tbuckley/cabot-search huggingface dataset:
HOUT-08. COMORBID MEDICAL CONDITIONS AS PREDICTORS OF OVERALL SURVIVAL IN SURGICAL PATIENTS WITH GLIOBLASTOMA
Authors: Matthew Carr, Alper Dincer, Lakshmi Ravindra, Fan Zhang, Camille Hochheimer, Andrew Rock, Charles Opalak, Aravind Somasundaram, Kathryn Workman, Adam Sima, Hope Richard, William Broaddus
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is a common, fast-growing central nervous system tumor with poor prognosis. Survival from diagnosis to death is estimated to range from 7.2 to 26.6 months. Only a few predictors of survival have been well-established, including age, extent of resection (EOR), performance status, and MGMT status. Our objective was to determine whether demographic characteristics and comorbid medical conditions influence overall survival (OS) in surgical GBM patients. Data came from the Virginia Commonwealth University (VCU) Brain and Spine Tumor Data Registry, which collects retrospective information on all patients who presented to VCU Health with a CNS tumor between January 2005 and February 2015. Patients diagnosed with GBM who underwent surgery and/or biopsy were included in this study. Cox proportional hazards regression controlling for age, EOR, and tumor location was used to assess the relationship between OS and sex, race, insurance status, marital status, alcohol/tobacco use, initial tumor volume, and comorbidities. Individual analyses were performed for each predictor and those with p<0.15 were entered into multivariate models. There were 163 patients who met inclusion criteria. Mean OS was 10.6 months with a survival probability of 66% at 6 months, 46% at 12 months, and 21% at 24 months. After individual analysis, sex (HR: 1.37, 95% CI: 0.98–1.92, p=0.07) and history of asthma (HR: 2.04, CI: 0.98–4.28, p=0.06), hypercholesterolemia (HR: 1.69, CI: 0.95–3.01, p=0.07), and depression/anxiety (HR: 1.81, CI: 1.04–3.16, p=0.04) were included in the final model. In multivariate modeling, no demographic characteristics or comorbidities were significantly associated with OS. History of depression/anxiety was significantly associated with OS on individual analysis. However, this association did not remain significant in final multivariate modeling. The potential link between depression/anxiety and survival in GBM patients needs further evaluation in studies with greater power, given this could be amenable to intervention.
Abstract 225: Early Defibrillation, Mainly by Bystanders and First Responders, Associated with Higher Survival in Statewide Data
Authors: Carolina Malta Hansen, James G Jollis, Matthew Dupre, Bryan McNally, Lisa Monk, Clark Tyson, David A Pearson, R Darrell Nelson, Brent Myers, Christopher B Granger
Journal: Circulation (2014)

Objective: Early defibrillation is strongly associated with increased survival after out-of-hospital cardiac arrest. Statewide efforts to increase early defibrillation by bystanders and first responders were initiated in 2010. The aim of this study was to examine time to defibrillation (according to who defibrillated patients) and survival during 2010-2013 in North Carolina. Methods: Through the Cardiac Arrest Registry to Enhance Survival, we identified out-of-hospital cardiac arrests of presumed cardiac etiology and not witnessed by the Emergency Medical Services (EMS) during 2010-2013 in North Carolina. Only counties with complete data reporting were included in the analyses (n=12). Results: A total of 5114 cardiac arrests were identified. The median age was 66 years; 61.8% were men, 2297 (44.9%) were witnessed and 1155 (22.6%) had initial ventricular fibrillation or pulseless ventricular tachycardia. Bystanders and first responders initiated CPR in 2353 (46.1%) and 2065 (40.4%) of the cases, respective...
PDCT-13. PINEOBLASTOMA IN CHILDREN: THE HEAD START EXPERIENCE
Authors: Mohamed AbdelBaki, Mohammad Abu Arja, Zachary Funk, Joseph Stanek, Tom Davidson, Jason Fangusaro, Ira Dunkel, Girish Dhall, Sharon Gardner, Jonathan Finlay
Journal: Neuro-Oncology (2018)

