tbuckley/cabot-search huggingface dataset:
After the asthmas: Star Wars and Star Trek
Authors: Andrew Bush, Ian D. Pavord
Journal: European Respiratory Journal (2017)

A long time ago in a galaxy far, far away (1958, Derby, UK in fact), Harry Morrow-Brown used his microscope from his medical school days to show that only those adults with airway disease and sputum eosinophilia responded to oral prednisolone [1], thus preventing this most powerful of medications being consigned to the asthma dustbin of history. Subsequent work led to steroid therapy moving from oral to inhaled [2], and thus nearly three decades ago came, not the dawning of the Age of Aquarius, but that of the age of inhaled corticosteroids (ICS). This age brought undoubted and huge benefits, and there can be no question but that low dose ICS when regularly and properly administered are one of the safest and most effective treatments in the respiratory armamentarium. However, in the aftermath of the discovery of a really effective treatment, instead of kicking on to the next stage, we have stagnated in an unsatisfactory comfort zone. Asthma diagnosis is inaccurate [3–5], but this does not matter, because ICS are so safe you may as well try them for any respiratory symptoms, and anyway, there is a big placebo effect. Medications are escalated uncritically, without thought as to why low doses are not working. Asthma mortality does remain unacceptably high [6], a red flag in our present morass of complacency. Finally, we get into sterile debates about whether, for example, survivors of pre-term birth have “asthma”. Crucially, we have lost sight of the great lesson taught to us by Dr Morrow-Brown, namely that all asthmas are not equal. The age of ICS, which started as the first use of personalised treatment, did not become the platform for building precision medicine, but instead, has reached an era of “put steroids in the tap water”, and writing and re-writing “evidence based guidelines”, which assume homogeneity and have signally failed to improve outcomes, while replacing serious thought about the problems. T he Lancet commission on asthma proposes new paradgims; especially to ask “what asthma do I have?” <http://ow.ly/YVpG30eaeN5>
THU0637 Patient's and rheumatologist's perspectives on the follow-up interval as a tool for optimized outpatient treatment
Authors: S Hermann, S Fügner, E Wiebe, T Alexander, GR Burmester, F Buttgereit
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Scientific progress and better disease awareness constantly lead to increasing patient numbers in rheumatology which requires optimization of patient care. <h3>Objectives</h3> The aim of this study was to evaluate and to optimize the procedures of patient care in an university-based outpatient rheumatology setting in Berlin, Germany. <h3>Methods</h3> One hundred patients with rheumatoid arthritis (80 women, 20 men, mean age 61.2 years, mean disease duration 12.9 years) were independently assessed both by a rheumatologist and via patient-reported self-assessment questionnaires. Current follow-up interval (usually 3 months), patient9s perspective on follow-up intervals, signs of disease activity as well as individual patient concerns were recorded. Satisfaction with follow-up intervals was grouped into three categories: too early, just right/optimal, too late. <h3>Results</h3> Based on the physicians perspective, 46 patients presented at the optimal time point, 51 too early, and three too late. The patients reported the category "just right" in 82 cases, too early follow-up in 10 cases and too late in 8 cases. Of note, 51% (42 individuals) of all patients with self-reported satisfactory follow-up interval were judged to visit the out-patient department too early by the expert rheumatologist. When taking into account the follow-up interval and optimal satisfactory levels, 62% of patients were concluded to visit the department too early in those revisited after 3–4 months (n=65), and in 12% of those who were seen again after 5–6 months (n=17). 82% of patients in the latter group were judged to revisit just right by the physician. <h3>Conclusions</h3> There was a high proportion of overlap in the views on the satisfaction with follow-up intervals between physicians and patients. Especially in patients who were seen every 3–4 months, a high proportion was deemed to could have come later to the out-patient care unit from a purely medical point of view. Here we see a way to stretch the interval to 5–6 months without risking a long-term deterioration in patient care. However, this measure should be flanked by patient education and good collaboration with the general practitioners. <h3>Acknowledgements</h3> We thank AbbVie for financial support in the development of measures to optimize out-patient management in patients with rheumatoid arthritis. The sponsor did not influence the scientific results. <h3>Disclosure of Interest</h3> None declared
THU0187 Do we today alternative therapies rheumatoid arthritis two or more disease-modifying drugs? the story of how a simple drug pentoxifylline may enhance the action of methotrexate in rheumatoid arthritis
Authors: DS Bublikov, DA Anchugina, IE Babushkin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The treatment of patients with RA (rheumatoid arthritis) is a complicated task, because the achievement of remission and low level of activity often requires administration of 2–3 disease-modifying drugs. In such conditions we often face with the rise of treatment costs and with the increase of therapy side effects. That is why relevant is the search of the drugs increasing the effect of the "gold standard" of RA – therapy - methotrexate, and also frequently used sulphasalazine and leflunomid. Treatment of prior to "Treat to target" is difficult enough, forcing researchers around the world to look for the ways to improve the effectiveness of RA treatment. <h3>Objectives</h3> To explore the possibilities of reducing RA activity on the disease activity score DAS28 CRP by adding pentoxifylline to the methotrexate, sulfasalazine and leflunomide treatment. <h3>Methods</h3> This study included women (n=131) with RA longer than 1 year in duration, having a seropositive rheumatoid factor, and DAS28 CRP activity score of 3.2–5.1. Middle aged – 46.44±3.24 years old. All patients received a 15.50±2.50 mg oral dose of methotrexate per week, 2000±500 mg oral dose of sulfasalazine per day, 20±5 mg oral dose of leflunomide per day. Patients were divided into two groups - those who only had disease-modifying drugs (DMARDs) (n=80) and those who were treated with an oral dose of methotrexate and 1200 mg of pentoxifylline per day (n=51). <h3>Results</h3> The baseline for both groups of RA patients did not differ significantly in terms of the level on the DAS28 CRP (p=0.812). On 14th day of the group who were taking pentoxifylline, the DAS28 CRP disease activity score was significantly lower by 12.5% (p&lt;0.001). After 28 days, the users had a DAS28 CRP disease activity score index difference. The difference between two groups is statistically significant. In the group that were treated with pentoxifylline in addition to DMARDs (p=0.001) the index was found to be 8.3% lower. For 28 days, the methotrexate group9s disease activity according to the DAS28 CRP activity score significantly decreased by 14.3% from the baseline (p&lt;0.001). For 28 days, the pentoxifylline + DMARDs group also achieved a statistically significant reduction in the index according to the DAS28 CRP activity score by 20.5% (p&lt;0.001) The disease activity index for the two groups for 14 and 28 days is shown in the table. <h3>Conclusions</h3> Thus, converting the monotherapy DMARDs to pentoxifylline will significantly reduce the activity of RA, while avoiding many of the adverse effects of the other combination therapies. This data requires further long-term research. <h3>Disclosure of Interest</h3> None declared
Surgery versus primary endocrine therapy for elderly women with estrogen receptor-positive early operable primary breast cancer: Survival analysis and correlation with oestrogen receptor positivity
Authors: B. M. Syed, S. J. Johnston, D. W. M. Wong, D. A. L. Morgan, I. O. Ellis, K. L. Cheung
Journal: Journal of Clinical Oncology (2009)

