tbuckley/cabot-search huggingface dataset:
Creation of an EGFR somatic mutation database (www.egfr-mutations.org)
Authors: S. Murray, I. J. Dahabreh, H. Linardou, P. Kosmidis
Journal: Journal of Clinical Oncology (2008)

11111 Background: Following the discovery of somatic mutations in the tyrosine kinase domain (exons 18–24) of the epidermal growth factor receptor (EGFR) correlating with dramatic responses of non-small cell lung cancer (NSCLC) to the tyrosine kinase inhibitors gefitinib and erlotinib (TKIs), there has been increasing interest in utilizing this molecular marker for treatment selection. We aimed to analytically catalogue the mutational spectrum of somatic mutations in EGFR and correlate specific mutations with clinico-pathological factors and TKI efficacy. Methods: A computerized search of the PubMed database (01/Jan/04 - 30/June/07) was performed to identify published articles dealing with the identification of somatic mutations in EGFR pertaining to NSCLC. Only peer-reviewed articles were considered eligible. Demographic, clinico-pathological, mutational and efficacy data were abstracted. Results: From a total of 202 articles, we abstracted data on 12,244 patients with 3,381 somatic EGFR mutations. The mutational spectrum ranged across the 186 amino acids of exons 18–21, with 109 (58.6%) being associated with a somatic mutation. The majority of mutations have been reported on only one occasion (158 of 254, 62.2%), with only 9 different mutations occurring at a rate of ≥1%. The two most common mutations, L858R and delE746-A750 account for 32.84% and 24.28% of all mutations respectively. Deletions’ and ‘deletional-insertions’ in Exon 19 alone account for 47.35%. Although a meta-analysis of all articles was considered inappropriate, there was a clear association between the presence of mutations and response to TKIs. The dataset also highlighted the correlation of mutations with the accepted clinico-pathological factors (gender, histology, ethnicity and smoking status). Conclusions: We have generated a free-access online analytical database of somatic EGFR mutations in NSCLC. Cumulative information will be made available through a routine update of both database tables and associated graphical representations. Updates and submissions directly through the online site (www.egfr-mutations.org) are encouraged, as are comments and suggestions. The first 6-month update of the database will be presented at the meeting. No significant financial relationships to disclose.
APPROPRIATENESS OF MYOCARDIAL REVASCULARIZATION ASSESSED BY SYNTAX SCORE II IN A CENTRE WITHOUT ON-SITE CARDIAC SURGERY
Authors: Bojan M. Stanetic, Miodrag Ostojic, Kurt Huber, Carlos Campos, Tamara Kovacevic-Preradovic, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2015)
Abstract 1581: Identification of novel HLA-restricted T-cell epitopes specific for the breast cancer-associated tumor antigen NY-BR-1
Authors: Adriane Gardyan, Wolfram Osen, Maria Jesiak, Inka Zörnig, Dirk Jaeger, Stefan B. Eichmueller
Journal: Cancer Research (2012)

Abstract Out of all malignancies, breast cancer resembles the most common malignant caner type (26%) of women in the western world and the second most frequent cancer related cause of death (15%) in women. Efficient treatment options are available for early stage breast cancers yielding five year survival rates of up to 85%, however for metastasized breast cancer types, five year survival rates are resided at much lower levels (20%) and therapy options are very limited. It is therefore of great importance to establish innovative therapy strategies which will affect the late stage breast cancer tumors. Immunotherapy approaches, particularly adoptive T cell transfer, constitute an attractive strategy to develop new therapy options for metastasized mammary carcinomas. The differentiation antigen NY-BR-1 was found to be expressed on mRNA level in breast tissue, testis, prostate, and most notably in 80% of tested breast cancers. Among normal tissues, expression of the NY-BR-1 protein was present solely in ductal epithelium of the breast. Compared to healthy breast tissue NY-BR-1 protein levels are highly elevated in invasive breast tumors and their corresponding metastasis. Thus, NY-BR-1 can be considered as a breast cancer associated tumor antigen that might represent a suitable target antigen for T cell based immunotherapy approaches. The main focus of this project is to identify novel HLA-restricted T cell epitopes that could be used in clinical trials. Therefore, various HLA-transgenic (tg) mouse strains (DR4tg, DR3tg and HHDtg mice), were immunized with the NY-BR-1- encoding expression plasmid pcDNA3.1-NY-BR-1 followed by ex vivo analyses of the NY-BR-1-specific T cell responses with a synthetic peptide library covering the entire NY-BR-1 protein. Applying this strategy, four potential HLA-DRB1*0301 restricted epitopes and three HLA-DRB*0401 restricted candidate epitopes could be determined. The relevance of these new epitopes for the human system will be analyzed by screening of PBMCs from tumor patients and healthy donors for the presence of cognate T cells. Such T cells will be expanded and used as donors for high affinity NY-BR-1-specific TCRs in order to establish autologous TCR-transduced T cells ready for adoptive transfer of breast cancer patients. Currently, blood-samples of NY-BR-1+ patients are being collected for subsequent in vitro analyses of HLA-restricted, NY-BR-1-specific T cell responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1581. doi:1538-7445.AM2012-1581
Steeple Sign of Croup
Authors: Chun-Chao Huang, Shin-Lin Shih
Journal: New England Journal of Medicine (2012)

