tbuckley/cabot-search huggingface dataset:
Abstract 3515: Pathway convergent evolution underscores treatment response to MTOR inhibitors in kidney cancers.
Authors: Martin H. Voss, A Ari Hakimi, Can G. Pham, A Rose Brannon, Ying-Bei Chen, Luis F. Cunha, Oguz Akin, Han Liu, Shugaku Takeda, Sasinya N. Scott, Nicholas D. Socci, Agnes Viale, Nikolaus Schultz, Chris Sander, Victor E. Reuter, Paul Russo, Emily H. Cheng, Robert J. Motzer, Michael F. Berger, James J. Hsieh
Journal: Cancer Research (2013)

Abstract Despite the established role of MTOR inhibitors (rapalogs) in treating advanced kidney cancer, therapeutic benefit varies and predictive biomarkers are lacking. Intratumor branching heterogeneity, a recently discovered hallmark of this disease, has raised concerns about the feasibility of developing genomic biomarkers for targeted agents in kidney cancer. We undertook an outlier approach to interrogate the genetic determinants underlying long-term therapeutic response (&amp;gt;20 months) to rapalogs in 6 patients. An integrated ultra-deep targeted-exome (∼500x) and standard whole-exome (∼100x) sequencing was performed. Additionally, to address intratumor and intertumor heterogeneity, spatially separated tumor specimens from the same individuals were analyzed whenever possible. Multiregional sequencing unveiled surprising MTOR pathway convergent evolution, manifested by MTOR pathway activation by means of distinct genomic events in spatially separate sites of disease within the same individual. Amongst the core components of the MTORC1 pathway, complete functional loss of TSC1 and TSC2, and a hyperactive MTOR mutant were discovered in 4 of 6 long-term responders. Mutations in MTOR Clustered at FAT and kinase domains confer hyperactivity and yet remain sensitive to rapamycin. Here, we affirm intratumor heterogeneity, identify genomic determinants of drug response, and discover pathway convergent evolution in the majority of long-term responders. We propose a “river” model in which intratumor and intertumor clonal heterogeneity in cancer patients evolves like a branching river that converges at critical nodes. These convergent points provide unique opportunities for the treatment of genetically diverged yet functionally converged cancers in any given patient. Citation Format: Martin H. Voss, A Ari Hakimi, Can G. Pham, A Rose Brannon, Ying-Bei Chen, Luis F. Cunha, Oguz Akin, Han Liu, Shugaku Takeda, Sasinya N. Scott, Nicholas D. Socci, Agnes Viale, Nikolaus Schultz, Chris Sander, Victor E. Reuter, Paul Russo, Emily H. Cheng, Robert J. Motzer, Michael F. Berger, James J. Hsieh. Pathway convergent evolution underscores treatment response to MTOR inhibitors in kidney 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 3515. doi:10.1158/1538-7445.AM2013-3515
Cost Containment through Risk-Sharing by Primary-Care Physicians
Authors: Stephen Moore
Journal: New England Journal of Medicine (1979)

Abstract A new type of independent practice association has been organized to encourage primary-care physicians in private practice to become coordinators and financial managers for all medical care. Each patient chooses one internist, family or general physician or pediatrician and must be referred by that physician for all specialized care. The primary-care physician authorizes payment from his own account for all care provided to his patients. He shares any deficit or surplus remaining at the end of the year. After four years of operation, United Healthcare has 610 primary-care physicians treating 23,000 patients. Total hospital use during 1978 was 293 beddays per 1000 patients, as compared with 479 for Blue Cross. The hospital-admission rate per 1000 was 88, as compared with 101 for Blue Cross. Average lengths of stay were 3.3 and 4.7 days, respectively. This plan represents another means to control costs in the private medical marketplace. (N Engl J Med 300:1359–1362, 1979)
S79 Sputum Inflammatory Cell Profile in Children with Acute Asthma and Following Recovery: Abstract S79 Table 1
Authors: KG Staley, G Fisher, CE Brightling, P Bradding, D Parker, EA Gaillard
Journal: Thorax (2012)

