tbuckley/cabot-search huggingface dataset:
REOPERATION IN GLIOBLASTOMA: IS IT WORTH IT?
Authors: Benjamin Hall, Emmanuel Chavredakis, Sally-Ann Price, David D A Lawson, Catherine McMahon, Andrew R Brodbelt, Catherine E Gilkes, Paul R Eldridge, Jibril O Farah, Michael D Jenkinson
Journal: Neuro-Oncology (2018)

The most common primary intracranial malignancy, glioblastoma (GBM) carries an exceptionally poor prognosis. Though first line management has seen some standardisation in recent years, the approach to recurrence is more heterogenous. To determine whether resection of recurrent GBM impacts survival, cases between January 1st 2015 and 31st December 2016 were retrospectively reviewed. Eligible patients had: (i) primary GBM; (ii) undergone resection for initial tumour (iii) received treatment for recurrence that could include chemoradiotherapy, reoperation or Gliadel. Data collected included tumour location and volume, extent of resection, ECOG, time to progression and death. Univariate and multivariate analyses were then performed. 136 eligible patients were identified with a median age of 61.5 years, of whom 78 (57%) were males. Tumours were predominantly temporal and frontal (70%), with a mean volume of 34300mm3. 36% of patients had initial gross total resection (GTR), with 81% going on to receive temozolomide and radiotherapy as part of the Stupp protocol. Median time to recurrence was 7.4 months, with 30 patients (22.1%) receiving reoperation; resulting in a significantly longer OS of 29.4 months compared to 13.5 in the non-reoperation group (P<0.05, 95% 0.180–0.990, 0.42), without an increase in morbidity when compared to first surgery. 15.4% of patients suffered complications at initial operation, while 12.1% did so at reoperation. (P>0.05). Cox regression analysis confirmed initial GTR as a significant predictor of survival, providing an OS of 20.5 months vs 16.4 months in the subtotal group (P<0.05, 95% 0.220–0.870, 0.44). MGMT methylation also significantly, positively influenced OS (P<0.01, 95% 0.083- 0.629, 0.21), whilst an older age conferred a worse prognosis (P=0.02, 95% 1.005–1.079, 1.04). Overall, in keeping with existing literature, reoperation in recurrent GBM is shown to be an effective means of prolonging OS, without deleterious effects on neurological function.
GP at Hand adverts were misleading to patients, watchdog rules
Authors: Abi Rimmer
Journal: BMJ (2018)

The UK’s advertising watchdog has ruled that GP at Hand can no longer use adverts that don’t make it clear to patients that they must deregister from their current practice to use the service.

The ruling from the Advertising Standards Authority (ASA) came after eight complainants, including a GP, challenged whether the adverts were misleading.1

GP at Hand, run by an NHS general practice in Hammersmith in partnership with the technology company Babylon, offers patients GP consultations 24/7 on their smartphone or in person at five clinics in London. To use the service, patients are required to deregister with their existing GP.

In March, GPs in Hackney, London, warned that some of their patients had signed up for the service without realising that this deregistered them from their local surgery. …
Obinutuzumab plus Lenalidomide (GALEN) for the treatment of relapse/refractory aggressive lymphoma: a phase II LYSA study
Authors: Roch Houot, Guillaume Cartron, Fontanet Bijou, Sophie de Guibert, Gilles A. Salles, Christophe Fruchart, Krimo Bouabdallah, Marie Maerevoet, Pierre Feugier, Steven Le Gouill, Hervé Tilly, Rene-Olivier Casasnovas, Cécile Moluçon-Chabrot, Eric Van Den Neste, Pierre Zachee, Marc Andre, Christophe Bonnet, Corinne Haioun, Achiel Van Hoof, Koen Van Eygen, Lysiane Molina, Emmanuelle Nicolas-Virelizier, Philippe Ruminy, Franck Morschhauser
Journal: Leukemia (2018)
Abstract 14404: O-GlcNAc Mediates Cardioprotection by Remote Ischemic Preconditioning and Induces a State of Chronic Cardioprotection in Diabetes Mellitus
Authors: Rebekka V Jensen, Natasha E Zachara, Per H Nielsen, Hans H Kimose, Steen B Kristiansen, Hans E Bøtker
Journal: Circulation (2012)

Posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardioprotective but its role in cardioprotection by remote ischemic preconditioning (rIPC) and the reduced efficacy of rIPC in type 2 diabetes mellitus is unknown Hypothesis: The remote stimulus mediating and the target organ response eliciting the cardioprotective effect of rIPC in non-diabetic and diabetic myocardium activates O-GlcNAcylation. Methods and Results: The cardioprotective capacity and influence on myocardial O-GlcNAc levels of plasma dialysate from 8 healthy volunteers and 8 type 2 diabetic patients drawn before and after rIPC, were tested on human isolated atrial trabeculae subjected to ischemia-reperfusion injury. Dialysate from healthy volunteers exposed to rIPC improved post ischemic hemodynamic recovery (40±6% vs 16±2%; p<0.01) and increased myocardial O-GlcNAc levels (Figure 1a, left columns). Similar observations were made with dialysate from diabetic patients before exposure to rIPC (43±3% vs...
Hypertrophic Cardiomyopathy
Authors: Perry Elliott
Journal: Circulation (2018)

The first patient to have surgical treatment (back in 1958) was a young man in whom the late Paul Wood had clearly identified the features of functional dynamic left ventricular outflow tract obstruction.He survived into middle age, with gradual reduction in wall thickness, loss of systolic efficiency, and relative dilatation of the previously small left ventricular cavity, and died in congestive failure from what is now recognised to be a progressive myopathy.
Generation and Characterization of Anti–Citrullinated Protein Antibody–Producing B Cell Clones From Rheumatoid Arthritis Patients
Authors: Kristine Germar, Cynthia M. Fehres, Hans U. Scherer, Nathalie van Uden, Sabrina Pollastro, Nataliya Yeremenko, Monika Hansson, Priscilla F. Kerkman, Ellen I. H. van der Voort, Evan Reed, Hanna Maassen, Mark J. Kwakkenbos, Arjen Q. Bakker, Lars Klareskog, Vivianne Malmström, Niek de Vries, René E. M. Toes, Karin Lundberg, Hergen Spits, Dominique L. Baeten
Journal: Arthritis & Rheumatology (2018)