A 1-year-old boy presented with a 3-day history of intermittent fever, barking cough, and hoarseness. Physical examination revealed neck lymphadenopathy and audible stridor, but the patient was not in respiratory distress and was not drooling.
Agenesis of the Right Lobe of the Liver
Authors: FERNANDO CESANI, ERIC M. WALSER, BRIAN GOODACRE, KHANH HUYNH, SEHAM A. ALI, ELMA G. BRISCOE
Journal: Clinical Nuclear Medicine (1996)

A 70-year-old man had hepatobiliary scintigraphy, which showed agenesis of the right lobe of the liver and hypertrophy of the left lobe. There was no scintigraphic evidence of emptying of the radiotracer into the small bowel. Agenesis of the right lobe of the liver is an extremely rare congenital anomaly. This anomaly is thought to be caused by failure of the right portal vein to develop or an error of mutual induction between the primitive diaphragm and the endodermal diverticulum, which represents the primitive liver.
796 FACTORS ASSOCIATED WITH SUSTAINED VIROLOGICAL RESPONSE IN HCV/HIV PATIENTS RETREATED WITH PEG-INTERFERON-a2a-360 μg/wk AND RIBAVIRIN HIGH DOSE: RESULTS OF THE ANRS-HC-20 ETOC STUDY
Authors: P. Bonnard, S. Dominguez, H. Driss, M.-A. Valantin, K. Lacombe, Y. Yazdanpanah, A. Pinta, G. Pialoux, P. Halfon, L. Piroth, J. Izopet, F. Carrat
Journal: Journal of Hepatology (2013)
Management of Atrial Fibrillation
Authors: Alastair J.J. Wood, Edward L.C. Pritchett
Journal: New England Journal of Medicine (1992)

