tbuckley/cabot-search huggingface dataset:
NIMG-36. THE SIGNIFICANCE OF PUNCTATE CONTRAST-ENHANCING LESIONS IN TREATED HIGH GRADE GLIOMA
Authors: Orna Aizenstein, Felix Bokstein, Moran Artzi, Dror Limon, Dafna Ben Bashat, Deborah Blumenthal
Journal: Neuro-Oncology (2018)

We report on a series of nine patients with high grade glioma (HGG) who developed punctate contrast-enhancing foci on MRI, several years after tumor treatment. The lesions were considered suspicious for tumor progression at their onset, but were proven over time to be benign in nature. Five of the patients were treated for glioblastoma; 3 for anaplastic astrocytoma, and one for anaplastic oligodendroglioma. Median age of the patients at diagnosis was 48 years (31–62 years). The mean time of onset of “suspicious spots” following treatment was 51 months after diagnosis (6–170 months). Of note, median overall survival of the group is 96 months; with none of the nine patients deceased, and only 2 patients known to have progression. The remainder of the 7 patients are free of active tumor and being followed off treatment. No apparent clinical manifestations of the lesions have been observed. The majority of the punctate lesions were of a dynamic nature; they appeared and spontaneously disappeared over time, without intervention. All lesions developed within the field of radiation treatment; some were contralateral to the tumor. Radiological characteristics of the lesions including analysis of SWI, DWI, and DCE magnetic resonance imaging sequences will be reported. Punctate enhancing foci in the region of radiation treatment are phenomena which may be manifestation of delayed treatment sequelae in HGG. Patients with these lesions are on average of younger age and have a particularly long survival. These lesions appeared several years following oncological treatment. The foci should be initially followed more closely until shown to be of a non-progressive nature; they should not be presumed to be indicative of tumor recurrence. Possible etiology of the lesions may be related to vascular changes induced by radiation.
Abstract 16341: Biomarkers Predicting Cardiovascular Events Following Drug-Eluting Stent Implantation
Authors: Takashi Unoki, Shuichi Ura, Daisuke Takagi, Nobutoyo Masunaga, Mitsuru Ishii, Moritake Iguchi, Kensuke Takabayashi, Yugo Yamashita, Yasuhiro Hamatani, Hisashi Ogawa, Kyohma Wada, Noriko Satoh-Asahara, Akira Shimatsu, Mitsuru Abe, Kazuhiko Kotani, Masaharu Akao, Koji Hasegawa, Hiromichi Wada
Journal: Circulation (2017)

Background: Vascular endothelial growth factor-C (VEGF-C) plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. H...
QOLP-25. QUALITY OF LIFE FOLLOWING RE-IRRADIATION FOR RECURRENT HIGH GRADE GLIOMA
Authors: Christina Amidei, Karan Dixit, Priya Kumthekar, Tim Kruser, Sean Sachdev, John Kalapurakal, Vinai Gondi, Sean Grimm, Martin Nicholas, Rimas Lukas, Steven Chmura, Minesh Mehta, Jeffrey Raizer
Journal: Neuro-Oncology (2018)

Re-irradiation has recently garnered interest as a treatment option for recurrent high grade glioma. Evidence supporting benefits in this population is evolving, but little is known about impact on quality of life (QOL). QOL patient reports were collected in a phase II hypofractionated re-irradiation study. Patients with recurrent anaplastic glioma or glioblastoma were stratified into four groups based on histology and prior bevacizumab exposure. Treatment consisted of 45 Gy radiation delivered in 25 fractions with daily temozolomide 75 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. This was followed by adjuvant daily temozolomide 50 mg/m2 for 6 weeks and bevacizumab 10 mg/kg every 2 weeks in an 8 week cycle for up to 6 cycles, or until progression or intolerance. FACT-Brain and FACIT-Fatigue were collected as secondary end-point data prior to treatment start, at end of the concurrent phase, and after each cycle. Of 54 patients treated, 42 (78%) had evaluable QOL data. Mean baseline FACT-Br and FACIT-Fatigue scores were within expected ranges for persons with brain tumors. Significant declines were noted in FACT-Br Total (p=0.4), FACT-Br TOI (p=.05) and FACIT-Fatigue (p<.01) at the end of concurrent treatment, but FACT-Br Total and FACT-Br TOI scores rebounded to baseline level by end of cycle 1 and were maintained at cycle 2 end. Fatigue scores improved after cycle 1 but did not return to baseline until after cycle 2. Re-irradiation with temozolomide and bevacizumab is associated with decline in QOL immediately after concurrent treatment but QOL improves over time. This QOL pattern is similar to that seen with initial radiation treatment and suggests that re-irradiation does not progressively adversely affect QOL for at least the first four months after treatment.
ACTR-44. PRELIMINARY RESULTS FROM THE NCT02770378 PROOF-OF-CONCEPT CLINICAL TRIAL ASSESSING THE SAFETY OF THE CUSP9v3 PROTOCOL COMBINED WITH METRONOMIC TEMOZOLOMIDE FOR RECURRENT GLIOBLASTOMA
Authors: Marc-Eric Halatsch, Richard Kast, Georg Karpel-Massler, Carl Schmidt, Birgit Schmelzle, Fadi Awad, Patricia Panther, Tim Heiland
Journal: Neuro-Oncology (2018)

