tbuckley/cabot-search huggingface dataset:
THU0309 Measles, mumps and rubella vaccination safety in patients with juvenile rheumatic diseases taking immunosuppressive drugs
Authors: G.S. Pileggi, M.T.R.A. Terreri, C.P. Barbosa, V.P.L. Ferriani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In Brazil, there was a National immunization campaign against measles in 2011, using measles, mumps and rubella (MMR) vaccine in children aged 1-7 years. <h3>Objectives</h3> The aim of this study was to document whether MMR vaccination aggravated the course of underlying disease in children with rheumatic diseases (RD) or presented risks in these patients when taking immunosuppressive drugs. <h3>Methods</h3> In order to accomplish this, a prospective observational study was performed. All 68 patients in this age groupwho had confirmed diagnosis of a juvenile rheumatic diseaseand have been following at two pediatric rheumatology outpatient clinics in Brazil were eligible. They were invited by phone call or during their regular visits to participate in this study. Signed informed consents were obtained from their parents. The first interview was done 2 weeks post vaccination and subsequently the patients were seen monthlyfor 3 monthsin order to access the occurrence of flare-ups or aggravation of disease activity after vaccination and side effects such as clinically overt measles. <h3>Results</h3> Twenty-eight/68 (41%) patients vaccinated with MMR were selected (for two of them the vaccine was their first dose and for 26 it was a booster). Twenty of them were male and the mean age was 4.5 years; 22 had Juvenile Idiopathic Arthritis (JIA), 4 with juvenile dermatomyositis and 2 scleroderma. At the time of vaccination 21/28 met no active disease criteria and 9/21 were in remission without medication. Regardless of disease activity, 19 patients were on medication, all of them using methotrexate (MTX); 5 were also receiving prednisone, and 2 were on anti-TNF agents too. During the follow-up period of 3 months only one patient with active systemic JIA, for whom the MMR vaccine was the first dose, reported worsening of fever and skin rash 20 days after vaccination; and no worsening of clinical parameters, flare-ups or changes in doses of medications was observed in the patients for whom the MMR was a booster.No overt measles infections and no severe adverse reactions were observed, despite the fact that the patients were receiving immunosuppressive medication or biological agents. <h3>Conclusions</h3> Conclusions: Most patients with RD can be vaccinated safely with MMR boosters. However, should be considered postponing the vaccination in patients with active disease, especially when the vaccine is the first dose. <h3>Disclosure of Interest</h3> None Declared
TCT-655 Contribution of In-Stent Neoatherosclerosis to Late Stent Failure Following Bare Metal and 1st- and 2nd-Generation Drug-Eluting Stent Placement: An Autopsy Study
Authors: Fumiyuki Otsuka, Kenichi Sakakura, Kazuyuki Yahagi, OSCAR D. SANCHEZ, Robert Kutys, Elena Ladich, David R. Fowler, Frank D. Kolodgie, Harry R. Davis, Michael Joner, Renu Virmani
Journal: Journal of the American College of Cardiology (2014)
Colorectal endoscopic submucosal dissection: when and by whom?
Authors: Michael Bourke, Horst Neuhaus
Journal: Endoscopy (2014)

Endoscopic submucosal dissection (ESD) was developed in Japan more than a decade ago for the treatment of early gastric cancer (EGC) [1]. The drivers for this remarkable innovation were the heavy burden of disease and the desire to develop a minimally invasive and definitive therapy for the numerous EGCs detected in the screening program. Embracing simple oncological principles, the aim was to realize a technique to achieve reliable en bloc excision of appropriately selected gastric neoplasms with free lateral and deep margins. Although no randomized trial exists or is ever likely to be conducted, in EGC it has steadily become the standard of care throughout large parts of the world, particularly where disease prevalence is high, due to its greater safety, markedly reduced cost, and similar therapeutic outcomes compared with surgery in cases where the risk of lymph node metastasis is low [2] The justifications for the use of ESD for EGC are multifaceted and hard to argue against, particularly as there are no other effective endoscopic therapies and surgery carries a significant risk of peri-operative morbidity and long-term digestive dysfunction.
Abstract 2522: Identification and characterization of new highly selective and potent BRAF inhibitors
Authors: Maurizio Pulici, Nadia Amboldi, Sonia Biondaro, Francesco Caprera, Elena Casale, Fabio Gasparri, Antonella Leone, Rosita Lupi, Chiara Marchionni, Michele Modugno, Wilma Pastori, Gabriella Traquandi, Fabio Zuccotto, Francesco Colotta, Daniele Donati, Eduard R. Felder, Arturo Galvani, Antonella Isacchi, Enrico Pesenti, Marina Ciomei
Journal: Cancer Research (2010)