THE treatment of atrial fibrillation and the prevention of its complications are primarily pharmacologic problems. Treatment has two principal objectives. One is to use antiarrhythmic therapy to relieve symptoms; the other is to use prophylactic therapy to reduce the risk of stroke that accompanies atrial fibrillation. In planning the management of atrial fibrillation, it is useful to consider patients who are permanently in atrial fibrillation as having chronic atrial fibrillation and patients who have sinus rhythm punctuated by attacks of fibrillation as having paroxysmal atrial fibrillation. The two forms overlap, however, because many patients with chronic atrial fibrillation first present . . .
AB0176 P38 MAPK phosphorylation as a rheumatoid arthritis biomarker
Authors: M. Lopez-Santalla, I. Gonzalez-Alvaro, A. Lamana, A.M. Ortiz, S. Castañeda, J.M. Salvador
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> p38 MAPK plays an important role in inflammatory processes involved in the development of rheumatoid arthritis (RA). In T cells, p38 can be activated through the MAPKK family, by phosphorylation at Thr180-Tyr182 residues, after different types of stress (proinflammatory cytokines, osmotic shock and UV radiation) or by phosphorylation at Tyr323 through tyrosine kinases Lck and Zap70, after T cell receptor (TCR) activation. Gadd45a is a negative regulator of the TCR-mediated p38 phosphorylation on Tyr323. Our group has shown that constitutive activation of Tyr323p38 leads to spontaneous development of autoimmune disease in murine models and that T cells from active RA patients have an increased phosphorylation on Tyr323 compared to T cells from healthy controls, ankylosing spondylitis and RA patients in remission. <h3>Objectives</h3> Analysis of p38 phosphorylation and Gadd45a expression in T cells from early arthritis (EA) patients to identify variables associated with disease activity. <h3>Methods</h3> We studied 49 patients with EA (42 women). Median age at disease onset was 54 years [p25-p75: 47-63] and disease duration at the inclusion in the register, 4 months (3 - 7). We analyzed the p38 MAPK phosphorylation (at Thr180-Tyr182 and Tyr323) by flow cytometry in T cells purified from peripheral blood samples. We measured the expression level of GADD45a by quantitative RT-PCR adjusted by the expression of β-actin. <h3>Results</h3> At the first visit, we observed a significant correlation between pTyr323 levels and the DAS28 value. Patients with a family history of RA had higher levels of pTyr323 (p=0.01), suggesting a genetic component in the pTyr323 hyperactivation. pTyr323 levels were also higher in those cases who met EULAR/ACR 2010 criteria for RA. There wasa decreased expression of Gadd45a mRNA (p&lt;0.05) in T lymphocytes of RA patients compared to T cells from healthy controls. <h3>Conclusions</h3> Our results indicate that the phosphorylation status of p38a on Tyr323 can be used to evaluate the inflammatory activity of RA patients. Decreased expression of Gadd45a in T cells from active RA patients can increase the activation of p38a MAPK. Our results suggest that inhibition of this activation pathway is an attractive therapeutic target to modulate the activation of p38 in a specific manner in T cells. <h3>Disclosure of Interest</h3> None Declared
AB0278 Mri-Proven Osteitis at Baseline Predicts the Development of RAPID Radiographic Progression at 1 Year toward Patients with Early-Stage Rheumatoid Arthritis: Results from Nagasaki University Early Arthritis Cohort
Authors: N. Yoshikazu, T. Mami, K. Junko, T. Ayuko, N. Ayako, S. Takahisa, H. Yoshiro, K. Shinya, I. Naoki, I. Kunihiro, A. Kazuhiko, N. Hideki, O. Tomoki, U. Masataka, A. Kiyoshi, E. Katsumi, K. Atsushi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA) states that magnetic resonance imaging (MRI) bone oedema (osteitis) is a strong independent predictor of subsequent radiographic progression in early RA and should be considered for use as a prognostic indicator. The development of rapid radiographic progression (RRP) is considered as a representative poor outcome in patients with RA. <h3>Objectives</h3> We have tried to examine the variables that predict the development of RRP in patients with early-stage RA from Nagasaki University Early Arthritis Cohort. <h3>Methods</h3> This is a 1 year observational study from seventy-six early-stage RA patients recruited consecutively from Nagasaki University Early Arthritis Cohort in which the subjects received Gd-enhanced MRI of both wrists and finger joints. All of the patients had been received DMARDs during 1 year. MRI-proven osteitis was scored by Rheumatoid Arthritis Magnetic Resonance Imaging score (RAMRIS). Plain radiographic outcome of both wrists and finger joints was scored by Genant-modified Sharp score and the development of rapid radiographic progression (RRP) at 1 year in this study was identified as a score &gt;3/year. The clinical response toward introduction of DMARDs at 3 months was defined according to DAS28-EULAR response criteria. Variables with a <i>p</i> value less than 0.20 were selected for the following multivariate logistic regression analyses. Starting with a full model, the most appropriate model was selected on the basis of Akaike9s information criteria in the SAS system®, version 9.2. <h3>Results</h3> Median age and disease duration at entry were 54.5 y.o and 3 months, respectively. The rate of ACPA-positive was 83%. Median RAMRIS osteitis score and that of Genant-modified Sharp score at entry were 1 and 0, respectively. RRP was developed in 12 patients at 1 year. Multivariate logistic regression analyses have identified that RAMRIS osteitis score at baseline (<i>p</i>=0.0009, Odds ratio 1.10, 95% CI 1.04-1.16) and the introduction of biologic DMARDs within 1 year (<i>p</i>=0.044, Odds ratio 5.46, 95% CI 1.05-28.57) are independent predictors toward the development of RRP at 1 year. <h3>Conclusions</h3> Present data suggest that MRI-proven osteitis is closely associated with poor radiographic outcome in patients with early-stage RA. The use of biologic DMARDs may reflect the severe disease status. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5218
A STUDY OF HUMAN MYOCARDIAL THALLIUM KINETICS.
Authors: Richard C. Brunken, Randall Hawkins, Francine Aguilar, Marti Martinez, Luis Chica, Donna Marciano, Michael Phelps
Journal: Clinical Nuclear Medicine (1988)