BACKGROUNDDespite refinements of neurosurgical techniques and emerging adjuvant therapies, patients with recurrent glioblastoma continue to face a dismal prognosis. We report preliminary results of a clinical trial evaluating a protocol of 9 repurposed drugs (aprepitant, minocyclin, disulfiram, celecoxib, sertraline, captopril, itraconazole, ritonavir, auranofin) and low-dose metronomic temozolomide in patients with recurrent glioblastoma.
Abstract P118: Changes in Physical Activity by Self-Weighing Trajectory Groups
Authors: Yaguang Zheng, Susan M Sereika, Linda J Ewing, Cynthia A Danford, Bonny Rockette-Wagner, Christopher C Imes, Hu Lu, Ran Sun, Lora E Burke
Journal: Circulation (2015)

Introduction: Numerous studies have established a significant association between regular self-weighing and weight loss; however, few studies have examined how self-weighing patterns are associated with lifestyle changes, e.g. physical activity (PA). The aim was to examine the association between frequency of self-weighing and changes in PA levels. Hypothesis: We hypothesized that higher frequencies of self-weighing are associated with greater increases in PA levels. Methods: This was an analysis of data from a 12-mo behavioral weight loss intervention study. Each subject was given a Wi-Fi scale and instructed to weigh daily. The scale transmitted weight values to a central server. PA was objectively assessed by an accelerometer (ActiGraph GT3x) at 0 and 6 mos. Participants were instructed to wear the accelerometer for ≥ 3 weekdays, one weekend day, ≥10 hours/day. General linear model was used for data analysis. Results: The sample (N=89) was largely female (89.9%), White (82%), with a mean age (±SD) of 51.9±9.3 years, and a mean BMI of 33.6±4.5 kg/m2. Our previous analysis using group-based trajectory modeling identified 3 self-weighing patterns: high/consistent (self-weighed 5-6 days/week regularly); moderate/declined (declined from 4-5 to 2 days/week); minimal/declined (declined from 5-6 to 0 days/week). As shown in the table, compared with minimal/declined self-weighing group, the high/consistent group had a significant increase in energy expenditure, steps, light and moderate PA levels as well as average activity/day, while the moderate/declined group had a significant increase in steps and average activity/day. Conclusions: The differences in PA level changes across the trajectory groups suggest that improved adherence to self-weighing carried over to improved PA behavior changes. It is unclear if self-monitoring weight and observing the results led participants to regulate their PA behavior accordingly. Future research needs to examine the mechanisms of how daily weighing impacts the level of daily PA.
Abstract 19222: Hypoxia Regulated Circular RNAs Control Endothelial Cell Functions <i>(Best of Basic Science Abstract)</i>
Authors: Andreas W Heumüller, Jes-Niels Boeckel, Nicolas Jaé, Yuliya Ponomareva, Wei Chen, Reinier A Boon, David John, Andreas M Zeiher, Shizuka Uchida, Stefanie Dimmeler
Journal: Circulation (2015)

