tbuckley/cabot-search huggingface dataset:
RARE-37. OCCURRENCE OF GLIOMA IN PREGNANT PATIENTS: INSTITUTIONAL CASE SERIES AND REVIEW OF THE LITERATURE
Authors: Pawan Singh, Edward Pan, Josie Sewell, Kimmo Hatanpaa
Journal: Neuro-Oncology (2018)

The treatment of glioma in pregnant patients has limited data in the literature. There are no guidelines in place currently for this population. Another controversial topic is the use of gadolinium contrast in pregnant patients. This retrospective institutional case review series looks at the extent of resection, grade of tumor, use of contrast and outcome. This case series is the first to document IDH-mutation and MGMT methylation status either by immuno-histological stain or by genetic sequencing. 5 patient cases were reviewed by retrospective search with diagnosis of glioma and pregnancy. 4 patients were diagnosed with glioma during pregnancy; 1 patients were diagnosed with glioma prior to pregnancy. 3 patients were monitored with contrasted MRIs after 2nd trimester, there were no adverse effects to the fetus. Only 1 patient developed progression during course of chemotherapy, the remaining 4 patients remained progression free after completion of chemotherapy. This case series documented that 3 of 5 patients had IDH-mutated gliomas; 1 of 3 glioblastomas (GBM) were MGMT methylated. 3 of 5 patients achieved gross total resection. All intracranial neoplasms were of astrocytic lineage: 3 GBMs, 1 anaplastic astrocytoma and 1 diffuse astrocytoma. All patients delivered healthy infants. 4 patients continue to be progression free since completion of chemotherapy with 1 patient experiencing progression during course of chemotherapy. Median progression free survival was 20 months, all patients are alive at time of publication. This case series highlights how individualized care through a multi-disciplinary approach can result in favorable outcomes in this patient population.
Abstract 15146: Updated Meta-Analysis of Role of Angiotensin Blockade in Reducing Aortic Dilatation in Patients With Marfan Syndrome
Authors: Amartya Kundu, Partha Sardar, Saurav Chatterjee, Wilbert S Aronow, Linda Pape
Journal: Circulation (2015)

Introduction: Patients with Marfan Syndrome have an increased risk of sudden death due to aortic dissection, mostly preceded by aortic dilatation.There has been considerable interest in evaluating the role of angiotensin blockade with Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARB) on reducing the progression of aortic root dilatation in these patients. While earlier studies showed considerable benefit with ACE/ARB, recently large scale Randomized Control Trials showed conflicting results. The purpose of this meta-analysis was to assess the role of angiotensin blockade in reducing the rate of aortic root dilatation in patients with Marfan Syndrome. Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Clinical Trials from the inception to May 30, 2015 using the terms “Marfan syndrome”, “angiotensin converting enzyme inhibitors” and “angiotensin II-receptor blockers”. Data was extracted using standardized protocol.The main outcome of the present analysis was the change in aortic root diameter with ACE/ABR therapy compared to control. The random effects model of DerSimonian and Laird was used. The statistical analysis was done in line with recommendations from the Cochrane Collaboration using Review Manager (RevMan) version 5.3. Results: Six studies enrolling a total of 1252 patients were included in the final analysis. Five were randomized controlled trials and one was an observation study. Analysis showed that there was no significant benefit with ACE/ARB in reducing aortic root dilatation rate compared to control [Mean Difference of -0.24 ; 95 % CI -0.36 to -0.13, P &lt; 0.00001]. Conclusion: Based on the results of this meta analysis which includes data from the most recent trials, there is no significant benefit with ACE/ARB treatment on reducing the rate of aortic root dilatation in patients with Marfan Syndrome.
Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis
Authors: Yayuan Zheng, Jianhong Zhu, Yuyu Liu, Weiguang Lai, Chunyu Lin, Kaifen Qiu, Junyan Wu, Weimin Yao
Journal: BMJ (2018)

Abstract Objective To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD). Design Systematic review and meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018. Eligibility criteria Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available. Data extraction and synthesis Data were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation). Results 21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87). Conclusions Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD. Study registration Prospero CRD42018077033.
ACTR-25. UPDATED RESULTS FROM A PROSPECTIVE, RANDOMIZED PHASE 2 STUDY IN PATIENTS WITH FIRST RELAPSE OF HIGH-GRADE ASTROCYTOMA USING TVB-2640 IN COMBINATION WITH AVASTIN VERSUS AVASTIN ALONE
Authors: Brandon Konkel, Laura Caflisch, Aldolfo Enrique Diaz Duque, Andrew J Brenner
Journal: Neuro-Oncology (2018)

