tbuckley/cabot-search huggingface dataset:
A longitudinal analysis of pneumococcal vaccine serotypes in pneumonia patients in Germany
Authors: Christina Bahrs, Miriam Kesselmeier, Martin Kolditz, Santiago Ewig, Gernot Rohde, Grit Barten-Neiner, Jan Rupp, Martin Witzenrath, Tobias Welte, Mathias W. Pletz
Journal: European Respiratory Journal (2021)

<b>In Germany, the recently approved 20-valent pneumococcal conjugate vaccine had a substantially higher coverage against pneumonia in adults than the 13-valent vaccine, while the coverage gap compared to the 23-valent polysaccharide vaccine was small</b>https://bit.ly/3q4skov
Abstract 13991: Angiopoietin-2 in Patients With Atrial Fibrillation - Associations With Clinical Characteristics and Outcomes
Authors: Alexander P Benz, Ziad Hijazi, Johan Lindbäck, Stuart J Connolly, John W Eikelboom, Peter Kastner, Andre Ziegler, Jonas Oldgren, Agneta Siegbahn, Lars Wallentin
Journal: Circulation (2021)

Introduction: Natriuretic peptides and cardiac troponin are associated with clinical outcomes in patients with atrial fibrillation (AF) but the search for disease-specific biomarkers is ongoing. We evaluated a novel candidate biomarker of endothelial remodeling and vascular growth, Angiopoietin-2 (Ang2), and its associations with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Methods: We used a prototype electroimmunoassay (Roche Diagnostics) to measure levels of Ang2 in plasma samples obtained at baseline from patients with AF randomized to aspirin monotherapy in two clinical trials. Associations of Ang2 with clinical characteristics and outcomes were explored using linear and Cox regression models. Results: A total of 2,987 patients were included (median age 71 years, 58% male and 13% with prior stroke). Median (25th-75th percentile) Ang2 plasma level was 3.12 (2.15-4.88) ng/mL. In adjusted analyses, Ang2 showed significant associations with AF-rhythm on the baseline ECG, age, heart failure, non-paroxysmal AF, female sex, active smoking, higher body mass index, creatinine and diabetes. Adjusting for age and other clinical characteristics, Ang2 was associated with subsequent ischemic stroke (third vs. first quartile, hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.19-2.61), heart failure hospitalization (HR 1.75, 95% CI 1.27-2.41), cardiovascular (HR 2.01, 95% CI 1.36-2.97) and all-cause death (HR 1.24, 95% CI 1.01-1.53), but not major bleeding. The association with heart failure remained after additional adjustment for N-terminal pro-B-type natriuretic peptide (p=0.002). There was no interaction with cardiac rhythm at baseline for any of the outcomes. Conclusions: Plasma levels of circulating Ang2 were associated with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Ang2 was a particularly strong predictor of heart failure hospitalization.
Abstract 10959: Phenotypic Age Mediates the Effects of Life's Simple 7 on Reduced Mortality Risk in the US Adults
Authors: Haiming Yang, Yueqing Wang, Meng Xiao, Yuxuan Zhao, Mingyu Song, Huan Yu, chunxiao liao, Yuanjie Pang, Canqing Yu, Wenjing Gao, Shengxu Li, Tao Huang, Jun Lv, Wei Chen, Lu Qi, Liming Li, Dianjianyi Sun
Journal: Circulation (2021)

Background: Phenotypic age, a newly developed marker for biological aging, improves risk prediction for adverse health events than chronological age. "Life’s Simple 7" (LS7) is a set of 7 recommended healthy lifestyle metrics proposed by the AHA to improve cardiovascular health. It is unknown, however, whether phenotypic age mediates the protective effects of healthy lifestyles on cardiovascular disease (CVD)- and all-cause mortality. Methods: Prospective analyses were performed using NHANES 1999-2010 data (6 cycles) on 9842 adults with linked death records till Dec 31, 2015. Adjusted hazard ratios (aHR) were estimated for phenotypic age, LS7-score, and LS7’s individual components for all-cause and cardiovascular mortality. Mediation analyses were performed using structural equation modeling. Results: One point increment in LS7-score was associated with a 0.92 (95% CI 0.87-0.98) year younger in phenotypic age, independent of general demographic characteristics and chronological age. During a median of 10.33-year follow-up, 1616 deaths were recorded, 323 being cardiovascular. One year increment in phenotypic age was associated with a higher risk of all-cause (aHR=1.05, 95% CI 1.04-1.05) and cardiovascular (1.04 [1.03-1.06]) mortality. The mediation analysis revealed that phenotypic age was estimated to mediate 66% and 42% of the total effects of LS7 on all-cause and cardiovascular mortality, respectively. Conclusion: Our data indicate that adherence to LS7 guidelines significantly slows down biological aging, which results in a prolonged lifespan as well as a reduced risk of cardiovascular mortality.
