tbuckley/cabot-search huggingface dataset:
AB1326 Rheumatoid arthritis 6 years after diagnosis – still associated with high direct costs and increasing loss of productivity (the swedish TIRA project)
Authors: E. Hallert, M. Husberg, T. Skogh, L. Bernfort
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous reports from the TIRA cohort have shown that total costs were unchanged during the first 3 years after diagnosis of early rheumatoid arthritis (RA). Ambulatory visits and hospitalization decreased but surgery and drugs increased. Sick leave also decreased, but was offset by early retirement, resulting in unchanged net costs. The present study reflects a period of 6 years after diagnosis, during which there was a paradigm shift, with biological drugs being introduced around year 3. <h3>Objectives</h3> To calculate direct and indirect costs during 6 years after diagnosis and analyze changes in health care utilization and development of working capacity. <h3>Methods</h3> One-hundred and twenty-five patients with early (≤1 year) RA, recruited 1996-98, were assessed during 6 years from diagnosis. Clinical and laboratory data were collected and patients were provided with diaries and reported prospectively all health care utilization and number of days lost from work. Annual direct and indirect costs and EQ-5D scores were calculated. Costs were also compared between patients prescribed biologics and non-users. <h3>Results</h3> Outpatient visits and days in hospitalization decreased during the first 3 years, but costs for surgery and drugs increased. Around year 3, biologics were introduced. Direct costs continued to increase, mainly due to increasing drug costs but also due to increasing surgery and hospitalization. Women had higher costs for surgery, all total joint replacements in hip and knee, except one, were performed in women. During the first 3 years, sick leave decreased, but was offset by a similar increase in disability pensions. Over the following years, sick leave decreased further, but disability pensions increased even more, leading to increasing total indirect costs every year. After initial improvement in EQ-5D, scores slowly deteriorated again. Patients, prescribed biologics, had higher direct costs before prescription, compared to non-users. Apart from surgery, higher costs were maintained after instituting biologics and to some extent, even increased. <h3>Conclusions</h3> Despite access to biologic drugs, costs continued to increase and drug costs were not offset by reduction in other costs. Effects of biologics must, however, be evaluated over longer time frames, comparing health care utilization and working ability, before and after introduction of biologics. Comparisons with the general population must also be taken into account, since health care utilization differs over time and levels of sick leave and disability pensions are strongly dependent on changing policies and economic conditions in society. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-520: PTPN14 interacts with and negatively regulates the oncogenic function of YAP
Authors: Xiaojun Liu, Nuo Yang, Sheila A. Figel, Kayla E. Wilson, Carl D. Morrison, Irwin H. Gelman, Jianmin Zhang
Journal: Cancer Research (2012)

Abstract ABSTRACT The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers where it promotes epithelial-to-mesenchymal transition (EMT) and malignant transformation. Using IP Mass-spec analysis, we have identified a novel regulatory mechanism for the YAP oncogenic function via direct interaction with non-receptor tyrosine phosphatase 14 (PTPN14). PTPN14 interacts with YAP through PPxY domain, and overexpression of PTPN14 increases the inactive cytoplasmic form of YAP and decreases the transcriptional co-activator activity of YAP. Moreover, knockdown of PTPN14 induces nuclear retention of YAP and increases YAP-dependent cell migration. In summary, our study indicate a potential tumor-suppressor role for PTPN14 in the Hippo pathway and demonstrate a novel mechanism in YAP regulation. 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 LB-520. doi:1538-7445.AM2012-LB-520
Abstract 4275: Production and characterization of ErbB1 (EGFR) associated with nanolipoprotein particles via cell-based and cell-free methods.
