tbuckley/cabot-search huggingface dataset:
HOUT-25. HOSPITAL ACQUIRED CONDITIONS (HACs): PREDICTORS AND IMPLICATIONS FOR OUTCOMES FOLLOWING SPINE TUMOR RESECTION
Authors: Nikita Lakomkin, Constantinos Hadjipanayis
Journal: Neuro-Oncology (2017)

Hospital acquired conditions (HACs) significantly compromise patient safety and have been identified by policy makers as events that will be associated with penalties for providers. The mitigation of HACs, which are defined as provider-preventable complications spanning wound infection, venous thromboembolism, and urinary tract infection, must be an important consideration in the postoperative management of patients undergoing spine tumor resection. The purpose of this study was to identify the risk factors for HACs and characterize the relationship between HACs and other postoperative adverse events following resection. The 2008-2014 National Surgical Quality Improvement (NSQIP) database was used to identify adult patients undergoing the surgical resection of intramedullary, intradural extramedullary, and extradural spine lesions via CPT and ICD-9 codes. Demographic, comorbidity, and operative variables were evaluated via bivariate statistics before being incorporated into a multivariable logistic regression model to identify the independent risk factors for HACs. Associations between HACs and other postoperative events, including death, readmission, prolonged length of stay (LOS), and various complications were determined through multivariable analysis while controlling for other significant variables. The c-statistic was computed to evaluate the predictive capacity of the regression models. Of the 2,170 patients included in the study, 195 (9.0%) developed a HAC. Only two perioperative variables, functional dependency and high BMI, were risk factors for developing HACs (AUC=0.654). HACs were independent predictors of all examined outcomes and complications, including death (OR: 2.26, 95%CI:1.24-4.11, P=0.007), prolonged LOS (OR: 2.74, 95%CI: 1.98-3.80, P<0.001), and readmission (OR:9.16, 95%CI:6.27-13.37, P<0.001). The AUCs for these models ranged from 0.750 to 0.917. HACs may be influenced by hospital-associated factors, rather than perioperative comorbidities, and were found to be risk factors for a variety of adverse events. These findings highlight the need for continued development of evidence-based protocols designed to reduce the incidence and severity of HACs.
TMIC-15. CHD7 IS SUPPRESSED IN THE PERINECROTIC/ISCHEMIC MICROENVIRONMENT AND IS A NOVEL REGULATOR OF ANGIOGENESIS
Authors: Nathaniel Boyd, Kiera Walker, James Mobley, James Hackney, Kai Jiao, Eli E Bar, Anita Hjelmeland
Journal: Neuro-Oncology (2017)

The ischemic microenvironment characterized by low oxygen and glucose due to poor blood supply occurs in both solid tumors and non-neoplastic tissue injury. Ischemia occurs in regions of pseudopalisading necrosis, a hallmark of the most common and deadly primary brain tumor in adults, glioblastoma. Modeling physiologic low oxygen and glucose in glioblastoma in vitro, we identified chromodomain helicase DNA binding protein 7 (CHD7) as a novel ischemia-regulated gene. CHD7 is an epigenetic modifier regulating neural stem cell maintenance and mutated in CHARGE syndrome, a developmental disorder associated with cranial nerve abnormalities. Microenvironment-mediated decreases in CHD7 protein and mRNA levels were observed in glioblastoma and neural progenitor cells in vitro, and CHD7 levels were reduced in the perinecrotic niche of GBM patient and xenograft sections. Genetic targeting of CHD7 increased angiogenesis in vitro in association with differential regulation of angiogenesis associated genes as determined in RNA sequencing analysis. Further suggesting the importance of CHD7 levels in glioblastoma, patient gene expression datasets show a correlation between down regulation of CHD7 and increasing glioma grade and worse patient outcomes. Together, our data provide insight into the molecular responses to ischemia that regulate angiogenesis.
P1.13-008 Evaluation of Clinical Associated Factors for Lung Adenocarcinoma by TNM 8th Edition with Unexpected N2 disease
Authors: Y. Kidokoro, T. Haruki, W. Fujiwara, T. Ohno, K. Hosoya, Y. Kubouchi, M. Wakahara, Y. Yurugi, Y. Takagi, K. Miwa, K. Araki, Y. Taniguchi, H. Nakamura
Journal: Journal of Thoracic Oncology (2017)
Owen Morris Jonathan
Authors: David Jonathan
Journal: BMJ (2017)

