tbuckley/cabot-search huggingface dataset:
AB0424 Has the role of ana in differential diagnosis of connective tissue diseases been changed after technological developments?
Authors: O. Karadag, L. Kilic, A. A. Erbil, N. N. Aydın, O. Tuncer, A. Akdogan, S. A. Bilgen, B. Sener, I. Ertenli, S. Kiraz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The mostly recommended method used in the detection of auto-antibodies for ANA is immune fluorescent antibody technique (IFA). In parallel with technological developments, new patterns as actin, ku, granular chromosomes (DFS-70) are also reported. However, clinical significance of these findings is currently not very well understood. <h3>Objectives</h3> We aimed to investigate the concordance of ANA results with clinical diagnosis of connective tissue diseases, and meanings of new patterns for autoimmune diseases. <h3>Methods</h3> The results of Immunology laboratory between January - June 2012 was used for this study. Totally 2195 ANA-IFA results of 2114 patients who were followed in our rheumatology clinic were reevaluated. ANA analysis, the IFA method using Hep-2, and liver cells (Euroimmun, Germany) was performed and the results were reported by an experienced specialist in microbiology. Clinical data were obtained from hospital records. For each connective tissue disease and the IFA pattern, ANA titers were identified. The clinical significance of the IFA patterns in connective tissue diseases and other diseases were investigated. <h3>Results</h3> Among the study group 850 (40.2%) patients had a connective tissue disease. 227 patients had non-inflammatory musculoskeletal disorders. Distribution and patterns of ANA positivity in patients were shown in table 1. In 29 (11.4%) SLE patients, ANA was negative at the time of study. Seventeen of them had ANA positivity in previous tests. The other 9 ANA negative SLE patients were under treatment when tested and 3 (1.2%) patients were ANA (-) since the beginning of the disease. The frequency of newly reported patterns (cytoplasmic, ku, nuclear membrane, actin and dense fine granular (DFS70)) were as 11.8%, 0.6%, 1.8%, 0.4% and 9.7%, respectively. Regarding DFS70 pattern positive 104 patients; 52.8% did not have a rheumatic disease, but in 19.2% had RA (p &lt;0.001). In nuclear membrane positive 17 patients, 8 didn't have a rheumatic disease, but 5 had RA. There was no difference between the groups regarding cytoplasmic, ku and actin patterns. <h3>Conclusions</h3> ANA tests requested in rheumatology clinic can be false positive up to %35. However, only 12.3% of them had a titer ≥1/320. The sensitivity of the ANA in patients with SLE as assessed by IFA was more than 98%. Nuclear membrane and DFS70 patterns are not specific to any connective tissue disease and they can be detected positive in rheumatoid arthritis and in the absence of any rheumatic disease <h3>Disclosure of Interest</h3> None Declared
S92 Nebulised Amphotericin in Allergic bronchopulmonary Aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS)
Authors: L Chishimba, P Langridge, G Powell, DW Denning, R Niven
Journal: Thorax (2013)

<h3>Background and Rationale</h3> Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) are debilitating lung diseases whose treatment is not yet fully established. Some published case series suggest that nebulised amphotericin may have a role in the treatment of cystic fibrosis ABPA but little is known regarding its appropriateness in asthmatic ABPA and SAFS patients. We assessed the efficacy and safety of nebulised Amphotericin as second and third line therapy. <h3>Methods</h3> 20 adult asthmatics with SAFS (n = 11) and ABPA (n = 9) were treated with nebulised amphotericin (January 2011- May 2013). All patients had either failed itraconazole (n = 8), voriconazole (n = 5) or developed adverse events (AEs) to either agent (n = 7). 10mg of Nebulised amphotericin B (Fungisone) was administered using a nebulizer twice/day. We audited clinical, radiological and immunological response, including change in the Asthma Quality of Life Questionnaire (AQLQ-J) scores. We also examined Asthma Control Questionnaire (ACQ) scores, change in lung function (FEV1), change in IgE (total and specific) and healthcare utilisation. Patients were followed up for 12 months. <h3>Results</h3> There were 20 patients analysed (SAFS, n = 11) and (ABPA n = 9), M: F = 8:12, median age 65.5 yrs (range = 24–78). The median duration of therapy was 30 days (IQR, 0.0–142). Clinical benefit was observed in 2 (10%) in which mean ACQ score improved from 6 to 2, overall mean AQLQ score improved by 0.95 and mean FEV1 improved by 1.2 L ( 63.1%). Seven (35%) failed the challenge due to bronchospasm. 11 (55%) discontinued within 12 months of therapy due to delayed bronchospasm (n = 3, within 4 weeks), equipment problems (n = 4) and lack of clinical benefit (n = 4) (fig 1). There were no significant changes in immunological and radiological outcomes. <h3>Conclusion</h3> Our data suggests that the overall efficacy of nebulised amphotericin in this group of patients may be poor and is associated with high frequency of adverse events. However, the responses were excellent in 2 (10%) patients. It is not clear which patients are likely to respond. Further studies need to be conducted to establish the optimal dose range (dose, frequency), nebulizer type, pressures and identification of patients who may respond.
