tbuckley/cabot-search huggingface dataset:
Changes in the Association of Rising Infective Endocarditis With Mortality in People Who Inject Drugs
Authors: Linda W. Njoroge, Sadeer G. Al-Kindi, George Augustine Koromia, Chantal A. ElAmm, Guilherme H. Oliveira
Journal: JAMA Cardiology (2018)

Changes in the Association of Rising Infective Endocarditis With Mortality in People Who Inject DrugsDeaths from opioid abuse have increased markedly among an otherwise young and healthy population. 1 Approximately a million people used heroin in the United States in 2016, 2 times more than the number who used heroin in the entire period between 2002 and 2013. 2 Because people who inject drugs (PWID) are at risk for bacteremia, we hypothesized that their mortality from infective endocarditis has increased.
Nanocellulose‐Based Antibacterial Materials
Authors: Juanjuan Li, Ruitao Cha, Kaiwen Mou, Xiaohui Zhao, Keying Long, Huize Luo, Fengshan Zhou, Xingyu Jiang
Journal: Advanced Healthcare Materials (2018)

In recent years, nanocellulose-based antimicrobial materials have attracted a great deal of attention due to their unique and potentially useful features. In this review, several representative types of nanocellulose and modification methods for antimicrobial applications are mainly focused on. Recent literature related with the preparation and applications of nanocellulose-based antimicrobial materials is reviewed. The fabrication of nanocellulose-based antimicrobial materials for wound dressings, drug carriers, and packaging materials is the focus of the research. The most important additives employed in the preparation of nanocellulose-based antimicrobial materials are presented, such as antibiotics, metal, and metal oxide nanoparticles, as well as chitosan. These nanocellulose-based antimicrobial materials can benefit many applications including wound dressings, drug carriers, and packaging materials. Finally, the challenges of industrial production and potentials for development of nanocellulose-based antimicrobial materials are discussed.
IMMU-20. HEMATOPOIETIC STEM CELLS POTENTIATE EFFICACY OF ADOPTIVE CELL THERAPY AGAINST BRAIN STEM GLIOMA
Authors: Catherine Flores, Tyler Wildes, Ginger Moore, Brandon Wummer, Duane Mitchell
Journal: Neuro-Oncology (2018)

Adoptive cell therapy has been demonstrably promising in the treatment against cancer, but two major barriers have prevented its application to brain stem gliomas (BSG). First is the penetrance of T cells into BSGs, and the second is that the heterogeneity of brain tumors inevitably results in antigen loss variants when targeting single tumor antigens. We address both limitations with a novel approach of concomitant transfer of hematopoietic stem and progenitor cells (HSC) with adoptive cell therapy in two preclinical models of BSG. We use syngeneic models of brain stem glioma, one with wildtype H3.3 and another that harbors the H3.3K27M mutation. Tumor cells were implanted into the brain stems of mice. HSCs were isolated from bone marrow. Tumor-reactive T cells were generated ex vivo against each tumor line by employing dendritic cells pulsed with tumor-RNA. Tumor-reactive T cells were adoptively transferred into tumor bearing mice with or without HSC co-transfer. The efficacy of adoptive cell therapy was significantly increased in cohorts that received HSC co-transfer against both brain stem glioma models. Interestingly, T-cell infiltration into BSGs was only detected in cohorts that received HSC co-transfer. In addition, our observations provide evidence that HSCs co-transferred with IFNγ-secreting anti-tumor T cells differentiate into professional antigen presenting cells as characterized by CD11c, MHC-II, and a lack of MDSC markers. These cells then mount the capacity to capture and cross-prime tumor-derived antigens to both adoptively transferred T cells and host T cells, addressing the diversity of antigens within brain tumors.
A phase I/II Trial of CRISPR-Cas9-mediated PD-1 knockout Epstein-Barr virus cytotoxic lymphocytes (EBV-CTLs) for advanced stage EBV associated malignancies - Trial in progress
Authors: J. Wei, J. Yan, S. Su, J. Shao, Y. Zhao, Q. Xu, Y. Yang, Z. Zou, X. Huang, B. Liu
Journal: Annals of Oncology (2018)