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). Aside from autoantibody production, the function of autoantigen-specific B cells remains poorly understood in the context of this disease. This study set out to elucidate autoantigen-specific B cell functions through the isolation and immortalization of unique citrullinated protein/peptide (CP)-reactive B cell clones from RA patients.B cell clones from either the blood or synovial fluid of cyclic citrullinated peptide 2 (CCP2) antibody-positive RA patients were immortalized by genetic reprogramming with Bcl-6 and Bcl-xL. Enzyme-linked immunosorbent assay and flow cytometry were used to identify CCP2-reactive clones and to further characterize surface marker and cytokine expression as well as B cell receptor signaling competence. Global gene expression profiles were interrogated by RNA sequencing.Three unique CP-reactive memory B cell clones were generated from the blood or synovial fluid of 2 RA patients. CP-reactive memory B cells did not appear to be broadly cross-reactive, but rather had a fairly restricted epitope recognition profile. These clones were able to secrete both pro- and antiinflammatory cytokines and had a unique surface profile of costimulatory molecules and receptors, including CD40 and C5a receptor type 1, when compared to non-CP-reactive clones from the same patient. In addition, CP-reactive clones bound citrullinated protein, but not native protein, and could mobilize calcium in response to antigen binding.CP-reactive memory B cells comprise a rare, seemingly oligoclonal population with restricted epitope specificity and distinct phenotypic and molecular characteristics suggestive of antigen-presenting cells. Cloning by genetic reprogramming opens new avenues to study the function of autoreactive memory B cells, especially in terms of antigen processing, presentation, and subsequent T cell polarization.
AB0575 Clinical analysis of 22 cases of systemic lupus erythematosus complicated with hemophagocytic lymphohiscytiosis
Authors: D. xu, L. zhang, Y. li, D. jiang, Y. guo, J. tang, X. zheng, L. lu, Z. li, Y. li, G. gao
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To investigate the clinival features of hemophagocytic lymphohiscytiosis (HLH) in systemic lupus erythematosus(SLE). <h3>Methods</h3> Twenty – two cases of systemic lupus erythematosus complicated with hemophagocytic syndrome were retrospectively analysed. The clinical manifestations, laboratory tests and prognosis were collected. <h3>Results</h3> Twenty-two patients with systemic lupus erythematosus complicated with hemophagocytic syndrome developed fever in 22 patients, including 18 with hyperpyrexia, 20 with hyperferricin, 20 with cytopenia, 10 with splenomegaly, 6 with hyperglycemia, 5 cases of hypofibrinogenemia, 14 cases of bone hemoptysis occurred in the bone wear, nk cell activity decreased or absent in 7 cases, 15 cases of lymphadenopathy, mostly bilateral armpit lymph nodes and neck bilateral lymph nodes, liver function Abnormalities/hepatic insufficiency in 11 cases, ultrasound showed 10 cases of cardiac involvement, MRI showed 5 cases of cumulative brain. 22 patients were diagnosed with high-dose glucocorticoid, 9 cases of hormonal impact, 17 cases of human immunoglobulin immunosuppression in 9 cases, 4 cases of ganciclovir, 1 cases of acyclovir, 1 case of relying on Park Glycosides. 21 cases improved, 1 case to persuade invalid to abandon treatment and discharge. <h3>Conclusions</h3> SLE and hemophagocytic syndrome have some similarities. The clinical diagnosis is easy to miss. When patients with SLE continue to have high fever, splenomegaly, blood cells decrease, phagocytosis occurs in bone wears, coagulation dysfunction should be combined with vigilance HLH, Improve the relevant inspection. High-dose glucocorticoid combined with immunosuppressive agents, human immunoglobulin therapy can effectively improve the prognosis. <h3>Reference</h3> [1] Henter JI, Horne A, Arico M, etc. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Padiatr Blood Cancer Infections associated with haemophagocytic syndrome. Reactive hemophagocytic syndrome in adult systemic disease:report of twenty-sixcases and literature review. Advances in Macrophage Activation Syndrome Ma Jie, Zheng Wenjie, Tang Fulin. <h3>Disclosure of Interest</h3> None declared
Abstract 11932: Timing of Hormone Replacement Therapy and Coronary Artery Calcium: The Multi Ethnic Study of Atherosclerosis
Authors: Negin Nezarat, Yanting Luo, Dong Li, Lyndia Brumback, Nasir Khurram, Bahram Khazai, Lily Honoris, Matthew Budoff
Journal: Circulation (2015)

Introduction: Cardiovascular disease is a leading cause of mortality in post-menopausal women. Although hormone replacement therapy (HRT) is not recommended for prevention of coronary artery disease, recent evidence suggests the timing of HRT may derive different effects on atherosclerosis formation. Hypothesis: We hypothesize that women who are given HRT closer to the onset of menopause will have less coronary artery calcium (CAC). Method: Study participants were 3,174 women from the Multi-Ethnic Study of Atherosclerosis (MESA). Women who had not yet started menopause, had started menopause but not yet started HRT, had started HRT before menopause, or did not report age of menopause and/or starting HRT were excluded. To evaluate the association between presence of CAC and timing of HRT, we used logistic regression with presence of CAC as the response and with timing of HRT as a continuous linear predictor. We also used predefined categories of the timing of HRT as a predictor. Result: Among the 1396 participants who had gone through or were going through menopause and started HRT post-menopause, the prevalence of CAC was 42%, the mean of CAC was 77 (221) Agatston units, and the median was 0 (0-34).The odds of having CAC was 1.06 (95% CI: 1.04, 1.08; p&lt;0.001) times higher for starting HRT 1 year later post-menopause. The odds ratio was 1.03 (1.01, 1.04; p=0.008; N=1358) after adjustment for traditional cardiovascular risk factors, 1.02 (1.00, 1.05; p=0.02; N=1336) after further adjustment for duration of HRT, and 1.01 (0.99, 1.04; p=0.3; N=839) after further adjustment for type of HRT. The mean difference in CAC associated with starting HRT 1 year later post-menopause was 5.1 Agatston units (3.0, 7.2; P&lt;0.0001); the mean difference was smaller and not significantly different from 0 after adjustment for other risk factors. Conclusion: While this study does not provide evidence that the timing of HRT post-menopause is associated with the amount of CAC, it does provide evidence that starting HRT earlier post menopause is associated with lower odds of CAC.
A new era for treatment of drug-resistant tuberculosis
Authors: Neel R. Gandhi, James C.M. Brust, N. Sarita Shah
Journal: European Respiratory Journal (2018)