Abstract Aberrant activation of the MAPK-mediated pathway components, RAF-MEK-ERK, is frequently found in human cancers and clearly contributes to oncogenesis. In particular, one of the three isoforms of RAF, BRAF, presents activating somatic mutations in 70% of melanomas, 50% of thyroid cancers, 10% of colon and 20% ovarian carcinomas. The most common BRAF mutation, substitution of glutamic acid for valine at position 600 within the activation segment of the kinase domain, accounts for 90% of mutated BRAF cases, and results in elevated kinase activity with consequent enhanced promotion of cell survival and proliferation. Here we describe the in vitro and in vivo properties of a novel class of potent and selective BRAF inhibitors. Starting from a series of arylpyrazole derivatives that were found to be active against wild-type and mutated BRAF, an expansion and optimization program was undertaken. This led to the identification of both inhibitors of the active conformation and inhibitors of the inactive conformation of the enzyme, as confirmed by co-crystallography studies. Among the former category, a sub-series endowed with high potency and selectivity was identified, with compounds possessing low nM affinity for BRAFV600E and negligible cross-reactivity against a panel of 44 kinases. Members of this sub-series inhibited 72-hour proliferation of cell lines harboring the BRAFV600E mutation with IC50s below 100 nM and with greater than 100-fold selectivity compared to lines with wild-type BRAF. Consistent with this observation, inhibition of the MAPK signal transduction pathway was highly selective for cell lines with mutated BRAF. Biochemical profile, potency in cell proliferation assays, and cellular mechanism of action compared favorably among the sub-series to a reference BRAF inhibitor, PLX-4720, tested in parallel. The most potent compounds (e.g. NMS-P730 and NMS-P383) were selected for in vivo evaluation. In vivo, potent tumor growth inhibition was observed in the A375 xenograft model following oral administration, with no overt toxicity, and with corresponding modulation of the MAPK pathway, consistent with expected mechanism of action. Selection of candidates most suitable for further development is underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2522.
P662Pleiotropic heart rate-independent cardioprotection by ivabradine: reduction of reactive oxygen species formation and improved viability in cardiomyocytes
Authors: P Kleinbongard, N Gedik, G Heusch
Journal: Cardiovascular Research (2014)