Long-term follow-up of subtotal splenectomy for hereditary spherocytosis: a single-center study
Authors: Thomas Pincez, Corinne Guitton, Frédéric Gauthier, Guénolée de Lambert, Véronique Picard, Madeleine Fénéant-Thibault, Ali Turhan, Narla Mohandas, Gil Tchernia, Loïc Garçon
Journal: Blood (2016)
Tongue Fasciculations in Amyotrophic Lateral Sclerosis
Authors: Jaime Toro, Saúl Reyes
Journal: New England Journal of Medicine (2014)

A 47-year-old man presented with a 1-year history of progressive, involuntary muscle twitching and leg cramps. Examination revealed slurred speech, tongue atrophy and fasciculations, and weakness of the sternocleidomastoid muscle. A video shows the tongue fasciculations.
INTRACRANIAL GERM CELL TUMORS WITH MTOR MUTATION ARE COMMON IN BASAL GANGLIA
Authors: R. Nishikawa, K. Fukuoka, K. Ichimura
Journal: Neuro-Oncology (2014)

BACKGROUND: Intracranial germ cell tumors (iGCTs) are the second most common CNS tumors in patients under 14 years old in Japan. But, their molecular genetic profile is largely unknown. METHODS: We have analyzed a total of 198 germ cell tumors (GCTs) including 133 iGCTs (69 pure germinomas, 56 non-germinomatous GCTs and 8 metastatic tumors) as well as 65 testicular germ cell tumors (tGCTs) (39 seminomas and 26 non-seminoma GCTs) were collected from 13 centers participating in the Intracranial Germ Cell Tumor Consortium in Japan. Somatic mutations in all coding exons were investigated by whole exome sequencing (WES) using SureSelectXT Human All Exon v4 and a GAIIx or HiSeq 2000 system in 41 tumors and the matched normal DNAs. Targeted sequencing with a set of custom made PCR primers was performed using either an IonTorrent PGM or Proton System. The results were integrated with the patients' clinical information that was available for 124 iGCT patients. RESULTS: On average, 15.4 non-synonymous somatic mutations were observed in each tumor, ranging from 1 to 140 by WES in 41 iGCTs. MTOR was the second most frequently mutated in both iGCTs (9 cases, 7%) and tGCTs (6%). Collectively, the genes involved in the PI3K/MTOR pathway (e.g., MTOR, PTEN) were mutated in 13% of all GCTs. Clinical parameters of the 9 iGCTs with MTOR mutation were: median age of onset = 15 years old; 7 males and 2 females; 5 germinomas, 3 teratomas and one yolk sac tumor; 5 basal ganglia tumors, 2 pineal tumors, one neurohypophyseal tumor and a medulla oblongata tumor. Age, sex, histology and clinical behavior are within the scope of iGCT except for extraordinary high frequency of basal ganglia GCTs. CONCLUSIONS: iGCTs with MTOR mutation are frequent in iGCTs in basal ganglia. SECONDARY CATEGORY: Pediatrics.
