tbuckley/cabot-search huggingface dataset:
Abstract 20935: Improving Spinal Cord Protection During the Frozen Elephant Trunk Technique: Effect of a Dedicated Neuroprotection Protocol
Authors: Mauro Iafrancesco, Aaron Ranasinghe, Donald Adam, Martin Claridge, Ian McCafferty, Peter Riley, Paul Clift, Jorge Mascaro
Journal: Circulation (2017)

Introduction: The frozen elephant trunk (FET) technique may be complicated by a risk of spinal cord injury (SCI) which has been reported as high as 10%.Precise mechanisms responsible for SCI after FET are still unclear and so the best protection strategy to avoid it. Hypothesis: We aim to review our experience with a specific protocol developed to reduce the risk of SCI during open surgery of the descending aorta applied to patients operated with FET in order to increase spinal cord protection Methods: Spinal cord protection protocol included: 1.Careful preoperative planning to deploy of stent above the level of the 10th thoracic vertebra and preserving the patency of the left subclavian artery; 2.Postoperative management with goal directed therapy aimed to achieve mean systemic blood pressure between 85 and 105 mmHg, cardiac index &gt;2.4 l/min/m2, urine output &gt;1 ml/Kg/min, a base excess of 0±5, a pH&gt;7.3 and haemoglobin level &gt;10 g/dl; 3.Cerebrospinal fluid (CSF) drainage was used in 4 patients (5.8%) only Results: From April 2006 to December 2015 69 patients underwent aortic repair with the FET at our Institution.There were 31 males (51.7%). Median [IQR] age was 69 [59-75] years and median [IQR] Log EuroSCORE was 20.3 [13.9-36.2]. There were 19 (27.5%) reoperations. Operative times and outcomes are reported in Table 1. Conclusions: SCI remains the Achilles’ heel of the FET procedure.Elevated blood pressure in the preoperative period may reduce the risk of SCI by increasing the collateral network remodeling.Careful preoperarative planning and avoidance of sacrifice of all thoracic segmental arteries and preservation of left subclavian artery patency may reduce the risk of SCI maintaining good collateralization of the spinal cord perfusion network.Attention to all haemodynamic and metabolic parameters may avoid further ischemic insults to the spinal cord. CSF drainage may not be necessary in all cases of FET
Digital technologies and adherence in respiratory diseases: the road ahead
Authors: John D. Blakey, Bruce G. Bender, Alexandra L. Dima, John Weinman, Guilherme Safioti, Richard W. Costello
Journal: European Respiratory Journal (2018)

Outcomes for patients with chronic respiratory diseases remain poor despite the development of novel therapies. In part, this reflects the fact that adherence to therapy is low and clinicians lack accurate methods to assess this issue. Digital technologies hold promise to overcome these barriers to care. For example, algorithmic analysis of large amounts of information collected on health status and treatment use, along with other disease relevant information such as environmental data, can be used to help guide personalised interventions that may have a positive health impact, such as establishing habitual and correct inhaler use. Novel approaches to data analysis also offer the possibility of statistical algorithms that are better able to predict exacerbations, thereby creating opportunities for preventive interventions that may adapt therapy as disease activity changes. To realise these possibilities, digital approaches to disease management should be supported by strong evidence, have a solid infrastructure, be designed collaboratively as clinically effective and cost-effective systems, and reflect the needs of patients and healthcare providers. Regulatory standards for digital interventions and strategies to handle the large amounts of data generated are also needed. This review highlights the opportunities provided by digital technologies for managing patients with respiratory diseases.
HOUT-12. CHARACTERIZATION OF SYMPTOM BURDEN IN MINORITY PATIENTS WITH CNS TUMORS: A REPORT FROM THE NEURO-ONCOLOGY BRANCH (NOB) NATURAL HISTORY STUDY (NHS)
Authors: Sonja Crandon, Elizabeth Vera, Alvina Acquaye, Christine Siegel, Orwa Aboud, Lisa Boris, Miranda Brown, Nancy Garren, Ming Ji, Jason Levine, Carlos Romo, Jennifer Reyes, Jing Wu, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2018)