Background: In pigs, ivabradine reduced infarct size even when given only at reperfusion and in the absence of heart rate reduction (atrial pacing). The mechanism of such non-heart rate-related cardioprotection is unknown. Methods: Pentobarbital-anesthetized C57Bl/6J mice received ivabradine (1.7 mg/kg i.v. ± left atrial pacing) or placebo and were subjected to occlusion (30 min) and reperfusion (120 min) of the left anterior coronary artery (n=5, each). Area at risk was measured with phthalo blue and infarct size was measured with triphenyl tetrazolium chloride staining. In separate experiments, ventricular cardiomyocytes were enzymatically isolated from mouse hearts (n=9). Simulated ischemia was induced (hypoxia, pH 6.5, 310 mOsm/l, without glucose, 60 min) and followed by reperfusion (normoxia, pH 7.4, 250 mOsm/l, 10mmol/l glucose, 5 min) ±3 μmol/l ivabradine given 10 min before and during reperfusion. Viability (trypan blue exclusion) was quantified in >200 cells/per preparation. Reactive oxygen species (ROS) formation was detected fluorometrically (540/580nm, Amplex Red) in the extracellular space at baseline and after simulated ischemia/reperfusion (n=9 hearts). Mitochondria were isolated from mouse hearts (n=5) by differential centrifugation and incubated ±3 μmol/l ivabradine in glutamate/malate and ADP-containing buffer at 37°C; mitochondrial ROS formation was detected fluorometrically (540/580nm, Amplex Red). Results: Ivabradine reduced infarct size from 39±5 % to 17±4% of the area at risk (p=0.01), this benefit remained with pacing (20±5%). Viability was comparable at baseline (control, 74±2%; ivabradine, 73±3%) and remained relatively stable with 60 min normoxia (53±3 vs. 62±2%). Viability was reduced with simulated ischemia/reperfusion (10±2%), but better preserved with ivabradine (28±4%, p<0.001). Cellular ROS formation was comparable at baseline, but reduced with ivabradine after ischemia (19±3 vs. 12±3 μmol H2O2/100 μg protein, p<0.001) and reperfusion (33±7 vs. 21±3 μmol H2O2/100 μg protein, p=0.02), respectively. Mitochondrial ROS formation was also reduced by ivabradine (0.31±0.8 vs. 0.17±0.7 μmol H2O2/100 μg protein, p=0.03). Conclusion: Ivabradine reduces infarct size with or without heart rate reduction and improves ventricular cardiomyocyte viability, possibly by reduction of ROS formation.
LOW USE OF ORAL ANTICOAGULATION IN PATIENTS WITH ATRIAL FIBRILLATION AND RISK FOR STROKE IN THE UNITED STATES
Authors: Sean Pokorney, Richard Platt, Lisa Ortendahl, Tiffany Woodworth, Noelle Cocoros, Cheryl Walraven, Jeffrey Brown, Vinit Nair, Emily O'Brien, Meena Rao, Lesley Curtis, Pamela Tenaerts, Hussein Al-Khalidi, Christopher Granger
Journal: Journal of the American College of Cardiology (2016)
PTH-114 Assessing Osteoporosis In Coeliac Disease: Is The Who Frax Tool A Good Screener?
Authors: J Weightman, M Bridges, A Dhar
Journal: Gut (2014)

<h3>Introduction</h3> Osteoporosis is a well-recognised complication of intestinal malabsorption related to Coeliac Disease. It is diagnosed by dual energy x-ray absorptiometry (DXA). While referral for DXA scanning in other conditions is widely based on 10-year fracture risk calculated by the FRAX tool designed by the WHO, the 2007 BSG guidelines advise screening patients with a higher risk of osteoporosis with a DXA scan, irrespective of 10-year fracture risk as calculated by FRAX. <h3>Methods</h3> Aim: We aimed to establish whether the FRAX and linked NOGG tool was a good screener to determine the need for DXA scan in patients with coeliac disease who are at risk of osteoporosis. Methods: We used the Hospital Nuclear Medicine database to retrieve the records of 50 patients with a diagnosis of coeliac disease who had been investigated with a DXA scan to assess osteoporosis. Using their medical records, we then calculated their FRAX score for risk of major osteoporotic fracture and hip fracture, and the corresponding NOGG guidance. A 10-year fracture risk of 10% or the linked NOGG guidance was considered to be significant to have a DXA scan. <h3>Results</h3> Of the 50 patients with Coeliac disease who had DXA scans, 10 had osteoporosis and 40 had either a normal result or osteopaenia. Of these 10 cases, 9 would have also been referred on the basis of a calculated FRAX score and only one case would have been falsely reassured. Of the 40 cases with either a normal DXA scan or osteopaenia, 31 would have been referred for DXA on the basis of the FRAX score, resulting in an unnecessary test. We concluded that a positive FRAX score does not accurately predict osteoporosis in Coeliac disease. The positive predictive value of the FRAX tool to detect osteoporosis in Coeliac disease is low at 22.5%; however the negative predictive value is high, 90%. <h3>Conclusion</h3> The use of FRAX to identify patients with Coeliac disease at risk of osteoporosis has a high negative predictive value. It therefore has merit as a screening tool but has little value as a diagnostic test. Although the sample size was too small to show statistical significance, we suggest that FRAX tool could potentially be adopted as a screener in the context of celiac disease to prevent unnecessary DXA scanning. A osteoporosis risk of &lt;10% or a NOGG guidance of reassurance is likely to be associated with a normal DXA scan. Further large studies are needed to validate this hypothesis and also to determine cost benefit of a FRAX driven strategy for osteoporosis in Coeliac Disease. <h3>Disclosure of Interest</h3> J. Weightman: None Declared, M. Bridges: None Declared, A. Dhar Consultant for: Honoraria for advisory roles ot the Pharmaceutical Industry, Speaker bureau with: Warner Chilcott UK, Falk Pharma UK, Almirall, Ferring Pharma UK, Astellas UK.
Anorectal three-dimensional quantitative ultrasonography - new concept
Authors: F Castro-Poças, P Lago, M Guardão, J Areias
Journal: Endoscopy (2006)

