tbuckley/cabot-search huggingface dataset:
One in three with cancer diagnosed as emergency had not seen GP, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Nearly a third of patients with cancer diagnosed as an emergency presentation had not previously consulted their GP about relevant symptoms, a UK study has found.1

Many patients with cancer have it diagnosed as an emergency, and their symptoms are often assumed to have been missed during previous consultations with GPs. But information is limited on how many patients with cancer diagnosed after emergency presentation had previously been …
Engineered Erythrocytes As an Anti-Tumor Therapy through Induction of Apoptosis or Immune-Checkpoint Inhibition
Authors: Sivan Elloul, Claire Depew, Sujata Nerle, Tiffany Chen, Samuel Kaplan, Nathan Dowden, Jordi Mata-Fink, Avak Kahvejian, Robert Deans
Journal: Blood (2016)
Trends in Repeat Births and Use of Postpartum Contraception Among Teens — United States, 2004–2015
Authors: Deborah L. Dee, Karen Pazol, Shanna Cox, Ruben A. Smith, Katherine Bower, Martha Kapaya, Amy Fasula, Ayanna Harrison, Charlan D. Kroelinger, Denise D’Angelo, Leslie Harrison, Emilia H. Koumans, Nikki Mayes, Wanda D. Barfield, Lee Warner
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

For this report, the term "teen" refers to a person aged <20 years.
Roles of functional catechol-O-methyltransferase genotypes in Chinese patients with Parkinson’s disease
Authors: Yiwei Qian, Jiujiang Liu, Shaoqing Xu, Xiaodong Yang, Qin Xiao
Journal: Translational Neurodegeneration (2017)

Recent studies have found that the functional catechol-O-methyltransferase (COMT) gene may be associated with the susceptibility to and pharmacotherapy of Parkinson's disease (PD). In this case–control study, we investigated the most common functional COMT gene haplotypes that had been shown to influence COMT enzymatic activity and the association of the single and combined COMT haplotypes with clinical symptoms and pharmacotherapy in Chinese patients with PD. One hundred forty-three patients with idiopathic PD and 157 healthy individuals were enrolled in this study. Four single nucleotide polymorphisms (SNPs) in the COMT gene (formed by SNPs) were genotyped in each participant: rs6269 A > G; rs4633 C > T; rs4818 C > G; and rs4680 G > A. The frequencies of rs4633 T carriers, rs4680 A carriers and the two linked rs4633-rs4680 T/A carriers were significantly higher in the early onset PD group than in the healthy controls (all P < 0.05). Homozygosity for rs4633 (TT), rs4680 (AA) and of the two linked rs4633-rs4680 (TT/AA) was significantly more frequent in patients who exhibited the "wearing-off" phenomenon, longer disease duration, higher levodopa equivalent doses (LED) and higher Unified Parkinson's Disease Rating Scale (UPDRS) scores (P < 0.05). No significant differences were observed in the clinical features of patients who carried individual rs6269 and rs4818, the two linked rs6269-rs4818 and the four combined COMT SNPs. The results showed a possible association of combined functional COMT SNPs with PD risk, disease duration, the "wearing-off" phenomenon, daily LEDs and higher UPDRS scores, which may be useful in instituting individualized therapy for patients with PD.
P09.52 Extra central nervous system metastases from glioblastoma: a clinical case
Authors: G. Simonetti, P. Gaviani, A. Botturi, L. Fariselli, A. Hottinger, E. Lamperti, G. Pesce, A. Silvani
Journal: Neuro-Oncology (2017)

Introduction: Extra cranial metastasis of glioblastoma (GBM) are fairly rare event: they occur in only 1% of all GBM patients. The most frequent sites of colonization are generally cervical lymph nodes, lungs, liver, bones and the spine. The most common way of metastasis spread is hematogenous but also through lymph nodes, especially in patients undergoing surgical resection. METHODS: We report the case of a 38 year old male that in 2012 underwent to surgical resection of GBM (methylated MGMT, negative IDH1, MIB1 20%), followed by radiotherapy (RT) (60 Gy) and subsequently treated with concomitant and adjuvant Temozolomide (TMZ) up to 6 cycles. The patient remained stable over the year when he was re-operated due to recurrence. Because of the extremely good response to prior TMZ schedule, it was decided to try a rechallenge with adjuvant TMZ for 6 months. The sudden onset of of paresthesia and hypoesthesia on the right upper limb, induced physicians to performed an MRI that showed an increase of the lesion with nodular component parasagittal. After surgery, the patient was treated with anti-angiogenic treatment achieving a good radiological response and stabilization of disease. In February 2016, due to a neck pain associated with weakness of upper right limb, MRI found significant reduction of the lesion but revealed the presence of pathological enhancement at C4- C7. In suspicion of dissemination of the disease, chest-abdomen CT scan was performed showing 3 suspected pulmonary nodules metastasize. Results: Biopsy confirmed the presence of compatible tissue with GBM metastases and PET TC total body highlighted a mass effect in highly hypermetabolic character that stretched from C4 to C6-C7. Also it showed accumulations in the lymph nodes, lungs, and in the right iliac crest, and multiple thoracic vertebrae. The patient was radiated on bone localization and promptly started a new chemotherapy treatment with etoposide and oncocarbide but he died on 09.04.2016. CONCLUSION: Despite the peculiar tendency of GBM to remain confined within the central nervous system, a low percentage of them may metastasize. The biological-genetic mechanisms involved in the pathogenesis remain unclear but risk factors seems to include long survival, surgery procedures and vascular involvement. Therapeutic experience is limited making the management of GBM an even greater challenge.
Dermoscopy use by Canadian dermatologists and dermatology residents: a cross‐sectional nationwide study
Authors: T. Burbidge, W. Davidson, L. Robertson
Journal: British Journal of Dermatology (2017)