Pineoblastoma is a rare malignant pineal region tumor, the optimal management of which in young children remains unclear. We report the outcomes of 23 children with pineoblastoma prospectively enrolled on three sequential Head Start (HS) trials between 1990 and 2009. The HS treatment strategy included maximal surgical resection followed by five cycles of intensive induction chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following recovery from consolidation was reserved for children over six years old or with residual tumor. Data on 23 children with pineoblastoma including two with trilateral retinoblastoma aged 0.44–5.72 (median 3.12) years were analyzed. Median overall survival (OS) was 12 months (95% CI: 7.6–29.7 months). The 3-year progression-free survival (PFS) and OS were 14.5% (95% CI: 5.1–41.2%) and 17.4% (95% CI: 7.1–42.4%), respectively. Three patients were long-term survivors beyond 5 years. Eight patients experienced progressive disease (PD) during induction chemotherapy, six following the fourth and fifth cycles. Ten patients proceeded to consolidation with HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation with boost(s) (median dose 20.7 (18–36) Gy), three patients as adjuvant therapy and four upon progression/recurrence. Favorable prognostic factors were administration of radiotherapy (hazard ratio (HR) for OS=0.30 (0.11–0.86), p<0.025), and undergoing HDCx/AuHCR (HR for OS=0.40 (0.16–0.99), p<0.047). There were no statistically significant associations between age, metastasis and extent of surgical resection and OS. CONCLUSIONS: Radiotherapy and HDCx/AuHCR were the sole driving factors for positive impact on survival. No benefit of high-dose methotrexate during induction was demonstrable. The high PD rate during later induction cycles as well as following consolidation chemotherapy warrant consideration of (1) fewer induction cycles prior to consolidation, (b) intensification of consolidation with multiple cycles of marrow-ablative chemotherapy and (c) judicious post-consolidation irradiation, in order to improve outcomes.
RTHP-22. RADIATION-INDUCED CENTRAL DEMYELINATION, A RARE SUBACUTE COMPLICATION IN 2 CASES
Authors: Christopher Trevino, Arnold Paulino, Jose Perez-Regadera, Juan Ruiz-Morales, Marta Penas-Prado
Journal: Neuro-Oncology (2018)

The mechanisms of neurotoxicity from radiation therapy include vascular injury, oxidative damage to neural stem cells and oligodendrocytes, and demyelination, though the pathophysiology is not fully understood. We present 2 cases of an unusual subacute complication of radiation treatment. Case 1: 40-year-old woman with right sided sensorineural hearing loss, progressive gait instability and paresthesias in the right hemiface, diagnosed with a right vestibular schwannoma and treated with surgical resection and fractionated stereotactic radiosurgery. She developed symptomatic central demyelination within the isodose curve of 10 Gy 2 months after radiation, which improved with steroids. Case 2: 26-year-old woman with a right frontal grade II astrocytoma, IDH1 mutant, ATRX loss, treated with resection and external beam radiotherapy (54 Gy in 30 fractions by VMAT). She developed left leg weakness, and MRI evidence of multifocal acute demyelinating lesions within the isodose curve of 10–30 Gy 10 weeks after completing radiation. She improved with high dose steroids and was subsequently able to resume adjuvant temozolomide. None of these 2 patients had a previous history of demyelinating disorder. The most frequent acute or subacute complications after radiation therapy are increased contrast enhancement and perilesional edema. Subacute demyelination is a rare entity with only a few cases described in the literature. No prior reported cases have been associated with treatment of vestibular schwannomas with stereotactic radiosurgery. Interestingly in both of the above cases, demyelination occurred within the lower isodose zone ranging from 10–30 Gy. subacute radiation induced demyelination is a rare complication in brain tumor patients that can be successfully managed with steroids. Demyelination should be on the differential diagnosis for new distant enhancing lesions following radiation in the primary brain tumor population.
Abstract 12002: Delayed Inhalation of Hydrogen Improves Myocardial dysfunction in a Porcine Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Zhengfei Yang, Tao Yu, Cai Wen, Xiaozhu Zhai, Mary Ann Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: Immediate inhalation of hydrogen (H 2 ) has been demonstrated to improve post-resuscitation (PR) myocardial dysfunction. In this study, we investigated the effects of delayed treatments with H 2 on myocardial dysfunction in a porcine model of cardiac arrest (CA). Hypothesis: Delayed inhalation of H 2 improves myocardial dysfunction after resuscitation in a CA porcine model. Methods: Twenty male pigs weighing 39±2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. All the animals were successfully resuscitated manually and then randomized into two groups: delayed inhalation of H 2 (DH group) or continuous inhalation of room air (C group). Animals in DH group were ventilated with 2% H 2 /21% oxygen from PR 2h till PR 4h. Left ventricle pressure (LVP) was recorded continuously and cardiac output (CO) was measured by the thermo-dilution technique at baseline (BL) and then hourly after resuscitation for 6 hours. Serum levels of troponin T (Tn T) and N-terminal probrain natriuretic peptide (NTpro-BNP) were measured by ELISA at BL, PR 180 min and PR 360 min. Results: Deteriorations in maximum rate of LVP increase (dp/dtmax), maximum rate of LVP decline (-dp/dtmax) and CO were observed in all the animals after PR 4 h (Figure 1). However, better dp/dtmax, -dp/dtmax and CO were achieved in the DH group after PR 5h when compared with the C group. Although levels of both Tn T and NTpro-BNP in serum increased after resuscitation, they were significantly lower in animals of DH group in comparison with C group (Figure 2). Conclusion: Delayed treatment of H 2 attenuates myocardial injury and improves myocardial dysfunction after resuscitation.
NCMP-16. RADIATION RECALL MYELITIS FOLLOWING PACLITAXEL CHEMOTHERAPY IN METASTATIC BREAST CANCER WITH PRIOR SPINAL STEREOTACTIC BODY RADIOTHERAPY: THE FIRST REPORTED CASE
Authors: Shearwood McClelland III, Paul Cooper, Anupama Acheson, Jeremy Ciporen, Jerry Jaboin, Timur Mitin
Journal: Neuro-Oncology (2018)