Owen Morris Jonathan was born in Bodedern, Anglesey, to Owen Arthur and Hanna Esther Jonathan. His mother’s family were Anglesey farmers, but he was brought up in Tywyn, Merionethshire, where his father was the proprietor of a well known haberdashery and general store, as well as being chairman of Merionethshire County Council.

Mr Jonathan was educated at what was originally called Tywyn Intermediate School (now Ysgol Uwchradd Tywyn) and then, after matriculating, at Aberystwyth University, where he completed his first MB before moving on to Guy’s Hospital, from which he qualified in 1942. He then gained his commission in the Royal Army Medical Corps and, after training in Northern Ireland …
Recherche de Trichinella dans la viande (porc, viande chevaline et gibier) dans l’UE : les techniques disponibles et leur mise en œuvre actuelle
Authors: P Webster, C Maddox-Hyttel, K Nöckler, A Malakauskas, J van der Giessen, E Pozio, P Boireau, C M O Kapel
Journal: Eurosurveillance (2006)

Une nouvelle directive de l’UE portant sur la recherche de Trichinella dans la viande, qui devrait entrer en vigueur en 2006, impose des modifications importantes a la legislation actuelle. Cependant, plusieurs questions appellent une attention particuliere. Une optimisation des methodes, en particulier en termes de sensibilite et de digestibilite de la viande a controler, ainsi qu’une simplification de la legislation quant au nombre de techniques acceptees sont recommandees, afin de garantir que tous les Etats membres de l’UE disposent du meme niveau technique necessaire a l’inspection de la viande de consommation. De plus, des recommandations et des protocoles sont indispensables pour optimiser les procedures d’analyses. Cet article presente une vue d’ensemble des methodes utilisees actuellement pour la recherche de Trichinella dans la viande, et de leur mise en place dans l’UE, et donne les avantages et les inconvenients de chaque methode decrite, en y ajoutant quelques suggestions pour des ameliorations sur des points specifiques.
CMET-39. IMPACT OF CEREBROSPINAL FLUID SHUNTING ON SURVIVAL IN PATIENTS WITH HYDROCEPHALUS RELATED TO LEPTOMENINGEAL METASTASIS
Authors: Koichi Mitsuya, Shouichi Deguchi, Nakamasa Hayashi, Yoko Nakasu
Journal: Neuro-Oncology (2017)

