tbuckley/cabot-search huggingface dataset:
In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI
Authors: Gian Matteo Rigolin, Maurizio Cavallari, Francesca Maria Quaglia, Luca Formigaro, Enrico Lista, Antonio Urso, Emanuele Guardalben, Carmine Liberatore, Danilo Faraci, Elena Saccenti, Cristian Bassi, Laura Lupini, Maria Antonella Bardi, Eleonora Volta, Elisa Tammiso, Aurora Melandri, Massimo Negrini, Francesco Cavazzini, Antonio Cuneo
Journal: Blood (2017)
P12.21 Surveillance of Incidental Meningiomas: A systematic Review and Meta-Analysis
Authors: A. P. Perera, K. M. Mahmoud
Journal: Neuro-Oncology (2017)

Introduction: Incidental meningiomas pose a prognostic challenge; while conservative management is generally accepted there are no definitive statistics which tell us which proportion of these patients progress and how best to predict this. A number of studies have reported the natural history of incidental meningiomas however it is challenging to accurately identify trends in isolation. To this end we aimed to undertake the first systematic review and meta-analysis of papers reporting on the surveillance of incidental meningiomas. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA statement and was prospectively registered with the PROSPERO database (CRD42016045550). Pubmed, CINAHL, google scholar and Embase were searched for the MeSH terms “incidental meningioma follow up” and “asymptomatic meningioma follow up”. Searches were conducted independently by two of the authors AP and KA and disputes were resolved until mutual agreement was reached. Papers including surveillance of asymptomatic meningiomas were included. Papers describing any interventions at the initial stage of management were excluded. Results: 11 papers were identified totalling 800 patients. 34% (weighted mean) of tumours showed progression along the course of surveillance with a weighted average of 54 months follow up. 4 papers reported the number of patients who developed symptoms which ranged from 3.4% to 12.5%. Calcification significantly reduced the risk of having tumour growth: OR 3.18[1.87,5.40] (P<0.0001). Time to progression was only reported in two studies ranging between an average of 2.96 and 4.95 years. CONCLUSION: Based on the results of this study we can conclude that surveillance is a safe management plan for incidental meningiomas, around a third of patients will display progression during follow up but less than 15% will become symptomatic. Calcification is the best predictor of a static tumour cutting the risk of progression by 3. However time to progression was a poorly reported outcome and further research into this would be beneficial in order to help guide the length of follow up of these patients.
Patient and partner empowerment programme for idiopathic pulmonary fibrosis
Authors: Mirjam J.G. van Manen, Adriaan van 't Spijker, Nelleke C. Tak, Carla T. Baars, Sandra M. Jongenotter, Liesbeth R. van Roon, Jitske Kraan, Henk C. Hoogsteden, Marlies S. Wijsenbeek
Journal: European Respiratory Journal (2017)

Idiopathic pulmonary fibrosis (IPF) is a progressive, deadly disease with a devastating impact on patients' and their partners' quality of life (QoL) [1]. Many studies have shown the need for support groups, better information resources and disease education in IPF [2–6]. Although these needs have been identified, few studies currently exist concerning interventions that can fulfil them and possibly improve QoL for patients and their partners [7]. In our study, we determined the effect of a short multidisciplinary empowerment programme on the QoL for patients with IPF and their partners. PPEPP, a short multidisciplinary empowerment programme, improves quality of life for IPF patients and their partners <http://ow.ly/zAbb3096waC> We respectfully acknowledge the valuable input given by Mr van der Steen and Mr van Poppel, whose personal and professional experiences have provided indispensable guidance for design of the PPEPP programme.
Outcome of Patients Younger Than 50 Years Old Diagnosed with Myelodysplastic Syndromes (MDS): Single Institution Experience
Authors: Aref Al-Kali, Rong He, Mrinal M Patnaik, David S Viswanatha, Patricia T. Greipp, Darci Zblewski, Michelle Elliott, Naseema Gangat, Ayalew Tefferi, Mark R. Litzow, Phuong L. Nguyen
Journal: Blood (2016)
Abstract 272: RBPJ Controls the Angiogenic Response of Mouse Adult Cardiomyocytes
Authors: Ramon Diaz Trelles, Maria Cecilia Scimia, Pilar Ruiz Lozano, Mark Mercola
Journal: Circulation Research (2012)