Stereotactic body radiotherapy (SBRT) of the spine has become an increasingly utilized modality in the United States, most commonly for metastatic disease (McClelland et al., 2017). Spinal SBRT in patients with spinal instrumentation has been sparsely examined. We report a patient who developed myelitis following spinal SBRT to a region with existing hardware. A 55-year-old woman with Stage IV breast cancer developed a T4 vertebral body metastasis and underwent tumor debulking with posteriorly instrumented T3-T5 fusion. Postoperatively she proceeded with SBRT to the T3-T5 vertebral bodies, receiving 30 Gy in 6 Gy/fraction. Six months later, she underwent palliative RT for a new right clavicle metastasis (20 Gy in 4 Gy/fraction). She subsequently required paclitaxel chemotherapy for new liver metastases. Seven months following spine SBRT, shortly after having started chemotherapy she developed intractable back pain and right lower extremity numbness which improved upon receiving steroids for weekly chemotherapy; the numbness subsequently spread to her left leg. Thoracic spine MRI revealed a 1.7 cm ovoid focus of T4-T5 spinal cord enhancement with extensive surrounding cord edema extending superiorly to C6-C7, consistent with radiation myelitis. Hyperbaric oxygen moderately improved her symptoms; fortunately, she never developed motor symptomatology or bowel/bladder dysfunction. Thorough re-evaluation of the original thoracic spine SBRT plan revealed no deviations from the standard of care, nor did re-planning with alternate treatment planning software demonstrate any significant difference in maximum cord dosage than the original plan. CONCLUSIONS: The timing of symptomatology related to chemotherapy administration is consistent with radiation recall myelitis, which has yet to be reported following SBRT. Given the potentially disastrous consequences of myelitis, patients with metastatic disease previously treated with spine SBRT may be susceptible to developing radiation recall myelitis if treated with paclitaxel chemotherapy.
Tenascin-C protects against acute kidney injury by recruiting Wnt ligands
Authors: Shuangqin Chen, Haiyan Fu, Songzhao Wu, Wenjuan Zhu, Jinlin Liao, Xue Hong, Jinhua Miao, Congwei Luo, Yongping Wang, Fan Fan Hou, Lili Zhou, Youhua Liu
Journal: Kidney International (2018)
Abstract 14077: Use of Cardiac Troponin I to Identify Acute Myocardial Infarction in Patients With Impaired Renal Function
Authors: Beatrice von Jeinsen, Stergios Tzikas, Lars Palapies, Tanja Zeller, Christoph Bickel, Karl J Lackner, Stephan Baldus, Stefan Blankenberg, Thomas Muenzel, Andreas M Zeiher, Till Keller
Journal: Circulation (2015)

