tbuckley/cabot-search huggingface dataset:
P12.26 Outcomes analysis of malignant meningioma (WHO III) patients from a single institution
Authors: G. H. Stevens, M. Sharma
Journal: Neuro-Oncology (2017)

Purpose: To retrospectively analyze and assess the outcomes and prognostic factors in patients with malignant meningioma (WHO Grade III). Materials/Methods: Clinical data and outcome (overall (OS) and recurrence-free (RFS) survival) from 18 patients with Grade III meningioma (MM, based on World Health Organization 2007 definition) initially treated between March 2000 and June 2015 were analyzed. 61% (11/18) of patients were male, median age at diagnosis was 63 (range 48-86), and 55% (10/18 patients) had good performance status (KPS≥80). 7 patients (39%) had lower grade disease (grade I - n=2; grade II - n=5) 6.7-218.2 months prior to diagnosis of MM (median 29.2 months). A total of 26 surgeries were performed (18 primary and 8 salvage). Also, 37 courses of radiotherapy (RT) were performed, including fractionated RT in 10 patients after primary surgery, salvage fractionated RT in 8 patients, stereotactic radiosurgery (SRS) boost along with primary RT in 1 patient and salvage SRS to 18 separate areas in 8 patients. Salvage chemotherapy was mainly considered in third or fourth recurrences. Results: 13 (72%) patients recurred and 11 (61%) have died. Follow-up for the 7 patients still being followed ranges from 5.0-75.4 months (median 38.5). The median time to recurrence was 14.5 months (95% C.I. 6.9-22.2). The 5-year survival rate was 36%± 14% and median OS was 55.8 months (95% C.I. 23.7-80.3). Of all factors, only performance status (KPS) affected outcome (RFS p=.0003; OS p=.002). CONCLUSION: Our results though consistent with existing reports of the overall poor outcomes for MM patients, shows a better median OS of 4.6 years compared to 3.4 years reported earlier from our institution. From the available data, surgical resection followed by RT and salvage radiosurgery and/or chemotherapy can lead to extended survival; however the benefit may decrease with successive treatments.
Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients
Authors: Javier M Figueroa, Johan Skog, Johnny Akers, Hongying Li, Ricardo Komotar, Randy Jensen, Florian Ringel, Isaac Yang, Steven Kalkanis, Reid Thompson, Lori LoGuidice, Emily Berghoff, Andrew Parsa, Linda Liau, William Curry, Daniel Cahill, Chetan Bettegowda, Frederick F Lang, E Antonio Chiocca, John Henson, Ryan Kim, Xandra Breakefield, Clark Chen, Karen Messer, Fred Hochberg, Bob S Carter
Journal: Neuro-Oncology (2017)

RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-associated amplifications and mutations in epidermal growth factor receptor (EGFR).CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs.EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM.Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.
P08.50 Epithelial growth factor receptor expression influences 5-ALA glioblastoma induced fluorescence
Authors: M. M. Reinert, D. Piffaretti, F. Marchi, F. Burgio, A. Faia-Torres, P. Paganetti, U. Pieles, A. O. Fontana
Journal: Neuro-Oncology (2017)

BACKGROUND: The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in glioma surgery. Although the intensity of the 5-ALA induced fluorescence has been described to vary in confirmed glioma, the detection method is currently subjective and non-quantitative. We correlated 5-ALA induced fluorescence with the quantitative expression of Epithelial Growth Factor Receptor (EGFR) in different glioblastoma (GBM) cell lines. METHODS: To elucidate the role of EGFR in the metabolism of 5-ALA in (U87MG and BS153), we analyzed the activation of EGFR by its primary ligand EGF, and its downstream effect on Heme oxygenase-1 (HO-1), a key enzyme regulating the metabolism of Protoporphyrin IX (PpIX), the fluorescent metabolite of 5-ALA. Effects of direct pharmacological inhibition by Tin(IV)-Protoporphyrin (SnPP) or gene knockdown by small interfering RNA on HO-1 enzyme were analyzed in respect to 5-ALA induced fluorescence. Results: A significant difference in 5-ALA induced fluorescence was obtained in U87MG compared to BS153 cell lines, correlating with the different quantitative EGFR expression. Treatment of U87MG cells with EGF was able to promote HO-1 transcription and expression in a concentration-dependent manner, leading to a reduced cellular fluorescence. This effect could be reversed by EGFR-specific siRNA treatment. Reducing HO-1 activity by SnPP or HO-1-specific siRNA significantly enhanced fluorescence, independently of EGFR quantitative expression. CONCLUSION: EGF-induced HO-1 protein expression was identified as a negative regulator of 5-ALA induced fluorescence, thus dependent of EGFR expression. These findings justify the clinical observation of different intensities of 5-ALA induced fluorescence in glioblastoma surgery.
A Day in the Life: NICU Medical Director Tends to Infants With Neonatal Abstinence Syndrome
Authors: Jennifer Abbasi
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 298: Diastolic Dysfunction Predicts Remodeling in Mice Following Transverse Aortic Constriction: A Potential Model of Heart Failure with Preserved Ejection Fraction
Authors: Julie A Garry, Gregory Shearer, Timothy D O’Connell
Journal: Circulation Research (2013)

