tbuckley/cabot-search huggingface dataset:
SAT0464 Disease Status Influences the Balance and Cytokine Profile in Patients with Juvenile Idiopathic Arthritis
Authors: G. Almanzar, K. Sustal, R. Trippen, K. Höfner, M. Prelog
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is an inflammatory disorder with heterogeneous clinical presentation. IL-17-producing T-cells (Th17) have been identified as pro-inflammatory cells in several autoimmune conditions. <h3>Objectives</h3> This study evaluated the phenotype and the cytokine-production profile of T-cells in JIA patients with active disease (group 1, n=17), remission on medication (group 2, n=39), remission off medication (group 3, n=10), disease flare after remission (group 4, n=16) and healthy donors (HD, n=28). <h3>Methods</h3> The phenotype characterization and the intracellular production of IFNgamma, TNFalpha, and IL-17 on naive (CD28+CD45RO-), memory (CD28+CD45RO+), effector (CD28-CD45RO+), terminally differentiated T-cells (CD28-CD45RO-) and regulatory T-cells (Tregs, CD25+CD127-FoxP3+) CD4+ T-cells were investigated by flowcytometry. <h3>Results</h3> IFNgamma-producing CD4+ T-cells (4.9% versus 6.9%) and Tregs (2.9% versus 3.8%) were significantly lower in JIA than HD. Moreover, memory CD4+ T-cells produced lower amounts of IFNgamma in JIA group 4 (6.3%), group 1 (6.3%) and group 2 (7.6%) compared to HD (11.3%). Interestingly, the memory CD4+ T-cell population also showed lower TNFalpha production in the same groups (group 4:20.3%; group 1:18.5%; group 2:20.0%; HD:29.9%). No differences were observed in the IL-17 production by CD4+ T-cells between JIA and HD. However, patients with disease flare showed higher proportions of IL-17-producing CD4+CD45RO-CD28-CD27- T-cells (1.3%) than patients in remission off medication (0.6%) <h3>Conclusions</h3> Our findingssuggest, depending on disease activity, an imbalance in the cytokine production profile in memory and effector T-cell subpopulations in JIA patients. This may be increasingly relevant for novel therapeutic approaches with early treatment of active disease with biologic drugs. <h3>Disclosure of Interest</h3> None Declared
Abstract 3642: AS1411 causes a specific increase in levels of cell surface nucleolin in responsive cell lines
Authors: Yun Teng, David Jones, Fiona McLaughlin, Paula J. Bates
Journal: Cancer Research (2010)

Abstract AS1411 is a 26-mer guanine-rich oligodeoxynucleotide that has antiproliferative activity against many types of cancer cells, but not against normal cells. It is currently being tested as an anticancer agent in Phase II clinical trials. Previously, we reported that this agent has a novel mechanism of action that involves formation of a stable G-quadruplex structure that can bind as an aptamer to nucleolin, a multifunctional protein expressed at high levels by cancer cells. Nucleolin is a predominantly nuclear protein, but can also be present in the cytoplasm and on the surface of cells, where it has been reported to mediate the endocytosis of several ligands. Cell surface nucleolin is believed to play an important role in AS1411 activity, although the precise details have yet to be elucidated. In the present study, we have evaluated the levels of cell surface nucleolin in human cell lines that are responsive or resistant to AS1411, before and after treatment with AS1411. Levels were examined by flow cytometry, with gating to exclude non-viable permeable (PI-positive) cells, and by western blotting of cell surface proteins, isolated using a cell-impermeable biotinylating agent. The amount of cell surface nucleolin appeared to be similar in untreated cells that were either sensitive to AS1411 (DU145 prostate cancer cells and MV-4-11 leukemia cells) or resistant to AS1411 (Hs27 non-malignant skin fibroblasts). However, in the sensitive cell lines, we observed a dramatic and time-dependent increase in levels of cell surface nucleolin in response to AS1411 treatment, whereas there was no significant change in the resistant Hs27 cells. We determined that this AS1411-induced increase in cell surface nucleolin in the cancer cells was not simply a reflection of apoptosis because it was not observed when apoptosis was induced by UV irradiation. We did not observe any changes in the levels of nucleolin in nuclear, cytoplasmic, or membrane extracts, or in total cell lysates, following treatment with AS1411, suggesting a specific re-localization of nucleolin rather than an increase in overall levels. These new results do not support our previous hypothesis that baseline levels of cell surface nucleolin determine responsiveness to AS1411. However, they do clearly demonstrate that “externalization” of nucleolin is a specific response to AS1411 and thereby confirm the important role of cell surface nucleolin in the mechanism of action of AS1411. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3642.