Cardiac microvasculature density is critical for a correct cardiac function under normal and stress conditions. We found that the transcription factor RBPJ, downstream of the Notch signalling, can regulate angiogenic factors gene expression by repression (normal homeostasis) or activation (stress) and also by modulating the hypoxia induced angiogenic response. Accordingly, in normal conditions cardiomyocyte specific RBPJ KO adult mice hearts show a denser microvasculature. Isolated mouse adult cardiomyocytes show increased gene expression and promoter hyperacetylation and hypermethylation of angiogenic factors and Notch target genes (like HES1). Stress induced by myocardial infarction (MI) or cardiac overload (TAC) activate an angiogenic response to compensate the increased oxygen demand. Notch pathway is activated and RBPJ accumulated in the nucleus after MI and TAC. After TAC, deletion of RBPJ did not block hypertrophy induction, but prevented the increase in angiogenic factor production and microvessel density that normally occurs in response to increased workload. Remarkably, the KO preserved cardiac function and reduced cell death and fibrosis after myocardial infarction. Thus, RBPJ acts in cardiomyocytes as a master factor orchestrating homeostatic and disease-induced angiogenesis, and modulating RBPJ protects against ischemic injury.
Abstract 131: A microRNA Targets the Epigenetic Reader BRD4 to Suppress Transcription Elongation in the Heart
Authors: Matthew S Stratton, Bradley S Ferguson, Charles Y Lin, Priti Anand, Sean T Wickers, Philip D Tatman, James E Bradner, Saptarsi M Haldar, Timothy A McKinsey
Journal: Circulation Research (2015)

BRD4 is a member of the BET family of proteins, which contain tandem reader domains (bromodomains) that bind to acetylated histone tails within chromatin. We recently demonstrated that JQ1, a small molecule that prevents BRD4-chromatin interaction, potently blocks pathological cardiac hypertrophy and improves cardiac function in pre-clinical models. BRD4 functions as a nodal regulator of the transcriptional program for cardiac hypertrophy by recruiting P-TEFb to gene regulatory elements, resulting in phosphorylation of RNA polymerase II (Pol II), and subsequent transcription elongation. Here, we describe a signal-dependent mechanism for regulation of BRD4 in the heart. BRD4 protein expression is dramatically upregulated in cardiomyocytes exposed to cues for pathological, but not physiological, hypertrophy. In unstimulated cardiomyocytes, BRD4 protein expression is maintained at low levels by a microRNA, which directly targets the 3’ UTR of the BRD4 transcript, thereby preventing translation of this acetyl-lysine reader. In response to signals for hypertrophy, expression of the microRNA is down regulated through a histone deacetylase (HDAC)-dependent mechanism, resulting in robust induction of BRD4 protein synthesis. Whole genome analyses establish a crucial role for the microRNA in the control of Pol II elongation in the heart via BRD4 down regulation. These findings define a novel chromatin signaling axis that can be targeted at multiple levels (epigenetic reader, microRNA or HDAC) for the treatment of heart failure.
Risks associated with viral infections during pregnancy
Authors: Karen Racicot, Gil Mor
Journal: Journal of Clinical Investigation (2017)

Despite the prevalence of viral infections in the American population, we still have a limited understanding of how they affect pregnancy and fetal development. Viruses can gain access to the decidua and placenta by ascending from the lower reproductive tract or via hematogenous transmission. Viral tropism for the decidua and placenta is then dependent on viral entry receptor expression in these tissues as well as on the maternal immune response to the virus. These factors vary by cell type and gestational age and can be affected by changes to the in utero environment and maternal immunity. Some viruses can directly infect the fetus at specific times during gestation, while some only infect the placenta. Both scenarios can result in severe birth defects or pregnancy loss. Systemic maternal viral infections can also affect the pregnancy, and these can be especially dangerous, because pregnant women suffer higher virus-associated morbidity and mortality than do nonpregnant counterparts. In this Review, we discuss the potential contributions of maternal, placental, and fetal viral infection to pregnancy outcome, fetal development, and maternal well-being.
Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes
Authors: Vincent L. Aengevaeren, Arend Mosterd, Thijs L. Braber, Niek H.J. Prakken, Pieter A. Doevendans, Diederick E. Grobbee, Paul D. Thompson, Thijs M.H. Eijsvogels, Birgitta K. Velthuis
Journal: Circulation (2017)