<b>Adoption of new treatment regimens for drug-resistant TB has been slowed amid concerns regarding their efficacy and safety. Numerous studies worldwide now provide substantial evidence to support widespread implementation of these new drugs and regimens.</b>http://ow.ly/FX8I30lpANX
Thyroid hormone therapy does not improve symptoms in subclinical hypothyroidism, review finds
Authors: Susan Mayor
Journal: BMJ (2018)

Thyroid hormone therapy is not associated with improvements in thyroid related symptoms or general quality of life in adults with subclinical hypothyroidism, a systematic review and meta-analysis has found.1

Subclinical hypothyroidism, defined as elevated thyrotropin in combination with normal range free thyroxine, is relatively common, with a higher prevalence in women and older people. It is often treated with thyroid hormones (levothyroxine), particularly when patients have symptoms such as tiredness potentially attributable to hypothyroidism, but evidence of clinical benefit has …
Abstract 11162: Critical Window for Mechanically-Induced Arrhythmias Exists in Time and in Space
Authors: T Alexander Quinn, Peter Kohl
Journal: Circulation (2012)

Introduction: Mechanical stimuli can cause premature ventricular excitation (PVEM) which, during a narrow time-window of the early T-wave, have been reported to result in re-entrant arrhythmias. We tested a computational modelling-based hypothesis that spatio-temporal overlap of a mechanical stimulus with the local repolarization wave-edge is required for re-entry, explaining the shorter critical window for mechanically-induced PVEM compared to electrical stimulation. Methods: Epicardial mechanical stimuli were applied to the LV and RV freewall of Langendorff-perfused hearts from 1kg female rabbits (n=12). Coupling-interval was controlled from surface ECG R-wave. Optical voltage mapping was conducted (20μ L of 27.3mM di-4-ANBDQPQ) in mechanically-uncoupled hearts (10μ M blebbistatin). Fluorescence was excited by a red LED (640±10nm) and emission was collected by a 128×128 EMCCD at 511Hz (>690nm). Results: Diastolic mechanical stimuli (<0.5mJ, 3.1mm2 contact area, ~2mm epicardial deformation) caused PVEM, ...
Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials
Authors: Peter Willeit, Paul M Ridker, Paul J Nestel, John Simes, Andrew M Tonkin, Terje R Pedersen, Gregory G Schwartz, Anders G Olsson, Helen M Colhoun, Florian Kronenberg, Christiane Drechsler, Christoph Wanner, Samia Mora, Anastasia Lesogor, Sotirios Tsimikas
Journal: The Lancet (2018)
Abstract 12813: Orphan Nuclear Receptor Nur77 Inhibits Angiotensin Ii-induced Vascular Remodeling via Downregulation of β-catenin Activity
Authors: Mingli Cui, Zhaohua Cai, Shichun Chu, Ying Yu, Zhe Sun, Peng Nie, Shiqun Sun, Xiaolei Wang, Liuhua Hu, Jing Yi, Linghong Shen, Ben He
Journal: Circulation (2015)