612 Background: A recent Cochrane review of seven randomised trials involving 1,446 elderly women (unselected for oestrogen receptor (ER) status) has shown no significant difference in overall survival between surgery (with or without adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We now report results of a large series from a single centre with a dedicated elderly breast cancer service, with long term follow-up. Methods: During a period of &gt; 20 years, 1,031 elderly (&gt; 70 years) women with ER positive (H-score &gt;50) early operable primary breast cancer received either surgery (with or without adjuvant endocrine therapy) (N = 436) or primary endocrine therapy (N = 595) (&gt;80% using tamoxifen) as initial treatment, with complete follow-up information till deaths. The initial treatment was decided based on fitness for surgery and patient choice. Analysis was carried out on breast cancer specific survival and degree of ER positivity. Results: After a median follow up of 49 months (range 0 - 261 months), patients between 70 - 80 years, treated by surgery, had better 5-year breast cancer specific survival compared to their counterparts treated by primary endocrine therapy (95% versus 85%; p &lt; 0.001). For patients &gt; 80 years, there was however no statistical difference between the two groups (90% versus 90%; p = 0.813). The median survival has not reached yet in all groups. Patients in the latter group (&gt; 80 years) were found to have a higher chance of having strongly ER positive tumours (57% versus 50% in patients between 70 - 80 years with H-score &gt;200; p- &lt; 0.02). Conclusions: In a selected group of elderly women (&gt; 80 years) who tend to have strongly ER positive tumours, surgery and primary endocrine therapy did not appear to produce any difference in breast cancer specific survival. This subject is currently being investigated in a national randomised trial in the UK. No significant financial relationships to disclose.
Biosimilar filgrastim treatment patterns and relative dose intensity (RDI) maintenance in patients receiving chemotherapy (CT) for the treatment of solid tumor (ST) or lymphoid malignancies (LM): A French national observational study (The ZOHé study).
Authors: Gandhi Damaj, Omar Benbrahim, Jean-Christophe Eymard, Kun-Lun Liu, Inna Voronina, Camille Aubron-Olivier, Isabelle Gasnereau, Alain Toledano, Corinne Haioun, Philippe Solal-Celigny, Henri Hubert Roche
Journal: Journal of Clinical Oncology (2015)