Introduction: EBV associated malignancies exhibits high amplification of PD-L1 as distinguished from EBV non-associated malignancies (Kim et al. Gastroenterology 2015; Chen et al. Clinical Cancer Research 2013). The up-regulation of PD-L1 restricts antitumor effect of EBV-CTLs by immune tolerance and results in poor prognosis of patients. Our previous work has generated PD-1-disrupted CTLs by CRISPR-Cas9 system which could up-regulate IFN-γ production and enhance cytotoxicity in tumor cell lines and mouse model (Su et al. Oncoimmunology 2016). Methods: This phase I/II prospective single center clinical study (clinicaltrials.gov NCT03044743) was designed to evaluate the safety of PD-1 knockout EBV-CTLs in treating EBV positive advanced stage malignancies. Patients included should be pathologically verified EBV positive stage IV gastric carcinoma, nasopharyngeal carcinoma or lymphoma progressed after standard treatment with measurable lesions. Patients will be divided into three groups and receive 2 to 4 cycles of cell therapy according to their tolerance. PD-1 knockout EBV-CTLs from autologous origin will be generated and 2 x 10^7/kg of specific T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20%, 30% and 50% respectively. To modify immune microenvironment, Fludarabine at 30mg/m2 and cyclophosphamide at 300mg/m2 will be administered 3 days (intravenous injection, i.v.) before cell infusion. Interleukin-2 will be given daily (i.v.) from the first day of the cell infusion for 5 consecutive days at the dose of 4000,000 international unit (IU)/day to sustain the survival of infused T cells. The adverse events will be evaluated after each cycle by Common Terminology Criteria for Adverse Events (CTCAE v4.0) as primary endpoint. Progression-free survival (PFS), the duration of the normalization of tumor marker and immunological markers will be evaluated as the secondary endpoints. Immunological markers will continuously be examined every two cycles.
LGG-60. THE GENETIC LANDSCAPE OF PEDIATRIC LOW-GRADE GLIOMAS: INCIDENCE, PROGNOSIS AND RESPONSE TO THERAPY
Authors: Scott Ryall, Michal Zapotocky, Kohei Fukuoka, Ana Guerreiro-Stucklin, Julie Bennet, Anthony Arnoldo, Paul Kowalski, Monique Johnson, Alvaro Lassaletta, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Ellison, Uri Tabori, Cynthia Hawkins
Journal: Neuro-Oncology (2018)

Molecularly characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and their prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases is also unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 (81%) of the cohort. The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)), or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3A_K27M mutations (2%) and IDH1_R132H (0.5%), as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of BRAF-KIAA1549 patients compared to BRAF_V600E with 10-year OS 97.7% (95%CI 95.5-100) and 83.9% (95%CI 72.5-95.6) respectively. In addition to survival, the molecular alterations predict differences in response to conventional therapeutics; BRAF fused patients show a 46% response-rate, versus only 14% in V600E patients. pLGG harboring H3F3A_K27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1_N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.
Endoscopic detachable auxiliary manipulator in endoscopic submucosal dissection: Animal model studY
Authors: H. Jeon, H. Chun, B. Keum, J. Lee, S. Choi, S. Kim, J. Lee, H. Choi, E. Kim, Y. Jeen, H. Lee, C. Kim
Journal: Annals of Oncology (2018)

Introduction: Endoscopic submucosal dissection (ESD) is a difficult procedure due to lack of counter traction for unskilled endoscopists. Recently, auxiliary devices have been developed to alleviate the difficulties of ESD. We also developed new endoscopic technique using robotic manipulator. The purpose of this study is to evaluate the efficacy and safety of endoscopic detachable auxiliary manipulator (EDAM) in vitro animal study. Methods: A novel robotic manipulator is composed of a control panel and a working arm, which grasp and move objects at the end of scope. A total of 40 porcine stomachs were used for the test. Endoscopists were classified as expert or novice. As a preliminary work, operation time and perforation rate of the experts and novices were recorded when ESD was performed by the conventional method. (C-Expert group, C-Novice group). The same experiment was performed using EDAM (M-Expert group, M-Novice group). During this procedure, robotic manipulator lifts up dissected tissue of stomach to make better visibility. The results were compared. Results: The safety of the operation was greatly improved when using the EDAM. Perforation rate of the EDAM method was significantly lower than that of the conventional method in the novice group. (10% vs 60%, P = 0.002) There was no significant difference between the conventional method and the EDAM in the operation time in the novice group. Conclusion: As a result of this In-vitro test, the EDAM significantly improved the safety of ESD in the case of the novice, with no increase in operation time.
Competing priorities and the NHS
Authors: José G Merino
Journal: BMJ (2018)

Since the NHS was founded 70 years ago, the proportion of GDP that the UK spends on healthcare has doubled to around 10%, a level matching that of other European countries. As Anita Charlesworth and Karen Bloor argue in their analysis (doi:10.1136/bmj.k2373), the decision on how much to spend on healthcare involves tradeoffs between competing priorities and sources of revenue and is, at its core, political.