Abstract 13158: Improving Clinical Outcomes by Implementing a Multi-Disciplinary Pulmonary Vein Stenosis Team
Authors: Rachel D Vanderlaan, Andreea Dragulescu, Crystal Tran, Steve Fan, Andrea Wan, Shi Joon D Yoo, Mike Seed, Lars Grosse-Wortmann, Harmut Grasemann, Osami Honjo, David Barron, Jennifer L Russell, Christopher Caldarone
Journal: Circulation (2021)

Introduction: Pulmonary vein stenosis (PVS) is a rare disease that is associated with high mortality. In 2015, we instituted a multidisciplinary PVS team and surveillance protocol to aid disease detection and treatment. Hypothesis: Implementation of a PVS team will improve clinical outcomes in children with PVS Methods: In this retrospective study (2009-2019), we compared patient characteristics, disease surveillance and treatment practices for primary PVS patients prior to the introduction of the PVS team (NoPVT, first intervention between 2009-2014) and after the introduction of the PVS team (PVT, first intervention between 2015-2019). Results: In our cohort, there were 29 patients in the NoPVT group and 33 patients in the PVT group. We found no significant difference between the median age of first intervention (0.48 (0.22-0.92) years, NoPVT vs 0.66 (0.5-1.1) years, PVT), presence of bilateral disease (34%,NoPVT vs 65%, PVT) and number of veins diseased at diagnosis (2.1 ± 0.15 veins, NoPVT vs 2.3± 0.18 veins PVT). Following pulmonary vein interventions, more patients had surveillance axial imaging after introduction of the PVS team (28% NoPVT vs 72% PVT; p&amp;lt0.05), with an average number of surveillance scans increased per patient (1.2± 0.46 NoPVT vs 2.4±0.33 PVT, p=0.05). There was an increased number of reinterventions for disease recurrence (17% NoPVT vs 42% PVT; p=0.05). Freedom from death at 1 and 2 years was 56% and 52% in the NoPVT cohort and 83% and 70% in the PVT cohort (p=0.068). Conclusions: Adoption of a surveillance protocol and dedicated PVS team has the potential to improve outcomes in children with primary PVS.