Ambient Coarse Particulate Matter and Hospital Admissions in the Medicare Cohort Air Pollution Study, 1999–2010
Authors: Helen Powell, Jenna R. Krall, Yun Wang, Michelle L. Bell, Roger D. Peng
Journal: Environmental Health Perspectives (2015)

In recent years a number of studies have examined the short-term association between coarse particulate matter (PM(10-2.5)) and mortality and morbidity outcomes. These studies, however, have produced inconsistent conclusions.We estimated both the national- and regional-level associations between PM(10-2.5) and emergency hospitalizations for both cardiovascular and respiratory disease among Medicare enrollees ≥ 65 years of age during the 12-year period 1999 through 2010.Using air pollution data obtained from the U.S. Environmental Protection Agency air quality monitoring network and daily emergency hospitalizations for 110 large urban U.S. counties assembled from the Medicare Cohort Air Pollution Study (MCAPS), we estimated the association between short-term exposure to PM(10-2.5) and hospitalizations using a two-stage Bayesian hierarchical model and Poisson log-linear regression models.A 10-μg/m3 increase in PM(10-2.5) was associated with a significant increase in same-day cardiovascular hospitalizations [0.69%; 95% posterior interval (PI): 0.45, 0.92]. After adjusting for PM2.5, this association remained significant (0.63%; 95% PI: 0.38, 0.88). A 10-μg/m3 increase in PM(10-2.5) was not associated with a significant increase in respiratory-related hospitalizations.We found statistically significant evidence that daily variation in PM(10-2.5) is associated with emergency hospitalizations for cardiovascular diseases among Medicare enrollees ≥ 65 years of age. This association was robust to adjustment for concentrations of PM2.5.Powell H, Krall JR, Wang Y, Bell ML, Peng RD. 2015. Ambient coarse particulate matter and hospital admissions in the Medicare Cohort Air Pollution Study, 1999-2010. Environ Health Perspect 123:1152-1158; http://dx.doi.org/10.1289/ehp.1408720.
Cyclophosphamide, methotrexate, and fluorouracil: still the gold standard?
Authors: C A Hudis
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.7.1971 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8683226 Cyclophosphamide, methotrexate, and fluorouracil: still the gold standard? C A HudisxC A HudisSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.7.1971 First Page PDF © 1996 by American Society of Clinical Oncology
GE-08 * TARGETED NEXT GENERATION SEQUENCING OF ARCHIVAL FFPE SAMPLES FROM EORTC STUDY 26951 SHOWS STRONG PROGNOSTIC VALUE OF A MOLECULAR CLASSIFICATION IN LOCALLY DIAGNOSED GRADE III OLIGODENDROGLIOMA
Authors: H. Dubbink, P. Atmodimedjo, P. French, J. Kros, P. Wesseling, R. Enting, W. Spliet, C. Tijssen, A. Idbaih, W. Dinjens, T. Gorlia, M. van den Bent
Journal: Neuro-Oncology (2014)

BACKGROUND: Molecular holds promise for an improved classification of glial tumors. We analyzed samples of patients enrolled in EORTC study 26951 on adjuvant PCV in anaplastic oligodendroglial tumors to evaluate 1. The clinical significance of glioma classification with Next Generation Sequencing (NGS); and 2. The prognostic significance of CIC and FUBP mutations. MATERIAL AND METHODS: EORTC 26951 investigated adjuvant PCV in locally diagnosed anaplastic oligodendroglial tumors. NGS was performed on archival formalin fixed paraffin embedded (FFPE) samples using the Ion Torrent Personal Genome Machine for simultaneous detection of mutations in the genes for ATRX, CIC, EGFR, FUBP1, NOTCH1, PTEN, and TP53 and hot spot mutation regions in BRAF, H3F3A, IDH1, IDH2 and PIK3CA as well as imbalances on chromosome 1p, 10q, 7 en 19q. TERT mutations were assessed with PCR. RESULTS: At the time of abstract submission 89 cases have been investigated, more samples are being processed. In 62 tumors an IDH1 mutations was found, in 2 an IDH 2 mutation. Forty-eight tumors (54%) were 1p/19q codeleted, 29 (60%) of these had CIC mutations and 20 (42%) had FUBP mutations. All but one 1p/19q codeleted tumors showed TERT mutations. Ten tumors showed ATRX mutations, 5 also had PTEN mutations. Median OS was 136 months for CIC mutated 1p/19q co-delete tumors, and 95 months for CICwt tumors (p = 0.17); FUBP mutations showed no relation with OS. TERT mutations were found in 60 tumors (67%), OS in TERT mutated but 1p/19q intact tumors was 12 months. IDH mutations, TERT mutations and 1p/19q co-deletion were the most significant prognostic factors, distinguishing between groups with significantly different OS. CONCLUSIONS: The ongoing expansion of this series will show if CIC mutations have prognostic significance. Targeted NGS even on archival FFPE allows a clinically relevant prognostic classification of glioma, while simultaneously identifying relevant druggable targets.
