tbuckley/cabot-search huggingface dataset:
ATRT-31. SUCCESSFUL MULTIMODALITY MANAGEMENT OF ATRT OF THE LOWER DORSAL SPINE WITH SPINAL DROP METASTASIS
Authors: Ahitagni Biswas, Umesh Velu, Kalpana Kumari, Deepali Jain, Sameer Bakhshi
Journal: Neuro-Oncology (2020)

Abstract A 6 year old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5x1.5x4.7cm intradural mass extending from D10-D12, causing compression of the conus medullaris. With a preoperative diagnosis of intradural ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed a markedly cellular, malignant tumour with frequent mitotic figures. Cells were round to polygonal with vesicular nuclei, prominent nucleoli and were immunopositive for CK,EMA,p53 and immunonegative for MIC2,desmin,SMA,GFAP,INI-1(MIB1 labeling index-35–40%). The overall impression was spinal atypical teratoid rhabdoid tumour(ATRT). Post-operative neuraxis MRI revealed post-operative changes(D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no brain lesion. CSF cytology did not show any malignant cell. The metastatic work-up was normal. He was started on chemotherapy with ICE regimen (Ifosfamide-2g/m2IVD1–D3,Carboplatin-500mg/m2IVD3,Etoposide-100mg/m2IVD1–D3q3weeks). Subsequently he received craniospinal irradiation (CSI)-36Gray/20fractions/4weeks→ focal boost to primary tumour bed and spinal drop metastasis-14.4Gray/8fractions/1.5 weeks. Thereafter he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes(D10-D12) and 38.9%reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from initial diagnosis), he was neurologically intact and in CR. Multimodality management comprising GTR,CSI followed by focal boost and multiagent chemotherapy(ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.
INNV-08. COMPARATIVE STUDY OF THE CANCER TREATMENT POTENTIAL EFFECT OF TUMOR-TREATING FIELDS AND COLD ATMOSPHERIC PLASMA
Authors: Xiaoliang Yao, Isaac Goldstein, Li Lin, Jonathan Sherman, Michael Keidar
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Cold Atmospheric Plasma (CAP) is ionized gas close to room temperature that generates reactive oxygen and nitrogen species, an electromagnetic field (EMF) and UV, which are selectively cytotoxic to cancer cells. Tumor Treating Fields (TTFields) is an FDA approved cancer treatment that utilizes “low intensity” and “intermediate frequency” alternating electric fields to produce an inhibitory effect on cancerous cells. OBJECTIVES In this study, we directly compared CAP and TTFields treatments using U87 glioblastoma tumor cells. We aimed to assess the relative merits of both technologies as potential approaches for brain cancer treatment. METHODS In this in vitro study, the cells were treated with either CAP or TTFields at room temperature. In both cases in order the optimize the treatment parameters, the energy we applied was varied for both methods by changing the power and time of the treatment. The resulting cell viability changes were measured 72 hours after treatment. RESULTS The results revealed that increased energy resulted in decreased cell viability of U87 glioblastoma tumor cells with both CAP and TTFields treatment. The rate of U87 glioblastoma tumor cell viability under CAP treatment was 80% of the original viability after using 4.8J of energy, compared with 15,752J of energy with TTFields treatment. Additionally, the CAP displayed significantly greater time-efficiency as compared to TTFields. For instance, the most effective TTFields treatment took 4 hours, while the CAP treatment displayed a comparable effect on tumor cell viability with a treatment time of 30 seconds. CONCLUSIONS This preliminary in vitro study indicates that CAP treatment is potentially a more favorable effective method of brain cancer therapy. This data indicates that CAP is significantly more energy-efficient and requires significantly less treatment time than TTFields. Future research looks to compare the 2 treatments in an intracranial mouse xenograft model.
Diastolic Function and Clinical Outcomes After Transcatheter Aortic Valve Replacement
Authors: Geraldine Ong, Philippe Pibarot, Bjorn Redfors, Neil J. Weissman, Wael A. Jaber, Raj R. Makkar, Stamatios Lerakis, Deepika Gopal, Omar Khalique, Susheel K. Kodali, Vinod H. Thourani, Saif Anwaruddin, Thomas McAndrew, Yiran Zhang, Maria C. Alu, Pamela S. Douglas, Rebecca T. Hahn
Journal: Journal of the American College of Cardiology (2020)
SURG-15. THE SURGERY OF THALAMIC LESIONS IN PEDIATRIC BRAIN TUMORS
Authors: Yuzaburo Shimizu, Osamu Akiyama, Akihide Kondo
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric brain tumors are occurred in the center of central nervous system. Since mid-line glioma has defined in the new classification, thalamus has attracted attention as a site that requires surgical intervention. However, the surgery for thalamus is a challenging procedure for neurosurgeons. In this study, we studied our surgical cases of patients suffering from pediatric brain tumors in thalamus and/or thalamic regions to evaluate the safety of surgeries and the consideration of appropriate surgical approaches. METHODS We reviewed neuroradiological images, medical record, and, surgical videos for the assessment of surgical fields in patients under the age of 15 who had surgical treatments at our institution. RESULTS We had six cases that could be analyzed. The lesions in the posterior parts of the thalamus had been operated by the occipital transtentorial approach. The lesions in the superior parts of thalamus were treated with transcortical transventricle approach. It was possible to achieve sufficient removal of tumors and have good surgical view. The monitoring of motor function and visual function was used in all cases. After removal, we could have a nice view of the important structures around thalamus. CONCLUSIONS The surgeries for thalamus and thalamic regions were safety with enough considerations for neurological examinations and radiological imaging. The intra operative monitoring for motor and visual function should be used.
RADT-34. PREDICTIVE FACTORS FOR OVERALL SURVIVAL IN SURGICAL CASES OF GLIOMATOSIS CEREBRI FROM THE NATIONAL CANCER DATABASE
Authors: Adham Khalafallah, Srujan Kopparapu, Debraj Mukherjee
Journal: Neuro-Oncology (2020)