Abstract Dermoscopy has demonstrated clinical benefits in improving early melanoma diagnosis and reducing unnecessary biopsies. Despite this, the prevalence of dermoscopy use by dermatologists varies from 81% to 98% worldwide, with a lack of training being a commonly cited reason for non-use of dermoscopy. To date there are no studies examining the prevalence of dermoscopy use in Canada. Our study aimed to examine the use and learning of dermoscopy by Canadian dermatologists and dermatology residents, as well as the current state of dermoscopy teaching within Canadian dermatology residency programs. This article is protected by copyright. All rights reserved.
Hepatitis E and blood donation safety in selected European countries: a shift to screening?
Authors: Dragoslav Domanović, Richard Tedder, Johannes Blümel, Hans Zaaijer, Pierre Gallian, Christoph Niederhauser, Silvia Sauleda Oliveras, Joan O’Riordan, Fiona Boland, Lene Harritshøj, Maria São José Nascimento, Anna Rita Ciccaglione, Constatina Politis, Cornelia Adlhoch, Benoit Flan, Wahiba Oualikene-Gonin, Guy Rautmann, Paul Strengers, Patricia Hewitt
Journal: Eurosurveillance (2017)

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.
Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association
Authors: Sheryl L. Chow, Alan S. Maisel, Inder Anand, Biykem Bozkurt, Rudolf A. de Boer, G. Michael Felker, Gregg C. Fonarow, Barry Greenberg, James L. Januzzi, Michael S. Kiernan, Peter P. Liu, Thomas J. Wang, Clyde W. Yancy, Michael R. Zile
Journal: Circulation (2017)

Background and Purpose: Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers. Methods: The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through December 2016. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or contemporary clinical practice recommendations. Results: A number of biomarkers associated with HF are well recognized, and measuring their concentrations in circulation can be a convenient and noninvasive approach to provide important information about disease severity and helps in the detection, diagnosis, prognosis, and management of HF. These include natriuretic peptides, soluble suppressor of tumorgenicity 2, highly sensitive troponin, galectin-3, midregional proadrenomedullin, cystatin-C, interleukin-6, procalcitonin, and others. There is a need to further evaluate existing and novel markers for guiding therapy and to summarize their data in a standardized format to improve communication among researchers and practitioners. Conclusions: HF is a complex syndrome involving diverse pathways and pathological processes that can manifest in circulation as biomarkers. A number of such biomarkers are now clinically available, and monitoring their concentrations in blood not only can provide the clinician information about the diagnosis and severity of HF but also can improve prognostication and treatment strategies.
P04.17 Novel augmented reality-based neuronavigation using smart glasses and clinical application to brain tumor surgery
Authors: K. Maruyama, E. Watanabe, K. Saito, K. Sato, H. Yoshida, S. Kume, A. Noguchi, Y. Shiokawa, M. Nagane
Journal: Neuro-Oncology (2017)