Over the next five years NHS England will receive an average annual funding increase of …
Abstract P090: Younger Age of Immigration Mitigates Allostatic Load in Africans: The Africans in America Study
Authors: Anne E Sumner, Brianna A Bingham, Michelle T Duong, Paola C Aldana, Madia Ricks, Lilian S Mabundo, Margaret Udahogora, David Berrigan, Stephanie T Chung
Journal: Circulation (2016)

African immigrants living in the United States are exposed to the stress of changing continents and cultures. Therefore African immigrants are exposed to two types of environmental stress; first, stress related to navigating new social and economic realities; and second, stress due to work, education and a sedentary lifestyle in the United States. To evaluate the effect of these stressors on health, we calculated the allostatic load score in two groups of Africans: childhood immigrants who came to the United States before 18 years of age, and adulthood immigrants who came to the United States at 18 years of age or older. Allostatic load is a measure of the influence of environmental stress on physiological function. It is calculated for each individual by assigning one point for each high risk cardiovascular, inflammatory, and metabolic biomarker present. The higher the allostatic load score, the greater the impact of stress on physiologic dysregulation. As no consensus exists on which biomarkers to include in the calculation of allostatic load score, we used four different published equations to evaluate allostatic load in 213 African immigrants (age: 40±10y,(mean±SD) range 21-64y; BMI: 27.7±4.5 kg/m 2 ; male: 70% (149 of 213); adulthood immigrants: 81% (181 of 213)). By multiple regression, the effect of age, age at immigration, duration of stay in the United States, income, education and exercise on allostatic load score was determined. Overall, childhood immigrants were younger than adulthood immigrants (29±7 vs. 41±9y, P &lt;0.01). However, length of residence in the United States was longer for childhood immigrants than adulthood immigrants (19±8 vs. 12±9y, P&lt;0.01). Regardless of which equation for allostatic load score was used, childhood immigrants had lower allostatic load scores than adulthood immigrants, ( P &lt;0.01). Among adulthood immigrants, the age range of immigration was 18 to 61y; within this group, lower age of immigration was associated with lower allostatic load scores ( P &lt;0.05). In addition, as length of stay in the United States increased, allostatic load score increased in adulthood immigrants ( P &lt;0.01) but not childhood immigrants ( P &gt;0.6). For both groups of immigrants, low income, lack of a college education and low levels of exercise did not increase allostatic load score ( P &gt;0.3). Overall, the factor which appears to have the greatest impact on the physiologic health of African immigrants is age of immigration. Africans who emigrated as children experience less physiologic stress than their counterparts who emigrated as adults.
Abstract 17942: Functional Consequences of a Tissue-Engineered Myocardial Patch for Cardiac Repair in a Rat Infarct Model
Authors: Jacqueline S Wendel, Lei Ye, Pengyuan Zhang, Robert T Tranquillo, Jianyi Zhang
Journal: Circulation (2013)

This study evaluates the capacity of an aligned, fibrin-based, stretch-conditioned cardiac patch to ameliorate left ventricular (LV) remodeling in the acute phase post-infarction. Cardiac patches w...
CRAN-28. A SINGLE CENTER EXPERIENCE OF MANAGING A SERIES OF CHILDHOOD MACROPROLACTINOMAS
Authors: Antonia Dastamani, Chloe Bulwer, Marta Korbonits, Helen Spoudeas
Journal: Neuro-Oncology (2018)

Childhood prolactinomas often occur as aggressive macro (1-4cm) or giant (>4cm) tumours, with little consensus regarding timing of different therapies. AIM: To highlight the phenotype and the outcome of childhood macroprolactinomas. SUBJECTS AND Collected data from 10 children (<18 years) presenting to our centre between 2009–2017, with hyperprolactinaemia (>9000mU/L) due to macroprolactinomas. Age of symptoms onset was 8–15.8 years. Presenting symptoms included headaches (10/10), endocrinological signs (gynaecomastia, galactorrhoea, pubertal arrest, short stature,7/10) and visual deficit (3/10). The initial prolactin levels varied and reflected tumour’s size (9,176-1,238,960 mIU/L). At diagnosis, children had 1–4 pituitary hormone deficits, GH (7),TSH (6),LH/FSH (6) and ACTH (4).All patients had suprasellar extension and 9 had compromised cavernous sinus and optic pathway. All children had first-line cabergoline treatment apart from one misdiagnosed. Two patients required urgent transsphenoidal surgery for pituitary apoplexy and for CSF leak post cabergoline. Four patients experienced cabergoline side-effects (headaches, aggressive behavior, impulse control disorder). Five cases continue on dose-escalating cabergoline treatment. Five cases required surgery and one radiotherapy due to cabergoline side-effects(1), visual compromise(1)or tumour regrowth(2).One proved heterozygous for an MEN1 mutation. None harboured an AIP mutation. Cabergoline should be the first-line treatment in childhood-onset macroprolactinomas. Dose-escalation maybe is necessary for controlling disease, but needs monitoring of side-effects or complications. In resistant disease, surgery increases endocrine deficits and radiotherapy may be necessary. MEN1 and AIP analysis is strongly recommended to inform about pathogenesis, allow screening for other manifestations and to identify at-risk relatives.
Augmentation and eversion of lips without injections: The lip peel
Authors: Carlos G. Wambier, Ideli C. Neitzke, Kachiu C. Lee, Seaver L. Soon, Peter P. Rullan, Marina Landau, João Carlos L. Simão, J. Barton Sterling, Harold J. Brody
Journal: Journal of the American Academy of Dermatology (2018)
EPID-14. POPULATION-BASED ANALYSIS OF DEMOGRAPHIC AND SOCIOECONOMIC DISPARITIES IN PEDIATRIC CNS TUMOR SURVIVAL IN THE UNITED STATES
Authors: Shadi Zahedi, Robert Fineberg, Megan Eguchi, Myles Cockburn, Adam Green
Journal: Neuro-Oncology (2018)