Authors: Tiffany M. Scharadin, Christina Takanishi, Wei He, Matthew Saldano, Kermit L. Carraway, Matthew A. Coleman, Paul T. Henderson
Journal: Cancer Research (2013)

Abstract The four members of the ErbB family of mammalian receptor tyrosine kinases are essential for the development and maintenance of a variety of tissues. Aberrant activation or over-expression of these receptors leads to the progression of epithelial and brain tumors. An understanding of the mechanistic and structural changes that occur to activate the intracellular receptor tyrosine kinase domain via extracellular ligand binding and receptor dimerization is desirable for identifying specific and efficient methods to inhibit signal transduction. Previous methods to study this process achieved low success due to low protein yield, poor water solubility of the membrane protein, and the large size of receptor. We report progress on overcoming these technical hurdles by forming the ErbB family members in nanolipoprotein particles (NLPs), which are ∼20 nm disc-shaped cell membrane analogs. Here we compare an optimized cell-based method with a novel cell-free method to produce NLPs containing the ErbB1 receptor, also called EGFR. The cell-produced ErbB1-NLPs retain kinase activity compared to cell-free produced material with higher yields. However, the cell-free produced receptors have regions of correct folding and can be produced in less than a day. The cell-free produced constructs can be labeled conveniently with unnatural amino acids to enable characterization of dimerization interactions. These two receptor production systems can be utilized synergistically to enable new studies of conformational changes associated with ligand binding or protein mutations, as well as to identify small molecule inhibitors of these receptors. Citation Format: Tiffany M. Scharadin, Christina Takanishi, Wei He, Matthew Saldano, Kermit L. Carraway, Matthew A. Coleman, Paul T. Henderson. Production and characterization of ErbB1 (EGFR) associated with nanolipoprotein particles via cell-based and cell-free methods. [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 4275. doi:10.1158/1538-7445.AM2013-4275
AB0381 Impact of deformities on foot function in moroccan patients with rheumatoid arthritis
Authors: F. Wafki, B. Amine, Y. Ibnyacoub, A. Elhari, S. Elgueddari, R. Bahiri, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The aim of this study was to assess the type and frequency of foot deformities in rheumatoid arthritis (RA) patients, and to evaluate the impact of these deformities on Foot Function Index (FFI) and patient functional ability. <h3>Methods</h3> We conducted a cross-sectional study in 71 Moroccan patients with a disease duration over than 2 years. Sociodemographic, clinical and biological data were collected. We examined the feet of all patients for hallux valgus (HV) and rigidus (HR), quintus varus (QV), cock-up deformity (CD), clawing toe (CT), mallet finger (MF), Blast of wind peroneal (BWP) and tibial (BWT), and we measured calcaneal valgus angle (CV). Function status of feet, capacity, and health status was evaluated by using FFI, Steinbrocker Functional Class (SFC) and the Arabic version of HAQ respectively. Structural damage was assessed by using the modified Sharp score in the feet. <h3>Results</h3> 93% of patients were female. The mean age was 48.8±12.95 years old [22-82]. The mean disease duration was 10.59±8.34 years [2–35] and the mean score of DAS 28 was 5.3±1.8 [1.6-8.2]. Rheumatoid factor (RF) was positive in 80.3% of cases. Foot deformities were observed in 57 (80.3%) patients; HV (57.7%), CT (23.9%), CD (22.5%), BWP (21.1%), BWT (15.5%), HR (9.9%), QV (7%), MF (4.2%), CV (42.3%). Flat foot was found in 59.2% of cases and cavus foot in 21.1%. The mean of FFI score was 45.75±29.67 [0 – 98], of SFC was 2.15, of HAQ was 1.43 and the Scharp modified score was 14.91±11.83. 3 deformities were associated with the increase of disease duration: HV (p=0.001), HR and QV (p=0.01); HV was also correlated to RF (p=0.01). BWT was associated to FFI (p=0.04) and Sharp score (p=0.03). we did not find any correlation between deformities and HAQ. SFC was correlated with HAQ, structural damage and activity of RA. There was significant correlation between FFI and HAQ and high disease activity (p&lt;0.0001), followed by clinical deformities, SFC and feet structural damage. <h3>Conclusions</h3> Feet deformities are highly frequent in our RA patients. They may affect patient functional foot, especially BWT. <h3>Disclosure of Interest</h3> None Declared
GE-24 * CHARACTERIZING INTRATUMOR HETEROGENEITY AND TUMOR EXTENSION IN PEDIATRIC DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: E. Panditharatna, M. Kambhampati, C.-Y. Ho, H. Gordish-Dressman, A. Siu, E. Hwang, M. Stampar, R. Packer, J. Nazarian
Journal: Neuro-Oncology (2014)

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is an understudied pediatric brain cancer. The validity of at-diagnosis tumor biopsy is currently under debate with no published studies investigating tumor heterogeneity within the same patient. METHODS: Two whole brains obtained at postmortem from patients with DIPG were studied. Frozen and formalin fixed paraffin embedded (FFPE) specimens were stained for H&E, GFAP and Ki67. Histologic analysis revealed a high-grade infiltrating astrocytoma with variable cellularity and mitotic activity. Core punches representing different tumor anatomical locations, as well as tumor grades were obtained, and used for DNA and RNA extractions. DNA was analyzed for methylation (Illumina 450), and mRNA for NanoString expression profiling. To investigate molecular disparities within each grade, specimens were reanalyzed based on geographic location and pathology. Each tumor grade was then designated as classic or non-classic (not fitting all criteria for a specific grade). RESULTS: We show that mRNA profiles (unsupervised clustering) correspond to tumor grade across the brainstem (n = 12 per case). The expression pattern of twelve genes is sufficient for accurate molecular grading (WHO II, III, IV) of tissue specimens when compared with neuropathological assessment. We show detectable differential mRNA expression patterns within each grade, helping to discriminate between classic and non-classic specimens. Methylation analysis (n = 24, 12/case) verified the heterogeneous nature of mRNA expression data (within tumor grades), where WHO grade III non-classic specimens clustered with WHO grade II classic specimens. The largest molecular changes were observed in tumors from distinct geographic locations (brainstem versus lateral ventricles). CONCLUSIONS: Significant intratumor heterogeneity may affect the accuracy of targeted diagnosis in small biopsy specimens. A better understanding of these differences will help in improving therapy and devising accurate molecular-based tumor grading.