Circular RNAs (circRNAs) are non-coding RNAs generated by back-splicing. Back-splicing has been considered as a rare event, but circRNAs were recently found to be abundantly expressed among a variety of human cells and tissues. Nevertheless, the expressional regulation, processing and biological functions of circRNAs are largely unknown. Cytoplasmic circRNAs can bind and trap microRNAs, whereas nuclear circRNAs may affect host gene expression. However, the expression, regulation and functions of circRNAs in endothelial cells have not been determined so far. In this study, basal expression and regulation of circRNAs by hypoxia in human umbilical endothelial cells (HUVEC) were analyzed using deep sequencing. Among the identified 7,388 circRNAs, 2,875 had not been annotated before. We further validated the expression of 40 selected circRNAs by RT-PCR and found that the majority is resistant to RNase R digestion, lacks polyadenylation and is localized to the cytoplasm. Cloning and subsequent sequencing validated the newly generated back splice sites for selected circRNAs. Furthermore, analysis of RNA-seq data revealed that circRNAs, particularly the cytoplasmatic circular RNA cZNF292, are significantly regulated by hypoxia in HUVECs. The siRNA-mediated knockdown of HIF-1α had no effect on cZNF292 induction under hypoxia, suggesting a HIF-1α independent regulation. Most importantly, siRNA-mediated knockdown of cZNF292 significantly reduced spheroid sprouting and network formation of endothelial cells. Furthermore, knockdown of cZNF292 had no effect on its host gene expression. Exon array analysis after cZNF292 knockdown revealed a significant expressional upregulation of 167 as well as a significant expressional downregulation of 123 genes of which most were associated with metabolic processes according to GO annotation. Analysis of Ago-HITS-CLIP data revealed no putative miR-binding sites, suggesting that cZNF292 does not act as a miR-sponge. Taken together, we show for the first time the expression, regulation and function of circRNAs in endothelial cells. The circRNA cZNF292 is regulated by hypoxia and has an important angiogenic function in endothelial cells.
Abstract 17381: Arousals of Sleep Disorders: The Value of Ambulatory Blood Pressure Monitoring
Authors: Ivan Porter, William Haley, Nabeel Aslam, Nicolette Chimato, Paul Fredrickson
Journal: Circulation (2015)

Background: Ambulatory blood pressure monitoring (ABPM) is important for the diagnosis of hypertension (HTN) as well as variants such as nocturnal HTN (NH), masked HTN and a non-dipping pattern. NH and non-dipping, a failure of the normal circadian drop in blood pressure during sleep, have been associated with all-cause mortality and cardiovascular risk. Obstructive sleep apnea is associated with HTN and a growing body of evidence suggests that limb movement disorders of sleep may also influence cardiovascular morbidity. The present study investigates arousals of sleep disorders, limb movement or respiratory, and their relationship to ABPM measurements. Methods: A retrospective review (January 1, 2010 to December 31, 2014) was performed on patients that underwent both ABPM and polysomnography within a six months of each other. Socio-demographic data, results of 24 hour ABPM and polysomnography, concurrent medication use by class, comorbid conditions and laboratory data were recorded. Patients with incomplete polysomnography or ABPM measurements were excluded. Results: 330 individuals met criterion for inclusion; 59% male, 86% white. 211 (64%) were found to have NH, 106 (32%) had uncontrolled HTN and 202 (61%) had a non-dipping pattern. Patients with NH were more likely to have diabetes, hyperlipidemia and chronic kidney disease. Elevated arousal indices were more prevalent in those with NH, uncontrolled HTN and non-dippers. There was an association of NH with the total number of arousals per hour of sleep (p&lt;0.01), whether related to respiratory disturbances or limb movements. Limb movement index (LMI) was related to age (p&lt;0.0001) and was associated with all type arousals (p&lt;0.0001). Conclusions: ABPM revealed a high prevalence of NH, non-dipping, masked and uncontrolled HTN in patients with sleep disorders. Arousals of all types, whether accompanying respiratory or limb movements, were associated with NH and also with LMI.
Association Between Variation in Preoperative Care Before Arterial Switch Operation and Outcomes in Patients With Transposition of the Great Arteries
Authors: Michael L. O’Byrne, Andrew C. Glatz, Lihai Song, Heather M. Griffis, Marisa E. Millenson, Matthew J. Gillespie, Yoav Dori, Aaron G. DeWitt, Christopher E. Mascio, Jonathan J. Rome
Journal: Circulation (2018)