Heart failure (HF) secondary to hypertensive heart disease typically presents as heart failure with preserved ejection fraction (HFPEF), which now accounts for nearly half of all HF diagnoses. HFPEF pathology is characterized by interstitial fibrosis leading to ventricular stiffness, diastolic dysfunction, and ultimately HF. Clinically HFPEF is a significant problem, as standard HF therapies, which target heart failure with reduced ejection fraction, are ineffective in HFPEF. A major challenge to developing new therapies for HFPEF is the lack of an animal model. In mice, although transverse aortic constriction (TAC) induces significant systolic dysfunction, it produces ventricular remodeling similar to chronic, untreated hypertension, which is associated with concentric hypertrophy, interstitial fibrosis, and diastolic dysfunction. Here, we examined pathologic remodeling and ventricular dysfunction following TAC in mice to determine what factors drive remodeling. TAC mice developed significant hypertrophy after 4 weeks (HW/BW, TAC: 7.2±0.4, n=13; Sham: 4.5±0.2, n=3; P&lt;0.05 and Myocyte Area, TAC: 317±88μm2, n=13; Sham: 193±111μm2, n=3, P&lt;0.05). However, TAC mice varied in extent of fibrotic response. Four mice showed minimal fibrotic response (1.47±0.28% of total ventricular area), five developed only perivascular fibrosis (6.87±1.02%), and four developed perivascular and interstitial fibrosis (29.95±5.81%). At four weeks post-surgery, TAC mice developed systolic dysfunction, indicated by reduced EF (TAC: 47±1%, n=13; Sham: 66±2%, n=3 P&lt;0.05) and diastolic dysfunction, indicated by increased E/E’ (TAC: 44.9±4.5, n=13; Sham: 24.8±3.5, n=3; P&lt;0.05). Interestingly, pathologic remodeling following TAC, both hypertrophy and fibrosis, correlated with E/E’ at week 4 (HW/BW: R2=0.343, P=0.036; Fibrosis: R2=0.517, P=0.008), but not EF (P=NS for both). The data suggest that pathologic remodeling following TAC was driven by diastolic dysfunction and interstitial fibrosis, not systolic dysfunction, indicating TAC induced HF might have more similarities to HFPEF than previously recognized.
Abstract 17995: NT-proBNP Predicts Myocardial Damage and Correlates With Stem Cell Mobilization in Patients With ST-Eelevation Myocardial Infarction
Authors: Ahmed Asfour, Steve Leung, Mohammad F Mathbout, Yuri M Klyachkin, Ahmed Abdel-Latif, Khaled Ziada
Journal: Circulation (2015)