Background: Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis. Methods: Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants’ activity was categorized as &lt;1000, 1000 to 2000, or &gt;2000 MET-min/wk. Results: A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3–145.8). Athletes with a lifelong exercise volume &gt;2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0–60.9] versus 0 [interquartile range, 0–43.5]; P =0.02) and prevalence of CAC (68%; adjusted odds ratio [OR adjusted ]=3.2; 95% confidence interval [CI], 1.6–6.6) and plaque (77%; OR adjusted =3.3; 95% CI, 1.6–7.1) compared with &lt;1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR adjusted =1.47; 95% CI, 1.14–1.91) and plaque (OR adjusted =1.56; 95% CI, 1.17–2.08). Among participants with CAC&gt;0, there was no difference in CAC score ( P =0.20), area ( P =0.21), density ( P =0.25), and regions of interest ( P =0.20) across exercise volume groups. Among participants with plaque, the most active group (&gt;2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR adjusted =0.35; 95% CI, 0.15–0.85) and more often had only calcified plaques (38% versus 16%; OR adjusted =3.57; 95% CI, 1.28–9.97) compared with the least active group (&lt;1000 MET-min/wk). Conclusions: Participants in the &gt;2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants.
OS05.2 Burnout and Career Satisfaction among Neuro-Oncology Health Care Providers: An International Survey
Authors: S. Yust-Katz, B. J. O’Brien, A. Acquaye, T. Armstrong
Journal: Neuro-Oncology (2017)

BACKGROUND: Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and loss of meaning or purpose in work. Among oncologists, burnout has been reported to be significantly higher in those focusing on one type of cancer. CNS tumors are highly aggressive tumors with very poor prognosis. Caring for patients with CNS tumors can be challenging, and may place neuro-oncology health care providers at risk for burnout. The goal of this study was to explore the incidence and associated factors for burnout in neuro-oncology health care professionals. METHODS: We are conducting an international survey of health care providers of all professions treating patients with CNS tumors. The survey includes questions on demographic, career and lifestyle features. In addition, the Maslach Burnout Inventory, a 22-item questionnaire considered the gold-standard tool for measuring professional burnout, was incorporated. Results: Up to Nov 15th 324 SNO members have participated in the survey (53% females, 45% neuro-oncologists). Preliminary results indicate that 30% subjectively reported experiencing burnout and 45% reported experiencing burnout in the past. Most of the participants were from the United States (70%). More than 70% of the participants reported working more than 50 hours per week, and 95% reported working from home. Nearly half of participants reported significant stress, and did not meet exercise and sleep recommendations for a healthy lifestyle. 55% considered their income not adequate for the time and effort they devote to their profession. CONCLUSION: Burnout among neuro-oncology health care providers is a common problem. Estimating the prevalence of burnout and associated risk factors is imperative for improving professional and personal satisfaction and patient care. Expanding survey participation worldwide is needed to better understand the impact on the neuro-oncology community and to ultimately establish strategies for better support for neuro-oncology providers.
Daunorubicin and Cytarabine Compared with Daunorubicin, Cytarabine and the MDR1 Reversal Agent PSC-833 in Elderly Patients with Acute Myelogenous Leukemia.
Authors: Bronno van der Holt, Pieter Sonneveld, Alan K. Burnett, Paula J.M. Vossebeld, Berna Beverloo, Gerd Rosenkranz, Margaret Dugan, Wim L.J. van Putten, Keith Wheatley, Bob Lowenberg
Journal: Blood (2004)
P14.05 How far can they grow... - Two clinical examples
Authors: V. Espírito Santo, M. Mendes, R. Almendra, A. Veiga, A. Velon, P. Guimarães
Journal: Neuro-Oncology (2017)