Introduction: anorectal ultrasonography had a significant advance in the last years. Three-dimensional (3D) ultrasonography might be an important complement to conventional ultrasonography. The systems of 3D image acquisition obtain the images of two elementary dimensions at a established acquisition rate, assuming that the ultrasonography probe is moved at a constant velocity; however, if the movement is made by human hand it is obtained a distorted geometrical 3D image with consequent problems in the morphologic and quantitative 3D analysis.
PTH-029 Bowel Screening Wales Network Multidisciplinary team and National Referral Centre – the First 100 Cases
Authors: S Dolwani, H Heard, M Davies, N Williams, G Tudor, M Morgan, A Maw, R Davies, C Lewis
Journal: Gut (2013)

<h3>Introduction</h3> The Bowel Screening Wales (BSW) Network Multi Disciplinary Team (NMDT) and National Referral Centre (NRC) pilot was established in October 2011 to offer the opportunity for expert opinion and discussion of therapeutic options for participants with complex benign polyps detected on the Welsh bowel screening programme. <h3>Methods</h3> Participants with lesions that satisfied the agreed criteria were referred to the NMDT for advice from the expert panel regarding management. Recommended outcomes included local endoscopic or surgical treatment or referral to the NRC for endoscopic or surgical treatment. Between the 17<sup>th</sup> of October 2011 and the 20<sup>th</sup> August 2012 October 2012 100 cases from all over Wales were discussed at NMDT meetings by video conference. Referrals were received from all 6 Health Boards in Wales and 11 of the 14 Local Assessment Centres (LAC) during this time frame. Referral data and NMDT decisions were prospectively stored on a shared drive and a comprehensive data set entered onto the BSW registry for complex polyps. <h3>Results</h3> The first 100 cases discussed at NMDT meetings satisfied the following referral criteria: 21 lesions with difficult to access 17 lateral spreading tumours &gt; 2cms 11 participants with polyps greater than 4cms 20 participants with polyps in the right colon &gt; 2cms 7 participants with residual polyps 24 others 52 cases were referred back to Local Assessment Centres for treatment, and 48 to the NRC for treatment. Detailed data on procedure type and final outcome will be presented in June. All cases referred to the NMDT for discussion were thought to be benign at the time of referral which was confirmed by initial biopsy. Final histology was found to be adenocarcinoma in 6 cases. Data analysis will continue and include recurrence rates at 3, 6 and 12 months, post procedure complication rates and final number of procedures undertaken per participant for each lesion removed. <h3>Conclusion</h3> The BSW NMDT and NRC have facilitated equity of service for participants of the bowel screening programme in Wales with complex benign polyps. Referrals to surgery for benign disease have been reduced as a result. This process has also facilitated central referral for specialist endotherapy and surgical procedures. <h3>Disclosure of Interest</h3> None Declared.
Role of Intraoperative Skeletal Scintigraphy in the Localization of Osteoblastomas
Authors: LAURA A. DRUBACH, LEONARD P. CONNOLLY, TINA Y. POUSSAINT, PETER N. FAUL, S. TED TREVES
Journal: Clinical Nuclear Medicine (2000)

Osteoblastoma is a rare neoplasm that accounts for 1% of all primary bone tumors. It is histologically benign but locally aggressive and has a high tendency to recur if it is not resected completely. A case illustrating the use of intraoperative skeletal scintigraphy to facilitate complete removal of a recurrent aggressive osteoblastoma of L5 is presented.
ME-08 * NEURONS PROMOTE GLIOMA GROWTH IN AN ACTIVITY-DEPENDENT MANNER
Authors: T. Johung, H. Venkatesh, V. Caretti, A. Noll, M. Monje
Journal: Neuro-Oncology (2014)