Primary CNS tumor patients are highly symptomatic, with 40% of brain tumor patients reporting 3 moderate-severe symptoms. The five most commonly reported are fatigue, drowsiness, difficulty remembering, disturbed sleep in brain and in spine patients, pain, numbness, leg weakness, and autonomic dysfunction (bowel and sexual dysfunction). Twenty-five percent reported interference with activity and mood. These reports are limited to primarily white patients, with limited studies exploring in more diverse samples. Fifty patients self-identified as non-white are included in this report of symptom burden (MD Anderson Symptom Inventory-Brain and Spine Tumor), depression and anxiety (PROMIS measures). Descriptive statistics, and standardized classification of severe symptoms and mood are used to describe the sample characteristics Chi-square and Fishers exact test were used to identify associations. Significance level was set at p< 0.05. The majority of patients were male(62%), Black/African American(38%). Median age 40(range 14–69), 44% had a gross total resection at diagnosis. Glioblastoma was the most common diagnosis(40%) with 1/3 having a poor(KPS 80) and a recurrence, and 56% having completed treatment. All spine and 34% of brain tumor patients had at least three symptoms rated as moderate-severe. The top five among brain tumor patients were weakness in arms/legs, fatigue, disturbed sleep, difficulty remembering, and feeling irritable and 57% reported moderate-severe activity related interference from symptoms. Fourteen percent of patients reported having moderate-severe depression and anxiety symptoms at study entry. Diagnosis other than glioblastoma was associated with depression symptoms (X2(1)= 5.4, p< 0.04), but no associations between clinical and demographic factors were found with interference, depression, or anxiety. Minority populations are highly symptomatic, but differences in symptoms reported as most severe were found when compared to historical data which is a restricted patient demographic. Future studies exploring symptom prevalence, underlying risk and treatment in diverse populations are warranted.
Highly Efficient In Vivo Targeting of the Pulmonary Endothelium Using Novel Modifications of Polyethylenimine: An Importance of Charge
Authors: Andrew W. Dunn, Vladimir V. Kalinichenko, Donglu Shi
Journal: Advanced Healthcare Materials (2018)

Abstract Pulmonary vascular disease encompasses a wide range of serious afflictions with important clinical implications. There is critical need for the development of efficient, nonviral gene therapy delivery systems. Here, a promising avenue to overcome critical issues in efficient cell targeting within the lung via a uniquely designed nanosystem is reported. Polyplexes are created by functionalizing hyperbranched polyethylenimine (PEI) with biological fatty acids and carboxylate‐terminated poly(ethylene glycol) (PEG) through a one‐pot 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride/ N ‐hydroxysuccinimide reaction. Following intravenous injection, polyplexes show an exceptionally high specificity to the pulmonary microvascular endothelium, allowing for the successful delivery of stabilized enhanced green fluorescent protein (eGFP) expressing messenger ribonucleic acid (mRNA). It is further shown, quantitatively, that positive surface charge is the main mechanism behind such high targeting efficiency for these polyplexes. Live in vivo imaging, flow cytometry of single cell suspensions, and confocal microscopy are used to demonstrate that positive polyplexes are enriched in the lung tissue and disseminated in 85–90% of the alveolar capillary endothelium, whilst being sparse in large vessels. Charge modification, achieved through poly(acrylic acid) or heparin coating, drives a highly significant reduction in both targeting percentage and targeting strength, highlighting the importance of specific surface charge, derived from chemical formulation, for efficient targeting of the pulmonary microvascular endothelium.
CSIG-08. DYNAMICS OF GLIOMA GROWTH: SELF-ORGANIZATION GUIDES THE PATTERNING OF THE EXTRACELLULAR MATRIX AND REGULATES TUMOR PROGRESSION
Authors: Andrea Comba, Daniel B Zamler, Patrick Dunn, Anna Argento, Padma Kadiyala, Viveka Nand Yadav, Alon Kahana, Phillip E Kish, Felipe Nunez, Carl Koschmann, Neha Kamran, Sebastien Motsch, Maria G Castro, Pedro Lowenstein
Journal: Neuro-Oncology (2018)