Abstract Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI]=11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p=0.01) while radiation therapy (p=0.07) and extent of resection (p=0.48) did not. On multivariate analysis, older patients (hazard ratio [HR]=1.07, CI=1.03-1.11, p&amp;lt; 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR=3.47, CI=1.40-8.60, p&amp;lt; 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.
Direct and Indirect Regulators of Epithelial–Mesenchymal Transition–Mediated Immunosuppression in Breast Carcinomas
Authors: Anushka Dongre, Mohammad Rashidian, Elinor Ng Eaton, Ferenc Reinhardt, Prathapan Thiru, Maria Zagorulya, Sunita Nepal, Tuba Banaz, Anna Martner, Stefani Spranger, Robert A. Weinberg
Journal: Cancer Discovery (2020)

The epithelial-to-mesenchymal transition, which conveys epithelial (E) carcinoma cells to quasi-mesenchymal (qM) states, enables them to metastasize and acquire resistance to certain treatments. Murine tumors composed of qM mammary carcinoma cells assemble an immunosuppressive tumor microenvironment (TME) and develop resistance to anti-CTLA4 immune-checkpoint blockade (ICB) therapy, unlike their E counterparts. Importantly, minority populations of qM cells within a tumor can cross-protect their more E neighbors from immune attack. The underlying mechanisms of immunosuppression and cross-protection have been unclear. We demonstrate that abrogation of qM carcinoma cell-derived factors (CD73, CSF1, or SPP1) prevents the assembly of an immunosuppressive TME and sensitizes otherwise refractory qM tumors partially or completely to anti-CTLA4 ICB. Most strikingly, mixed tumors in which minority populations of carcinoma cells no longer express CD73 are now sensitized to anti-CTLA4 ICB. Finally, loss of CD73 also enhances the efficacy of anti-CTLA4 ICB during the process of metastatic colonization. SIGNIFICANCE: Minority populations of qM carcinoma cells, which likely reside in human breast carcinomas, can cross-protect their E neighbors from immune attack. Understanding the mechanisms by which qM carcinoma cells resist antitumor immune attack can help identify signaling channels that can be interrupted to potentiate the efficacy of checkpoint blockade immunotherapies.This article is highlighted in the In This Issue feature, p. 995.
Abstract P527: Body Mass Index (bmi, Kg/m <sup>2</sup> ) vs. Body Fat % (bf%): Battle of Obesity Classification Metrics to Inform Underlying Cardiometabolic Risk
Authors: Andrew O Odegaard, Mercedes R Carnethon, Sarah M Camhi, Lisa Chow, Myron D Gross, David R Jacobs
Journal: Circulation (2020)