Abstract 14307: Circulating Whole Blood Gene Expression Profiles Correlate With Intracranial Aneurysm Risk Across Multiple Metrics
Authors: Kerry E Poppenberg, Sanyasi Sricharan Veeturi, Hamidreza Rajabzadeh-Oghaz, Kenneth V Snyder, Adnan H Siddiqui, Vincent M Tutino
Journal: Circulation (2021)

Introduction: Intracranial aneurysm (IA) rupture is the primary cause of non-traumatic hemorrhagic stroke. Deciding which unruptured IA should be treated is difficult, as rupture rates are low but complication risks of treatment can be high. Thus, there is a critical need for biomarkers of high-risk IAs. Hypothesis: Patients harboring high-risk IAs have distinct gene expression profiles in their circulating blood. Methods: We collected whole blood RNA, imaging, and data from patients with IA undergoing angiographic imaging. Next-generation RNA sequencing was used to obtain transcriptomes. Based on images and medical data, high-risk IAs were defined by two metrics: 1) IA size (≥5 mm) from UCAS study and 2) morphologic Rupture Resemblance Score, based on IA Size Ratio (RRS≥0.30). We implemented the widely-used bioinformatics pipeline edgeR to identify significantly differentially expressed genes (q-value&lt;0.05) between high-and low risk groups. Pearson correlation analysis was used to identify which significant genes were correlated with each risk metric (r &gt;0.3). These genes were then used to train a multivariate regression model of IA risk, using 500 Monte-Carlo cross-validation iterations with a 70%:30% training:testing split. Results: This study included 91 IAs from 70 patients. Differential whole blood RNA expression was able to delineate high- and low-risk IAs on principal component analysis. 16 differentially expressed genes associated with IA size produced a 4-gene classifier with average AUC=0.82, accuracy=71%, sensitivity=67%, and specificity=76%. Conversely, the 14 differentially expressed genes associated with RRS yielded a 7-gene classifier with better performance, with average AUC=0.84, accuracy=79%, sensitivity=39%, and specificity=93%. Conclusions: Whole blood transcriptomes have the potential to reflect IA risk. This work lays the foundation to develop minimally invasive, low cost blood diagnostics for IA risk assessment.
Tisagenlecleucel and Axicabtagene Ciloleucel Expansion Kinetics and CAR T Cell Attributes in the Infusion Products Are Early Predictors of Clinical Efficacy
Authors: Cristiana Carniti, Chiara Monfrini, Vanessa Aragona, Martina Magni, Cristina Vella, Eugenio Fardella, Riccardo Betta, Anisa Bermema, Federico Stella, Anna Dodero, Annalisa Chiappella, Anna Guidetti, Paolo Corradini
Journal: Blood (2021)
IMMU-06. COMBINATORIAL IMMUNE CHECKPOINT INHIBITORS FOR TARGETED INTRATUMORAL DELIVERY IN GBM
Authors: Stephanie Sanders, Denise Herpai, Waldemar Debinski
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is an immunologically cold tumor. Using single cell sequencing of CD45+ cells we confirmed that T cells are present within GBM samples. These T cells are positive for exhaustion markers such as LAG3 and TIGIT, as well as CTLA4 and PD1 checkpoint receptors. Modulating T cell activity through use of immune checkpoint inhibitors (ICIs) has shown efficacy in the treatment of a variety of solid tumors, and the combination of anti-CTLA4 and anti-PD1 ICIs has shown increased efficacy over use of a single therapeutic. Additionally, targeting ICIs to the tumor cells may increase efficacy of this treatment. We therefore constructed a combinatorial ICI redirected to GBM via interleukin 13 receptor alpha 2 (IL13RA2), a receptor over-expressed on the majority of GBM cells but not normal brain. The first component of the construct, labeled with a histidine tag, targets CTLA4 while the second component, tagged with a StrepII tag, targets PD1. The tags added to the constructs will allow for purification of a combinatorial heterodimer simultaneously targeting PD1, CTLA4 and IL13RA2. We purified individual components via fast protein liquid chromatography (FPLC) using a proteinG column followed by a HisTrap or StrepTrap column. We obtained a recombinant, targeted multivalent ICI at &amp;gt; 95% purity. We found that these constructs are able to bind their target receptors via ELISA in which the Kd values ranged from picomolar to low nanomolar range. Additionally, our constructs bind their target on live cells by flow cytometry. We next designed a heterodimeric construct which can combinatorially target CTLA4 and PD1 while also directing the ICI therapy to GBM. These constructs in conjunction with other immune stimulants like cytotoxic therapies are intended to facilitate the interaction between T cells and GBM tumor cells directly in a tumor microenvironment.