Malignant central nervous system (CNS) tumors are the most common cause of childhood cancer mortality. Minority race/ethnicity and socioeconomic disadvantages have been established as risk factors for poorer outcomes in adult and pediatric cancers; however, these issues are understudied in brain tumors. We investigated demographic and socioeconomic risk factors for poorer survival in childhood CNS tumors. We used the Surveillance, Epidemiology, and End Results (SEER) 18 registries to obtain overall survival (OS), stage, demographic, insurance, and socioeconomic (by census tract) data on children 0-19 years old at diagnosis of malignant CNS tumors (ependymoma, glioma, medulloblastoma, other embryonal (PNET/pineoblastoma/ATRT), and unspecified/other) from 2000-2013. Univariate and multivariable analyses were performed. On multivariable analysis, Black (HR 1.381, p=0.0038) and Hispanic (HR 1.215, p=0.043) patients showed poorer OS overall than White and non-Hispanic patients, respectively. Black patients with glioma and ependymoma also had significantly poorer OS than White patients. Medulloblastoma patients living in language isolated areas, and other embryonal tumor patients living in high poverty areas, had significantly poorer OS than those living in low language isolation and low poverty areas, respectively. We did not find a higher likelihood of metastatic disease at diagnosis for these groups. However, many of the OS disparities were still present when patients were subgrouped by local/metastatic disease, suggesting potential treatment disparities. Disparities in OS of pediatric brain tumors exist based on race, ethnicity, and some socioeconomic factors. Our subsequent efforts will attempt to isolate and address specific causes of these disparities.
HGG-11. SURVIVAL OUTCOMES AND PROGNOSTIC FACTORS OF LOW-INCIDENCE HIGH-GRADE CNS MALIGNANCY IN CHILDREN: A SINGLE-CENTRE STUDY
Authors: Serag Saleh, Robert Smee
Journal: Neuro-Oncology (2018)

AIM: The aims of this study are to summarise and quantify survival outcomes in the paediatric high-grade central nervous system (CNS) malignancy population with low-incidence tumours at the Sydney Children’s Hospital, and identify key variables that influence survival outcomes. A retrospective review was conducted to identify patients aged ≤18years at the Sydney Children’s Hospital treated at the Department of Radiation Oncology between April 1992 and April 2016, identifying thirty-five eligible patients with pathology-confirmed high-grade disease. Overall survival (OS) and progression-free survival (PFS) were evaluated to determine the impact of presenting clinical features and treatment on survival outcomes. The full cohort had a median OS of 16.7 months and a median PFS of 8.8 months. Histological subtype, headache, negative glial fibrillary acidic protein (GFAP) immunochemistry, gross total resection, definitive radiation therapy, radiation dose of 5000cGy-5999cGy, and definitive chemotherapy were found to improve OS on univariate analysis (p<0.05). Histological subtype, headache and nil limb signs were also found to improve PFS on univariate analysis (p<0.05). Multivariate analysis identified surgical resection, histological subtype and presence of headache at presentation as independent prognosticators of OS. Survival outcomes at the Sydney Children’s Hospital are comparable to the literature for PFS, but OS outcomes are below what would be expected in this population. Observed survival outcomes and clinical prognosticators need to be validated through studies with larger samples to produce more robust findings and ensure the external validity of the conclusions obtained.
Germline Genetic Testing for Pancreatic Ductal Adenocarcinoma at Time of Diagnosis
Authors: Sapna Syngal, C. Sloane Furniss
Journal: JAMA (2018)

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Endoscopic treatment of concurrent colorectal anastomotic stricture and prolapse
Authors: Freeha Khan, Bo Shen
Journal: Endoscopy (2018)

A 47-year-old man presented to our Interventional IBD Unit with dyschezia, bloating, fecal incontinence, fecal urgency, and frequent bowel movements. He had been diagnosed with stage IV rectosigmoid cancer (T4aN0MX) in 2014. He underwent palliative low anterior resection of the rectum and sigmoid with end colostomy, resection of colostomy, Hartmann reversal operation with colorectal anastomosis. He had been receiving capecitabine since 2017.