Management of leptomeningeal metastasis related hydrocephalus (LM-H) is particularly challenging to control devastating symptoms by intracranial hypertension. We analyzed the outcome in patients with LM-H surgically treated on the basis of multidisciplinary team since 2007. The authors reviewed 49 patients with LM-H required CSF shunting between October 2007 and May 2017. CSF shunting was indicated when a patient had (1) controlled extra-CNS metastases and (2) systemic life expectancy longer than three months after control of LM-H. The patients underwent either ventriculo-peritoneal or lumbo-peritoneal shunting. The outcomes were analyzed with Kaplan-Meier estimates. The patients consisted of 33 women and 16 men with a median age of 58 years (range 35–76). Primary cancers were lung in 31, breast in 9, gastric in 6, and cholangiocarcinoma, pharyngeal and unknown origin in one each. Twenty-one patients underwent whole brain radiotherapy (43%), nine craniospinal irradiation (18%), and 26 (53%) systemic chemotherapy after CSF shunting. CSF shunt surgery yielded an immediate improvement of their performance status (PS) in 95% of patients. There was a statistically significant difference between PS at diagnosis of LM-H and that after CSF shunting (p<0.0001, Wilcoxon signed-rank test). The median overall survival (OS) was 4.5 months from the diagnosis of LM-H. Age, PS at diagnosis of LM-H, and maintenance chemotherapy after shunt surgery were significant prognostic factors for OS in univariate analysis using log-rank test. Age and PS at diagnosis of LM-H were significant prognostic factors for overall survival in multivariate analysis by Cox regression analysis. Post-surgical complications were infection and shunt malfunction in one each and symptomatic peritoneal dissemination in two patients. CSF shunting is a safe and effective strategy for patients with LM-H. Further clinical investigations are needed to clarify appropriate assessments and surgical indication for patients with LM-H.
P3.01-042 Efficacy &amp; Tolerability of Afatinib in NSCLC Patients Prior Exposure to 1st Generation EGFR TKI: Thailand Multicenter Study
Authors: T. Reungwetwattana, S. Laohavinij, W. Lamlertthon, B. Chewaskulyong, A. Dechaphunkul, S. Detarkom, D. Muntham, N. Poovorawan, V. Srimuninnimit, V. Sriuranpong
Journal: Journal of Thoracic Oncology (2017)
A melanin-mediated cancer immunotherapy patch
Authors: Yanqi Ye, Chao Wang, Xudong Zhang, Quanyin Hu, Yuqi Zhang, Qi Liu, Di Wen, Joshua Milligan, Adriano Bellotti, Leaf Huang, Gianpietro Dotti, Zhen Gu
Journal: Science Immunology (2017)

Transdermal microneedle patch integrated with whole tumor lysate containing melanin facilitates cancer immunotherapy upon near-infrared light irradiation.
TMIC-17. THE ROLE OF TUMOR-ASSOCIATED MACROPHAGES IN A MURINE SONIC HEDGEHOG MEDULLOBLASTOMA MODEL
Authors: Victor Maximov, Zhihong Chen, Yun Wei, M Hope Robinson, Dolores Hambardzumyan, Anna Kenney
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB), the most common pediatric brain tumor, has a 70% survival rate but standard treatments often lead to devastating life-long side effects, and recurrence is fatal. MB was classified based on molecular and genetic profiles and resulted in four distinct subgroups. The most common subclass of MB is SHH, which accounts for approximately 30% of cases. This class has been successfully modeled in vivo in murine models, which closely recapitulate human disease, providing a convenient and relevant model system for analyzing the SHH MB subclass in vivo. To better understand the mechanisms of tumor growth and recurrence, recent attention has been focused on determining the composition and role of non-tumor cells comprising the tumor microenvironment (TME). Tumor-associated macrophages (TAM) are a key component of the TME that could have two opposite effects on tumor. TAMs can help tumors to evade the immune system by suppressing other immune cell functions, and contribute to tumor growth by promoting angiogenesis. On the other hand, they could suppress tumor growth and delay tumor development. Recently, it was reported that of the subgroups, human SHH MB has the greatest number of TAMs, as well as increased expression of macrophage-associated genes. However, to date, there are no studies addressing the functional role of TAMs in SHH MB. In this work, we demonstrate a functional role of TAMs in both in vitro and in vivo models. We show that reduction of macrophage numbers leads to increased animal mortality in a murine model of SHH MB. Further investigation of the TME and TAMs in MB has the potential to elucidate immune system involvement in the disease and lead to development of novel treatment options.
NIMG-16. IMAGING PREFERENCES IN LOW-GRADE GLIOMAS - RESULTS OF A MULTINATIONAL SURVEY
Authors: Christian Freyschlag, Sandro M Krieg, Johannes Kerschbaumer, Emmanuel Mandonnet, Claudius Thomé
Journal: Neuro-Oncology (2017)