Standard of care for glioblastoma multiforme (GBM) is surgical resection followed by temozolamide, with Avastin given at relapse. Responses to Avastin remain brief; resistance may involve overexpression of Fatty Acid Synthase (FASN). Our institution is conducting a phase 2 study of Avastin with or without the FASN inhibitor TVB-2640 in patients with GBM in first relapse. This is a prospective, randomized, phase 2 study of Avastin with or without TVB-2640 in patients with GBM in first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. Randomization is into 2 separate arms. Patients in arm 1 receive Avastin every 2 weeks in combination with TVB-2640. Patients in arm 2 receive Avastin alone every 2 weeks. MR-Spectroscopy (MRS) and serum sampling for exosome analysis will be obtained on all patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients will converge to a single arm and will continue to receive Avastin in combination with TVB-2640. A total sample size of 24 patients will provide 90% power to detect a 4 month difference in PFS (3 months for Bev alone (historic controls) versus 7 months for TVB-2640 in combination with Bev, (i.e., a hazard ratio of 0.43) using a one-sided log-rank test with alpha=0.1. We have enrolled 13 patients to date, 12 have started therapy; 1 came off study early due to intracranial hemorrhage. No grade 3 or higher treatment related AEs have occurred. Updated results will include PFS, response, and biomarker analysis (exosome, MRS). The combination of TVB2640 with Avastin appears to be well tolerated. Enrollment will continue with planned completion in early 2019. (Clinical trial registry number: NCT03032484).
Abstract P057: The Association Between Diabetes and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis
Authors: Lu Yao, Aaron Folsom, Alvaro Alonso, James Pankow, Weihua Guan, Weihong Tang
Journal: Circulation (2018)

Objectives: Data regarding the relationship between diabetes and abdominal aortic aneurysm (AAA) are inconsistent across studies: some studies showed an inverse relationship while others did not show an association. We conducted a meta-analysis to examine the association between diabetes and AAA based on published data from case-control and cohort studies. Methods: We searched literature in English from online databases including MEDLINE (1966-), EMBASE and Web of Science as of July 2017, plus a manual examination of references in selected articles. The eligibility criteria included (1) a case-control or cohort study conducted in adults; (2) diabetes is the exposure variable and AAA risk is the outcome variable; and (3) association estimates (hazard ratios, odds ratios or relative risks) and measurement of variance (P value, confidence interval, or standard error) were available. The literature review and data abstraction were conducted in duplicate by independent investigators. A DerSimonian and Laird random effects model was used to pool association estimates and their 95% confidence intervals from studies using STATA 13. The Cochran’s Q test was used to assess the presence of heterogeneity and the I-square index to quantify the extent of heterogeneity. Results: We included in the meta-analyses a total of 10 cohorts with 10,771 AAAs in 2,625,318 participants and 4 case-control studies with 1,065 AAAs and 11,009 controls that met the pre-determined eligibility criteria. The samples were predominantly white (88%). Study-specific relative risk and pooled relative risk as well as heterogeneity test results were shown in Figure. Diabetes was inversely associated with AAA risk (pooled relative risk: 0.55; 95%CI: 0.49 - 0.61, Figure) . Results were overall consistent by sex, study design and setting (hospital- vs community-based). Conclusions: The findings suggest that diabetes is strongly and inversely associated with the risk of AAA. Future studies are warranted to investigate the potential mechanisms.
Abstract 16331: Impact of Previous Peripheral Artery Disease on Prognosis After Myocardial Infarction-The J-Minuet Study-
Authors: Hirokuni Akahori, Tohru Masuyama, Koichi Nakao, Yukio Ozaki, Kazuo Kimura, Junya Ako, Teruo Noguchi, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Takashi Morita, Wataru Shimizu, Yoshihiko Saito, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Toshiaki Mano, Kazuhiro Hirata, Kengo Tanabe, Yoshisato Shibata, Mafumi Owa, Kenichi Tsujita, Hiroshi Funayama, Nobuaki Kokubu, Ken Kozuma, Shirou Uemura, Tetsuya Toubaru, Keijirou Saku, Shigeru Ohshima, Kunihiro Nishimura, Yoshihiro Miyamoto, Hisao Ogawa, Masaharu Ishihara
Journal: Circulation (2017)