Background: The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied. Methods: A multicenter retrospective cohort study of infants undergoing neonatal ASO between January 2010 and September 2015 at hospitals contributing data to the Pediatric Health Information Systems database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied with multivariable mixed-effects models. Results: Over the study period, 2159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of ASO varied broadly. At the subject level, older age at ASO was associated with higher mortality risk (age &gt;6 days: odds ratio, 1.90; 95% CI, 1.11–3.26; P =0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (odds ratio, 0.32; 95% CI, 0.17–0.59; P &lt;0.001), cost, and length of stay. Later hospital median age at ASO was associated with higher odds of mortality (odds ratio, 1.15 per day; 95% CI, 1.02–1.29; P =0.03), longer length of stay ( P &lt;0.004), and higher cost ( P &lt;0.001). Other hospital factors were not independently associated with the outcomes of interest. Conclusions: There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine whether modifying practice on the basis of the observed associations translates into improved outcomes.
INNV-30. TUMOR TREATING FIELDS AND RADIOTHERAPY FOR NEWLY DIAGNOSED GLIOBLASTOMA: SAFETY AND EFFICACY RESULTS FROM A PILOT STUDY
Authors: Rachel Grossman, Felix Bokstein, Deborah Blumenthal, Carmit Ben Harush, Dror Limon, Zvi Ram
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment comprising low intensity alternating electric fields. In the phase 3 EF14 study in newly diagnosed glioblastoma (ndGBM), TTFields/temozolomide significantly improved survival versus temozolomide alone. TTFields increased glioma cells undergoing cellular death following radiotherapy (RT), suggesting a radiosensitizing effect that enhances RT efficacy. This single center study is the first to investigate TTFields concomitant to RT in ndGBM. Enrolled ndGBM patients (N=10), KPS 70 had recovered from maximal debulking surgery or biopsy. Patients started TTFields prior to or at the time of RT, and were on stable/ decreasing corticosteroids doses for 7 days pre-enrollment. Patients received TTFields (200 kHz; 18 hours/day) with daily removal of transducer arrays during RT, temozolomide (75 mg/m2/daily for 6 weeks) and 60 Gy RT. Endpoints included safety of TTFields/RT (primary) and preliminary efficacy. Patients were 59 years (42–71), KPS 90 (80–100) and mostly male (80%). Five patients (50%) underwent gross total resection while rest had biopsy only. Median dose of RT was 60 Gy (range 52–60 Gy). Six patients (60%) reported have an adverse event (AE) to-date. The most common AE was TTFields-related skin toxicity in 4 (40%) patients; none were severe. All other AEs reported occurred in only one patient and be attributed to underlying disease or chemotherapy. Two reported serious AEs (seizures and general deterioration) were considered unrelated to TTFields. Median PFS was 10.5 months (95%CI 2.67–10.5). PFS rate at 6 months was 80% (95%CI 40.9–91.6). The proportion of TTFields-related skin toxicity (40%) was similar to that reported in phase III study (52%), where patients started TTFields > 4 weeks after RT. No other TTFields-related toxicities were reported, nor was there an increase in RT- or temozolomide-related toxicities from combining TTFields with these therapies. Preliminary survival data are encouraging.
Relationship between amorphous solid dispersion in vivo absorption and in vitro dissolution: phase behavior during dissolution, speciation, and membrane mass transport
Authors: Venecia Wilson, Xiaochun Lou, Donald J. Osterling, Deanne F. Stolarik, Gary Jenkins, Wenqing Gao, Geoff G.Z. Zhang, Lynne S. Taylor
Journal: Journal of Controlled Release (2018)
PATH-23. GERMLINE GNAS MUTATION IN AN 18-MONTH-OLD WITH MEDULLOBLASTOMA
Authors: Jacquelyn Crane, Vivian Chang, Hane Lee, William Yong, Noriko Salamon, Jessica Kianmahd, Naghmeh Dorrani, Julian Martinez-Agosto, Tom Davidson
Journal: Neuro-Oncology (2018)

Medulloblastoma is the most common malignant brain tumor of childhood. It is a molecularly and clinically heterogeneous tumor. There are currently four recognized molecular subtypes of medulloblastoma, one of which is sonic hedgehog (SHH)-activated medulloblastoma. We discuss a case of an 18-month-old male with a desmoplastic SHH-activated TP53-wildtype medulloblastoma, failure to thrive, global developmental delay, and polydactyly found to have a novel de novo heterozygous c.565-568delGACT germline GNAS frameshift mutation on the paternal allele identified through peripheral blood trio clinical exome sequencing. Germline GNAS mutations are known to be associated with several diseases. However, to the authors knowledge, this is only the second report in the literature of a germline GNAS mutation in a patient with medulloblastoma. GNAS is a known tumor suppressor of the SHH pathway. A prior study has shown that low somatic GNAS expression characterizes a subset of patients with aggressive SHH-activated medulloblastoma. The normal function of GNAS encoded Gas is to stimulate adenylyl cyclase activity to produce intracellular cyclic adenosine monophosphate (cAMP), which activates the cAMP-dependent protein kinase A (PKA), and inhibits SHH signaling. Thus, low or loss of GNAS expression leads to aberrant SHH pathway activation. Upregulation of the SHH pathway results in increased granule cell progenitor proliferation and tumor formation. This provides insight into the mechanism by which our patients GNAS mutation may have fueled development of medulloblastoma. Germline GNAS mutation must be considered in patients with SHH-activated medulloblastoma and in particular, in patients with phenotypic similarities to our patient including developmental delay, small size for age, and polydactyly. Advancing our understanding of medulloblastoma development through the study of germline and tumor genomics including better understanding the role of GNAS, holds great promise for enabling improved treatments and patient outcomes.
Abstract O.23: Lysyl Oxidase Expression In The Patients With Kawasaki Disease
Authors: Chisato Shimizu, Cassidy YunJing Huang, Anne Phan-Huy, Andrea Salgado, Lilia Antonio, John T Kanegaye, Adriana H Tremoulet, Alessandra Franco, Jane C Burns
Journal: Circulation (2015)