Preliminary Results of the Mutational Analysis of the TP53 Gene in Women Diagnosed with Breast Cancer before the Age of 35 Years and Negative for BRCA1 and BRCA2 Mutations.
Authors: J. Balmaña, J. Ferro, S. Gutierrez-Enríquez, M. Masas, N. Gadea, D. Fortuny, C. Saura, O. Díez, O. Díez
Journal: Cancer Research (2009)

Abstract Background: Early onset breast cancer is part of the tumor spectrum in the Li-Fraumeni syndrome (MIM 151623), which is associated with germ-line mutations in the TP53 gene. The aim of the study is to determine the presence of inherited mutations in TP53 in women with early onset breast cancer regardless of their family history and after having obtained a negative result for the BRCA1 and BRCA2 mutations. Patients and methods: We analyzed 41 women with breast cancer (BC) diagnosed before the age of 35 years and a negative result for the BRCA1 and BRCA2 genes (analyzed by direct sequencing and MLPA). Patients were classified according their family history in three groups: A) no family history of cancer (n=11); B) family history of breast/ovarian cancer (BC/OC) (n=22); C) family history of other neoplasms (pancreas, kidney, brain, leukemia) without fulfilling the classical Li-Fraumeni criteria (n=8). The analysis of the TP53 gene was carried out by PCR amplification and direct sequencing of the exons 4 to 10. Analysis of the remaining exons, the 5' and 3' UTR regions of the gene, and the detection of large rearrangements are in progress. Results: Among the 41 women we identified two (4.8%) deleterious mutations, and both were observed in group C (2/8, 25%): c.375G&amp;gt;A in exon 4 (splicing mutation) and c.524G&amp;gt;A in exon 5 (p.R175H). Conclusions: These preliminary results suggest that, after a negative result in the analysis of the BRCA1 and BRCA2 genes, TP53 mutations may play a relevant etiological role in the genetic predisposition of early onset BC, especially in those families with presence of different neoplasms Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4072.
SP0110 European Initiative in Pediatric Rheumatology. the Example of the Paediatric Rheumatology International Trials Organisation (PRINTO)
Authors: N. Ruperto
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The existence of large networks such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), the Pediatric Rheumatology European Society (PRES) and more recently the Childhood Arthritis (Research Alliance (CARRA) has greatly facilitated the possibility of implementing collaborative studies either academic or in collaboration with pharmaceutical companies in the field of pediatric rheumatology. In the last few years PRINTO has concentrated its efforts to provide facilities to its membership for the conduct of international research projects. The ongoing initiative are as follow: A pharmacovigilance registry for children with juvenile idiopathic arthritis (JIA) treated with biologics ± methotrexate and financed by the European Union which has collected data for almost 6000 JIA children. A sub-project called Abirisk, in collaboration with an adult international consortium financed by IMI, is evaluating the development of antibodies against biologic drugs and its correlations with safety and efficacy results. The Eurofever registry has collected clinical and laboratory data for almost 3,000 children and adults with auto-inflammatory syndromes. The EPidemiology, treatment and Outcome of Childhood Arthritis throughout the world (EPOCA) study has collected has the goal to define and compare the epidemiology, treatment and outcome of the JIA categories around the world. The project has collected more than 7,000 JIA patients and 2,000 healthy controls. Another project has the goal to develop new classification criteria for macrophage activation syndromes (MAS) in systemic JIA and has collected 360 MAS cases and 750 controls (400 systemic JIA cases without MAS and 350 sepsis). In addition PRINTO is working to update information for families of children with pediatric rheumatic diseases (www.pediatric-rheumatology.printo.it) and characterize the current pattern of care through the Share project financed by the EU. The PRINTO networks can be seen as a model for international cooperation in rheumatology and other paediatric subspecialties. <h3>Disclosure of Interest</h3> N. Ruperto Grant/Research support from: The Gaslini Hospital, which is the public Hospital where I work as full time employee, has received contributions to support the PRINTO research activities from industries: Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Conflict with: Abbott, AbbVie, Astellas, Alter, AstraZeneca, Boehringer, BMS, CD-Pharma,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex Pharmaceuticals Servier <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6138