TAMI-36. TAMEP ARE BRAIN TUMOR PARENCHYMAL CELLS CONTROLLING NEOPLASTIC ANGIOGENESIS AND PROGRESSION
Authors: Roland Kälin, Linzhi Cai, Yuping Li, Ines Hellmann, Rainer Glass
Journal: Neuro-Oncology (2021)

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor-parenchymal cells may promote specific phases of disease-progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Strikingly, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell-population, by conditional Sox2-knockout, drastically reduced glioblastoma-vascularization and -size. TAMEP manipulation profoundly altered vessel function and strongly attenuated the blood-tumor barrier. Hence, our data indicate TAMEP and their progenitors as new targets for glioblastoma therapy.
Abstract 13805: Accuracy of the Apple Watch Electrocardiogram to Detect Atrial Fibrillation in a Real-World Clinical Setting
Authors: Shari Pepplinkhuizen, Wiert F Hoeksema, Willeke van der Stuijt, Lonneke Smeding, Arthur A Wilde, Reinoud E Knops
Journal: Circulation (2021)

Introduction: The Apple Watch is the first commercially available wearable device with built-in electrocardiogram (ECG) electrodes to perform a one-lead ECG to detect atrial fibrillation (AF). Studies on the accuracy of the one-lead ECG of the Apple Watch (AW ECG) are limited and show inconclusive results. Our aim is to study the accuracy of the AW ECG in a real-world clinical setting. Methods: Patients with AF who were scheduled for electrical cardioversion (ECV) were included in this study. The Apple Watch series 6 was used with WatchOS 7.2 or 7.3. The AW ECG and 12-lead ECG were obtained pre-ECV. Post-ECV the ECGs were only obtained when the ECV resulted in sinus rhythm (SR). In case of an inconclusive measurement or poor recording, the AW ECG was repeated up to three times. All 12-lead ECGs were blindly adjudicated by two physicians. The AW ECG notification was compared to the physicians ‘gold-standard’ interpretation of the 12-lead ECG. Sensitivity and specificity of the AW ECG and Kappa coefficient between AW ECG and 12-lead ECG were calculated. Results: In total, 74 patients were included. Mean age was 67.1 ± 12.3 years, 20.3% were female, 18.9% had a cardiac implantable electronic device and the mean BMI was 28.1 ± 6.0 kg/m 2 . In total, 65 AF and 64 SR AW ECG and 12-lead ECG measurements were obtained. The first measurement with the Apple Watch compared to the 12-lead ECG showed a sensitivity of 93.5% and specificity of 100% (K=0.94). There were 7.0% inconclusive measurements and 17.8% poor recordings. A second measurement in patients with inconclusive or poor recordings resulted in a sensitivity of 94.6%, specificity of 100% (K=0.95) and 3.9% inconclusive measurements and 7.8% poor recordings. A third measurement in patients with two times an inconclusive or poor recording resulted in a sensitivity of 93%, a specificity of 96.5% (K=0.90) and 3.1 % inconclusive measurements and 5.4% poor recordings. Conclusions: The one-lead ECG of the Apple Watch shows a high accuracy for detecting AF in a real-world clinical setting. Repeating the measurement once decreases the total of unclassified recordings, however a third measurement resulted in a lower accuracy and the occurrence of false positive measurements.