Introduction: The WHO defines overweight and obesity as abnormal or excessive fat accumulation that may impair health. However, for population and clinical classification of overweight and obesity BMI is most commonly used as a proxy for adiposity. Despite the strength of the association between higher BMI and cardiometabolic disease risk across populations, and minimal direct comparison of BMI v. BF%, BMI draws significant criticism as a metric to classify obesity and screen for cardiometabolic risk. Hypothesis: BF% defined obesity classification categories have higher underlying cardiometabolic risk compared to equivalent BMI categories. Methods: We analyzed data from CARDIA study participants from the year 20 exam with concurrent measures of BMI, and BF% measured by Dual-energy X-ray absorptiometry (DXA), plus clinical measures. Sex specific BF% obesity classification categories were defined by evidence-based diagnostic and classification performance measures vs. standard BMI cut points. Underlying cardiometabolic risk was defined by a continuous metabolic syndrome risk score (MetS), consisting of the averaged standardized deviates of the 5 ATP III components. Higher MetS z-scores indicate higher overall risk. MetS z-scores between categories (e.g. obesity defined by BMI v. BF%) were compared by z-tests. Results: The figure reports the distribution of obesity classification categories by the different metrics and underlying cardiometabolic risk. The MetS risk score was significantly higher in BMI defined overweight and obesity compared to BF% defined categories; and BF% defined obesity categories classify a greater prevalence of the population as obese compared to BMI. Results for MetS risk did not differ by race/sex or when including prevalent cardiometabolic disease. Conclusions: Physiologically defined BF% obesity categories classify a greater prevalence of obesity in CARDIA at year 20, whereas there was higher underlying cardiometabolic risk in BMI defined obesity classification categories.
Cardiac Allograft Vasculopathy in Heart Transplant Patients: Pathologic and Clinical Aspects for Angioplasty/Stenting⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jon A. Kobashigawa
Journal: Journal of the American College of Cardiology (2006)
Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs
Authors: Shuai He, Lin-He Wang, Yang Liu, Yi-Qi Li, Hai-Tian Chen, Jing-Hong Xu, Wan Peng, Guo-Wang Lin, Pan-Pan Wei, Bo Li, Xiaojun Xia, Dan Wang, Jin-Xin Bei, Xiaoshun He, Zhiyong Guo
Journal: Genome biology (2020)

Abstract Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH + fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.
Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase <scp>II</scp> pediatric‐like <scp>GIMEMA LAL</scp>‐1308 trial
Authors: Anna Maria Testi, Martina Canichella, Antonella Vitale, Alfonso Piciocchi, Anna Guarini, Irene Della Starza, Marzia Cavalli, Maria Stefania De Propris, Monica Messina, Loredana Elia, Maria Luisa Moleti, Bruno Martino, Mario Luppi, Marianna D'Aloisio, Anna Candoni, Valentino Conter, Paola Fazi, Marco Vignetti, Sabina Chiaretti, Roberto Foà
Journal: American Journal of Hematology (2020)