PDGFR is activated through an autocrine mechanism in ovarian cancer
Authors: D. Matei, Y.-C. Lai, J. Rao, R. Emerson, D. Donner
Journal: Journal of Clinical Oncology (2005)

5073 Background: We demonstrated PDGFRα expression in ovarian cancer cells and in ovarian tumors using microarray hybridization and immunohistochemistry (Matei, Oncogene, 2002 and Matei, Clin Cancer Research, 2004). This led us to hypothesize that the PDGFR is activated through an autocrine or paracrine mechanism and stimulates proliferation and expansion of ovarian tumors. To test this hypothesis we tested expression of PDGFR ligands (PDGF A, B, C and D) in ovarian tumors, ovarian cell lines and ascites fluid from patients with ovarian cancer. Methods: Semi-quanitative RT-PCR tested for PDGF expression in ovarian tumor specimens, Western blots for PDGF in conditioned media from ovarian cancer cells and ELISA for PDGF in ascites fluid from ovarian cancer patients. Results: We detected strong PDGF A and C expression by RT-PCR in most ovarian tumors (n=12), but not in normal ovarian tissue. PDGF B was expressed weakly in 2 of 12 tumors tested and PDGF-D weakly in 10 of 12 ovarian tumors. We detected secreted PDGF in ascites fluid exceeding a concentration>50pg/mL in 15 of 29 specimens compared to 1 of 6 specimens from non-ovarian cancer (average PDGF concentration in ovarian cancer samples=120pg/mL). Similarly we detected PDGF AB in conditioned media from ovarian cancer cell lines expressing PDGFR, but not in media collected from normal ovarian primary cells. To test whether secreted PDGF from ovarian cancer cells has functional significance, we evaluated if serum free conditioned media from immortalized ovarian primary cells expressing PDGFR activates the signaling pathway. We noted PDGFR activation and phosphorylation of MAPK and AKT induced by conditioned media. These effects were blocked by pre-incubation of the media with neutralizing anti-PDGF antibody. Conclusion: Our data suggest that PDGF is expressed in ovarian tumors, ovarian cell lines and is secreted in ascites fluid. Secreted PDGF activates the PDGF receptor, suggesting that an autocrine loop may be functional in ovarian carcinoma. These data support clinical investigations directed at blocking PDGFR in ovarian tumors. No significant financial relationships to disclose.
Abstract 5000: Tolerogenic transcription regulator Foxp3 controls the expression of immunosuppressive cytokines in melanoma cells
Authors: Samuel Y. Olson, Cynthia Chen, Diana C. Marquez, Kevin W. Bruhn, Noah A. Craft, Hermes J. Garban
Journal: Cancer Research (2011)

Abstract Foxp3 is a critical transcription regulator that is found commonly expressed in a subset of immunosuppressive CD4+/CD25+ T cells characterized as regulatory T cells (Tregs) in the immune system. Foxp3 is a member of the forkhead/winged-helix family of transcriptional regulators exhibiting both, activation and repression of transcription. Foxp3 is critically important for the development and function of Tregs and the consequent definition of immune-tolerance. Ectopic Foxp3 expression has been shown to -phenotypically and functionally- convert T cells to Tregs. Recently, we have characterized the expression of Foxp3 in a variety of human and mouse cancerous cells, either in tissue or in cultured cell lines. Although of cardinal importance, the specific role and mechanisms involved in the Foxp3-mediated immunosuppressive activity remains elusive. Thus, we hypothesize that tumor-derived Foxp3 is controlling the transcriptional expression of immunosuppressive cytokines by tumor cells and inducing immunotolerance in the tumor microenvironment. We have tested this hypothesis by interrogating the well-characterized B16-C57BL/6 syngeneic mouse model of melanoma. Foxp3-expressing B16-F0 cells (B16-Foxp3+) where specifically and stably knockdown for Foxp3 expression by lentivirus-mediated shRNA (B16-Foxp3-). In order to determine the specific role and mechanisms of melanoma-derived Foxp3 in controlling the expression of immunosuppressive cytokines generated by melanoma cells, we have evaluated the differential cytokine expression profile between the B16Foxp3+ and the B16-Foxp3- cultured cells using Multiplex Bead Immunoassay, Immunoblotting Assay of Proteins and Semiquantitative RT-PCR. Our results demonstrated that the suppression of expression of Foxp3 in melanoma cells showed a significant downregulation of a selected group of immunosuppressive cytokines, in particular IL-4, IL-6, IL-10, IL-12, TNF-alpha and GM-CSF. In contrast, Foxp3 did not have an appreciable effect on the expression of IL-1, IL-2, IL-5, and IFN-gamma. Altogether, our data suggest the specific role of tumor-derived expression of FOXP3 in the control of the expression of tolerogenic/immunosuppressive cytokines secreted by melanoma cells to the tumor microenvironment. Furthermore, selective suppression of Foxp3 expression and/or activity in cancerous cells may help to develop better and more effective targeted immunotherapy as treatment for malignant melanoma. 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 5000. doi:10.1158/1538-7445.AM2011-5000