<h3>Background</h3> Airway inflammation in children experiencing an acute asthma exacerbation has been little studied. A previous study (1) reported high numbers of sputum inflammatory cells in children with acute asthma and a significantly lower number two weeks after the acute episode. Our principal objective was to study children after a longer follow-up period when the effects of oral steroid therapy has subsided and to compare children with asthma to a healthy control group. <h3>Methods</h3> We collected sputum from children attending hospital with acute asthma following salbutamol bronchodilation, and, if necessary (and FEV1&gt;50% predicted), after nebulisation with 0.9% saline. Following recovery, sputum was obtained using hypertonic-saline induction. We also studied a control group of healthy children. Sputum samples were processed within 6 hours and a differential cell-count was obtained by counting inflammatory cells on a cytospin slide (2). <h3>Results</h3> Paired sputum samples were obtained from fifteen children (median-age 11 years) and eight controls (median-age 13.5 years). Median number of days between sputum samples for children with asthma was 82 days (range 21–313). Sputum from children with acute asthma had a higher number of inflammatory cells and a higher percentage eosinophil count than control children (p=0.025, 0.015 respectively). Sputum from children with asthma at recovery had a higher percentage eosinophil count than control children (p=0.021), but total number of inflammatory cells were not significantly different. We did not find a significant decrease in total number of cells nor percentage neutrophils or eosinophils in the sputum of children with asthma between acute episode and recovery [see table 1]. In children with raised sputum eosinophils (&gt;2.5%) during acute asthma sputum eosinophilia persisted at recovery. <h3>Conclusion</h3> Sputum inflammatory cell counts and percentage eosinophils are elevated in children with acute asthma compared to children without asthma. We found no significant difference in either total or percentage neutrophil or eosinophil count between acute asthma and recovery. In children with eosinophilia &gt;2.5% during acute asthma this persisted at recovery. These findings have implications for our understanding of the causes of asthma exacerbations in children. Norzila MZ et al. AJRCCMed 2000:769–774 Pin I et al. Thorax 1992:25–29
PTH-074 Of What Value is A 1:1 Multidisciplinary Weight Management Clinic?
Authors: D Turner, S Jones, S Syal, J Gray, J Reynolds, A Weaver, N Haboubi
Journal: Gut (2013)

<h3>Introduction</h3> Obesity management in Wales includes provision of a 1:1 Multidisciplinary Weight Management Clinic (MDWMC). Strategic management of obesity in Wales is guided by The All Wales Obesity Pathway and recommends MDWMCs for people with obesity who have one or more co-morbidities and who have tried several interventions without success, or who have complex emotional relationships with food.<sup>1</sup> This service evaluation aimed to assess physiological benefits associated with attendance at a MDWMC. It also aimed to collect qualitative data in an attempt to explain any reasons for achieving benefits. <h3>Methods</h3> An approved questionnaire was used to conduct semi-structured interviews with 180 patients attending the MDWMC at Aneurin Bevan Hospital, Ebbw Vale, Wales. Quantitative data were tabulated and a thematic analysis was performed on free-text responses to collate qualitative data. <h3>Results</h3> The MDWMC supports weight loss with 95% of patients reporting loss. For those whom baseline data was available 73% lost at least 5% of initial body weight. 88% of patients prefer individual appointments and over 90% of patients who see each team member find consultations useful. 69% of patients report improved health mainly due to a decrease in obesity-related symptoms, and of patients taking obesity-related medication 48% report a reduction in dose of medication for asthma, 42% report a reduction in dose of antidepressants and 36% report a reduction in dose for medication for diabetes. Of employed patients 30% report a reduction of days taken off work due to sickness. 96% of patients would recommend the clinic to others. <h3>Conclusion</h3> A 1:1 Multi-disciplinary Weight Management Clinic provides value in reducing obesity and symptoms of obesity-related diseases. It also is a treatment choice favoured by patients. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Welsh Assembly Government.<i> All Wales Obesity Pathway.</i> 2009. Accessed at: http://wales.gov.uk/topics/health/improvement/index/pathway/?lang = en
Compensatory Enlargement of Human Atherosclerotic Coronary Arteries
Authors: Seymour Glagov, Elliot Weisenberg, Christopher K. Zarins, Regina Stankunavicius, George J. Kolettis
Journal: New England Journal of Medicine (1987)

Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. The internal elastic lamina area correlated directly with the area of the lesion (r = 0.44, P<0.001), suggesting that coronary arteries enlarge as lesion area increases. Regression analysis yielded the following equation: Internal elastic lamina area = 9.26 + 0.88 (lesion area) + 0.026 (age) + 0.005 (heart weight). The correlation coefficient for the lesion area was significant (P<0.001), whereas the correlation coefficients for age and heart weight were not. The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P<0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography. (N Engl J Med 1987; 316: 1371–5.)
Abstract LB-66: Benefits and Barriers to Clinical Engagement with Cancer Consumer Representatives in New Zealand
Authors: Stephanie Fletcher
Journal: Cancer Research (2011)