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD <10-3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.
Tumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availability
Authors: Won Dong Lee, Anna Chiara Pirona, Boris Sarvin, Alon Stern, Keren Nevo-Dinur, Elazar Besser, Nikita Sarvin, Shoval Lagziel, Dzmitry Mukha, Shachar Raz, Elina Aizenshtein, Tomer Shlomi
Journal: Cell Metabolism (2020)
QOL-27. SWALLOWING ASSESSMENT IN PEDIATRIC PATIENTS WITH BRAIN TUMOR
Authors: Natalia Oliveira Machado, Ana Paula Duarte, Aline Azevedo dos Santos, Bruna Minniti Mançano, Carlos Almeida
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Neurosurgical intervention is the initial modality of treatment for the vast majority of pediatric brain tumors. However, studies on the swallowing process in pediatric patients with brain tumors are scarce, especially comparing changes that can be identified before and after surgery. In clinical practice, it is possible to observe that these patients may present modifications in the swallowing phases both before and after surgery. Therefore, we conducted a longitudinal study with a cohort of 20 patients ranging in age from 0 to 17 years, in order to characterize the swallowing disorders. RESULTS 30% of the patients presented some change in orofacial motricity in the organs related to initiation, coordination, and maintenance of swallowing at the time of hospital admission, and 65% of the patients exhibited these changes after surgery. Due to worsening in swallowing after surgery, 40% of the patients required modification of the consistence of oral diet or required the use of an alternative route of feeding. CONCLUSIONS There is a high prevalence of swallowing disorders in pediatric patients with brain tumors, mainly regarding the proper functioning of organs related to initiation, coordination, and maintenance of swallowing even before the surgical intervention, and these changes increase after surgery - especially in patients with posterior fossa tumors. The role of the speech/language pathologist is of paramount importance, given their role in the assessment and adequacy of the feeding route, identifying patients at risk of pulmonary aspirations, minimizing swallowing complications, and also facilitating communication with patients and their families.
Sam Simon Sebastian Gibbs
Authors: Lindsay Whittam, Jeremy Gibbs
Journal: BMJ (2020)

Sam Simon Sebastian Gibbs grew up in East Anglia with two other doctors in the family, his father a general physician and an older brother a neurologist. He studied medicine at Cambridge and the Middlesex Hospital in London. He subsequently spent six years working at Murgwanza missionary hospital in Ngara, Tanzania, before training in dermatology …
NIMG-41. VARIATION IN PERFUSION AND PERMEABILITY MRI DEPENDING ON VASCULAR INPUT FUNCTION SELECTION
Authors: Parandoush Abbasian, Lawrence Ryner, Jai Shankar, Marco Essig, Marshall Pitz
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND According to the updated RANO criteria, MRI contrast enhancement and peritumoral edema during the initial 12 weeks within the radiation field following chemoradiation may be pseudoprogression (PP) or true progression (TP). This ambiguity results in diagnostic uncertainty and delays in effective therapies. MRI perfusion and permeability imaging markers, including relative blood volume (rBV), and volume transfer constant (Ktrans), may be useful in differentiating PP from TP. Both techniques rely on identification of a vascular input function (VIF) to produce reliable output maps. METHODS Perfusion and permeability maps were acquired from 7 patients on a Siemens 3T Verio MRI as part of an ongoing prospective study on glioblastoma multiforme. Patients received standard surgical resection with concurrent chemo-radiotherapy treatment and MRI follow-up at one and every 2 months. Maps were based on the follow-up MRI. The 3D contrast enhancing lesion (CEL) was segmented from the T1-Post-Gd MRI. VIF pixels were identified in the internal carotid artery (ICA), the M2 segment of the middle cerebral artery (MCA2), the superior sagittal sinus (SSS), automatically using software (Olea Sphere 3.0.22), and auto-edited (removed pixels from the auto VIF definition that were outside the brain). RESULTS For the different VIF pixel selections (ICA, MCA2, SSS, Auto, Auto-edited), mean Ktrans values from CEL were 0.32, 0.48, 0.05, 0.09, 0.08, respectively, showing a 10-fold variation. Mean rBV values from CEL were 2.70, 2.36, N/A, 3.10, 3.19, respectively, showing a 1.3-fold variation. CONCLUSIONS VIF pixel selection is a critical step in generating reliable perfusion and permeability MRI maps. Variation of up to a factor of 10 in the Ktrans values, depending on VIF selection, was observed. SSS for the permeability VIF resulted in maps that most closely matched literature values, whereas perfusion imaging showed less sensitivity to VIF selection.