Abstract 10322: Mental Health Conditions Are Associated with Underuse of Rhythm Control Therapies in Patients with Atrial Fibrillation: The FinACAF Study
Authors: Konsta Teppo, Jussi Jaakkola, Juhani Airaksinen, Fausto Biancari, Olli Halminen, Jukka Putaala, Pirjo Mustonen, Jari Haukka, Juha Hartikainen, Janne Kinnunen, Paula Tiili, Miika Linna, Mika Lehto
Journal: Circulation (2021)

Introduction: Mental health conditions (MHCs) have been associated with undertreatment of unrelated medical conditions, but whether patients with MHCs face disparities in receiving antiarrhythmic therapies (AATs) for atrial fibrillation (AF) is currently unknown. We assessed the hypothesis that MHCs are associated with decreased use of AATs. Methods: The FinACAF cohort included records on all AF patients in Finland during 2007-2018 identified from nationwide registries covering all levels of care as well as their drug purchases. The main exposure was any MHC (previous diagnosis of depression, bipolar disorder, anxiety disorder or schizophrenia or fulfilled prescription of psychiatric medication within preceding year from first AF diagnosis) and the main outcome was use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. Results: We identified 239 222 patients with incident AF and the prevalence of any MHC was 19.9%. Mean age was 72.6 years (SD 13.2). Lower overall rate of any AAT use was observed in patients with any MHC than in those without MHC (16.9% vs. 22.9%, p&lt;0.001). Cumulative five-year incidence curve of any AAT is presented in Figure 1. Any MHC was associated with decreased use of any AAT, AADs, cardioversion and catheter ablation (adjusted hazard ratios (aHR) 95% CI 0.804 (0.784-0.823), 0.870 (0.839-0.902), 0.784 (0.762-0.806) and 0.832 (0.771-0.899), respectively). Depression, bipolar disorder, anxiety disorder and schizophrenia were individually associated with decreased use of any AAT (aHR 95% CI 0.879 (0.837-0.922), 0.871 (0.760-0.998), 0.786 (0.731-0.845), and 0.423 (0.358-0.500), respectively). A lower rate of AAT use was observed in patients with MHC across the study period and no meaningful temporal change was noted in the MHC related deficit. Conclusions: MHCs are associated with decreased use of rhythm control therapies in patients with AF.
Health-Related Quality of Life Following Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A in the Phase 3 Trial GENEr8-1
Authors: Brian O'Mahony, Johnny Mahlangu, Kathelijne Peerlinck, Jiaan-Der Wang, Gillian Lowe, Chee Wee Tan, Adam Giermasz, Huyen A Tran, Teh-Liane Khoo, Erin Cockrell, Dominic Pepperell, Hervé Chambost, María Fernanda López Fernández, Rashid Kazmi, Elaine Majerus, Mark W Skinner, Robert Klamroth, Jennifer Quinn, Hua Yu, Wing Yen Wong, Adebayo Lawal, Tara M Robinson, Benjamin Kim
Journal: Blood (2021)
INNV-19. NAVIGATING GLIOBLASTOMAS THE DIGITAL WAY: AN OBSERVATIONAL OVERVIEW OF THE USE OF A SMARTPHONE WEB APPLICATION IN A GBM PATIENT POPULATION
Authors: Catherine Fine, Jon Brown, Erin Tozour, Chris Mason, Stephanie Wels, Zack Radick, Simon Tucker, Alex Bilstein, Jordan Gottlieb, Tammy Lee, Ashley Devitte, Kevan Corbett, Stefan Scherer, Todd Meyerrose
Journal: Neuro-Oncology (2021)

Abstract There is limited data regarding the use of digital resources in the neuro-oncology clinic, and more specifically within the glioblastoma (GBM) patient population. Studies show that smartphone applications are feasible as a resource to improve patient-reported outcomes, produce actionable provider data, and actively engage patients in their care, leading to patients being empowered in their choices, apt to adhere to recommendations and producing quality conversations with providers. Navio, an oncology digital health company, helps patients, providers, researchers, and industry collaborators by offering personalized treatment regimens, appointment reminders, help with medication use, diagnosis education, resources, and a means to record quality of life and patient-generated health data, which can be surfaced in real-time to oncology care teams. Seventy-seven patients with a GBM, ages 25-74 years, who were beginning or receiving treatment, were invited via SMS text to access the Navio web application. Nine different GBM treatment plans and 10 different countries were represented among the patients. Patients were allowed unlimited access to all modules and encouraged by text to re-engage, at Navio-defined key moments. Of the invited patients, 58 / 77 (75 %) successfully self-onboarded to Navio’s app. Of the 58 patients onboarded, 77 % continued to engage with the application at various time points past day 1 and as far out as day 180. Engagement was seen across all age groups. Navio was able to re-engage 60 % of all patients who had 7 days of inactivity. Oncology digital resources, such as Navio’s app, are of increasing interest to gather and surface real-time data, and support patients outside of traditional clinic visits. Although early, Navio’s application represents a unique and expanding opportunity to engage and empower GBM patients, specifically during key treatment moments, to provide information for patients and their oncology care teams, and most importantly, to improve patient outcomes.