e20655 Background: Guidelines recommend granulocyte-colony stimulating factor use to reduce the risk of neutropenic complications in patients receiving CT and to enable delivery of full-dose CT. ZOHé is a French prospective non-interventional longitudinal study describing biosimilar (BS) filgrastim (Zarzio) use in routine practice. Methods: Patients ≥ 18 yo receiving treatment for ST or LM were recruited. This analysis reports BS filgrastim treatment characteristics along with CT in terms of dose, day of initiation, duration and proportion of patients for which CT RDI was conserved (dose maintained in ≥ 85% of CT cycles). Data were collected at BS filgrastim initiation and 3 months after inclusion. Results: 1756 evaluable patients were recruited from June 2013 to April 2014, among whom 1141 (65%) had ST and 615 (35%) had LM. In both cohorts, a median BS filgrastim dose of 30 MIU/day was used in the vast majority of cycles. BS filgrastim was started on average 4.3 ± 2.2 days and 6.5 ± 2.2 days after CT for the ST and LM cohorts respectively, and given for 5 ± 1.5 days (ST) and 5.9 ± 1.7 days (LM) (table). 775 (ST) and 420 (LM) patients were evaluable for RDI: the majority of patients (62.8% and 85.2%) had a preserved RDI over 3 months follow-up. 121 treatment-related adverse events were recorded. Conclusions: In this French cohort BS filgrastim appears effective for RDI maintenance in the majority of the patients. Use may vary according to tumor type, particularly in term of BS filgrastim initiation time: BS filgrastim was initiated mostly at day 4 after CT in ST patients and at day 6 for LM patients. BS filgrastim treatments patterns and occurrence neutropenia (NP) in evaluable patients. Patients (1756) ST (n=1141) LM (n=615) Day of initiation after start of CT (days) Analyzed patients 1139 615 Mean ± SD 4.3 ± 2.2 6.5 ± 2.2 Median (Min-Max) 4 (1-22) 6 (1-22) Duration of treatment (days) Analyzed patients 1141 614 Mean (± SD) 5 ± 1.5 5.9 ± 1.7 Median (Min-Max) 5 (1-14) 5 (1-15) Occurrence of at least one episode of: NP grade 3/4 (patients, %) 87 (7.6) 103 (16.7) Febrile NP (patients, %) 40 (3.5) 30 (4.9)
FRI0612 IGG4-related disease in eastern mediterranean: clinical features and outcomes of a large cohort
Authors: O Karadag, A Erden, AS Ayhan, EC Bolek, U Kalyoncu, B Armagan, A Sari, L Kilic, A Akdogan, T Hazirolan, B Akdogan, SA Bilgen, DE Baydar, S Kiraz, I Ertenli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Since majority of IgG4-related disease (IgG4-RD) patients in the literature are from Far East and United States, there is a lack of large series from other parts of the world. <h3>Objectives</h3> We aimed to identify the clinical characteristics and outcome of Turkish IgG4-RD patients from a tertiary center. <h3>Methods</h3> In step 1, clinical and histopathological features of patients having any disease under the clinical spectrum of IgG4-RD were retrospectively reviewed. For step 2, patients prospectively diagnosed are enrolled into the study. Patients fulfilling the "definite" diagnosis according to comprehensive diagnostic criteria were recruited (enrolled (n=52), excluded (n=47). <h3>Results</h3> Median age was 51.1 years and no gender predominance was observed (Male/female: 26/26). Retroperitoneal fibrosis is the most frequent presentation; others were lymphadenopathy, orbital pseudotumor, pancreas and salivary glands in decreasing order (Table). Twenty-four (46.1%) of patients had localized involvement. Corticosteroids were mainstay of treatment in 92.5% of patients, and in 57.5% with any immunosuppressive agents as first line treatment. Rituximab has been used for cases resistant to previous treatment or with relapses in 19 (47.5%) of patients. A complete response was achieved in 52.5% of patients and partial response (&lt;50% of regression) in 40%. Two patients deceased due to IgG4-RD attributed problems and no malignancy was observed (median follow up: 18 months). <h3>Conclusions</h3> We observed similar features with previous European cohorts however no male predominance was seen. Even though conventional immunosuppressives were used in more than half of patients, treatment had switched to rituximab ∼50% patients owing to resistance or relapses. <h3>Disclosure of Interest</h3> None declared
A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (n-pac) combined with OGX-427 (apatorsen) or placebo in patients (pts) with metastatic pancreatic cancer (mPaCa): The Rainier Trial.
Authors: Johanna C. Bendell, James D. Peyton, Scott Ryan Sommers, Henry Q. Xiong, Edward J. Crane, William N. Harwin, Mark Kozloff, Dianna Shipley, Dana Shelton Thompson, Mark Womack, Suzanne Fields Jones, Andrew H. Ko
Journal: Journal of Clinical Oncology (2014)