Despite recent advances in surgery, chemo- and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, is the first line of treatment. Apart from surgery, all other treatment modalities are handled very differently among different teams. Additionally, imaging of low-grade gliomas is a field of great variety throughout different centers. We aimed to obtain data on imaging in LGG, in order to identify a “minimal core of imaging” that is performed in every participating center. We carried out a survey among centers in Europe, sent through channels of the European Association of Neurosurgical Societies (EANS), the German and Austrian National Society (DGNC and OEGNC) and the ELGGN representing a multidisciplinary society. The online survey consisted of 38 items in total and took place in March and April 2017, during that time, 140 complete surveys were received. Descriptive analysis of results was performed. Of all centers submitting the survey, 73% were academic. Nearly half (46%) of the centers maintain a dedicated LGG-program in their practice. The annual amount of LGG-cases treated differed between 10 and 200. The heterogeneity of imaging protocols showed that 50% of centers are willing to use any recently performed MRI, whereas only 31% scan their own MRI protocol in patients with LGG. The results showed that only 36% of centers involved performed PET scans in patients with suspected LGG and 80% of centers relied on MRI to assess treatment response and progression. Further data obtained on treatment response showed that 41% of centers performed a linear measurements, whereas only 33% perform volumetric analysis. We could depict a minimal core of imaging, consisting of several MRI sequences, that will serve as foundation for future trials of treatment response and surgical accuracy.
P3.12-003 Optimized Inhaler Therapy Is Superior to Supportive Care Alone for Dyspnea in Patients with Coexisting COPD and Lung Cancer
Authors: D. Walder, R. Punwani, R. Gunapala, R. Kumar, A. Minchom, J. Bhosle, S. Popat, N. Yousaf, M. O’Brien
Journal: Journal of Thoracic Oncology (2017)
P2.14-002 Impact of Pre-Existing Cardiac Disease and Heart Doses on Survival in NSCLC Treated with Post-Operative Thoracic Radiotherapy
Authors: C.C. Lee, H. Zheng, Y.Y. Soon, B. Vellayappan, W.Y. Koh, C.N. Leong, J. Tey, I. Tham
Journal: Journal of Thoracic Oncology (2017)
Metformin and risk recurrence in resected stage II/III colon cancer (CC) patients (pts): subgroup analysis from the TOSCA trial
Authors: M. Di Bartolomeo, G. Rosato, M. Banzi, N. Pella, M.G. Zampino, L. Rimassa, E. Maiello, P. Marchetti, S. Lonardi, R. Labianca, A. Zaniboni, A. Sobrero, D. Ferrari, P. Bidoli, V. Iaffaioli, S. De Placido, L. Frassineti, S. Frustaci, M. Nicolini, C. Vernieri, F. Galli
Journal: Annals of Oncology (2017)
EXTH-01. ZIKA VIRUS TARGETING OF MALIGNANT HUMAN AND MURINE BRAIN TUMORS
Authors: Maple Shiao, Craig Bierle, Matthew Chrostek, Andrew Crane, Georgette Danczyk, Zach Miller, Clairice Pearce, Kyle Schaible, Mark Schleiss, Christopher Sipe, Elizabeth Straub, Nikolas Toman, Shivanshi Vaid, Joseph Voth, Walter Low
Journal: Neuro-Oncology (2017)