GBM remains the deadliest primary malignant brain tumor. Given the importance of invading cells, less attention has been paid to the tumor mass, even if such a mass eventually kills the patient. We previously demonstrated that human and mouse transplantable or GEMM gliomas display regular anatomical multicellular structures containing elongated cells which we named ‘oncostreams’. Oncostreams are 10–20 cells wide, 2–400 um long, and are distributed throughout the tumors. Furthermore, we uncovered a negative correlation between oncostream density and animal survival suggesting that oncostreams play a role in tumor malignancy. Further data indicate that oncostreams aid local invasion of normal brain. Co-implantation experiments demonstrated that oncostreams facilitate the intratumoral spread of slow migrating cells. To determine a possible molecular distinctiveness of oncostreams we used laser capture microdissection followed by RNA-Seq, bioinformatics and network analysis. Evaluation of the transcriptome demonstrated differential expression (DE) of genes between oncostreams and adjacent tumor. Functional enrichment of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented gene ontologies. Network analysis indicated that Col1a1, ACTA2, MMP9, MMP10 and ADAMTS2, genes important for cell migration and ECM interactions, are part of these networks. IHC and PCR were used to validate RNA-Seq expression changes. To understand the cellular dynamics in our system we used time lapse imagining and evaluated the results using high level statistical analyses. The following tests, i.e., velocity distribution, pair-wise correlation of local position, velocity correlation, etc. were used to characterize the dynamics of cellular intratumoral motility. These data demonstrate the existence of collective motion within glioma tumors. Taken together, our results show that oncostreams, move by collective motion, are anatomically and molecularly distinct, reveal the existence of glioma self-organization, and regulate glioma growth and invasion. Targeting oncostreams is a candidate therapeutic strategy.
EPID-15. INCIDENCE PATTERNS OF PRIMARY BRAIN AND OTHER CENTRAL NERVOUS SYSTEM TUMORS IN APPALACHIA
Authors: Quinn Ostrom, Haley Gittleman, Carol Kruchko, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2018)

The Appalachian region is a large geographic and economic region in the United States (US), representing 7.69% of the US population. This region is more rural, whiter, older, and residents are more likely to be under the poverty line as compared to the rest of the US. Limited research has been done on primary brain and other CNS tumor epidemiology in this region. In this analysis we characterized their incidence patterns. Data from 2006–2015 were obtained the Central Brain Tumor Registry of the US. Appalachian counties were categorized using the Appalachia Regional Council scheme. Overall and histology-specific age-adjusted incidence rates per 100,000 population were generated by region, sex, race, and age groups. Overall incidence within Appalachia was 22.62 per 100,000, which is not significantly different from the rest of the US (22.77, p=0.1189). Malignant incidence was 5% higher in Appalachia (7.55/100,000 as compared to 7.23/100,000, p<0.0001), while non-malignant incidence was 3% lower (15.07/100,000 as compared to 15.51/100,000, p<0.0001). The largest differences in histology-specific incidence were in oligodendroglioma, where non-Appalachian incidence was 24% higher (p<0.0001), and hemangioma, where Appalachian incidence was 20% higher (p<0.0001). Among Blacks, incidence of both malignant and non-malignant tumors was 8% lower in Appalachia as compared to the rest of the US (p<0.0001). Incidence was also lower in White Hispanics, where malignant incidence was 19% lower, and non-malignant incidence was 30% lower (p<0.0001). Evaluating place-based health disparities is critical to understanding population variation in incidence. Appalachian counties have increased malignant and decreased non-malignant brain tumor incidence as compared to the rest of the US. Incidence of non-malignant tumors was lower among all racial/ethnic groups, with the largest differences in Blacks and White Hispanics. These differences may be attributable to access to health care.
Abstract 18155: Sequential Changes of Mitral Annular Morphology in Patients With Atrial Mitral Regurgitation
Authors: Hironori Yamamoto, Kanako Kishiki, Yuji Itabashi, Haruka Fujimaki, Hidemasa Shitan, Takeshi Okubo, Mai Terada, Mika Saito, Keitaro Mahara
Journal: Circulation (2017)

Introduction, Hypothesis: Atrial mitral regurgitation (AMR) has been emerging pathophysiology relating to an increase in aged population with atrial fibrillation. The objective of this study was to...
Abstract 20168: Right Ventricular Global Longitudinal Strain is Correlated With Cardiovascular Magnetic Resonance Ejection Fraction and Provides Prognostic Value in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Tetsuari Onishi, Kosuke Yoshii, Masato Tsuru, Akira Shimane, Katsunori Okajima, Yasuyo Taniguchi, Hiroya Kawai
Journal: Circulation (2014)