Background: Patients with peripheral artery disease (PAD) is thought to have poor prognosis because of the high incidence of coronary or cerebrovascular events. It is also known that prognosis afte...
CBMT-19. RNU6-1 ANALYSED IN EXOSOMES FROM SERA AS A NOVEL DIFFERENTIAL BIOMARKER FOR GBM VS NON-NEOPLASTIC BRAIN LESIONS AND NSCPL
Authors: Montserrat Puigdelloses Vallcorba, Maider Varela-Guruceaga, Marisol González-Huarriz, Beatriz Zandio, Sarah Besora, Jordi Bruna, Gregorio Petrirena, Miguel Marigil, Ricardo Díez-Valle, Sonia Tejada, Jorge Nuñez, Marta M Alonso, Jaime Gállego Pérez-Larraya
Journal: Neuro-Oncology (2018)

The identification of circulating biomarkers by non-invasive methods would be helpful for glioma detection and response assessment. Strong evidences have shown that GBM cells release microvesicles containing proteins and RNA. We have previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to control samples; therefore it could serve as a non-invasive diagnostic biomarker for GBM. In this study, we set to investigate the role of RNU6-1 as a differential biomarker of GBM versus other brain diseases with similar radiological features. RNU6-1 expression was analysed by digital droplet PCR (ddPCR) in circulating exosomes from serum samples of GBM patients (n=18), healthy controls (n=28), and patients with different brain lesions: subacute stroke (n=30), acute-subacute haemorrhage (n=29), acute demyelinating lesions (n=19), brain metastases (n=21) and Primary CNS Lymphomas (PCNSL) (n=12). We observed that the expression of RNU6-1 was significantly higher in GBM patients (412 ± 550.48 copies/20µL) than in healthy controls (150 ± 224.35 copies/20µL; p=0.039) validating our preceding results. Furthermore, RNU6-1 levels were increased in exosomes from GBM patients than in exosomes from patients with non-neoplastic lesions (stroke [223 ± 709.8 copies/20µL; p=0,067], haemorrhage [127 ± 198.7 copies/20µL; p=0.010], demyelinating lesions [111.5 ± 250.35 copies/20µL; p=0.019]) and PCNSL [18.15 ± 245.7 copies/20µL; p=0.004]). Contrary, RNU6-1 levels were similar between brain metastases and GBM patients [325 ± 632 copies/20µL; p=0.573]. In addition, assessing RNU6-1 as a predictive marker of GBM by ROC curves analysis, we demonstrated that RNU6-1 was a robust diagnostic biomarker of GBM compared to subacute stroke [AUC=0.659; p=0.004], acute/subacute haemorrhage [AUC=0.724; p=0.006], acute demyelinating lesions [AUC=0.728; p=0.011] and PCNSL [AUC=0.814; p<0.001]; in contrast, it did not allow differentiating GBM from brain metastases [AUC=0.552; p=0.575]. Our data indicate that RNU6-1 from circulating exosomes could serve as a differential biomarker for GBM versus non-neoplastic brain lesions and PCNSL, therefore, be used as a non-invasive method for GBM diagnosis.
NIMG-70. QUANTITATIVE IMAGE ANALYSIS AND MACHINE LEARNING TECHNIQUES FOR DISTINGUISHING TRUE PROGRESSION FROM PSEUDOPROGRESSION IN PATIENTS WITH GLIOBLASTOMA
Authors: Hamed Akbari, Saima Rathore, Spyridon Bakas, MacLean Nasrallah, Martin Rozycki, Suyash Mohan, Ronald Wolf, Michel Bilello, Maria Martinez-Lage, Christos Davatzikos
Journal: Neuro-Oncology (2018)