Abstract The Central Cancer Network (CCN), established in 2007, is one of four regional cancer networks in New Zealand. These networks were developed to facilitate initiatives contained in the Cancer Control Strategy Action Plan 2005–2010. The Network serves an urban and rural mixed population of approximately one million people. The purpose of the Network is to take a proactive leadership, facilitation, collaborative and coordinated approach across organizational and service boundaries to ensure all providers of cancer prevention and care in the network area work together with the community to: manage the implementation of the Strategy and Action Plan in order to reduce the incidence and impact of cancer and the inequalities with respect to cancer, as well as to improve the journey of cancer patients and their family/wh ānau through the complex pathway of care, ensuring equitable, high quality, patient centered, evidence-based and multidisciplinary care. There is an immense amount of research looking at the involvement of consumers in decision-making advisory and working groups. In New Zealand, there are consumer groups successfully working with clinicians in mental health and diabetes service improvement. However, there is limited research into the clinician's role and their influence of the functioning of such groups. Sitzia, Cotterell and Richardson (2006) spoke of the challenge of managing change when both professionals and lay people are involved in determining service change. Their work found that if professionals did not hold a belief that patient involvement would lead to positive service engagement, then the motivation to engage would be lost. CCN proposes a two phased approach to improving clinical involvement with consumer representatives in cancer service improvement working groups: 1. Training workshops to disseminate the Health Service Co-Design Guide and Toolkit in 2011: The introduction of the Health Service Co-design Toolkit and Guide introduces the tools available to service providers to ensure that they fully utilize consumer experiences to enact service improvement. 2. Research proposal to conduct a qualitative research study in 2012, examining the barriers and benefits clinicians preserve enhance or hinder consumer participation in cancer service improvement groups. The research study will identify perceived barriers and benefits to clinicians engaging with consumer representatives and therefore work towards addressing the issues involved. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-66. doi:10.1158/1538-7445.AM2011-LB-66
Southeast Asian Countries Tackle Cancer Control
Authors: Veronica Lucey Conley
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Southeast Asian Countries Tackle Cancer Control Get access Veronica Lucey Conley Veronica Lucey Conley Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 326–327, https://doi.org/10.1093/jnci/83.5.326 Published: 06 March 1991
AB0159 Local overexpression of IGFBP3 ameliorates experimental arthritis in mice
Authors: H.-S. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Insulin-like growth factor binding protein 3 (IGFBP-3) is known to interfere NF-κB signaling pathway and thereby has an anti-inflammatory function. <h3>Objectives</h3> Due to the central role of NF-κB in rheumatoid arthritis (RA) development, we postulated that IGFBP3 could have anti-arthritic effects. <h3>Methods</h3> An adenovirus containing IGFBP3 cDNA (Ad-IGFBP3) was used to deliver IGFBP3 to collagen-induced arthritis (CIA) mice through an intraarticular injection into the ankle joints of the CIA mice. <h3>Results</h3> Mice with CIA had an increased incidence of disease and developed experimental arthritis in the hind paws. In contrast, in mice injected with Ad-IGFBP3, the severity of arthritis based on clinical scores, hind paw thickness, and radiological and pathological findings was significantly attenuated. In addition, Ad-IGFBP3 down-regulated local and systemic levels of pro-inflammatory cytokines compared with control virus-injected mice. The protective effects of Ad-IGFBP3 were mediated by the inhibition of the NF-κB signaling pathway. <h3>Conclusions</h3> These results suggest that blocking the NF-κB pathway by Ad-IGFBP3 in rheumatoid joints reduces tissue destruction. Therefore, the development of an immunoregulatory strategy based on IGFBP3 may have therapeutic potential for the treatment of rheumatoid arthritis. <h3>References</h3> Campbell IK, Gerondakis S, O’Donnell K, and Wicks IP Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis. J Clin Invest 2000;105:1799-806. Hah YS, Lee YR, Jun JS, Lim HS, Kim HO, Jeong YG, Hur GM, Lee SY, Chung MJ, Park JW, Lee SI, and Park BH A20 suppresses inflammatory responses and bone destruction in fibroblast-like synoviocytes and collagen-induced arthritic mice. Arthritis Rheum 2010;62:2313-21. Muller-Ladner U, Pap T, Gay RE, Neidhart M, and Gay S Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol 2005;1:102-10. Han J, Jogie-Brahim S, Harada A, and Oh Y Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-κB signaling. Cancer Lett 2011; 307: 200-210. Lee YC, Jogie-Brahim S, Lee DY, Han J, Harada A, Murphy LJ, and Oh Y Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-κB signaling through IGFBP-3R-mediated activation of caspases. J Biol Chem 2011; 286: 17898–17909 <h3>Disclosure of Interest</h3> None Declared