TPS4163 Background: Hsp27 (heat shock protein 27) is over-expressed in a variety of tumor types causing initiation, growth, and metastasis of cancer cells. OGX-427 (apatorsen) is an antisense oligonucleotide that binds to Hsp27 mRNA, inhibiting production of the Hsp27 protein. Pts with pancreatic adenocarcinoma have significantly higher levels of Hsp27 than healthy individuals. Preclinical studies with apatorsen showed inhibited proliferation, induced apoptosis, and enhancement of the effect of chemotherapy in pancreatic cancer models. This randomized, phase II trial evaluates the efficacy of gem/n-pac chemotherapy with or without apatorsen in patients with mPaCa. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate, CA19-9 response, and safety. Archival tissue will be collected and assessed for expression of Hsp27, PTEN (protein expression by IHC), and a panel of gene mutations for correlative analyses. Methods: A total of 130 patients are planned to be randomized in a 1:1 ratio to Arm A (gem, n-pac, apatorsen) or Arm B (gem, n-pac, placebo). Three loading doses of apatorsen 600 mg or placebo are given prior to start of chemotherapy. Apatorsen 600 mg or placebo IV is then administered weekly in 28 day cycles. Gem 1000 mg/m2 and n-pac 125 mg/m2 are administered IV on days 1, 8, and 15. Patients will be re-staged every 2 cycles per RECIST v 1.1 and will continue treatment until disease progression or other reasons for discontinuation. Key eligibility includes: stage IV pancreatic adenocarcinoma, ECOG PS of 0 or 1, adequate bone marrow and organ function, and no known CNS metastases or clinically significant cardiac disease. Serum Hsp27 levels will be collected at screening, baseline, and during treatment. Correlative analyses of clinical outcomes and between Hsp27 expression/percentage of tumors expressing Hsp27 will be explored. This trial is currently open to enrollment. Clinical trial information: NCT01844817.
SP0030 Beyond the recommendations: examples of systematic literature review in daily clinical practice
Authors: K Visser
Journal: Annals of the Rheumatic Diseases (2017)