Introduction: Cerebral metastases are the most common form of central nervous system (CNS) tumours in adults. However, malignant neoplasm may also involve structures external to the brain, such as tissue surrounding the base of the skull, and then metastasize to the brain either by direct invasion or by spreading by the cranial nerves. CASE1: A 74 year-old man, with a past history of chronic kidney disease due to renal artery thrombosis and hypertension, was admitted in the emergency room (ER) complaining of persisting pain in the superior half of the right hemiface and frontal region, refractory to analgesia, with 2 months of evolution. He also referred diplopia in the right eye, homolateral hearing loss and asthenia. Neurological examination revealed psychomotor retardation, right VI cranial nerve paralysis, right sensorineural hypoacusis and dysphagia. Brain and neck MRI showed a lesion in right nasopharynx that invaded the bony structures of the base of the skull, in particular the petrous apex, clivus and great sphenoid wing. It also had an endocranial soft tissue component that occupied the cistern of Gasser’s ganglion. He was diagnosed with a nasopharynx malignant neoplasm. His clinical status deteriorated rapidly and he died 1 month later. CASE2: A 68 year-old woman, with a past history of left great sphenoid wing meningioma that was removed 2 years ago, was admitted in the ER complaining of tinnitus and hearing loss in the left ear and dizziness. Neurological examination revealed peripheral left facial paralysis, which the patient claims to have arisen shortly after the previous surgery and left conductive hypoacusis. Brain MRI showed a lesion in the left parotid gland that invaded the petrous bone, infiltrating the jugular foramen and carotid canal, causing deformation of these vascular structures. She was diagnosed with a parotid gland malignant neoplasm that slowly grow in the last 2 years. By this moment, she is still waiting for a decision about the best treatment plan. Conclusions: With this work, we intend to exemplify two cases in which two different soft tissue tumours slowly grow until they caused symptoms due to direct invasion of base of the skull structures, which significantly complicate their treatment and these patients’ survival.
P10.09 Outcomes in elderly patients with low-grade glioma undergoing surgical resection
Authors: S. J. Han, R. A. Morshed, S. M. Chang
Journal: Neuro-Oncology (2017)

Introduction: Low-grade gliomas are mostly commonly diagnosed in patients in the third and fourth decade of life, and are not commonly seen in patients older patients. Thus there is a lack of consensus in disease management within this age group. While maximizing the extent of resection has been reported to improve outcomes in patients with low-grade gliomas, data in the subgroup of individuals over the age of 60 is limited, and there are some reports that outcomes are worse compared to younger counterparts. While in younger patients, an aggressive resection may obviate the need for adjuvant therapy, in older patients, upfront adjuvant therapy has been advocated regardless of the extent of resection achieved. Thus, some practitioners may feel an aggressive resection is worth pursuing in older patients given the increased perioperative morbidity profile. Materials and Methods: In order to assess whether these patients may be safely treated with and benefit from aggressive surgical resection, we identified 22 patients at least 60 years of age who had undergone resection of a ­low-grade glioma between January 1997 and September 2015. Pre-operative and post-operative tumor volumes were quantified using BrainLab Smartbrush software. To quantify tumor volume, manual segmentation was performed with region-of-interest analysis based on T2 or fluid-attenuated inversion-recovery (FLAIR) sequences from pre- and post-operative MRI scans. Results: Mean age at the time of surgery was 65.55 years (range 61.16 - 71.8) with a median follow-up period of 3.4 years. Pathologic diagnoses included oligodendrogliomas (65%), diffuse astrocytomas (18.18%), and mixed oligoastrocytomas (22.72%). Surgical resection was performed with either language and/or motor mapping in 82% of patients. Mean volumetric extent of resection was 75.05%. No worsened or new neurological deficits were seen in 73% of patients post-operatively. One- and 2-year progression free survival (PFS) rates were found to be 81.25% and 57.14%, respectively, for patients with adequate follow-up. CONCLUSION: This evidence suggests that an aggressive resection strategy can be applied safely to older patients with low-grade gliomas.
Analytic, Preanalytic, and Clinical Validation of p53 IHC for Detection of <i>TP53</i> Missense Mutation in Prostate Cancer
Authors: Liana B. Guedes, Fawaz Almutairi, Michael C. Haffner, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Kasra Yousefi, Rajni Sharma, Angelo M. De Marzo, George J. Netto, William B. Isaacs, Ashley E. Ross, Edward M. Schaeffer, Tamara L. Lotan
Journal: Clinical Cancer Research (2017)