Background: Angiotensin II (Ang II) is the predominant effector peptide of the renin-angiotensin system (RAS). Ang II contributes to vascular remodeling in many cardiovascular diseases (e.g., hypertension, atherosclerosis, restenosis, and aneurysm). Orphan nuclear receptor Nur77 has a crucial role in the functional regulation of vascular cells. The objective of this study was to define the specific role of Nur77 in Ang II-induced vascular remodeling. Methods and Results: Male Nur77 -/- and wildtype (WT) littermate control mice (12-16 weeks of age) were continuously infused with Ang II using a mini-osmotic pump. Nur77 expression was increased in medial vascular smooth muscle cells (VSMCs) of thoracic aorta from WT mice after 2 weeks of exogenous Ang II administration. Loss of Nur77 resulted in enhanced outward vascular remodeling as reflected by increased medial area (197000±7091 μm 2 vs . 174000±5927 μm 2 , p &lt;0.05) and luminal diameter (880.7±24.13 μm vs . 825.2±10.38 μm, p &lt;0.05), and more severe elastin disruption and collagen deposition. In situ immunofluorescence analysis indicated that there were increases in VSMC proliferation and matrix metalloproteinases (MMPs) production, and decreases in the expression of VSMC-specific contractile genes, accompanied by elevated β-catenin expression in remodeling aortas from Nur77 -/- mice compared with WT mice. We also isolated rat VSMCs from Sprague-Dawley rats and mouse VSMCs from WT and Nur77 -/- mice, and stimulated them with Ang II in vitro . Ang II increased Nur77 expression via the MAPK/PKA-CREB signaling pathway in rat VSMCs. Under both basal and Ang II-induced conditions, Nur77 -/- mouse VSMCs exhibited increased proliferation and migration, and reduced expression of VSMC-specific genes. The results of additional experiments suggested that Nur77 suppressed Ang II-induced β-catenin signaling pathway activation by promoting β-catenin degradation and inhibiting its transcriptional activity. Conclusions: These results indicated that Nur77 is a critical negative regulator of Ang II-induced VSMC proliferation, migration, and phenotypic switching via the downregulation of β-catenin activity. Nur77 may reduce the Ang II-induced vascular remodeling that occurs in many cardiovascular diseases.
Sedation for screening MRI in patients with congenital melanocytic naevi under the age of one is a successful, safe and economical first‐line approach
Authors: I. Plumptre, G. Stuart, A. Cerullo, V.A. Kinsler
Journal: British Journal of Dermatology (2018)

Sedation for screening MRI in patients with congenital melanocytic naevi under the age of one is a successful, safe and economical firstline approach
Lactic Acidosis, Metformin Use, and Dose-Response Association
Authors: Kamel Mohammedi, Laurence Blanco, Vincent Rigalleau
Journal: JAMA Internal Medicine (2018)

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Clinical significance of morphologic response and tumor shrinkage as predictive factors of Capeox+bevacizumab in 1st line treatment of metastatic colorectal cancer.
Authors: Tomoyuki Nagaoka, Eiji Shinozaki, Ryosuke Watanabe, Eiko Ueno, Yumiko Ota, Hiroki Osumi, Izuma Nakayama, Takeru Wakatsuki, Mariko Ogura, Mitsukuni Suenaga, Takashi Ichimura, Daisuke Takahari, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2018)

805 Background: Capeox + bevacizumab (BV) is one of the standard treatment for metastatic colorectal cancer (mCRC) and well known to sometimes cause morphologic response (MR). However, it is not well known the predictive value of MR in palliative chemotherapy of Capeox + BV as 1 st line. The aim of this study was to investigate the clinical significance of MR and tumor shrinkage as predictive factors of Capeox+BV in 1 st line treatment of mCRC. Methods: A total of 159 patients with CLM were selected from 316 mCRC patients treated with Capeox+BV as 1 st line chemotherapy from February 2006 to August 2016. Among these patients, 92 patients were enrolled in the this study, who satisfied following criteria; (1) tumor responce was assesed by enhanced computed tomography (CT) images every 2-3 months, and (2) dose intensity of BV at first 4 courses were above 80%. Tumor response of RECIST1.1 and MR were evaluated by 2 radiologists. They classified them as optimal, incomplete or no morphologic response according to the morphologic criteria. Results: An optimal morphologic response (OR) was observed in 34% of all patients. The median progression-free survival (mPFS) was 9.3 months in this cohort, 13.5 months in patients with OR and 11.6 months in those with incomplete/no morphologic response. And the median overall survival (mOS) was 19.5 months, 30.3 months and 23.8 months, respectively. There were no statistical significance between OR and the other, irrespective of mPFS and mOS. On the other hand, mPFS was 14.6 months in responder as CR or PR of RECIST and 8.6 months in non responder as SD or PD (p &lt; 0.0001). Furthermore, mOS, 31.9 months and 18.5 months, respectively (p &lt; 0.0001). Besides in 17 patients fulfilled both responder of RECIST and OR, the mOS reached 45.4 months, which was remarkably longer compared to the other groups ( &lt; 0.0001). Conclusions: Among mCRC patients with CLM treated with Capeox+BV as the 1 st line, the response of RECIST well reflected the therapeutic effect. On the other hand, MR solely was not a predictor of therapeutic effect in this study. However, both responder of RECIST and OR may be on-treatment predictors to identify excellent prognostic group.