Introduction: N-Terminal prohormone of brain natriuretic peptide (NT-proBNP) is released from cardiomyocytes during injury. However, the relationship between plasma levels, extent of myocardial damage and its correlation with bone marrow stem cell (BMSC) mobilization are poorly understood. Methods: Plasma levels of NT-proBNP (pg/ml), troponin I (ng/ml) and CK (IU/L) were assessed in 76 patients with ST-elevation myocardial infarction (STEMI) at baseline (time of successful primary percutaneous intervention) then at 6, 12, 24, and 48-hour intervals. Levels of circulating Lin-/CD45- cells that are positive for CXCR4, CD34 and CD133 (BMSCs) were examined at the same time points using flow cytometry. Echocardiography and cardiac MRI (CMR) were performed prior to hospital discharge for assessment of cardiac function and scar size. Extent of myocardial damage was quantified using peak biomarker levels and gadolinium enhancement on CMR. Results: Patients characteristics were consistent with the typical demographics for STEMI population (Panel A). Plasma levels of NT-proBNP increased steadily following STEMI to peak at 24 hours (Panel B). Peak NT-proBNP levels correlated positively with indices of myocardial damage such as peak troponin I (r=0.6, P&lt;0.001), peak CK (r=0.3, P=0.04) and late gadolinium enhancement on CMR examination (r=0.54, P=0.02) (Panels C-E). NT-proBNP levels correlated negatively with left ventricular ejection fraction and volume on echocardiography and CMR. There was strong correlation between peak NT-proBNP levels and peak numbers of circulating BMSCs such as Lin-/CD45-/CXCR4+ BMSCs (r=0.6, P&lt;0.001) (Panel F). Conclusion: Peak levels of NT-proBNP following STEMI are predictive of the extent of myocardial damage quantified by cardiac biomarkers or CMR. NT-proBNP levels are also associated with the extent of BMSC release, raising the possibility that it has a role in initiating the myocardial reparative process following STEMI.
P01.26 rs489693 Melacortin receptor gene polymorphism is associated with the progression-free survival of glioblastoma patients treated with concomitant radio-chemotherapy
Authors: M. Cantarella, A. Gonnelli, A. Molinari, P. Orlandi, T. Di Desiderio, V. Simeon, G. Lombardi, F. Pasqualetti, F. Paiar, G. Bocci
Journal: Neuro-Oncology (2017)
Association Between <i>SLC16A5</i> Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer
Authors: Britt I. Drögemöller, Jose G. Monzon, Amit P. Bhavsar, Adrienne E. Borrie, Beth Brooks, Galen E. B. Wright, Geoffrey Liu, Daniel J. Renouf, Christian K. Kollmannsberger, Philippe L. Bedard, Folefac Aminkeng, Ursula Amstutz, Claudette A. Hildebrand, Erandika P. Gunaretnam, Carol Critchley, Zhuo Chen, Liam R. Brunham, Michael R. Hayden, Colin J. D. Ross, Karen A. Gelmon, Bruce C. Carleton
Journal: JAMA Oncology (2017)

Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects.To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients.This retrospective study was performed by the Canadian Pharmacogenomics Network for Drug Safety using patients recruited from 5 adult oncology treatment centers across Canada. Male patients who were 17 years or older, diagnosed with germ cell testicular cancer, and previously treated with cisplatin-based chemotherapy were recruited from July 2009 to April 2013 using active surveillance methodology. Cisplatin-induced ototoxic effects were independently diagnosed by 2 audiologists. Patients were genotyped for 7907 variants using a custom pharmacogenomic array. Logistic regression was used to identify genetic variants that were significantly associated with ototoxic effects. The validity of these findings was confirmed through independent replication and cell-based functional assays.Cisplatin-based chemotherapy.Cisplatin-induced ototoxic effects.After exclusions, 188 patients (median [interquartile range] age, 31 [24-39] years) were enrolled in this study to form the discovery and replication cohorts. Association and fine-mapping analyses identified a protein-coding variant, rs4788863 in SLC16A5, that was associated with protection against cisplatin-induced ototoxic effects in 2 independent cohorts (combined cohort: odds ratio, 0.06; 95% CI, 0.02-0.22; P = 2.17 × 10-7). Functional validation of this transporter gene revealed that in vitro SLC16A5-silencing altered cellular responses to cisplatin treatment, supporting a role for SLC16A5 in the development of cisplatin-induced ototoxic effects. These results were further supported by the literature, which provided confirmatory evidence for the role that SLC16A5 plays in hearing.This study has identified a novel association between protein-coding variation in SLC16A5 and cisplatin-induced ototoxic effects. These findings have provided insight into the molecular mechanisms of this adverse drug reaction in adult patients with germ cell testicular cancer. Given that previous studies have shown that cimetidine, an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the findings from this study have important implications for otoprotectant strategies in humans.
OS01.1 Identification of the pre-malignant cell of origin in Human Glioblastoma Multiforme
Authors: S. S. Mitra, S. Gholamin
Journal: Neuro-Oncology (2017)