AB0782 Misdiagnosing Osteoarthritis as Rheumatoid Arthritis and IT High Cost for Colombian Health System
Authors: D. Gomez, V. Giraldo, G. Saavedra-Martinez, J. Bello-Gualtero, L. Villarreal, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is a lack of expertise in the rheumatoid arthritis (RA) diagnosis in primary level medical centers in Colombia. Frequently, patients with osteoarthritis (OA) are misdiagnosed as rheumatoid arthritis (RA) in primary care centers, leading to wrong treatment and consequent clinical and pharmacoeconomic impact, because there are an important number of those patients with OA misdiagnosed as RA treated as such with disease modifying anti-rheumatic drugs (DMARDs), leading to higher economic costs for health system. <h3>Objectives</h3> The aim of this study was to calculate costs of the OA patients misdiagnosed as RA in a 24 month period in a cohort of patients derived to a specialized RA center in Colombia. <h3>Methods</h3> A descriptive cross sectional study was performed. Patients derived during a 24 month period to a RA specialized center with presumptive diagnosis of this disease and found finally diagnosed with OA were included in analysis. We described the direct costs in US dollars (USD) of their care assuming an average of 4 visits/year to general practitioner ($4 USD/consultation), 2 visits/year for physiatrist and orthopedics ($17.33 USD/consultation) and 4 set/year of conventional laboratories ($46.14 USD/set). Cost of medication doses were calculated for an average use of methotrexate, sulfasalazine, chloroquine and prednisolone ($ 120.96 USD/monthly). Indirect costs were not calculated. <h3>Results</h3> We found 1116 OA patients misdiagnosed as RA in a period of 24 months. For each patient we calculated $16 USD/year for general practitioner visits, $34.7 USD/year for specialized medicine visits, $184.6 USD/year for laboratory sets and $1.451 USD/year for medications. This leads to a total cost of $1.686.8 USD/year per patient. From a total of 1116 misdiagnosed patients the cost rises to $19882.468.8 USD/year. These patients had an average of 4.5 years of wrong treatment for their misdiagnosis, making the cost rise up to $89471.106 million US dollars. <h3>Conclusions</h3> There is an important economic implication of the misdiagnosis of OA as RA, being this the most frequent mistake in the diagnosis of this disease. The implementation of educational programs for health care primary physicians and specialized RA centers could save this amount of money for the health system in Colombia. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5354
LOW BMI PATIENTS WITH ACUTE MYOCARDIAL INFARCTION HAVE SEVERE CALCIFICATION IN CULPRIT LESION AND HIGH LONG-TERM MORTALITY
Authors: Hiroaki Yokoyama, Takumi Higuma, Fumie Nishizaki, Kei Izumiyama, Takashi Yokota, Masahiro Yamada, Hirofumi Tomita, Ken Okumura
Journal: Journal of the American College of Cardiology (2016)
Poor Prognosis of p53 Gene Mutation and Nuclear Overexpression of p53 Protein in Inflammatory Breast Carcinoma
Authors: G. Riou, M. G. Le, J. P. Travagli, A. J. Levine, U. M. Moll
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Poor Prognosis of p53 Gene Mutation and Nuclear Overexpression of p53 Protein in Inflammatory Breast Carcinoma Get access Guy Riou, Guy Riou Laboratolre de Pharmacologie Clinique et Moléculaire, Institut Gustave RoussyVille-juif, France Correspondence to : Professor G. Riou, Institut Gustave Roussy, 94805 Villejuif Cedex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Monique G. Lê, Monique G. Lê Unité Epid´miologie des cancers, INSERM U351, Institut Gustave RoussyVille-juif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean Paul Travagli, Jean Paul Travagli Départment de Chirurgie, Institut Gustave RoussyVille-juif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Arnold J. Levine, Arnold J. Levine Department of Molecular Biology, Lewis Thomas Laboratory, Princeton UniversityPrinceton, NJ Search for other works by this author on: Oxford Academic PubMed Google Scholar Ute M. Moll Ute M. Moll Department of Pathology, State University of New York at Stony BrookN.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 21, 3 November 1993, Pages 1765–1767, https://doi.org/10.1093/jnci/85.21.1765 Published: 03 November 1993 Article history Received: 18 June 1993 Received: 02 August 1993 Accepted: 09 August 1993 Published: 03 November 1993