Pediatric high-grade gliomas (pHGG) are the leading cause of brain tumor death in children. Mounting evidence indicates that oligodendrocyte precursor cells (OPCs) represent the pHGG cell of origin. We recently demonstrated that active neurons exert a robust mitogenic effect on normal OPCs. To test the hypothesis that active neurons similarly promote pHGG proliferation, we employed in vivo optogenetic techniques in a patient-derived orthotopic xenograft mouse model of pHGG. pHGG cells were xenografted in the premotor cortex of juvenile immunodeficient (NOD-SCID-IL2 chain-deficient, NSG) mice expressing the excitatory opsin channelrhodopsin in cortical projection neurons (NSG;Thy1::ChR2 mice). Wild type NSG littermates (no opsin present) were identically manipulated. After an 11-week engraftment period, the unilateral premotor cortex was optogenetically stimulated (470nm light at 20Hz intermittently over 30 minutes) in awake mice, resulting in complex motor behavior (unidirectional ambulation). Mice were histologically evaluated 24 hours later. Neuronal activity promoted pHGG proliferation in vivo, increasing the mitotic index compared with xenografts in WT mice (10.53% +/- 0.01 vs. 7.48% +/- 0.008, P  10 kDa) from small molecules (<10 kDa), we found that the neuronal activity-regulated mitogen is present in the macromolecular fraction. Taken together, these data indicate that active neurons promote the growth of pHGG via secreted macromolecular factor(s) and identify neurons as an important component of the pHGG microenvironment.
A new congenital dysmegakaryopoietic thrombocytopenia (Paris-Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23 [see comments]
Authors: J Breton-Gorius, R Favier, J Guichard, D Cherif, R Berger, N Debili, W Vainchenker, L Douay
Journal: Blood (1995)
Questioning the Solution: The Politics of Primary Health Care and Child Survival, by David Werner, David Saunders
Authors: M. Schweiger
Journal: BMJ (1997)

David Werner, David Saunders Health Wrights, $25, pp 206 ISBN 0 9655585 2 5

The Declaration of Alma Ata, to which 134 nations subscribed in 1978, started from the affirmation that health is a fundamental human right, and strongly promoted the concept of Health for All by the Year 2000. With three years left to run, the target of health for all seems to be as remote as ever. David Werner and David Sanders have set out to find out why and have come up with some uncomfortable observations. The book is illustrated throughout with carefully drawn illustrations and cartoons.

Focusing on the development of oral rehydration as a valuable tool in the fight against deaths …
Abstract 3456: Macrophages as independent prognostic factors in small T1 breast cancers.
Authors: Roberto Carrio, Tulay Koru-Sengul, Feng Miao, Stefan Gluck, Omar Lopez, Yamil Selman, Consuelo Alvarez, Clara Milikowski, Carmen Gomez, Merce Jorda, Mehrad Nadji, Marta Torroella-Kouri
Journal: Cancer Research (2013)

Abstract Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignances. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 ER+ breast cancers across three different ethnic groups, i.e. African American, Latinas and Caucasian women. A retrospective pilot analysis of 30 T1 breast cancers cases encompassing these three ethnic groups was carried out. African American and Latina women present with less incidence but more aggressive breast cancer disease and therefore proportionally higher death rates. Using immunohistochemistry, we sought to find out whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data showed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African American and Latinas than in Caucasian patients. Interestingly but not surprisingly, the absence of PR associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities. Citation Format: Roberto Carrio, Tulay Koru-Sengul, Feng Miao, Stefan Gluck, Omar Lopez, Yamil Selman, Consuelo Alvarez, Clara Milikowski, Carmen Gomez, Merce Jorda, Mehrad Nadji, Marta Torroella-Kouri. Macrophages as independent prognostic factors in small T1 breast cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3456. doi:10.1158/1538-7445.AM2013-3456
LEFT VENTRICULAR NON-COMPACTION AS DIAGNOSED BY ESTABLISHED CARDIAC MAGNETIC RESONANCE IMAGING CRITERIA IS NOT ASSOCIATED WITH INCREASED ADVERSE EVENTS COMPARED TO NON-ISCHEMIC DILATED CARDIOMYOPATHY
Authors: Shermeen Memon, Lara Bakhos, Nathan Bibliowicz, Rajeev Fernando, Mark Rabbat, Thriveni Sanagala, Ari Goldberg, Mushabbar Syed
Journal: Journal of the American College of Cardiology (2015)