Introduction: Smart glasses became commercially available recently, and can overlay data onto the sight through the lenses. Its clinical application for surgical navigation has never been reported so far. Materials and Methods: Smart glasses Epson Moverio BT-200 were applied for newly developed augmented reality-based neuronavigation, which overlays 3D images onto the video image of patient's head, in two phantom heads and four patients with brain tumors (2 gliomas, 1 meningioma, 1 hemangioblastoma). Two phantom heads were created from a 3D printer XYZ printer. Three-dimensional computer graphics of the scalp, the brain, the brain tumors, and surrounding vascular structures were created from preoperative imaging studies by using the visualization software Amira. They were visualized through the glasses after registration based on a set of four markers. After measurement of accuracy, this technique was applied to four patients. Results: Image overlay through the smart glasses was successful in all the two phantom heads and four patients. By using 100 target points from phantoms (5 targets in 5 measurements for 4 sides), a mean preparatory targeting error was 1.9 mm with a standard deviation of 1.1 mm. A targeting error during the intraoperative visualization was 3 to 7 mm. All the tumors were totally removed successively, and the patients suffered no postoperative complications. Conclusions: Overlay of the three-dimensional computer graphics through the smart glasses provided clear and accurate localization of the targeted brain tumors by relatively simple procedure during the operation. Further improvement of accuracy is also underway.
The Wnt5a-β-catenin Pathway Triggers a Metabolic Switch That Drives Indoleamine 2,3-dioxygenase Activity and Dendritic Cell Tolerization in the Melanoma Microenvironment.
Authors: F Zhao, K Evans, C Xiao, A Holtzhausen, BA Hanks
Journal: Journal for ImmunoTherapy of Cancer (2017)
Abstract 326: TRPV2 Regulates Cardiomyocyte Function via Altering Ca <sup>2+</sup> Cycling
Authors: Xiaoqian Gao, Sheryl Koch, Min Jiang, Nathan Robbins, Wenfeng Cai, Priyanka Varma, Michael Tranter, W Keith Jones, Hong-Sheng Wang, Jack Rubinstein
Journal: Circulation Research (2012)

TRPV2 is a member of transient receptor potential vanilloid (TRPV) family. As a Ca 2+ channel, it can detect various stimuli such as noxious heat (&gt;52°C), membrane stretching, as well as a number of exogenous chemicals, including probenecid, 2-aminoethoxydiphenyl borate, and lysophospholipids. TRPV2 has been found in many tissue types, including neuron and kidney, but the function of TRPV2 in the heart is poorly understood. Here we show TRPV2 is involved in the Ca 2+ cycling process and then regulates the function of the cardiomyocyte. We identified the mRNA expression of TRPV2 in the cardiac tissues of mice using real-time PCR. By performing echocardiography we found that administration of probenecid, a selective TRPV2 agonist, increased cardiac ejection fraction in mice. This positive inotropic effect of probenecid was also shown in Langendorff perfused mice hearts as increased peak +dP/dt. In isolated ventricular myocytes, we found that probenecid significantly increased myocyte fractional shortening in a dose-dependent manner, which was fully blocked by ruthenium red, a non-selective TRPV2 blocker. We also performed fluorescent studies to examine myocyte Ca 2+ cycling. We found that probenecid significantly increased Ca 2+ transient and resting-state Ca 2+ sparks and this effect was eliminated by ruthenium red. When Ca 2+ storage in sarcoplasmic reticulum (SR) was depleted with caffeine, and SR Ca 2+ reuptake was blocked by thapsigargin at the same time, probenecid did not show any effects in either Ca 2+ transient or Ca 2+ sparks. Our patch clamp experiments indicate that probenecid treatment does not trigger any significant transmembrane Ca 2+ influx. These results point to the important role of TRPV2 in regulating SR Ca 2+ release. In conclusion, TRPV2 activation may contribute to increased SR Ca 2+ release, leading to the enhancement of myocyte contractility. Thus, TRPV2 plays a potentially important role in controlling the cellular function of heart.
P17.02 Assessing the role of aggressive surgical RESECTION for IDH mutated Anaplastic Glioma: reflections from tumour volume reduction and patterns of relapse following PET guided IMRT with sequential temozolomide
Authors: M. Back, G. Schembri, D. Brazier, M. Kastelan, H. Wheeler
Journal: Neuro-Oncology (2017)

AIM: In patients with Anaplastic Glioma (AG) and IDH mutation(IDHmut) assess reduction in tumour volume and patterns of failure following intensity modulated radiation therapy(IMRT) and sequential temozolomide (TMZ). METHODS: Patients managed for AG with IMRT from 2008-2015 were classified as Favourable(FAV) or non-Favourable(non-FAV) cohort based on presence of oligodendroglial features, 1p19q co-deletion or subsequent presence of IDHmut. From 2011 FAV received FET-FDGPET planning(PET-IMRT). Tumour volumes were created on representative T1/T2Flair MRI sequences using identical slice-levels in 3 planes for preIMRT, month+3 and month+12 postIMRT scans. Change in volumes was assessed between time periods. Progression-Free(PFS) was calculated from start RT and patterns of failure in relation to IMRT volume was recorded. ECOG Scale and Employment status were recorded as surrogates for functional status postIMRT. Results: 156 patients were included of which 124 FAV and 32 non-FAV. Median follow-up for survivors is 38.2 months. 18% received IMRT at second or later relapse. 66% received sequential chemotherapy. 50 relapses occurred for 5yPFS of 64.1%. Relapse was more frequent in nonFAV with 5yrPFS of 26.0% vs 75.3% for FAV (p<0.001). 56 FAV patients were managed with PET-IMRT since 2011, of which only 4 patients had no demonstrated residual disease on MRI/FET-PET. 12 patients relapsed for projected 3yr PFS of 74.4%; with only 5 relapses adjacent to initial surgical site. On MRI at month+3, the median volume for T1 and T2 reduced by 70.0% and 64.3% respectively; which further decreased to 82.8% and 81.0% at month+12. By month+12, 88.0% and 88.2% of patients had >60% volume reduction. 41 of 52 patients remain in paid employment, which was associated with improved ECOG and use of IMRT at diagnosis or first relapse, rather than delayed. Conclusion: Patients with a favourable molecular subtype anaplastic glioma, correlating with presence of IDH mutation, achieve marked reduction in residual tumour volume with IMRT. With more than 75% patients progression-free at 5yrs, and relapses postIMRT at distant rather than local sites, decision-making for initial surgical therapy should aim to minimize the risks of intervention related morbidity.
OS05.5 Pallative care in Brain Tumors: 15 years of activity of a Neuroncological Home Care Service
Authors: A. Pace, L. Guariglia
Journal: Neuro-Oncology (2017)