PTU-112 Rifaximin for Hepatic Encephalopathy is Cost Effective at Reducing Emergency Hospital Admission
Authors: J Orr, F Perez, H Mitchison, M Hewett, S Saksena, J Topping, A Grapes, A Reddy, D Jones, M Hudson
Journal: Gut (2013)

<h3>Introduction</h3> Overt Hepatic Encephalopathy (HE) frequently results in emergency admission to hospital. Treatment with the non-absorbable antibiotic rifaximin is effective at preventing recurrence of overt HE but there are concerns about the high cost of the drug. The aim of this study was to evaluate the cost-effectiveness of rifaximin at reducing emergency admission to hospital. <h3>Methods</h3> All patients commenced on rifaximin for HE from 1st January to 31st December 2011 were identified from the records of the pharmacy department at Freeman Hospital. The number and length of emergency hospital admissions for the period 1 year prior to starting rifaximin was compared to 1 year after starting the drug. Cost effectiveness was calculated using the standard British National Formulary (BNF) tariff for rifaximin and the estimated cost per day for acute inpatient admission to the Newcastle upon Tyne Hospitals Trust. <h3>Results</h3> 64 patients (75% male, 53% ALD) were identified, 40 (63%) were on concomitant lactulose. In 8 patients rifaximin was discontinued (5 after transplant and 3 when HE excluded). 23 (36%) patients died within 1 year (median survival 62 days (range 2–364) and 33 (52%) were alive at 1 year and remained on rifaximin. Mean MELD of survivors was significantly lower than non-survivors (13.0 vs. 19.0 P &lt; 0.05) and scores predicted 28 day mortality (median MELD 29 (range 4–37)). Complete data were available for 25 of the survivors and showed a significant reduction in the number of emergency admissions from a mean of 2.8 to 1.7 admissions per patient per year with rifaximin (P &lt; 0.05). Duration of inpatient admission decreased significantly from a mean of 30.2 to 9.8 bed days per patient per year (P &lt; 0.05). Taking into account the cost of one year's treatment with rifaximin (£3,687GBP) the reduction in the number of emergency admissions represents an annual saving of £3,468GBP per patient. <h3>Conclusion</h3> Treatment with rifaximin for secondary prevention of hepatic encephalopathy appears to be cost effective at reducing emergency admission to hospital. <h3>Disclosure of Interest</h3> None Declared
Shifting Vaccination Politics — The End of Personal-Belief Exemptions in California
Authors: Michelle M. Mello, David M. Studdert, Wendy E. Parmet
Journal: New England Journal of Medicine (2015)

Interview with Dr. Michelle Mello on a new California law that eliminates religious and philosophical exemptions for vaccination mandates. (06:47)Download A new California law ending religious and philosophical exemptions to vaccination requirements faces both legal and enforcement challenges. But other states will be watching closely to see whether it results in fewer vaccine-preventable illnesses.
P5-23-02: Clinicopathological Features of Young Patients Age &amp;lt;35 Years with Breast Cancer in Japan.