Brunken, Richard C.; Hawkins, Randall; Aguilar, Francine; Martinez, Marti; Chica, Luis; Marciano, Donna; Phelps, Michael Author Information
OP0292 The Diagnosis of Osteoporosis Using BMD and T Score Measurements at Specific Skeletal Sites
Authors: R. Sinha, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2014)

Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15–70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI.
SECOND-GENERATION VERSUS FIRST-GENERATION DRUG-ELUTING STENTS IN PATIENTS WITH AND WITHOUT DIABETES MELLITUS: POOLED ANALYSIS FROM THE RESET AND NEXT TRIALS
Authors: Kenji Nakatsuma, Hiroki Shiomi, Masahiro Natsuaki, Takeshi Morimoto, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2016)
P88 Real-Life Experience of Omalizumab in Children with Severe Asthma
Authors: MK Koo, CB Bossley, AC Carlton, AB Bush, SS Saglani, LF Fleming
Journal: Thorax (2013)

<h3>Introduction</h3> Therapeutic options for children with severe asthma are limited. Clinical studies support the use of the anti-IgE antibody, omalizumab, in children with severe atopic asthma. However, children included in these studies had less severe disease than those in whom omalizumab is currently recommended. Little is known about the clinical efficacy of omalizumab in children with severe therapy resistant asthma (STRA). <h3>Objectives</h3> To determine the short-term (16 weeks) and long-term (beyond 16 weeks) efficacy of omalizumab, and predictors of a successful therapeutic response in children with STRA in a clinical setting. <h3>Methods</h3> This was an observational, prospective study of children with STRA who were commenced on omalizumab. Spirometry, bronchodilator reversibility (BDR), exhaled nitric oxide (FE<sub>NO</sub>), asthma control test (ACT), mini asthma-related quality of life questionnaire (AQLQ), severe exacerbations (requiring a course of oral corticosteroids (OCS) for ≥3 days) and number of unscheduled healthcare visits (UHCV) and hospital admissions were recorded before and every 4 weeks after commencing treatment. Every 16 weeks, patients underwent a more thorough assessment to determine if the treatment should be continued. <h3>Results</h3> 33 children (22 male) aged 5–16 years were commenced on omalizumab. At 16 weeks there were significant improvements in mini-AQLQ; ACT; FE<sub>NO</sub>; maintenance OCS dose; severe exacerbations and UHCVs. 20/33 (60.6%) children continued omalizumab beyond the initial 16 weeks (up to 192 weeks). Compared to those who discontinued, at baseline these children had higher mini-AQLQ (4.28 vs. 3.05) and ACT (11 vs. 8), were younger (11 vs. 13 years) and were more likely to have been admitted to hospital (57.9% vs. 0%) and have had a severe exacerbation (95% vs. 50%) in the 16 weeks before starting omalizumab. Maximal reduction in number of exacerbations and hospital admissions was evident at 32 weeks; this was maintained for up to 144 weeks (Figure 1). <h3>Conclusion</h3> This is the first longitudinal study demonstrating long-term clinical efficacy of omalizumab as add-on therapy in children with STRA. Omalizumab was most effective in those with an exacerbation-prone phenotype at baseline, highlighting the importance of thorough patient characterisation when considering this treatment option.
Breast cancer mortality reduction in the western world: therapeutic versus diagnostic interventions. Implications for cancer care organization processes.
Authors: J Ragaz, JJ Spinelli, R Semeniciw, W Hryniuk, J Budlovsky, E Franco
Journal: Cancer Research (2009)