PURPOSE: Imaging follow up of glioblastoma patients, after maximal safe resection and radiochemotherapy, commonly demonstrates new/increasing enhancement around the tumor bed concerning for tumor progression/recurrence (TP). However, in ~50%, this enhancement represents primarily treatment-related changes including pseudoprogression (PsP) within six months from completion of chemoradiation. We seek non-invasive imaging biomarkers, reproducible via publicly-available software, capable of distinguishing TP from PsP. We hypothesize that quantitative analysis of extensive, complementary features extracted from multi-parametric magnetic resonance imaging (mpMRI), via advanced machine learning (ML) techniques, can yield such robust imaging biomarkers. We evaluated independent discovery (n=40) and replication (n=23) cohorts of glioblastoma patients, with available mpMRI (T1, T1-Gd, T2, T2-FLAIR, DTI, DSC) and who underwent second resection due to possible recurrence. Extensive features from the mpMRI scans were extracted and quantitatively analyzed via a dynamically-growing software platform specialized in radiographic analysis (cancer imaging phenomics toolkit, or CaPTk - www.cbica.upenn.edu/captk) to derive phenotypic imaging signatures of TP and PsP. Principal components analysis of intensity distributions, morphological, statistical, and texture descriptors, were integrated via support vector machines to evaluate the imaging profile of the target tissue and distinguish among i)TP, ii)mixed response, and iii)PsP. Independently, board-certified neuropathologists evaluated the resected tissue by blindly classifying it in the above three categories based on geographic necrosis, dystrophic calcification, vascular changes, mitotic figures, pseudopalisading necrosis, and Ki67. Tissue classified as TP by the neuropathologists revealed higher angiogenesis based on DSC-derived features; higher cellularity based on DTI-derived features; and lower water concentration (T2, T2-FLAIR). Our quantitative analysis detected TP with 83% accuracy (sensitivity:92%,specificity:73%,AUC:0.83) and PsP also with 83% accuracy (sensitivity:79%,specificity:100%,AUC:0.90). Advanced quantitative mpMRI analysis and ML reveals non-invasive in vivo markers of TP versus PsP of glioblastoma that are directly associated with pathological changes. Integration of the proposed method on CaPTk facilitates its potential widespread use.
Identification of inhibitory mechanisms in pseudo-allergy involving Mrgprb2/MRGPRX2-mediated mast cell activation
Authors: Ayako Takamori, Kumi Izawa, Ayako Kaitani, Tomoaki Ando, Yoko Okamoto, Akie Maehara, Atsushi Tanabe, Masakazu Nagamine, Hiromichi Yamada, Shino Uchida, Koichiro Uchida, Masamichi Isobe, Tomoki Hatayama, Daiki Watanabe, Taiki Ando, Takuma Ide, Moe Matsuzawa, Keiko Maeda, Nobuhiro Nakano, Naoto Tamura, Katsuhisa Ikeda, Nobuyuki Ebihara, Toshiaki Shimizu, Hideoki Ogawa, Ko Okumura, Jiro Kitaura
Journal: Journal of Allergy and Clinical Immunology (2018)
NCMP-01. COMPARISON AND QUANTITATION OF HISTOPATHOLOGY ABNORMALITIES IN SURGICALLY RESECTED CEREBRAL RADIATION NECROSIS AS COMPARED WITH RECURRENT BRAIN TUMOR FOLLOWING RADIATION
Authors: Lisa Rogers, Curt Tatsuoka, Mitchell Machtay, Chaitra Badve, Pallavi Tiwari, Prateek Prasanna, Andrew Sloan, Warren Selman, Mark Cohen
Journal: Neuro-Oncology (2018)

BACKGROUND The histologic features of radiation necrosis (RTN), a dysregulated repair process following brain radiation, have not been defined and distinguished from recurrent brain tumor (RBT) following brain radiation therapy. The aim of this study is to compare the type and severity of histologic characteristics of tissue specimens containing predominantly or totally RTN versus predominantly or totally RBT obtained at imaging progression after brain tumor radiation. METHODS Subjects were identified from brain tumor pathology reports of resected recurrent/progressing MRI enhancing lesions following brain radiation at UHCMC from 2004--2013. RTN was defined by < 20% active tumor, the remainder radiation treatment effects. RBT was defined by >80% active tumor. (Mixed cases were excluded). H & E slides were reviewed for 30 characteristics including vascular pathologies, necrosis, tumor features, tissue reaction, inflammatory infiltrate, blood products, and dystrophic calcification. Localization in grey/white matter and leptomeninges was noted. Each characteristic was graded in quartiles by one neuropathologist. The profile was compared with original tumor when available. RESULTS 66 patients were identified, 40 RBT (25 glioma, 15 metastasis) and 26 RTN (14 metastasis, 12 glioma). We identified significant differences in frequency and severity of zonal/geographic necrosis in RTN versus RBT in glioma (p=.002) and metastasis (p=.012) and nonsignificant difference in severity of vascular hyalinization in RTN versus glioma RBT (p=0.44). Demyelination was of borderline significance. Fibrinoid vascular necrosis, vessel wall thickening, and RT astrocytes were not significantly different in RTN versus RBT of either tumor type. In some cases, necrosis and vascular pathology were similar to pretreatment histology. CONCLUSION A multivariable assessment of histologic characteristics may assist neuropathologists in interpretation of surgically resected lesions following brain tumor radiation therapy, especially when pretreatment tumor is available for comparison. We will present imaging correlations with pathology findings. Grant support CTSC UL1TR000439
New Strategies for Surgical Myocardial Revascularization
Authors: Mario Gaudino, Faisal Bakaeen, Piroze Davierwala, Antonino Di Franco, Stephen E. Fremes, Nirav Patel, John D. Puskas, Marc Ruel, Gianluca Torregrossa, Michael Vallely, David P. Taggart
Journal: Circulation (2018)