Recommendations and guidelines for management and treatment of rheumatic diseases exist to help rheumatologists deliver optimal care for their patients in an evidence-based way. However, not all practical questions and medical difficulties encountered by rheumatologists in daily clinical practice can be addressed using these existing guidelines. Moreover, time in practice is limited and usually does not allow for extensive systematic literature research to find evidence regarding a specific medical question that needs answering in due time. Therefore, an essential skill for doctors and those in training, besides medical knowledge and examination skills, is to be able to search for, withdraw and appraise published evidence applicable to a confined topic. A so called CAT – critically appraised topic – is a compact systematic literature research following a strictly formulated PICO to answer a clinical question encountered in daily practice. Results can be presented in department meetings and stored in a database for education purposes and use in daily practice. This presentation will address the structure, the carrying out, as well as important pros and cons of the CAT. Examples will be given drawn from the experience of young rheumatologists in training in the Netherlands. <h3>Disclosure of Interest</h3> None declared
Clinical oncology
Authors: C. Brammer, G. Gerrard, R. Macdonald
Journal: BMJ (1998)

Treatment of cancer patients requires cooperation between members of a multidisciplinary team in cancer centres and units as recommended by the Calman Hine report.(1) In Britain the doctors in the team include clinical oncologists, medical oncologists, surgeons, palliative care physicians, haematologists, chest physicians, radiologists, and histopathologists. Clinical oncologists administer radiotherapy, chemotherapy, endocrine therapy, radioisotopes, and a wide range of medical modalities to treat cancer with both curative and palliative aims. Treating patients with cancer is challenging and rewarding, and far from depressing. In fact, the prognosis and quality of life of a good proportion of cancer patients is better than those with other chronic medical problems such as motor neurone disease, rheumatoid arthritis, or obstructive airways disease. However, improving quality of life for patients with incurable disease remains an important goal for oncologists, equally important as cure.

### Pros and cons of a career in clinical oncology

#### Advantages

#### Disadvantages

The specialty is predominantly clinical - that is, assessment of patients by history and examination - rather than technical - physics and big machines -although an understanding of the technical side is essential for the prescription of radiotherapy. Within the specialty clinical oncologists subspecialise by site. The proportion of radiotherapy to chemotherapy given by each consultant depends on their site specialty; consultants treating breast cancer deliver more chemotherapy than radiotherapy, whereas the opposite is true for those specialising in tumours of the head and neck. …
The effects of house dust mite sublingual immunotherapy tablet on immunologic biomarkers and nasal allergen challenge symptoms
Authors: Natasha C. Gunawardana, Qing Zhao, Leonidas N. Carayannopoulos, Kuenhi Tsai, Vladislav A. Malkov, Diana Selverian, Graham Clarke, Tim Mant, Brent D. Butts, Kaare Lund, Trevor T. Hansel, Hendrik Nolte
Journal: Journal of Allergy and Clinical Immunology (2017)
Cellular uptake of extracellular vesicles is mediated by clathrin-independent endocytosis and macropinocytosis
Authors: Helena Costa Verdera, Jerney J. Gitz-Francois, Raymond M. Schiffelers, Pieter Vader
Journal: Journal of Controlled Release (2017)

Recent evidence has established that extracellular vesicles (EVs), including exosomes and microvesicles, form an endogenous transport system through which biomolecules, including proteins and RNA, are exchanged between cells. This endows EVs with immense potential for drug delivery and regenerative medicine applications. Understanding the biology underlying EV-based intercellular transfer of cargo is of great importance for the development of EV-based therapeutics. Here, we sought to characterize the cellular mechanisms involved in EV uptake. Internalization of fluorescently-labeled EVs was evaluated in HeLa cells, in 2D (monolayer) cell culture as well as 3D spheroids. Uptake was assessed using flow cytometry and confocal microscopy, using chemical as well as RNA interference-based inhibition of key proteins involved in individual endocytic pathways. Experiments with chemical inhibitors revealed that EV uptake depends on cholesterol and tyrosine kinase activity, which are implicated in clathrin-independent endocytosis, and on Na+/H+ exchange and phosphoinositide 3-kinase activity, which are important for macropinocytosis. Furthermore, EV internalization was inhibited by siRNA-mediated knockdown of caveolin-1, flotillin-1, RhoA, Rac1 and PAK1, but not clathrin heavy chain. Together, these results suggest that EVs enter cells predominantly via clathrin-independent endocytosis and macropinocytosis. Identification of EV components that promote their uptake via pathways that lead to functional cargo transfer might allow development of more efficient therapeutics through EV-inspired engineering.