Abstract Abstract #6083 INTRODUCTION. Recent epidemiology data show a substantial Breast Cancer (BrCa) mortality reduction in the western countries over the last decade. The literature indicates that both Adjuvant systemic treatments (Adj. SystTh) and Screening mammography (ScrM) contribute, but their interaction is not clear.&amp;#x2028; Our study examines if contribution of Adj. SystTh separate from ScrM could be more clearly identified; and also, - as a second objective, - if organization of cancer care could be correlated with BrCa mortality outcomes.&amp;#x2028; METHODOLOGY:&amp;#x2028; The mortality trends were compared among three Provinces of Canada with different Levels of Provincial Diagnostic and Therapy Guidelines (PDTG):&amp;#x2028; LEVEL I: most uniform coordination of PDTG: British Columbia (Brit.Col.), with a single Provincial budget; earliest implementation of Provincial Community Oncology Program (since the mid-1970's); and a uniform start of Adj. SystTh (late 1970's); and of ScrM (late -1980's).&amp;#x2028; LEVEL II: medium (Ontario).&amp;#x2028; LEVEL III: least uniform (Atlantic Provinces)*.&amp;#x2028; BrCa annual age-standardized mortality rates per 100,000/population were obtained from Statistics Canada for the years 1950-2004, and expressed relative to the year 1950 (the baseline).&amp;#x2028; RESUTLS: The 1950 BrCa mortality rates were: 30.9 for Canada; 31.4 for BC; 30.7 Ontario; 26.1 for Atlantic Provinces*.&amp;#x2028; &amp;#x2028; CONCLUSIONS:&amp;#x2028; While both Adj. SystTh and ScrM contribute towards recent BrCa mortality reduction, the British Columbia data indicate that the impact of Adj. SystTh antedates that of ScrM, at least by a decade.&amp;#x2028; Our data support a correlation of BrCa mortality trends with the organization of cancer care: Effective implementation of PDTG (- i.e. incorporating early curative interventions into guidelines), will have a strong impact on mortality trends, particularly if executed&amp;#x2028; a. ongoingly,&amp;#x2028; b. uniformly, and&amp;#x2028; c. across the whole population.&amp;#x2028; Our data therefore indicate that early implementation of curative systemic therapy - or of any curative intervention - is essential, as their delay may prevent materialization of survival gains. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6083.
FRI0127 Subcutaneous nodules in rheumatoid arthritis: Insights from a large multinational cohort:
Authors: N. Khan, H. Spencer, T. Sokka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Subcutaneous nodules (SCN) are easily identifiable extra-articular manifestation of rheumatoid arthritis (RA) with characteristic histopathology. Identifying clinical characteristics associated with SCN may lead to better pathophysiological understanding of RA, and may enhance its utility as clinical marker of RA outcomes. <h3>Objectives</h3> To assess prevalence and associations of SCN in a large multinational cohort of RA patients. <h3>Methods</h3> A cross-sectional study of 8549 patients in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) database who received usual care from rheumatologists in 33 countries was done. Physicians recorded SCN presence. Multivariable logistic regression (MLR) was used to identify association of SCN with demographic and health characteristics [age, gender, race, smoking status, body mass index (BMI), co-morbidity burden by an index derived from 10 co-morbidities], RA characteristics [RA duration, rheumatoid factor (RF) titer (low &lt;25 IU/ml, moderate 25-100 IU/ml, high &gt;100 IU/ml), radiographic erosions, current RA activity by disease activity score 28 (DAS28), functional status by health assessment questionnaire (HAQ)], and RA treatment [corticosteroids, methotrexate, other disease modifying agents (DMARDs), and biologics]. <h3>Results</h3> 1787 (20.9%) had SCN. The SCN prevalence varied from 5.1% to 30.3% in different countries. The Table shows the patient characteristics independently associated with SCN. Men, white race, and current smoking were more likely to have SCN. RA duration, presence of erosive disease, high titer RF, but not the current RA activity increased likelihood of SCN. Use of methotrexate and biologics were associated with SCN presence. Patients with SCN had higher comorbidity burden, and were more likely to have higher BMI. <h3>Conclusions</h3> We confirm previously reported patient characteristics associated with SCN (race, gender, smoking, RA duration, erosive disease, RF titer, methotrexate use), and also report several new associations (biologics use, higher comorbidity burden, BMI). Further studies are needed to determine whether there is true biological basis for these associations. <h3>References</h3> Ann Rheum Dis 2006;65:601 Scand J Rheumatol 2011;40:81 <h3>Disclosure of Interest</h3> None Declared