We summarize the evidence on the new strategies for coronary artery bypass grafting (CABG). Hybrid CABG implies surgical grafting of the left anterior descending artery and percutaneous treatment of the other target vessels, with the promise of combining the durable benefits of surgery with the less invasive approach of percutaneous coronary interventions. Robotic CABG and minimally invasive CABG are performed through minimal incision or port access with dedicated equipment and instruments. Anaortic coronary artery bypass refers to off-pump CABG using only in-situ grafts. The use of multiple arterial grafts has been shown to improve patency and is potentially associated with better clinical outcomes. All these techniques require dedicated training and are more complex than conventional CABG but can significantly improve the results of surgery. Validation of the results of these new approaches in large randomized trials is a priority for the surgical community.
TMIC-33. THE ROLE OF FIBRINOGEN-LIKE PROTEIN 2 ON IMMUNOSUPPRESSION AND MALIGNANT PROGRESSION IN GLIOMA
Authors: Ganesh Rao, Khatri Latha, Jun Yan, Yuhui Yang, Ganiraju Manyam, Ravesanker Ezhilarasan, Erik Sulman, Arvind Rao, Amy Heimberger, Shulin Li
Journal: Neuro-Oncology (2018)

Virtually all low-grade gliomas (LGG) will progress to high-grade gliomas (HGG), including glioblastoma, the most common malignant primary brain tumor in adults. A key regulator of immunosuppression, Fibrinogen-like Protein 2 (FGL2), may play an important role in the malignant transformation of LGG to HGG. We sought to determine the mechanism of FGL2 on tumor progression and to show that inhibiting FGL2 expression had a therapeutic effect. We analyzed human gliomas that had progressed from low- to high-grade for FGL2 expression. We modeled FGL2 overexpression in an immunocompetent genetically-engineered mouse model to determine its effect on tumor progression. Tumors and their associated microenvironment were analyzed for their immune cell infiltration. Mice were treated with an FGL2 antibody to determine a therapeutic effect. We identified increased expression of FGL2 in surgically-resected tumors that progressed from low- to high-grade (N=10). TCGA data showed that LGG cases with over-expression of FGL2 (N=195) had statistically significantly shorter survival compared to cases with low-expression (N=325) (log-rank test, p<0.001). In a murine glioma model, HGGs induced with FGL2 exhibited a mesenchymal phenotype and increased CD4+ forkhead box P3 (FoxP3)+ Treg cells implicating immunosuppression as a mechanism for tumor progression. Macrophages in these tumors were skewed toward the immunosuppressive M2 phenotype. Depletion of Treg cells with anti-FGL2 statistically significantly prolonged survival in mice compared to controls (N=11 per group, log-rank test, p=0.004), shifted the phenotype from mesenchymal HGG to proneural LGG, and decreased M2 macrophage skewing. FGL2 facilitates glioma progression from low- to high-grade. Suppressing FGL2 expression holds therapeutic promise for halting malignant transformation in glioma by decreasing Tregs and polarizing macrophages away from the M2 phenotype.
Abstract 10299: Surgical Myectomy vs. Alcohol Ablation for Septal Reduction in Patients With Obstructive Hypertrophic Cardiomyopathy - Early and Late Outcomes in a Propensity Score Matched Cohort
Authors: Anita Nguyen, Hartzell V Schaff, Dustin Hang, Rick A Nishimura, Jeffrey B Geske, Joseph A Dearani, Brian D Lahr, Steve R Ommen
Journal: Circulation (2018)

Introduction: In patients with hypertrophic cardiomyopathy (HCM), obstruction of the left ventricular outflow tract (LVOT) can be relieved by surgical septal myectomy or alcohol septal ablation (AS...