Background: Histologic study of inflamed coronary arteries from the Kawasaki disease (KD) patients shows infiltration by immune effector cells, IL-17-producing myofibroblasts, and breaks in the internal elastic lamina. Transcripts from genes associated with cell trafficking (e.g. paxillin) are elevated in whole blood from acute KD patients. Lysyl oxidase (LOX) is a multifunctional protein affecting affecting “monocyte and smooth muscle cell migration, elastogenesis, and endothelial-to-mesenchymal transition. LOX promotes cell motility through paxillin phosphorylation, which influences T-cell trafficking via the calcium signaling pathway. We investigated the role of LOX in the pathogenesis of KD. Methods: Agilent microarray data using whole blood were analyzed for differential expression of enzymes in the LOX family (LOX, LOX-like (L)1-4) in acute and convalescent KD samples (n=19). LOXL1 results were validated using RT-PCR in an independent cohort (n=20). LOXL1 transcripts levels were measured in KD whole blood, peripheral blood mononuclear cells (PBMC), T-cell clones, B-cell lines, and myeloid dendritic cells from acute KD patients. Immunohistochemical staining for LOXL1 was performed on coronary arteries from a KD patient who died on illness day 7. Result: LOXL1 expression by microarray was 3.2-fold higher in acute than convalescent samples (p&lt;0.001) and was validated in an independent cohort by RT-PCR (5.4-fold higher, p&lt;0.001). LOXL1 transcripts levels were 2-35 times higher in PBMC compared to whole blood (n=8). KD T cell clones had higher LOXL1 transcript levels than B-cells and dendritic cells. Immunohistochemical staining showed LOXL1-expressing inflammatory cells and smooth muscle cells in the coronary artery walls. Conclusion: LOXL1 may increase inflammation in acute KD by promoting the motility of infiltrating T cells and smooth muscle cells through focal adhesion formation. However, LOXL1 may also participate in arterial wall repair by crosslinking collagen and elastin. Statins inhibit focal adhesion formation and thus cell trafficking but not the crosslinking mediated by LOXL1. Studies of LOXL1 protein levels and paxillin phosphorylation in PBMC may further our understanding of their role in KD pathogenesis.
Abstract 15115: Incidence, Timing, and Type of First and Recurrent Ischemic Events in Patients With and Without Peripheral Artery Disease After an Acute Coronary Syndrome
Authors: Taku Inohara, Karen Pieper, Daniel Wojdyla, Manesh R Patel, William S Jones, Pierluigi Tricoci, Kenneth W Mahaffey, Stefan K James, John H Alexander, Lars Wallentin, E M Ohman, Matthew T Roe, Sreekanth Vemulapalli
Journal: Circulation (2017)

Background: Patients with peripheral artery disease (PAD) and acute coronary syndrome (ACS) are at increased risk for ischemic cardiovascular events. We hypothesize that the incidence, timing, and ...
Abstract 20082: Guideline-based Screening for Atrial Fibrillation: Analysis of Yield and Stroke Risk
Authors: Nicole Lowres, David A Fitzmaurice, F. D. Richard Hobbs, Femke Kaasenbrood, Vivian Lee, Robert Tieleman, Bryan Yan, S. Ben Freedman
Journal: Circulation (2017)

Introduction: ESC guidelines recommend opportunistic screening for atrial fibrillation (AF) in people aged ≥65 years. The diagnostic yield of such a screening policy is uncertain in individual age ...