley Goodwin, Tinatin Saralidze, Pedro A Villablanca, Maday Gonzalez, Juan Terre, Jose Wiley, Luigi Di Biase
Journal: Circulation (2021)

Introduction: To assess the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in very elderly patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR). Two efficacy outcomes were used: all-cause mortality and thromboembolic events (defined as stroke and/or transient ischemic attack and/or systemic embolism and/or valve thromboses) and one safety outcome: life-threatening or major bleeding events. There is a discrepancy between the results of previous studies on the appropriate anticoagulation regimen in patients with AF with CHA 2 DS 2 Vasc score≥2 undergoing TAVR Methods: A systematic review of Medline, Cochrane, and Embase was done to find all studies in which the previously described outcomes in AF patients undergoing TAVR were compared according to their use of DOACs vs. VKA. Results: Six studies with a total 3,631 participants, mean follow-up 19±9.4 months (male: 30.3%, mean ages were 82.8±1.1 years and 82.2±1.5 years for the DOAC and the VKA groups, respectively) were included in our analysis. No significant differences were found between the DOAC and VKA group in all-cause mortality (Risk Ratio [RR] 1.06, 95% Confidence Interval [CI] 0.84-1.35) or life-threatening or major bleeding events (RR 1.02, 95% CI 0.83-1.25). A significant increase in risk of thromboembolic events was found in the DOAC group (RR 1.23, 95% CI 1.05-1.44). Conclusions: VKA should be preferred over DOACs in very elderly patients with AF who undergo TAVR, given the significantly increased risk in thromboembolic events seen with DOACs and the lack of significant difference in all-cause mortality and bleeding. RCTs are needed to confirm or refute our findings.
Incidence of Nonfatal Traumatic Brain Injury–Related Hospitalizations — United States, 2018
Authors: Alexis B. Peterson, Karen E. Thomas
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Traumatic brain injury (TBI), which can disrupt normal brain function and result in short- and long-term adverse clinical outcomes, including disability and death, is preventable. To describe the 2018 incidence of nonfatal TBI-related hospitalizations in the United States by sociodemographic characteristics, injury intent, and mechanism of injury, CDC analyzed data from the Healthcare Cost and Utilization Project (HCUP) National (Nationwide) Inpatient Sample. During 2018, there were 223,050 nonfatal TBI-related hospitalizations; rates among persons aged ≥75 years were approximately three times higher than those among persons aged 65-74 years, and the age-adjusted rate among males was approximately double that among females. Unintentional falls were the most common mechanism of injury leading to nonfatal TBI-related hospitalization, followed by motor vehicle crashes. Proper and consistent use of recommended restraints (i.e., seatbelts, car seats, and booster seats) and, particularly for persons aged ≥75 years, learning about individual fall risk from health care providers are two steps the public can take to prevent the most common injuries leading to nonfatal TBIs. The findings in this report could be used by public health officials and clinicians to identify priority areas for prevention programs.