ALTERNATIVE MACROPHAGES PROMOTE INTRAPLAQUE ANGIOGENESIS AND VASCULAR PERMEABILITY IN HUMAN ATHEROSCLEROSIS
Authors: Aloke V. Finn, Hirokuni Akahori, Liang Guo, Rohini Polavarapu, Vinit Karmali, Adrienne King, Cheol Choi, Qi Cheng, Hanjoong Jo, Salim Thabet, Frank Kolodgie, Renu Virmani
Journal: Journal of the American College of Cardiology (2016)
AB1065 Diagnosing gout without joint fluid aspiration: A systematic literature review using monosodium urate crystals as a reference standard
Authors: F. Sivera, M. Andres, L. Carmona, D. van der Heijde, L. Falzon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The identification of MSU crystals in joints and tophi is the "gold standard" for the diagnosis of gout. Unfortunately and despite current recommendations, the search for crystals is not regularly performed [1] and many patients with gout are diagnosed on the basis of clinical and laboratory findings sometimes coupled with imaging techniques. <h3>Objectives</h3> To evaluate the diagnostic utility of clinical, laboratory and imaging for diagnosing gout. <h3>Methods</h3> A systematic literature search was performed in Medline, EMBASE and the Cochrane library from 1950 to October 2011 and in ACR and EULAR abstracts (2010-2011) identifying the studies on gout diagnosis. To be included, the studies had to evaluate the diagnostic value of clinical, laboratory or imaging features in gout and use MSU crystal identification as the reference standard. Titles and abstracts of the identified references were screened independently by 2 reviewers for the inclusion criteria. Subsequently, included articles were reviewed in detail and the data collected using ad hoc standard forms. A hand search was completed by reviewing the references of the included studies and all the publications or other information provided by experts were examined. Positive and negative likelihood ratios (LR) were calculated. Risk of bias was evaluated using the Cochrane tool for assessment of diagnostic tests. <h3>Results</h3> Of the 5,558 references retrieved, 5 papers (4 studies) fulfilled the inclusion criteria: 3 on clinical features, 1 on ultrasound (US) features and 1 on dual-energy CT (DECT). Overall risk of bias of these studies was moderate-low. Clinical and laboratory features that had a LR+ over 2.0 include: 1st MTP painful or swollen, unilateral podagra, unilateral tarsitis, presence of suspected tophi, response to colchicine, association of a cardio-vascular disease, beer consumption, hyperuricemia, serum uric acid (sUA) &gt;7.06 (males)/5.72 (females) mg/dL, sUA &gt;5.88 mg/dL, estimated glomerular filtration rate &lt;60ml/min. In X-rays, the presence of asymmetric swelling and the presence of subcortical cysts in the absence of erosions both showed LR+ over 2.0. In US, the presence of the double contour sign had a LR+ of 13.63 (LR- 0.65) and punctiform deposits in the synovial membrane LR+ 2.22 (LR- 0.35). In the DECT, the detection of urate deposits in joints had a LR+ of 9.5 (LR- 0.05). <h3>Conclusions</h3> MSU identification in a synovial fluid sample or after needling a tophus is the recommended diagnostic gold standard for gout diagnosis and should be performed whenever possible. However, some clinical, laboratory and imaging features show good LR and could be used as a diagnostic aid when MSU crystal identification is impracticable. <h3>References</h3> Perez-Ruiz F. J Clin Rheumatol 2011; 17 (7):349. <h3>Disclosure of Interest</h3> None Declared
P747 ASSOCIATION OF A GENETIC VARIANT OF THE MITOCHONDRIAL ANTIVIRAL SIGNALING PROTEIN (MAVS) WITH INTERFERON RESPONSE IN CHRONIC HEPATITIS C VIRUS INFECTION
Authors: J. Fischer, S. Böhm, D. Deichsel, V. Knop, H. Klinker, B. Möller, J. Rasenack, H. Hinrichsen, U. Spengler, P. Buggisch, C. Sarrazin, T. Berg
Journal: Journal of Hepatology (2014)
Case 30-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Edward F. Bland, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of CaseA 47-year-old man was admitted to the hospital because of right hemiplegia and aphasia.At the age of 16 years he spent nine months in a sanatorium because of pulmonary tuberculosis. He was well thereafter until six years before admission, when he was examined by a physician because of abdominal pain and was told that he had a peptic ulcer and a heart murmur. Three years later he was admitted to another hospital because of chest pain and was informed that he had pneumonia and heart disease, with electrocardiographic changes; he was discharged six weeks later on . . .
A new method to facilitate bilateral hepatic duct drainage: simultaneous insertion of two thin 6-Fr self-expandable metal stents
Authors: T. Nguyen-Tang, J.-M. Dumonceau
Journal: Endoscopy (2011)

An uncovered biliary self-expandable metal stent (SEMS) mounted on a 6-Fr delivery catheter has become available. It allows simultaneous side-by-side insertion of two SEMSs through the working channel of a standard therapeutic duodenoscope.