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by functional abnormalities of the right ventricular (RV). RV ejection fraction (EF) determined by cardiac magnetic resonance (CMR) imaging is accepted as gold standard measure of RV systolic function. Hypothesis: RV global longitudinal strain (GLS) by 2-dimensional speckle tracking echocardiography (2DSTE) is correlated with CMR-RVEF, and associated with cardiac events in patients with ARVC. Methods: We studied 50 patients referred with suspected ARVC. Of them, 19 patients (Group A) were diagnosed as ARVC, while remaining 31 patients (Group B) were not diagnosed due to not meeting criteria. All patients underwent CMR for measurements of RVEF, and echocardiography with conventional assessment including tricuspid annular plane systolic excursion (TAPSE), RV end-diastolic and end-systolic area (RVEDA, RVESA) and RV fractional area change (RVFAC), and with 2DSTE analyses of GLS which was expressed as the absolute value. The cardiac events, defined as death, hospitalization for heart failure, fatal arrhythmia and appropriate defibrillator shock, were followed up for patients in Group A. Results: Patients in Group A had significantly smaller values of TAPSE, RVFAC, GLS and RVEF and significantly greater values of RVESV compared with patients in Group B (p&lt;0.05 for all), while there were no significant differences in RVEDV between 2 groups. GLS were correlated with RVEF (P=0.001, r=0.4) as with RVEDA, RVESA, RVFAC and TAPSE (p&lt;0.01 for all). 4 appropriate defibrillator shocks were observed during averaged 724 days followed-up period in Group A. Dividing patients in Group A into 2 groups with median value of CMR-RVEF or GLS, Kaplan-Meier curve analysis revealed that GLS was significantly associated with outcome (P=0.02), while CMR-RVEF was not. Conclusions: GLS in the RV was significantly correlated with CMR-RVEF, and was associated with cardiac events in patients with ARVC.
PATH-39. ASTROCYTOMA OF THE SPINAL CORD: A GENETIC CHARACTERIZATION AFTER MICROSURGICAL RESECTION
Authors: Annamaria Biczok, Mario Dorostkar, Rupert Egensperger, Jörg-Christian Tonn, Stefan Zausinger
Journal: Neuro-Oncology (2018)

The revised version of the WHO classification system (2016) introduced molecular markers being of prognostic importance in gliomas. Primary spinal cord astrocytomas are very rare. Aggressive surgical resection is believed to be critical for extending progression free and overall survival. However, the prognostic significance of molecular variables remains unclear for these tumors. Herein we investigate molecular chances of spinal gliomas, which may allow more accurate risk stratification. We performed genome sequencing in 10 spinal astrocytomas undergoing surgical resection between 2000 and 2017. These spinal astrocytomas include glioblastomas (WHO grade IV), anaplastic astrocytomas (WHO grade III), diffuse astrocytomas (WHO grade II) and pilocytic astrocytoma (WHO grade I). We identified 5 spinal glioblastomas, 1 anaplastic astrocytoma, 2 diffuse astrocytomas and 2 pilocytic astrocytomas. Median overall survival (OS) was 6 months (range: 2–14 months) for grade IV tumors, 33 months (range: 30–136 months) for grade II and III tumors and 95 months (range: 49–141 months) for grade I tumors, respectively. One grade II and one grade I tumor were carrying the IDH1 and IDH2 mutation, all other tumors were IDH wild type (OS: 93 vs. 10 months). Gross total resection was not achieved in any patient. 9 patients received adjuvant radiotherapy. The most current findings in spinal GBM were H3F3A mutations (5/5) and ATRX mutation (3/5). H3F3A mutation was observed in 1 WHO grade II tumor with a OS of 33 months. Mutation in H3F3A and WHO grade was associated with shortened OS in univariate analysis. WHO grade II tumors were found to have mutations in CCND2, DDX3X, EGFR, HIST1H3B, KIT, MYC, PDGFRA, PTCH2, SMARCA4 and TSC2. Genomic analysis of spinal astrocytomas provides an opportunity to identify potential clinically relevant information. These data indicate an association between H3F3A mutation and a shortened overall survival in spinal astrocytomas.
FRI0081 The importance of transferrin saturation, serum ferritin, log ferritin and transferrin/log ferritin in differentiating iron deficiency anaemia from anaemia of chronic disease in rheumatoid arthritispatients
Authors: R.A. Abdel Noor, M.H. Abu-Zaid, S.A. Elshweikh, E.S. Rabee, G.E. Khedr
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The most common types of anaemia in rheumatoid arthritis (RA) are iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). The differentiation between both is very important and challenging. <h3>Objectives</h3> is to select the most simple, cheap, accurate method differentiate IDA from ACD in RA patients. <h3>Methods</h3> This case control study was carried out on 80 RA patients. Group I 40 RA patients with anaemia Group II 40 RA patients without anaemia, complete blood count, assessment of disease activity using DAS 28 score, serum iron, total iron binding capacity (TIBC) "transferrin level", transferrin saturation (TSAT), serum ferritin, log ferritin and transferrin/log ferritin were tested, then we divided the patients in group 1 into 2 subgroups according to TSAT : group Ia (RA patients with anaemia and low TSAT) and group Ib (RA patients with anaemia and normal TSAT) and we compared the parameters. <h3>Results</h3> There was a statistically significant difference between anaemic and non anaemic RA patients as regard serum iron level and transferrin saturation and there was no significant difference as regard serum ferritin, log ferritin, transferrin and transferrin/log ferritin. Among the anaemic group (67.5%) had low TSAT (IDA) and only (32.5%) had normal TSAT (ACD). In these 2 subgroups there was no significant differences as regard DAS28 score, blood indices, serum ferritin and transferrin/log ferritin) except Log ferritin and there was positive correlation between TSAT and (ferritin and log ferritin) and significant negative correlation between TSAT and transferrin/log ferritin. Figure 1 Correlation between TSAT and (serum ferritin, log ferritin and Transferrin/Log ferritin) <h3>Conclusions</h3> Iron deficiency anaemia is prevalent in RA patients. A combination use of serum ferritin and TSAT is the most simple, accurate parameter now to differentiate both. log ferritin, transferrin/log ferritin may be promising new parameters in diagnosis of IDA in general population but their use in inflammatory diseases like RA still has a limitation so we suggest further large studies to be done in order to assess their accuracy. <h3>References</h3> [1] Song J-S, Park W, Bae S-K, Kim S-S, Lee Y-H, Choi J-W, et al. The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumatoid arthritis: comparison with bone marrow iron study. Rheumatology International2001;21(1):24–9. [2] Castel R, Tax MG, Droogendijk J, Leers MP, Beukers R, Levin M-D, et al. The transferrin/log (ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia. Clinical Chemistry and Laboratory Medicine2012;50(8):1343–9. <h3>Disclosure of Interest</h3> None declared
ANGI-01. CORRELATION BETWEEN HISTOLOGICAL AND MRI MEASURES OF INFILTRATION IN A PRECLINICAL GLIOBLASTOMA MODEL
Authors: Gerard Thompson, Antoine Vallatos, Haitham Al-Mubarak, Lesley Gilmour, Joanna Birch, Lindsay Gallagher, James Mullin, Adam Waldman, William Holmes, Anthony Chalmers
Journal: Neuro-Oncology (2018)