One of the major difficulties in identifying the cell of origin for glioblastoma is the complex cellular composition of this disease. It is now hypothesized that the different subtypes of high-grade glioma may have different cell of origin and in mouse models it has been shown that the cell of origin resides within the progenitor populations. To identify the cell of origin in human GBM we decided to first dissect out the various stages of CNS stem cell differentiation in fetal and adult human brain. After a functional high throughput screen, we identified a panel of four antibodies (i.e CD15, Notch1, EGFR, and CD90) that in various combinations can separate long-term self-renewing multi-potent neural stem cells (NSCs: Lin-CD15+Notch1+EGFR-CD90-) from multi-potent progenitors with limited self-renewal capacity (NPC: Lin-CD15+Notch1+EGFR+CD90+) from non-neoplastic human fetal and adult Brain (sub-ventricular zone). FACS sorted cells were analyzed for single cell lineage multi-potentiality, lineage bias and self-renewal to trace and characterize their lineage relationships. In surgical human glioblastoma samples, however we observed in-vivo tumor initiating and in-vitro tumorsphere-forming frequency was predominant in the progenitor cells and not in the neural stem cells. Interestingly we did observe a small frequency of NSC cells forming distinct lesions in the brain, which on further analysis showed the presence of both the neural stem cells and Glioma stem cells, where as the tumor initiating enriched population (GSC: Lin-CD15+Notch1+EGFR-CD90-) did not show the presence of neural stem cells but only tumor initiating NPCs. In-vivo limiting dilution transplantation and serial transplantation confirmed the Lin-CD15+Notch1+EGFR-CD90- to have the highest frequency of self renewing cells compared to other populations. Taken together our data suggests the presence of “normal” or pre-malignant stem cells in glioblastoma, which suggests a possible mechanism of relapse. Using Transcriptome analysis and targeted sequencing of known mutations we identify the signal transduction and genomic events (PTEN point mutations vs Deletions) which distinguish pre-malignant neural stem cells from the tumor initiating glioma stem cells. We further show a significant enrichment of the protein translational machinery as cells transition from pre-malignant to tumor initiating cells. These pre-malignant cells comprise a cellular reservoir that needs to be targeted to prevent tumor relapse. Grants: SSM: Seibel Fellowship and Ludwig Cancer Center, ILW: National Institutes of Health, Ludwig Cancer Center, SHC: Stanford Child Health Research Institute, St Baldrick’s Foundation and Ludwig Cancer Center
Single IRBs in Multisite Trials
Authors: Robert Klitzman, Ekaterina Pivovarova, Charles W. Lidz
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Deregulated Expression of Long Non-Coding RNAs UCA1, NEAT1 and BDNF-As in Multiple Myeloma
Authors: Lenka Sedlarikova, Barbora Gromesova, Jana Filipova, Veronika Kubaczkova, Lenka Radova, Martina Almasi, Miroslav Penka, Zdenek Adam, Ludek Pour, Marta Krejci, Sabina Sevcikova, Roman Hajek
Journal: Blood (2016)
A More Common Massive Retroperitoneal Mass
Authors: Brock O’Neil, Benjamin Maughan
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
P17.04 Gamma knife surgery for Cavernous sinus cavernous hemangioma - comparative results to surgery and radiation therapy
Authors: J. Cho, K. Sung, W. Chang, H. Jung, K. Lee, Y. Park, J. Chang
Journal: Neuro-Oncology (2017)

Objectives: Cavernous hemangiomas occur very rarely in the cavernous sinus. These lesions share the same histologic features as intracerebral lesions, but their clinical picture is quite different. The objectives of this study are to evaluate the efficacy of Gamma Knife Surgery (GKS) on cavernous sinus cavernous hemangiomas (CSCHs) and to compare the results of GKS to those of surgical treatment and fractionated radiation therapy (FRT). Methods: Before 2000, we operated 7 cases of CSCHs. We have performed GKS for 26 cases and FRT for 4 cases since 2000. Among 26 cases that were treated by GKS, two patients were performed other treatment before GKS (surgery and FRT). Thirteen patients were diagnosed incidentally during the work up of other reason such as headache or head trauma. Most common symptom was cranial nerve palsy (ptosis, diplopia and facial sense change) in 12 cases. Results: Of 7 surgically treated cases, 4 patients had already had extraocular muscle palsy preoperatively. Gross total resection (GTR) was achieved using extradural approach in all 7 cases and there has been no tumor recurrence during follow up. However, 2 new trigeminal nerve deficits developed after operation. FRT was performed for 4 cases, usually large ones. All 4 tumors were well controlled, however, symptomatic radiation necrosis was developed at brainstem in 1 case. Twenty-six patients were treated by GKS. The mean tumor volume was 9.7 cm3 (range 0.5-31.6). The prescription dose to the tumor margin varied from 13 to 15 Gy by the proximity to the optic pathway. The mean follow up period was 46.1 months (range 11.1-131.1). Eleven patients showed marked clinical improvement within 3 months. All the cases showed significant shrinkage of the tumors was noted within 6 months and 11 patients had complete remission at the last follow up (34%). Mean residual volume comparing to pre-GKS initial volume was 20.8% (range 0-70%). There was no complication related to GKS during their follow up. Conclusion: Even though surgical resection for CSCHs is curative treatment, it is not always easy and safe. Because of the radiosensitive nature of CSCHs, FRT could be another treatment option in case of large CSCHs, but it has potential radiation-related risk. GKS is an effective and safe treatment modality and could be a treatment of choice for CSCHs.