PATH-33. MOLECULAR TYPING AND MUTATION SPECTRUM OF CHINESE CHILDREN WITH MEDULLOBLASTOMA WERE IDENTIFIED BY NEXT-GENERATION SEQUENCING
Authors: Juan Li, Mingyao Lai, Qingjun Hu, Ruyu Ai, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract There are few reports on molecular typing and mutation spectrum of Chinese children with medulloblastoma. Here, we aimed to update the clinical manifestations and MB transcriptional mutation spectrum in Chinese Mb patients. Medical records of 59 Mb patients were reviewed. Genomic DNA was extracted from pathological tissues of children. Mutation analysis of whole coding regions, promoter regions and flanking splice sites in whole genome sequencing was performed. Nine cases (15%)with WNT subtype: CTNNB1 mutation was found in all specimens, and TP53 mutation was found in 33.3%. DDX3X mutation occurred in 33.3%. 33.3% had SMARCA4 mutations. Chr6 - associated large fragment deletion occurred in 88.9s. Comparison results between 19 cases (32%) with SHH data and previous studies: The proportion of SHH-TP53 mutants was11% ( 2/19).The proportion of SHH-TP53 wild-type was 89%.The prognosis of the mutated SHH-TP53 was worse than that of the wild-type SHH-TP53, and patient follow-up information could be integrated for comparison. Secondly, PTCH1 is more prevalent in patients with SHH (16%). The DDX3X mutation proportion was 11%. The mutation ratio of Gli2 amplification5%.The mutation ratio of MYCN amplification was 5%.Comparison results of 3 cases with G3 subtype data and previous studies: Variations mainly occur at the chromosomal level. Only one G3 patient had a genetic mutation (TP53 mutation). The proportion of Chr17q+ was 33.3%. CHR7 + proportion was 33.3%. The incidence rates of CHR10Q and CHR11Q were 66.7%.No MYC amplification was found. For 28 cases with G4 subtype: Chr17q +, Chr7 +, Chr18 +, and Chr8 - are the major chromosomal mutations. The incidence rate of CHR17Q + was 61%, and CHR7 + was 61%. CHR8- occurred in 11%. The above results are consistent with previous reports. The Chinese population and other population have similar molecular genotyping gene variation map on medulloblastoma.
CD19.CAR-T Cell Analysis Using Flow Cytometry and PCR
Authors: Nicola Schanda, Alexander Kunz, Tim Sauer, Maria-Luisa Schubert, Felix Korell, Angela Hückelhoven-Krauss, Brigitte Neuber, Mandy Hinkelbein, Carsten Müller-Tidow, Michael Schmitt, Anita Schmitt
Journal: Blood (2021)
Clinical Impact of DES in Treating Protected and Non-Protected LMT Lesion, Stratifying DES Types
Authors: Shimizu Shiho, Misumi Kazuo, Udoh Akihiro, Misaki Atsushi, Hoshina Mizuho, Nakamura Ryuta, Kawasaki Tomohiro, Makino Masato, Takase Tetsuro, Ebihara Toshiro, Taniguchi Yu, Tone Kentaro, Hirose Makoto, Yoshiwara Hirotaka, Itakura Yasumasa, Hirono Yoshiyuki, Iizuka Daisuke, Nitta Masamitsu, Yoshida Toshihiko, Hashimoto Toru, Kuramochi Takehiko
Journal: Circulation (2013)