Introduction: Cardiac troponins are the gold standard to diagnose acute myocardial infarction (AMI). Troponin I (TnI) levels are known to be increased in patients with chronic kidney disease (CKD) irrespective of an AMI. The established diagnostic TnI cut-off to detect AMI is calculated based on a healthy reference population and might not be representative for CKD patients. Hypothesis: The aim of this study was to investigate TnI levels in patients with and without CKD with suspected AMI and to calculate CKD- optimized diagnostic TnI thresholds. Methods: Of 1572 patients enrolled with suspected AMI, 266 patients showed an impaired renal function with estimated glomerular filtration rate (eGFR) of less then 60ml/min and were classified as patients with CKD. N=77 (34%) of patients with CKD and n=278 (24%) without CKD had the final diagnosis AMI. TnI was measured on admission and after 3h. Based on receiver operator characterics curve analyses (AUROC) of the baseline levels CKD optimized TnI threshold were derived. Sensitivity and specifity were calculated for the 99th percentile cut-off (30.0 pg/mL), the optimized cut-off (58.0 pg/mL) and the change in TnI concentration within 3h after admission. Results: Patients with CKD had higher TnI levels then patients without CKD (6.0pg/mL vs. 20.9pg/ml; p&lt;0.001). This difference was more pronounced in patients without AMI (median 9.1 vs. 4.4; p&lt;0.001), whereas the difference diminished in AMI patients (median 337.4 vs. 238.6; p=0.83). In CKD patients TnI remained a strong marker to detect AMI with AUROC of 0.933 compared to 0.969 in patients without CKD. Applying the 99th percentile threshold it was associated with a relevant loss of specificity in CKD patients with 80% compared to 96% in patients without CKD. This poor specificity could be regained by use of a higher CKD-optimized threshold or use of the change in TnI concentration within 3h leading to specificities of 90% and 96%, respectively. Conclusions: Patients presenting with suspected AMI and CKD have higher TnI levels on admission compared to patients without CKD leading to a low specificity detecting AMI in CKD patients. Using an CKD-optimized TnI cut-off level on admission or using the change in TnI concentration within 3h is able to regain this lost specificity.
Flexible traction method for endoscopic resection by using an endoscopic hand suturing technique
Authors: Osamu Goto, Motoki Sasaki, Teppei Akimoto, Mitsuru Kaise, Katsuhiko Iwakiri, Naohisa Yahagi
Journal: Endoscopy (2018)

In endoscopic resection, for example endoscopic submucosal dissection (ESD), optimal traction of the target lesion facilitates the subsequent procedure [1]. We devised a new traction method by using an endoscopic hand suturing (EHS) technique [2], in which a lesion is suspended by attaching it to the contralateral side using a barbed suture, and maintaining the traction force by inflating the tract or by pulling the needle side of the suture thread.
Abstract 17672: Myosin Binding Protein C Gene Mutation ( <i>S593Pfs*9</i> ) Induces Heart Failure and Reduced Ca Transient Amplitude in Zebrafish
Authors: Akiyoshi Ogimoto, Gabriel Musso, Andreas A Werdich, David A White, Manu E Beerens, Patrick Sips, Sunil Kapur, Micah L Burch, Ludmila M Flores, Jitsuo Higaki, Calum A MacRae
Journal: Circulation (2015)

Introduction: Mutations in the cardiac myosin-binding protein C ( MYBPC3 ) gene have been implicated in over one third of hypertrophic cardiomyopathy (HCM) cases. These mutations have been reported to be associated with delayed expression of hypertrophy and a relatively good prognosis. However, we previously reported that a patients with a S593Pfs*9 mutation (a single base deletion of a thymidine residue at nucleotide 11645 in exon 18) in this gene deteriorated into the“end-stage” HCM, characterized by left ventricular systolic dysfunction, cavity dilation, and heart failure. This mutation causes a truncated MYBPC3. The precise functional and pathological consequences of this mutation are not fully characterized. The aim of this study was to recapitulate the S593Pfs*9 mutation in the zebrafish to define the pathologic mechanisms. Methods: We used the CRISPR/Cas9 system to generate a genocopy of the S593Pfs*9 with a specific guide RNA injected with Cas9 into one-cell stage embryos. Results: Gross morphological examination of the mutants showed a smaller ventricle and pericardial edema compared with controls. There were significant reductions in heart rate (125 +/- 31 vs 148 +/- 9 /min), end-diastolic volume (EDV) (0.41 +/- 0.16 vs 0.72 +/- 0.18 nl), end-systolic volume (ESV) (0.24 +/- 0.08 vs 0.36 +/- 0.13 nl), stroke volume (SV) (0.16 +/- 0.12 vs 0.36 +/- 0.09 nl) in mutants compared with control embryos at 48 hours post fertilization (hpf). In addition, the calcium transient amplitude (0.17 +/- 0.02 vs 0.23 +/- 0.02 ratio units) was also significantly reduced in the mutant hearts compared with the control hearts at 48 hpf. Conclusions: Our data demonstrate that the S593Pfs*9 mutants exhibit reduced EDV, ESV, and SV and define early abnormalities of Ca 2+ handling that may drive the development of heart failure at later stages. This model will allow the mechanistic dissection of MYBPC-associated heart failure and enable chemical screens for novel drugs.
NCMP-25. SEIZURE INCIDENCE AND CONTRIBUTING FACTORS IN PATIENTS WITH LEPTOMENINGEAL DISEASE
Authors: Laura Zima, Sunil Tulpule, Kaeli Samson, Nicole Shonka
Journal: Neuro-Oncology (2018)

