tbuckley/cabot-search huggingface dataset:
RADIOMIC FEATURES FROM PHYSIOLOGICAL MRI SHOWS IMPROVED ACCURACY OVER STRUCTURAL MRI IN PREDICTING MGMT PROMOTER METHYLATION IN GLIOBLASTOMA
Authors: Chao Li, Shuo Wang, Florian Markowetz, Stephen Price
Journal: Neuro-Oncology (2018)

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is widely used as an independent favorable prognostic factor in glioblastoma patients. However, the evaluation depends on the tissue obtained via surgery. The purpose of this study is to determine whether radiomic features of magnetic resonance imaging (MRI) can be used for predicting MGMT prompter methylation status, and to compare the accuracies of physiological and structural sequences in prediction. Pre-operative MRI scan was performed on 111 primary glioblastoma patients. MRI sequences include structural sequence (T1-weighted, T2-weighted, post-contrast T1-weighted and T2-weighted fluid attenuated inversion recovery [FLAIR]) and physiological sequence (dynamic susceptibility contrast-enhancement [DSC] and diffusion tensor imaging [DTI]). All images were co-registered to T2-weighted images. DTI and DSC were processed as previously. Mean diffusivity (MD), fractional anisotropy (FA), DTI-p and DTI-q were generated from DTI. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated from the DSC. Radiomic features which describe the shape, margin, intensity histogram and texture of the tumor were extracted from each imaging modality. The least absolute shrinkage and selection operator (LASSO) regularization was used for feature selection. Support Vector Machines (SVM) was used for the prediction of MGMT prompter promoter methylation status, which was determined using pyrosequencing. A total of 15 features were selected from the structural imaging and 21 features were selected from the physiological imaging. An accuracy of 0.71 was achieved from the selected structural imaging features, while an accuracy of 0.79 was obtained from the selected physiological features. Our findings showed that radiomic features are useful in predicting MGMT promoter methylation status of glioblastoma using supervised machine learning schemes. Physiological imaging features may have the potential to make more accurate prediction than structural imaging features. Texture analysis may extract the most useful features for the prediction.
Engineering resistance to CD33-targeted immunotherapy in normal hematopoiesis by CRISPR/Cas9-deletion of CD33 exon 2
Authors: Olivier Humbert, George S. Laszlo, Sophie Sichel, Christina Ironside, Kevin G. Haworth, Olivia M. Bates, Mary E. Beddoe, Ray R. Carrillo, Hans-Peter Kiem, Roland B. Walter
Journal: Leukemia (2018)
Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab
Authors: Nicolas A. Giraldo, Peter Nguyen, Elizabeth L. Engle, Genevieve J. Kaunitz, Tricia R. Cottrell, Sneha Berry, Benjamin Green, Abha Soni, Jonathan D. Cuda, Julie E. Stein, Joel C. Sunshine, Farah Succaria, Haiying Xu, Aleksandra Ogurtsova, Ludmila Danilova, Candice D. Church, Natalie J. Miller, Steve Fling, Lisa Lundgren, Nirasha Ramchurren, Jennifer H. Yearley, Evan J. Lipson, Mac Cheever, Robert A. Anders, Paul T. Nghiem, Suzanne L. Topalian, Janis M. Taube
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified. <h3>Methods</h3> Pretreatment FFPE tumor specimens (<i>n</i> = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (<i>n</i> = 16), to identify cell types expressing PD-1. <h3>Results</h3> Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm<sup>2</sup>, 70.7 vs. 6.7, <i>p</i> = 0.03; and 855.4 vs. 245.0, <i>p</i> = 0.02, respectively). There was no significant association of CD8+ cell density with clinical response. Quantification of PD-1+ cells located within 20&nbsp;μm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was associated with clinical response (<i>p</i> = 0.03), but CD8/PD-L1 proximity was not. CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1. <h3>Conclusions</h3> While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, T<sub>regs</sub>, and CD20+ B-cells, supporting the notion that multiple cell types may potentiate tumor regression following PD-1 blockade.
FoxO1 is a critical regulator of M2‐like macrophage activation in allergic asthma
Authors: Sangwoon Chung, Ji Y. Kim, Min‐Ae Song, Gye Y. Park, Yong G. Lee, Manjula Karpurapu, Joshua A. Englert, Megan N. Ballinger, Navjot Pabla, Hae Y. Chung, John W. Christman
Journal: Allergy (2018)

Abstract Background The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment. Methods We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2‐8 weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1 fl/fl LysMcre). Cytokine level in biological fluids was measured by ELISA and the expression of encoding molecules by NanoString assay and qRT ‐ PCR . Results We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro‐asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro‐asthmatic and pro‐fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma. Conclusion Targeting FoxO1 with its downstream regulator IRF 4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.
Conservative conference: Hancock pledges extra cash for social care and expansion of genomic medicine
Authors: Adrian O’Dowd
Journal: BMJ (2018)

The health and social care secretary has pledged an extra £240m (€270m; $312m) for social care this year to help avoid a winter crisis in the NHS.