Previous studies have demonstrated that the tropism of Zika virus (ZIKV) for human neural stem cells (NSCs) leads to severe brain malformations. The proposed mechanisms underlying these brain malformations are thought to include the induction of apoptosis in neural progenitor/stem cells (Zhang et al., Nucleic Acid Res. 44:8610–8620, 2016). Previously, we observed many similarities between NSCs and brain tumor stem cells (BTSCs) (Wu et al., Stem Cells Dev., 17:173–184, 2008) and sought to determine if BTSC could support ZIKV replication. ZIKV infection of skin cells in vitro is mediated by the receptors AXL, DC-SIGN, TIM1, and TYRO3 (Hamel et al., J Virol. 89:8880–8896, 2015). We examined human embryonic brain tissue and have observed that the putative ZIKV receptor TIM1 is expressed by neuronal and astrocytic progenitor cells. Given the similarities between NSCs and BTSCs we examined human and rodent brain tumor cells for putative ZIKV receptor expression. We found TIM1 expression by human GBM6 glioma cells and murine GL261 gliomas. In tissue culture studies, incubation of ZIKV with human GBM6 cells led to high levels of infection. To determine the effects of ZIKV on tumor growth in vivo, we transplanted GL261 cells into the striatal area of the brain in syngeneic C57B/6 mice. Intra-tumoral injections of ZIKV were administered immediately after intra-cranial tumor implantation. Tumor-bearing mice receiving intra-tumoral injections of ZIKV exhibited prolonged survival in comparison to untreated mice. Together these results suggest that ZIKV may have potential as an oncolytic virus for targeting malignant brain tumors. (This work was supported in part by a grant from the Randy Shaver Cancer Research Foundation).
PUB080 A Phase II Study of BGB324 in Combination with Pembrolizumab in Patients with Previously Treated Advanced Lung Adenocarcinoma
Authors: K. Wnuk-Lipinska, K. Davidsen, M. Blø, A. Engelsen, J. Kang, L. Hodneland, K. Aguilera, E. Milde Nævdal, A. Boniecka, O. Straume, S. Chouaib, R. Brekken, G. Gausdal, J. Lorens, M. Yule
Journal: Journal of Thoracic Oncology (2017)
EXTH-63. A LIQUID BIOPSY TO ASSESS TUMOR RECURRENCE: PRESENCE OF MO-MDSC AND CD14+ VNN2+ CELLS IN PERIPHERAL BLOOD AS A BIOMARKER TO DISTINGUISH BRAIN METASTASIS (BM) FROM RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY
Authors: David Soler, Andrew Young, Amber Kerstetter-Fogle, Jill Barnholtz-Sloan, Kevin Cooper, Thomas McCormick, Andrew Sloan
Journal: Neuro-Oncology (2017)

Brain metastasis (BM) are the most common type of brain tumor with an estimated incidence of 200,000–400,000/yr. in the US alone. BM are also the most common indication for stereotactic radiosurgery (SRS). However, while SRS is highly effective in achieving local control, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatment for primary systemic cancers improves. Among the challenges at the time of apparent imaging recurrence is differentiating “true” recurrence of BM from RN. Since conventional imaging is not always reliable for this, many patients must undergo surgical biopsy or resection due to this uncertainty. Here, we demonstrate the utility of the novel biomarker Vanin-2 (VNN2) combined with expression of MHC Class II molecule HLA-DR on CD14+ cells in order to differentiate recurrent BM from RN. Our preliminary data indicate that presence of Mo-MDSC is significantly increased in BM compared to RN (49% vs 4%, p=0.005). In contrast, VNN2 expression on CD14+ in BM is decreased compared to RN (4.3% vs 36%, p=0.02). In order to further decrease overlap between outliers in each group of patients, we define the ratio of HLA-DR expression to VNN2 expression on CD14+ cells from as the DR-VNN Index or DVI. While a DVI >1 is considered BM (average= 15.5), a DVI<1 is considered RN (Average 0.07). This increases the receiver operator curve (ROC) and thus the reliability of the biomarker. These results suggest that the novel biomarker VNN2 in conjunction with HLA-DRneg/low on CD14+cells, could be useful to differentiate BM from RN using a minimally invasive blood sample. Thus, the DVI has the potential to serve as an inexpensive and non-invasive biomarker in helping to manage clinical care. Further studies are indicated.
Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort
Authors: Freek de Bruin, Anoek de Koning, Rosaline van den Berg, Xenofon Baraliakos, Juergen Braun, Sofia Ramiro, Floris A van Gaalen, Monique Reijnierse, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To develop the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) to assess structural damage in the spine of patients with ankylosing spondylitis (AS) and test its reliability. Methods Patientswith AS in the SIAS cohort had whole spine ldCT at baseline and 2 years. Syndesmophytes were scored in coronal and sagittal planes in eight quadrants per vertebral unit (VU) as absent=0, &lt;50% of the intervertebral disc space (IDS)=1, ≥50%=2 or bridging the IDS=3 (range 0–552). Images were scored by two readers, paired by patient, blinded to time order. Whole spine and spinal segment status and change scores were calculated. Inter-reader reliability was assessed by intraclass correlation coefficient (ICC), smallest detectable change (SDC) and frequency of scores per VU. Results 49 patients (mean age 50 years (SD 9.8), 84% men, 88% human leucocyte antigen B27 positive) were included. Mean (SD) scores of reader 1 were: whole spine baseline status score 163 (126) and change score 16 (21), spinal segment baseline status scores 30 (41), 97 (77) and 36 (36) and change scores 2 (7), 12 (18) and 3 (4) for the cervical, thoracic and lumbar spine, respectively. Scores of reader 2 were similar. Whole spine status score ICC was 0.99 and 0.97–0.98 for spinal segments. Whole spine change score ICC was 0.77 and 0.32–0.75 for spinal segments. Whole-spine SDC was 14.4. Score distribution pattern per VU was similar between readers. Conclusions Using the CTSS, new bone formation in the spine of patients with AS can be assessed reliably. Most progression was seen in the thoracic spine.
METB-06. OXIDATION OF KETONE BODY IN HUMAN GLIOBLASTOMA CELL LINES USING 13C NMR SPECTROSCOPY
Authors: Omkar Ijare, Athena Hoppe, Cole Holan, David Baskin, Kumar Pichumani
Journal: Neuro-Oncology (2017)