missense mutations may help to identify prostate cancer with lethal potential. Here, we preanalytically, analytically, and clinically validated a robust IHC assay to detect subclonal and focal
Management of chronic pain using complementary and integrative medicine
Authors: Lucy Chen, Andreas Michalsen
Journal: BMJ (2017)

Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic pain is the leading indication for use of CIM, and about 33% of adults and 12% of children in the US have used it in this context. Although advances have been made in treatments for chronic pain, it remains inadequately controlled for many people. Adverse effects and complications of analgesic drugs, such as addiction, kidney failure, and gastrointestinal bleeding, also limit their use. CIM offers a multimodality treatment approach that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. This review focuses on the use of CIM in three conditions with a high incidence of chronic pain: back pain, neck pain, and rheumatoid arthritis. It summarizes research on the mechanisms of action and clinical studies on the efficacy of commonly used CIM modalities such as acupuncture, mind-body system, dietary interventions and fasting, and herbal medicine and nutrients.
OS07.1 Molecular differences in IDH wild type glioblastoma according to MGMT promoter methylation status
Authors: T. Kessler, F. Sahm, A. Sadik, A. Hertenstein, M. Bendszus, A. von Deimling, M. Platten, W. Wick
Journal: Neuro-Oncology (2017)

Background:O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a biomarker for patients with glioblastoma treated with alkylating agents. We investigated whether this marker just predicts the efficacy of alkylating chemotherapy or defines a molecularly distinct tumor subpopulation with clinically different outcome. Methods: Isocitrate dehydrogenase (IDH) 1/2 wild type MGMT promoter methylated (mMGMT) vs. unmethylated (uMGMT) glioblastomas were assessed for differences in copy number variation, methylation, mutation and RNA expression. We analyzed copy number variation and methylation profiles in a series of 1106 glioblastomas from the Heidelberg Neuropathology database, including 66 recurrent samples. DNA mutation data was obtained from 182 glioblastoma samples of The Cancer Genome Atlas (TCGA). RNA expression data was obtained from 107 TCGA and 55 Chinese Glioma Genome Atlas samples. We investigated differences between short (< 6 months) and long survivors (> 12 months) in the TCGA dataset. Results: At primary diagnosis, mMGMT and uMGMT tumors did not show different copy number alterations or specific gene mutations, but a moderately higher mutation rate in mMGMT tumors. Most of the differentially methylated positions were hypermethylated in the mMGMT group. Gastrulation brain homeobox (GBX) 2, which promotes tumor growth in prostate cancer, was found to be hypermethylated and two-fold downregulated in the mMGMT group. TCGA expression subtypes showed a trend towards more proneural tumors in the mMGMT group and RNAseq data revealed increased expression of resistance-associated genes in uMGMT tumors. In the recurrent setting, platelet-derived growth factor receptor (PDGFR)A and GLI family zinc finger (GLI)2 amplifications were enriched in mMGMT tumors. Amplification of chromosome 19 and the C19MC oncogenic miRNA complex were more frequent in recurrent mMGMT tumors. These tumors also showed a hypermethylation of the protocadherin (PCDH) gene cluster at recurrence, which had been linked to aggressiveness in neuroblastoma. Glioblastoma patients with short survival and MGMT promoter methylation harbored less EGFR amplifications, more TP53 mutations and higher TNF-NFκB pathway activation compared to long survivors. Patients with uMGMT tumors and long survival showed an increased interferon signaling, which has been shown to downregulate MGMT and induce chemosensitivity. Conclusions:MGMT promoter methylation status serves as a biomarker for alkylating therapy and does not describe a molecular distinct glioblastoma subpopulation in the primary setting. However, recurrent mMGMT glioblastomas and mMGMT tumors of patients with short survival tend to have specific, more unfavorable molecular profiles, which could be a leverage point for further research.