SP0129 How to Treat/Hot - Localized Rheumatic Syndromes
Authors: P. Haerle
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Localized painful, rheumatic syndromes are very common in rheumatology daily practice, but are sometimes hard to differentiate and treat. The underlying pathology may be triggered by inflammation, overuse or degeneration of structures like joints, ligaments, tendons, tendon sheets, bursae, entheses, or periosteal structures. Even with the best treatment strategy relating to non-biologic DMARDs, biologic DMRADs, glucocorticoids or non-steroidal anti-inflammatory drugs, and opioid analgesics painful, localized syndromes may persist. Furthermore, in the case of only localized painful problems an increase of the mentioned systemic treatment options may tremendously increase the risk of severe side effects and is therefore not a wise treatment choice. A precise history, clinical examination and the use of ultrasound may unravel the underlying problem for the localized pain. Because of the localized nature, the best treatment option often is a local application of drugs, especially anesthetics and glucocorticoids. This talk discusses: – Typical sonographic appearances and treatment options in common localized painful rheumatic syndromes occurring in daily practice. – Why local therapy is superior to systemic therapy in localized syndromes? – Which problems might occur with local application of glucocorticoids? – How to learn ultrasound guided treatment easily? <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6182
PWE-156 Post-oesophagectomy diaphragmatic hernias: an increasing problem with the move to minimally invasive oesophagectomy
Authors: J Matthews, S Bhanderi, H Mitchell, R Vohra, EA Griffiths
Journal: Gut (2015)

<h3>Introduction</h3> Post-oesophagectomy diaphragmatic hernias (PODHs) are serious complications following oesophagectomy. However, the incidence of PODHs are unknown. The aim of this study was to describe and compare the incidence of PODHs over time and analyse the outcomes of patients who develop a PODH. <h3>Method</h3> A prospective database of all oesophagectomies performed for cancer between 2001 to 2014 was analysed. Patients diagnosed with PODH were identified and data extracted regarding demographics, details of oesophagectomy, pathology, PODH symptoms, diagnosis and treatment. <h3>Results</h3> A total of 507 transthoracic oesophagectomies were carried out between 2001 and 2014. Overall, 21 patients (18 males and 3 females) developed PODH. The incidence of PODH after open 2 or 3 stage oesophagectomy was 3/221 (1.3%) compared to 14/212 (6.6%) following laparoscopic hybrid oesophagectomy and 4/68 (5.9%) following minimally invasive oesophagectomy (MIO). Median age was 63 (range 55 to 82) years. 17 (81%) had surgery for lower oesophageal or gastro-oesophageal junctional adenocarcinoma. Of those who developed a PODH, 10 (48%) patients presented as an emergency and 11 (52%) patients with outpatient symptoms. Common presenting symptoms were shortness of breath, chest pain, vomiting and cough. Five (24%) patients develop PODH within 7 days of the index surgery, a further 3 (14%) within 90 days, 8 (38%) at 2 years and 4 (24%) at 5 years. Twenty patients had corrective surgery for PODH with hiatal suture repair (n = 15), hiatal mesh repair (n = 2), and other surgical procedures (n = 3). These were performed either laparoscopically (n = 15) or as open repairs (n = 5). However, 4 patients required conversation. Median length of stay was 12 days (range 3 to 48 days); but shorter when successfully treated laparoscopically. Thirty day post-operative mortality was 10% (n = 2) and 20% (n = 4) recurred requiring further surgery. <h3>Conclusion</h3> PODH is a common complication following hybrid oesophagectomy and MIO. One hypothesis is there is less intra-abdominal adhesions formed when minimal access techniques are used. Careful thought is needed to identify surgical techniques to prevent PODH forming when minimal access oesophagectomy are performed. <h3>Disclosure of interest</h3> None Declared.