In a keynote speech to the Conservative Party’s annual conference in Birmingham on 2 October, Matt Hancock also vowed to expand genomic medicine and new technology as part of efforts to reform the health service and guarantee its long term future.

Announcing an extra £240m for local councils to fund social care this winter, he said, “We will use this money to get people who don’t need to be in hospital, but do need care, back home, back into their communities, so we can free up those …
Durable response to mTOR inhibition in a patient with relapsing papillary tumor of the pineal region
Authors: Mattias Belting, Anna Bång-Rudenstam, Elisabet Englund, Torsten Pietsch
Journal: Neuro-Oncology (2018)

Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IGF-1R, insulin-like growth factor 1 receptor; KPS, Karnofsky Performance Scale; RT, radiotherapy; SOC, standard of care; TMZ, temozolomide.
Terlipressin Is Superior to Noradrenaline in the Management of Acute Kidney Injury in Acute on Chronic Liver Failure
Authors: Vinod Arora, Rakhi Maiwall, Vijayaraghavan Rajan, Ankur Jindal, Saggere Muralikrishna Shasthry, Guresh Kumar, Priyanka Jain, Shiv Kumar Sarin
Journal: Hepatology (2018)

Hepatorenal syndrome (HRS) carries a high short-term mortality in patients with cirrhosis and acute on chronic liver failure (ACLF). Terlipressin and noradrenaline are routinely used in cirrhosis with HRS and have been found to be equally effective. There are no data comparing the efficacy of terlipressin with noradrenaline in ACLF patients with HRS. In an open-label, randomized controlled trial (RCT), consecutive patients with ACLF diagnosed with HRS acute kidney injury (AKI) were randomized to albumin with infusion of terlipressin (2-12 mg/day; n = 60) or noradrenaline (0.5-3.0 mg/h; n = 60). Response to treatment, course of AKI, and outcome were studied. Baseline characteristics, including AKI stage and sepsis-related HRS-AKI, were comparable between groups. Compared to noradrenaline, terlipressin achieved greater day 4 (26.1% vs. 11.7%; P = 0.03) and day 7 (41.7% vs. 20%; P = 0.01) response. Reversal of HRS was also better with terlipressin (40% vs. 16.7%; P = 0.004), with a significant reduction in the requirement of renal replacement therapy (RRT; 56.6% vs. 80%; P = 0.006) and improved 28-day survival (48.3% vs. 20%; P = 0.001). Adverse events limiting use of drugs were higher with terlipressin than noradrenaline (23.3% vs. 8.3%; P = 0.02), but were reversible. On multivariate analysis, high Model for End-Stage Liver Disease (MELD; odds ratio [OR], 1.10; confidence interval [CI] = 1.009-1.20; P = 0.03) and noradrenaline compared to terlipressin (OR, 3.05; CI = 1.27-7.33; P = 0.01) predicted nonresponse to therapy. Use of noradrenaline compared to terlipressin was also predictive of higher mortality (hazard ratio [HR], 2.08; CI = 1.32-3.30; P = 0.002). Conclusion: AKI in ACLF carries a high mortality. Infusion of terlipressin gives earlier and higher response than noradrenaline, with improved survival in ACLF patients with HRS-AKI.
Acceleration of BMI in Early Childhood and Risk of Sustained Obesity
Authors: Mandy Geserick, Mandy Vogel, Ruth Gausche, Tobias Lipek, Ulrike Spielau, Eberhard Keller, Roland Pfäffle, Wieland Kiess, Antje Körner
Journal: New England Journal of Medicine (2018)

The dynamics of body-mass index (BMI) in children from birth to adolescence are unclear, and whether susceptibility for the development of sustained obesity occurs at a specific age in children is important to determine.
Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Margreet Kloppenburg, Roberta Ramonda, Klaus Bobacz, Wing-Yee Kwok, Dirk Elewaut, Tom W J Huizinga, Féline P B Kroon, Leonardo Punzi, Josef S Smolen, Bert Vander Cruyssen, Ron Wolterbeek, Gust Verbruggen, Ruth Wittoek
Journal: Annals of the Rheumatic Diseases (2018)