INTRODUCTION: Maximal safe cytoreductive surgery is the therapeutic ideal in GBM. Occult, non-enhancing, infiltrative disease ultimately drives treatment failure. Diffusion-weighted imaging (DWI) assessment of tumor margins through apparent diffusion coefficient (ADC) transition coefficients shows promise in non-invasive molecular subtyping and relating potentially-invasive behavior to survival. ADC non-specificity limits biomarker interpretation. We aimed to explore histological tumor cell burden relationship to ADC measurements at the macroscopic margin in a GBM model. G7 GBM orthotopic xenografts were implanted into nude mice. T2-, and diffusion-weighted images were acquired at 7T. Brains were extracted and fresh-frozen to minimise fixation artefacts and preserve morphology. Cryosections were stained with human leucocyte antigen (HLA) marker specific for human-derived GBM cells. Confocal HLA photomicrographs (10x) and high resolution T2w MRI were linearly co-registered and resampled to match DWI. Macroscopic tumour margin was visually delineated using the low ADC/high-T2w-signal region. Linear profiles perpendicular to these boundary voxels produced serial, centrifugal, spatially-congruent measurements of ADC and HLA across the infiltrating edge over 0.7mm. Spearman’s rho was calculated in each subject for every profile. 5 mice were suitable for analysis. In 72% of tumor boundaries (n=562), there was a statistically significant (p<0.05) inverse correlation (<-0.8) between ADC and HLA. Areas with insignificant/positive correlation represented distinct physical boundaries such as pia/ependyma or artefact. DISCUSSION: Characterizing microinvasive disease which ultimately leads to treatment failure in maximally-resected GBM is challenging. Research dwells on the enhancing disease which is excised. Margin assessment provides an opportunity to characterize tumor behavior at the crucial interface between dividing bulk tumor and the parenchymal infiltration which predicates recurrence. The spatially-consistent inverse correlation between tumor margin HLA and ADC values for almost all profiles at the tumor-parenchyma interface indicates that ADC transition profiles relate to tumor infiltration as previously hypothesised, with lower ADC related to higher tumor burden.