Authors: A Kataoka, E Tokunaga, N Masuda, T Shien, S Ohno, T Kinoshita, C Shimizu
Journal: Cancer Research (2011)

Abstract Background: The aim of this study is to clarify clinicopathological features of breast cancer in young women. Materials and methods: Clinicopathological characteristics were compared between young (&amp;lt;35) patients and non-young (≥35) patients among 109,617 records of JBCS database registered from 2004 to 2009, and overall survival (10-yr OS) were calculated among 146,690 records from 1975 to 2000 with 8.6 years of median follow up period. Results: Clinicopathological factors of 2,982 young patients (2.7%) were compared with 106,295 non-young patients. Young patients had more familial history of breast cancer, more subjective symptom, less bilateral tumor, lower BMI, larger tumor, more inflammatory breast cancer, more positive node, less ER-positive, more HER2−positive, more triple-negative tumor, and more advanced TNM-stage. Comparison of clinicopathological factors between young and non-young patients with breast cancer Young patients were received more neoadjuvant chemotherapy and breast conserving therapy (BCT), compared with non-young patients. Comparison of treatments between young and non-young patients with breast cancer Eighty-percent of patients were received adjuvant therapy, among them, treatment rate of chemotherapy, molecular targeted therapy and radiation therapy was significantly higher in young patients than non-young patients. There was significant difference in 10-yr OS between young and non-young patients with Stage I-IIIA disease (Stage I 80% vs. 90%, IIA 78% vs. 85%, IIB 67% vs. 78%, IIIA 42% vs. 64%), but not with Stage IIIB and IIIC. Advanced TNM stage, lymph node metastasis and ER-negative tumor were significantly poorer prognostic factors for young patients by univariate analysis. Approximately 9% of young patients were at pregnancy at the time of diagnosis had more advanced disease and worse prognosis. Conclusions: We conclude that young patients with breast cancer have an advanced or an endocrine-unresponsive tumor and have unfavorable outcome. Advocacy for awareness of breast cancer to young women and development of new targeted therapy against advanced, HER2−positve and triple-negative tumor are important to improve the survival of young patients with breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-02.
Gastric pneumatosis: a radiological diagnosis with a wide clinical spectrum
Authors: A. Ferreira, A. Loureiro, H. Sousa, J. Brito
Journal: Endoscopy (2012)

We present the case of a 72-year-old woman with a history of type 2 diabetes, ischemic stroke, and fracture of the femur. She presented to the emergency department with a 3-day history of vomiting and epigastric pain. Her physical examination was remarkable only for a distended but nonpainful abdomen. She had a mild leucocytosis (11.3 × 109/L) and elevated C-reactive protein (113 mg/L). Radiographs of her chest ([Fig. 1]) and abdomen ([Fig. 2]) showed intramural gas in the gastric wall, a pneumoperitoneum, and massive esophageal dilatation. These findings were also observed in a subsequent abdominal computed tomography (CT) scan ([Fig. 3]).
THE PROGNOSTIC SIGNIFICANCE OF POSITIVE ELECTROCARDIOGRAPHY FINDINGS WITH NORMAL EXERCISE ECHOCARDIOGRAPHY
Authors: Joseph Sivak, Melissa Daubert, Stephanie Minter, Alicia Armour, Amanda Tinnemore, Ross Smith, Linda Benedict, Brian Coyne, Zainab Samad, Eric Velazquez
Journal: Journal of the American College of Cardiology (2015)
P13.24 * A COMPARISON OF TWO STEREOTACTIC RADIOSURGERY DELIVERY TECHNIQUES IN THE TREATMENT OF BRAIN METASTASIS
Authors: A. Williamson, A. James, B. Clark, M. Mackinnon, A. Chalmers, S. Smith
Journal: Neuro-Oncology (2014)