Abstract 4388: LipoplatinTM: A less neurotoxic formulation of Cisplatin
Authors: Annalisa Canta, Alessia Chiorazzi, Valentina A. Carozzi, Norberto Oggioni, Barbara Sala, Massimo Zucchetti, Guido A. Cavaletti
Journal: Cancer Research (2011)

Abstract Purpose: Cisplatin is one of the most effective cytotoxic agent in the treatment of solid malignancies, but its use is limited by several side effects. Among them, peripheral neurotoxicity can be dose-limiting. A liposomal formulation of cisplatin, LipoplatinTM, was developed to reduce the systemic toxicity of cisplatin but preventing its efficacy. Aim of this study was to test in an animal model through a multimodal approach if chronic treatment with two different schedules of LipoplatinTM selected in the range of its anticancer effective dose is less neurotoxic than cisplatin administrations. Methods: Female Wistar rats were treated intraperitoneally with cisplatin at the dose of 4mg/kg or with LipoplatinTM 12 and 24mg/kg once weekly for 4 times. General toxicity was assessed by daily observation, body weight change, hematological and blood chemistry analysis and histopathology of liver and kidney. The onset of the peripheral neurotoxicity was assessed using tail nerve conduction velocity (NCV), morphological and morphometrical analysis of dorsal root ganglia (DRG) and by morphological analysis of sciatic nerve. Results: Cisplatin induced a statistically significant reduction in body weight, the development of renal failure and the impairment in NCV with pathological alterations in the DRG and sciatic nerve. By contrast no significant weight gain reduction was observed in animals treated with both doses of LipoplatinTM. Moreover the lowest dose induced a less severe damage to the peripheral nervous system with a moderate decrease of NCV and mild pathological alterations of DRG and sciatic nerve. Conclusions: The results suggest that LipoplatinTM 12mg/kg is less neurotoxic than cisplatin 4mg/kg, thus opening the possibility to use this new formulation in future studies where its anticancer activity and the peripheral neurotoxicity will be assessed in parallel. This study was supported by “Fondazione Banca del Monte di Lombardia” Regulon supported this study exclusively by providing LipoplatinTM 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 4388. doi:10.1158/1538-7445.AM2011-4388
A COMPARATIVE META-ANALYSIS FOR LONG-TERM STROKE IN PATIENTS RECEIVING EDWARDS-SAPIEN VERSUS COREVALVE
Authors: Saurabh Gaba, Navkaranbir Bajaj, Himanshu Aggarwal, Vikas Bhatia, Federico De Puy, Michael Mack, David Holmes, Oluseun Alli
Journal: Journal of the American College of Cardiology (2015)
Durable Responses With Maintenance Dose-Sparing Regimens of Romidepsin in Cutaneous T-Cell Lymphoma
Authors: M. Estela Martinez-Escala, Timothy M. Kuzel, Jason B. Kaplan, Adam Petrich, Beatrice Nardone, Steven T. Rosen, Joan Guitart
Journal: JAMA Oncology (2016)

Romidepsin is a histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma (CTCL). Durable responses have been published without establishing a standard recommendation about duration of treatment.To review the long-term use of romidepsin in responders who received a dose-sparing regimen.Retrospective review of medical records of patients with a diagnosis of CTCL, including mycosis fungoides (MF), Sézary syndrome (SS), or CTCL not otherwise specified seen at a multidisciplinary clinic at Northwestern University from 2009 until December 2014.Doses administered and different regimens of romidepsin were reviewed.Duration of treatment, participants receiving dose-sparing regimen.Of 47 patients identified, 23 had MF, 15 had SS, and 9 had other types of CTCL. None of these 9 (mostly cytotoxic lymphomas) achieved a durable response. Of the remaining 38 patients, 17 were considered long-term responders (>6 months of treatment). Nine of these patients received a dose-sparing regimen. The median (range) duration of treatment was 15 (7-34) months; the frequency of patients with SS (10 of 15) in the long-term group was significantly higher than that of patients with MF (7 of 23; P = .046). Adverse events were reported in 29 (69%) of 42 patients for whom data were available. There was no significant difference in the incidence of AEs between the short-term and long-term groups (12 of 21 vs 12 of 17; P = .50).Decreasing the frequency of infusions in patients with MF or SS who achieve a response with romidepsin therapy may provide a practical strategy to prolong response.
Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis
Authors: Peter E. Lipsky, Desiree M.F.M. van der Heijde, E. William St. Clair, Daniel E. Furst, Ferdinand C. Breedveld, Joachim R. Kalden, Josef S. Smolen, Michael Weisman, Paul Emery, Marc Feldmann, Gregory R. Harriman, Ravinder N. Maini
Journal: New England Journal of Medicine (2000)

Neutralization of tumor necrosis factor α (TNF-α) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known.
THU0587 Empirically Derived Classification of Fibromyalgia Patients: Subgroup Differences in the Processing and Regulation of Emotions
Authors: I. López-Chicheri, H. van Middendorp, R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with fibromyalgia vary widely in their physical and psychological functioning, and in how they perceive their disease. It has been reported that only one-third of patient benefits from treatment [1]. Multidimensional classification might help to tailor psychological treatment to the characteristics of patients [2]. <h3>Objectives</h3> 1) To replicate and describe the Multidimensional Pain Inventory (MPI) classification [3] in women with fibromyalgia and to examine whether the three MPI-classified subgroups differ in emotions, emotion processing styles, and emotion regulation strategies. 2) To study the association of emotion processing styles and emotion regulation strategies with fibromyalgia impact and positive and negative affect in MPI-classified subgroups. <h3>Methods</h3> Participants were 291 women with fibromyalgia. Cluster procedures, analyses of covariance, and moderator and simple slope regression analyses were conducted. <h3>Results</h3> Dysfunctional patients (DYS, 35% of the sample) presented the worst heath status and the highest levels of negative emotions, followed by the interpersonally distressed (ID, 26%) and the adaptive copers (AC, 38%) (all <i>p</i>&lt;.01). The subgroups significantly differed on all of the emotion processing styles and emotion regulation strategies (all <i>p</i>&lt;.05), except for cognitive reappraisal. DYS showed the highest levels of affect intensity, alexithymia, and emotional suppression, followed by ID and AC, while emotion expression was highest in AC. Higher alexithymia and affect intensity were related to more negative affect and to less positive affect in DYS and AC. DYS patients with higher cognitive reappraisal and ID patients with higher emotion expression showed less negative affect, whereas emotion expression was related to high positive affect in DYS and AC. Only in the ID-group, emotion suppression was related to more negative and less positive affect. <h3>Conclusions</h3> This study confirms the importance of subdividing patients into subgroups and it highlights the possible differential impact of emotion processing styles and emotion regulation strategies on affect in each subgroup. Clinicians should take this into account when tailoring interventions to patients with fibromyalgia. <h3>References</h3> Turk DC. Fibromyalgia: A patient-oriented perspective. In: Dworkin RH, Breitbart WS, eds. <i>Psychosocial and psychiatric aspects of pain: A handbook for health care providers</i>. Seattle, WA: IASP Press 2004:309–338. Turk DC. The potential of treatment matching for subgroups of patients with chronic pain: Lumping versus splitting. Clin J Pain 2005;21:44–55. Turk DC, Rudy TE. Toward an empirically derived taxonomy of chronic pain patients: Integration of psychological assessment data. J Consult Clin Psychol 1988;56:233–238. <h3>Disclosure of Interest</h3> None Declared