Seizures are a well-known complication of CNS malignancy, however there is little in the literature regarding leptomeningeal disease (LMD) and seizures. The incidence of seizures is unknown in this specific cohort as is the use or potential benefit of preventative anti-seizure medications (AEDs). Additionally, factors that might predispose LMD patients to seize or affect their survival are largely unexplored. Retrospective review of 79 patients with a diagnosis of LMD treated at a single institution from August 2012 to August 2017. Associations between categorical variables were tested using Fisher’s Exact tests. Differences in survival between groups were plotted with Kaplan Meier curves and tested using log-rank tests. All analyses were performed using SAS software. Seizure incidence in those with and without brain metastases was 22%. Of those who seized, 65% were admitted for this at least once while only one patient required intubation. Primary malignancy, type or route of chemotherapy administration, form of radiation therapy (craniospinal, focal, or whole brain), and number of brain metastases did not influence seizure development. Only 8% of patients who never had seizures were on a prophylactic AED. In patients who had brain metastasis, there was no significant difference in incidence of seizure before vs after LMD diagnosis suggesting that LMD does not significantly increase the risk of seizure compared to brain metastasis alone. There was additionally no significant difference in survival time between patients who did or did not seize. Median survival time of patients after LMD diagnosis was 4 months. The incidence of seizure in LMD patients is 22%. There were no statistically significant predisposing factors to seizure development. Additionally, the development of seizures does not affect survival in patients with LMD.
NIMG-53. REPEATABILITY OF O-(2-18F-FLUOROETHYL)-L-TYROSINE POSITRON EMISSION TOMOGRAPHY (FET-PET) SCANNING AND THE INFLUENCE OF PROTEIN INTAKE IN GLIOMA
Authors: Sarah Chehri, Otto Mølby Henriksen, Lisbeth Marner, Mette Christensen, Hans Poulsen, Ian Law
Journal: Neuro-Oncology (2018)

FET-PET scanning is used in routine clinical management and evaluation of glioma brain tumours. Clinical guidelines recommend fasting 4–6 hours before a FET-PET scan. Animal studies indicate that protein intake prior to the scan does not reduce FET-uptake in tumours, but there are no human studies published. Critical knowledge of test-retest variation of FET-PET imaging of glioma tumour volume as well as uptake and the impact of protein intake is sparse. AIM: This study investigated the repeatability of FET-PET scanning and the impact of protein-intake prior to FET-PET scanning of gliomas. MATERIALS AND 20 histologically confirmed glioma patients were included in this prospective study. Subjects were divided into two groups; no protein (NP, n=11) and protein (P, n=9). All subjects underwent two 40 min. dynamic FET-PET scans on a Siemens PET/CT scanner with an interval of maximum 7 days between each scan. Group P consumed 24g of protein (Nutricia Nutridrink Compact®) orally an hour before the second scan. Blood samples were drawn before and after protein intake for determining the plasma-amino-acid concentration. None of the patients were in treatment at the time of the scans. Volumes of interest were delineated on the 20–40 min 18F-FET PET acquisition co-registered to contrast enhanced T1-weighted MRI. The two scans were compared by calculating the absolute change between healthy appearing cortex (B), the maximal and the mean tumour uptake normalized to B (Tmax/B; Tmean/B) and by measuring the biological tumour volume (BTV) defined as uptake above 1.6 mL of mean in healthy appearing brain. The absolute change in FET tumour metrics, mean (range) Tmax/B: NP=0.12[-0.11;0.52] P=0.16[-0.11;0.82] Tmean/B: NP=0.20[-0.06; 2.00] P=0.06[-0.03;0.22] BTV(mL): NP=0.76[-1.50;3.30] P=2.59[-0.02; 12.0] All results were non-significant, p-value > 0.05 Tumour day-to-day variation might be greater than first anticipated. Updated results will be presented.