Introduction: Recent studies report that early integration of palliative care approach with standard oncologic care in cancer patients may have a beneficial effect on quality of life and mood disorders. In Brain Tumor patients, however, the provision of supportive and palliative care often occurs late and the timing and the role of palliative care in brain tumor patients remain to be better defined. Since October 2000 in the Regina Elena National Cancer Institute of Rome, we started a palliative home-care project for patients affected by malignant BTs, with financial support of Regional Health System. The aims of this model of assistance are to meet patient’s needs of care during the evolution of the disease, to provide palliative care, to support the families and to facilitate death at home. Methods: in the first fifteen years of our program 873 patients have been assisted at home and 618 died. Home assistance includes neurological visits, neuro-rehabilitation at home, psychological support for patients and families and nursing assistance. Results: among the 410 patients who were assisted at home until death (410/618, 66%), the most frequent symptoms in the last 4 weeks of life were: epilepsy 37%, headache 36%, drowsiness 85%, dysphagia 85%, death rattle 12%, agitation and delirium 15%. The large majority of BT patients die with a process that has been defined as “peaceful death”, with progressive neurological deterioration. In some case, however, patients may present bad symptom control with agitated death that requires pharmacological sedation (15,7%). The early provision of home palliative care enables family caregivers to continue caring at home until death and allow to discuss timely with patient and family the End of Life Advance Care Planning, avoiding hospitalisation or Emergency room access in case of acute symptoms. CONCLUSION: early integration of palliative care model in the trajectory of desease of Brain Tumor patients is critical to providing more effective support, to enhancing the likelihood of a desired home death and to support the psychological and spiritual needs of patients and families.
P10.21 2-hydroxyglutarate as a biomarker for IDH mutation in low grade gliomas
Authors: R. Nejad, H. Sim, K. Aldape, W. Mason, M. Bernstein, F. Gentili, S. Kalia, T. Tung, E. Chen, G. Zadeh
Journal: Neuro-Oncology (2017)

Glioma patients continue to carry a very poor prognosis despite maximal therapy. Several genetic alterations are linked with better survival outcome in glioma patients, including mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). The product of IDH mutation is the chemical 2-hydroxyglutarate (2-HG), which is a metabolite linked to cancer development. Currently, there is no method by which we can determine the IDH status of glioma during surgery. A much-needed area of progress is the application of innovative methods to enable detection of IDH mutation intraoperatively to guide extent of resection while avoiding the need for a second high-risk cranial surgery. High performance liquid chromatography tandem mass spectrometry (HPLC-MS) was developed, validated and utilized to quantify the R-2-HG and S-2-HG enantiomers and total 2-HG levels in 38 frozen brain tumor samples (IDH WT n=14, IDH mutated n=24). Brain tumor samples were retrieved from the Toronto Western Foundation brain tumor bank. Glioma diagnosis and IDH status were determined by microscopy and immunohistochemistry. 30 patients had paired serum that was included in our analysis. Progression-free survival data for all patients was collected. We found that the R:S ratio of 2-HG within patient tumors corresponds with IDH status, with our IDH-mutant patients having an elevated R:S ratio of 1551 ± 457 in contrast to IDH-WT patients = 6.2 ± 4.4 (P<0.001). This trend was also confirmed when comparing total 2-HG levels (P<0.001). Of the patients with IDH-mutated tumors, a higher R:S ratio of 2-HG appears to be associated with worse survival, in contrast to total 2-HG levels, where there was no obvious correlation to survival. Finally, serum 2-HG levels did not correspond with IDH status. We believe the R:S 2-HG ratio can potentially be used as an intraoperative biomarker for IDH mutation detection to personalize glioma surgery.