Brain tumors are exposed to ketone bodies, fatty acids, as well as lactate, carbohydrates and other substrates for energy production in mitochondria. The overwhelming majority of studies in tumor metabolism focus on conversion of glucose to lactate through glycolysis. However, there is growing evidence that cancer cells appear capable of oxidizing substrates other than glucose. Recently, we have demonstrated that acetate acts as an alternative nutrient for human gliomas and brain metastases. Glucose and acetate together contribute only up to 63% of the acetyl-CoA synthesis in brain tumors. The rest of the acetyl-CoA must be derived from other nutrients. It is well known that the normal brain uses ketone bodies as fuel. There are a few reports on using ketogenic diet as nutritional therapy to treat gliomas based on the assumption that cancer cells do not oxidize ketone bodies. We aim to investigate whether human glioblastoma cells are capable of oxidizing ketone body to meet their bioenergetic requirements. GBM cells lines derived from three patients who underwent surgical resection of the tumor at Houston Methodist Hospital were used in this study. Cells were cultured with 4.0 mM [1,2,3,4-13C]β-hydroxybutyrate (BHB) for 3 hours prior to harvesting. Snap-frozen cells were extracted and studied using 1H/13C NMR spectroscopy. [1,2,3,4-13C]BHB gets converted to [1,2-13C]acetyl-CoA in the tumor mitochondria, which enters the TCA cycle leading to 13C labeling of carbons 4 and 5 of α-ketoglutarate and glutamate during the first turn of the cycle. From 13C NMR spectrum of C4 glutamate multiplets, we determined that 9.5% ± 2.5% of [1,2-13C]acetyl-CoA was produced from BHB in the GBM cell lines used in this study. Our preliminary findings demonstrate that human GBM cell lines are fully capable of utilizing ketone bodies which contradicts to the idea behind using ketogenic diet as a therapy to treat gliomas.
P1.03-036 Adjuvant Chemotherapy with Uracil-Tegafur for Pathological T1aN0M0 Lung Adenocarcinoma with Lymphatic Vessel Invasion
Authors: Y. Kitamura, W. Nishio, H. Tanaka, K. Minami, H. Okuma, M. Yoshimura
Journal: Journal of Thoracic Oncology (2017)