The Beatson West of Scotland Cancer Center (BWOSCC) has been treating brain metastasis using LINAC based stereotactic radiosurgery with micromultileaf collimator (Brain lab M3) since 2008. Patients are immobilised using Brainlab fixation and treated with static fixed fields (6MV photon), delivered at conventional dose rates of 400-600 monitor units per minute (MU/min). In August 2012 a TrueBeam STX (Varian Medical Systems) was installed. Patients with localised CNS lesions are now treated with 10MV FFF VMAT. METHOD: Treatment records for 10 for conformal static field patients and 10 VMAT FFF patients were reviewed on Varian Eclipse and Offline Review. Beam on time (BOT), time in room (TIR), and clinical dose rate (CDR) were compared. BOT (minutes:seconds) is the aggregate “beam-on” time for all fields or arcs in a given plan. TIR (minutes:seconds) is measured from the first alignment image to last beam off, inclusive of all pre-treatment imaging studies and/or shifts. CDR (MU/min) is the number of MU divided by the BOT.Static field patients had MV imaging only. VMAT patients had kV imaging and pre-treatment cone beam CT (CBCT). 18 patients had single metastasis, 2 patients had 2 mets. 11 patients were treated with 20Gy, 7: 18Gy and 2: 15Gy. RESULTS: Median Planning Target Volume was 5.41cm3 (min 0.98cm3 max 18.88cm3). 10 patients were treated with 6MV static fields (between 4 and 6 fields). 10 patients with 10MV FFF (All 10 Patients had 2 co-planar) arcs. Beam on time: 6X Static 5.85 (range 4.55-6.6), VMAT FFF 2.60 (range 2.01-3.9). Time In Room: 6X Static 34.17 (range 20.42-58.13) VMAT FFF 17.12 (range 12.42-28.28). Monitor Units: 6X Static 2726 (range 2119-3168) VMAT FFF 6216.5 (range 4472-9340). Clinical Dose Rate: 6X Static 600MU/Min VMAT FFF 2385.5MU/Min. CONCLUSION: VMAT FFF has dramatically reduced the TIR: shorter BOT reduces the likelihood of intrafraction motion. It is envisaged that VMAT FFF treatment times will be reduced further as Radiographer competency and skill increases. This is essential in busy RT departments where treatment slots are at a premium.
OP0175 The eurofever registry for autoinflammatory disease: Update on enrollment after 2 years
Authors: A. Naselli, J. Frenkel, S. Ozen, I. Konè-Paut, H. Lachmann, P. Woo, F. De Benedetti, M. Hofer, B. Neven, P. Dolezalova, J. Kümmerle-Deschner, V. Hentgen, I. Touitou, A. Simon, C. Wouters, N. Toplak, J. Anton, S. Stojanov, H. Girschick, R. Vesely, J.I. Arostegui, C. Rose, H. Ozdogan, N. Ruperto, A. Martini, M. Gattorno
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The main limitation to a better knowledge of Autoinflammatory diseases is related to the extreme fragmentation of the diagnosed cases that are spread over different centers and countries. The general aim of the Eurofever Project (agreement n 2007332, EAHC) is to build an international registry on Autoinflammatory diseases. <h3>Objectives</h3> To evaluate the number of patients enrolled in the Registry in the first 24 months after starting the enrolment. <h3>Methods</h3> A web-based registry collecting baseline and clinical information on Autoinflammatory diseases is available in the member area of the PRINTO web-site. The following monogenic autoinflammatory diseases were considered: FMF, CAPS, TRAPS, mevalonate kinase deficiency (MKD), Blau's syndrome, PAPA, DIRA, NLRP12-mediated periodic fever. Information on CRMO, Behcet's disease, PFAPA and undefined periodic fevers were also collected. <h3>Results</h3> During the first 24 months from the beginning of the enrolment 2293 patients from 51 centers in 38 countries have been entered in the registry. At present baseline demographic information from 2293 (M:F=1121:1172) patients are available. In 1797 (78%) complete information on clinical manifestations form disease onset to diagnosis and response to treatment is also available. For each disease the number of enrolled patients is: FMF 694 pts (493 with complete clinical data); TRAPS 215 pts (180 with with complete clinical data); CAPS 180 pts (155 with complete clinical data); MKD 129 pts (107 with complete clinical data); Blau's disease 30 pts (18 with complete clinical data); PAPA 8 pts (all with complete clinical data); NLRP-12 mediated periodic fever 6 pts – 4 with complete clinical data); DIRA 3 pts (all with complete clinical data). In total 19 new mutations have been reported in 22 pts. Among multifactorial autoinflammatory diseases: PFAPA 405 pts (264 with complete clinical data); CRMO 372 pts (334 with complete clinical data); pediatric Bechet disease 79 pts (64 with complete clinical data) and 173 patients with undefined periodic fever (167 with complete clinical data). <h3>Conclusions</h3> A common registry for collection of patients with Autoinflammatory disease is available and the enrolment is ongoing. The analysis of data on the clinical presentation, outcome and response to treatment of Autoinflammatory diseases and comparative studies among different Autoinflammatory conditions are ongoing. <h3>Disclosure of Interest</h3> None Declared