Hand osteoarthritis is a prevalent disease with limited treatment options. Since joint inflammation is often present, we investigated tumour necrosis factor (TNF) as treatment target in patients with proven joint inflammation in a proof-of-concept study.This 1-year, double-blind, randomised, multicentre trial (NTR1192) enrolled patients with symptomatic erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal anti-inflammatory drug washout were randomised to etanercept (24 weeks 50 mg/week, thereafter 25 mg/week) or placebo. The primary outcome was Visual Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS, n=54) and MRIs (n=20)).Of 90 patients randomised to etanercept (n=45) or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was not statistically significantly different (-5.7 (95% CI -15.9 to 4.5), p=0.27 at 24 weeks; - 8.5 (95% CI -18.6 to 1.6), p=0.10 at 1 year; favouring etanercept). In prespecified per-protocol analyses of completers with pain and inflammation at baseline (n=61), MD was -11.8 (95% CI -23.0 to -0.5) (p=0.04) at 1 year. Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD 2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD -0.22 (95% CI -0.35 to -0.09), p = 0.001); this was more pronounced in joints with baseline inflammation.Anti-TNF did not relieve pain effectively after 24 weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for effects on subchondral bone in actively inflamed joints, but future studies to confirm this are warranted.
Reply to M. von Wolff et al
Authors: Kutluk Oktay, Brittany E. Harvey, Alison W. Loren
Journal: Journal of Clinical Oncology (2018)

We thank von Wolff et al 1 for highlighting the important topic of ovarian tissue cryopreservation, and we appreciate their thoughtful application of a framework to define experimental, innovative, and established therapies.We also value their nuanced description of the procedure by subclassifying its use on the basis of the populations in whom it may be offered: children, women with hematologic malignancies or other cancers with a high risk of ovarian tissue involvement, and women with cancers that pose a low risk of ovarian metastases.The Fertility Preservation in Patients with Cancer Guideline Expert Panel acknowledges that ovarian tissue freezing followed by ovarian transplant is considered nonexperimental in some countries outside the United States, and this was mentioned in the guideline. 2The primary purpose of an ASCO guideline update is to provide state-of-the-art, evidence-based recommendations to providers of cancer care and to respond to signals 3 in the literature that suggest that a revision of a previous guideline may be warranted.The specific purpose of this guideline update was to provide additional guidance on the use of gonadotropin-releasing hormone agonists to preserve ovarian function in women with cancer, given the plethora of additional published data.However, we felt it was advisable to take this opportunity to discuss additional progress in the field of fertility preservation, and we included an expanded discussion of ovarian tissue cryopreservation, including a metaanalysis. 4he ASCO Expert Panel is responsive to progress in the field; for instance, our 2013 guideline update included explicit recognition that oocyte cryopreservation was no longer designated experimental and was accepted as an established procedure in 2012. 5We noted that the American Society of Reproductive Medicine (ASRM) still categorizes ovarian tissue cryopreservation as experimental and has not formally recommended a change in the designation of this procedure to established therapy.The Expert Panel felt that, as an organization for cancer specialists, ASCO would be overstepping the bounds of its territory by suggesting that ovarian tissue cryopreservation is no longer experimental.Instead, we felt this designation should originate from ASRM, on behalf of the specialists in reproductive medicine and surgery.We will remain responsive, however, and if ASRM elects to change the experimental designation of cryopreservation of ovarian tissue, ASCO may choose to reconvene the panel to review the evidence and issue a guideline update.
Abstract 19135: Gpr83 Function Contributes to Salt Resistance
Authors: Xiaoxu Zheng, Milan Patel, Prasad Konkalmatt, Laureano Asico, Pedro A Jose, Ines Armando
Journal: Circulation (2017)

The G protein–coupled receptor 83 (Gpr83) is an orphan receptor that has been associated with essential hypertension; single nucleotide polymorphisms in the Gpr83 gene predict a good blood pressure...
Acupuncture for Women Undergoing In Vitro Fertilization
Authors: Haiyong Chen, Mingxiao Yang, Lixing Lao
Journal: JAMA (2018)

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MEDULLOBLASTOMA INCIDENCE AND SURVIVAL - A POPULATION BASED STUDY
Authors: Maria Khan, Kwok Wong, Dem Jardel, John Broggio, Charles Stiller, Martin McCabe
Journal: Neuro-Oncology (2018)

Medulloblastoma can occur at any age, but is most frequent in infancy and childhood. There have been no previous detailed reports of incidence or survival across all age groups in the UK and few population-based reports internationally. This project provides for the first time population-based data on medulloblastoma incidence and survival across all ages in England. We extracted data for all patients with medulloblastoma diagnosed during 2001–2015, in England, from the English national cancer registry. The crude incidence rates per 100,000 were calculated, for all individuals and subdivided by age and 3/5yr periods. We also calculated 1-, 3-, 5- and 10-yr Kaplan Meier survival by 5-yr periods, for the overall cohort and by age group. The overall average crude incidence rate was 0.12 per 100,000 (2001–2015), with no significant trend between 5-yr periods. However, the incidence rate for the age groups 0–3 and 4–14 was significantly higher than the older age groups. Male incidence was significantly higher than female. The 1-, 3-, and 5-yr (2001–2005) survival was significantly lower for infants than for older children. There was no significant difference in survival between children and the Teenage/Young Adult (TYA) group, for 5-yr and 10-yr survival. For all age groups, 10-yr survival was lower than 5-yr. All age 1-yr survival improved in the most recent period (2011–2015), 87.2% compared to 84.9% in 2006–2010. Individuals aged 4–14 and 15–24 had the highest 1-yr survival (2006–2010), 90.1% and 92.3% respectively, 5-yr (2006–2010), 64.0% and 76.9%, 10-yr (2001–2005), 65.4% and 63.6% respectively. Medulloblastoma survival continues to decrease beyond 5-yr post diagnosis and varies by age group. Future investigation of whether variation in survival by age is related to systematic differences in tumour biology or in treatment could indicate ways of improving outcome for poorer-prognosis age groups.
IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
Authors: Rabea Wagener, Cristina López, Kortine Kleinheinz, Julia Bausinger, Sietse M. Aukema, Inga Nagel, Umut H. Toprak, Julian Seufert, Janine Altmüller, Holger Thiele, Christof Schneider, Julia Kolarova, Jeongbin Park, Daniel Hübschmann, Eva M. Murga Penas, Hans G. Drexler, Andishe Attarbaschi, Randi Hovland, Eigil Kjeldsen, Michael Kneba, Udo Kontny, Laurence de Leval, Peter Nürnberg, Ilske Oschlies, David Oscier, Brigitte Schlegelberger, Stephan Stilgenbauer, Wilhelm Wössmann, Matthias Schlesner, Birgit Burkhardt, Wolfram Klapper, Elaine S. Jaffe, Ralf Küppers, Reiner Siebert
Journal: Blood (2018)
Abstract 14884: Frailty Status and Transcatheter Aortic Valve Replacement Outcome Regardless of Society of Thoracic Surgery Risk Score
Authors: M Chadi Alraies, Homam Moussa Pacha, Kyle Buchanan, Arie Steinvil, Mohamad Soud, Toby Rogers, Edward Koifman, Rebecca Torguson, Linzhi Xu, Itsik Ben-Dor, Lowell F Satler, Augusto D Pichard, Ron Waksman
Journal: Circulation (2017)

Introduction: Society of Thoracic surgery (STS) risk score is used to determine transcatheter aortic valve replacement (TAVR) procedure risk. We sought to study the incremental improvement of STS r...
An audit of the management of elderly patients with glioblastoma in the UK: have recent trial results changed treatment?
Authors: Mr Ming Chong, Dr Cressida Lorimer, Dr Catherine Hanna, Ms Deborah Houston, Prof Anthony J Chalmers
Journal: Neuro-Oncology (2018)

A new treatment option for elderly patients with glioblastoma (GBM) became available in June 2016 with Perry’s presentation at ASCO showing that hypofractionated radiotherapy (40Gy in 15#) with concomitant and adjuvant temozolomide improved survival compared to hypofractionated radiotherapy only. We investigated uptake of this treatment regimen in two UK oncology centres. This retrospective study involved patients from NHS Greater Glasgow and Clyde and Brighton and Sussex University Hospitals. Patients aged 65 or over with a histological or radiological diagnosis of GBM were identified from multidisciplinary meeting and clinic lists between July 2016 and December 2017. 141 patients were identified. 72 had a pathological diagnosis and 69 had a radiological diagnosis of GBM. 23.6% of patients with a pathological diagnosis exhibited MGMT promoter methylation. Median age was 74.4 years and 43.3% of patients were female. 57.7% received at least one oncology appointment. 18.4% of patients received chemotherapy and radiotherapy, 8.5% chemotherapy only and 6.4% radiotherapy only. 63.8% did not receive either chemotherapy or radiotherapy. Patients who received treatment had a significantly lower median age at diagnosis than patients who did not receive treatment (69.4 years v. 76.8 years, P=0.000). Median overall survival was 6 months. Of 26 patients receiving radiotherapy and concomitant chemotherapy, 46.2% received hypofractionated radiotherapy and the remainder received standard radiotherapy (60 Gy in 30#). Median survival for both groups was 12 months (P=0.991). While both centres adopted the hypofractionated chemoradiation schedule, a significant proportion of elderly GBM patients received standard chemo-radiotherapy. Importantly, median survival of patients receiving hypofractionated chemo-radiotherapy was equivalent to that of patients receiving long course treatment. The shorter treatment time, better side effect profile and equivalent survival outcomes of the hypofractionated regime indicate that it should be used more widely in the management of GBM patients aged over 65.