tbuckley/cabot-search huggingface dataset:
THU0284 Work Disability Over Time in Behçet's Syndrome Patients
Authors: G. Hatemi, K. Tascilar, Y. Ozguler, S. Ugurlu, V. Hamuryudan
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Behçet9s syndrome (BS) is most active during young adulthood and may cause severe disability. We had previously observed a high frequency of work disability among our Behçet9s patients in a cross-sectional study. This time we aimed to evaluate the sustainability of work among our patients who did have a job 5 years ago. <h3>Methods</h3> We had surveyed work disability among 300 consecutive Behçet9s syndrome patients who attended our clinic in 2009. We had observed that after excluding students, homemakers and retired patients, among the 149 work eligible patients 29 (21%) were unemployed and 120 were employed. We now evaluated those patients who did have a job 5 years ago regarding work loss and reasons for work loss, using a standard questionnaire. We also checked their hospital charts for new types of organ involvement that developed during these 5 years, and any new medications that were started. <h3>Results</h3> Among the 120 patients who did have a job in 2009 (87 men, 33 women, mean age 36±8.6, disease duration 9.7±7.1 years, 48% with major organ involvement), we were able to contact 97 patients. Sixteen patients (16%) had lost their jobs during the previous 5 years. Nine of these (11%) were related with Behçet9s syndrome and the rest were due to other causes (5 had retired, 1 had a baby, 1 was doing his military service). Among the 81 patients who were still working, 10 (10%) had to change their work place during the last 5 years and were unemployed for a mean of 6.7±5.3 months between these jobs. <h3>Conclusions</h3> Work disability is an important problem among Behçet9s syndrome patients. During a 5 year follow-up, 11% of patients lost their jobs due to their disease, and a further 11% had to interrupt work and change their work places. We were only able to evaluate work disability in this study, and work productivity is another important issue that needs to be studied among patients with Behçet9s syndrome. <h3>Disclosure of Interest</h3> None declared
Hematopoietic Stem Cell Maintenance and Differentiation Are Supported by Embryonic Aorta-Gonad-Mesonephros Region–Derived Endothelium
Authors: Osamu Ohneda, Christopher Fennie, Zhong Zheng, Christopher Donahue, Hank La, Ricardo Villacorta, Belinda Cairns, Laurence A. Lasky
Journal: Blood (1998)
Randomized phase III study comparing paclical-carboplatin with paclitaxel-carboplatin in patients with recurrent platinum-sensitive epithelial ovarian cancer.
Authors: Ignace Vergote, Arija Brize, Alla Sergeevua Lisyanskaya, Mikhail Lichinitser
Journal: Journal of Clinical Oncology (2015)

5517 Background: Paclical (Pcal), a CremophorEL-free formulation of paclitaxel (Oasmia Pharmaceutical AB) was compared with Paclitaxel (Pxel). Pcal can be administered without anti-allergic premedication as an iv infusion over 1 hour. Methods: Primary objective: To show non-inferiority between Pcal and Pxel in PFS using CT scans (RECIST) in platin-sensitive recurrent ovarian, fallopian tube or peritoneal carcinoma. To obtain 379 events of progression 850 were estimated to be accrued (non-inferiority HR = 1.2; α = 0.25 (one-sided); β = 0.8). Patients were randomized to Pcal 250 mg/m2 iv 1 hr or Pxel 175 mg/m2 iv 3 hrs, both followed by Carboplatin, AUC 5-6, q 3 wks. Stratification factors: CA 125 value ( < 250 U/L or ≥ 250 U/L) and relapse (1st or 2nd). CT scans were done before treatment, after 3 and 6 cycles and at the time of clinical symptoms or CA125 progression. A subset of 243 patients had CTs done every 3rd month until progression. Main inclusion criteria: response to prior platin containing treatment, > 6 months platin-free interval (PFI), and CA 125 > 2 x UNL. Patients with a history of severe allergy to study drugs were excluded. Results: 789 patients were 1:1 randomized in the period 2009 to 2012 in 81 centers. Inclusion was stopped when 437 patients showed progression. Main baseline characteristics were similar (PFI 6-12 months: 40% vs 43 %, > 12 months 58% vs 57%; second line: 76% vs 76% for Pcal and Pxel, respectively). Non-inferiority of PFS for Pcal (10.3 months) compared to Pxel (10.1 months) was observed (HR:0.86 CI:0.72-1.03 p = 0.0938). In the subgroup of patients with CTs performed every 3rd month during follow-up the PFS was 12.2 versus 10.2 months, respectively (HR:0.76 CI:0.56-1.03 p = 0.0798). Response according to RECIST: 67% vs 65%; according to GCIG CA125 criteria: 86% vs 85%, respectively. AEs were noted in 90% in the Pcal group and 87% in the Pxel group. All grade peripheral neuropathy were 29% vs 32% and myalgia 11% vs 13%, respectively (NS). Severe allergic reactions were seen in 2% vs 1%. Conclusions: Pcal-treatment is as effective and safe as Pxel, without standard use of premedication and a shorter infusion time. Clinical trial information: NCT00989131.
Using QOPI metrics for physician incentive compensation.
Authors: Grace Makari-Judson, Tamara Wrenn, Wilson C. Mertens, Gordon Josephson, James A. Stewart
Journal: Journal of Clinical Oncology (2012)

241 Background: Physician incentive or variable compensation (VC) models are typically based on work relative value units (wRVU). Baystate Medical Practices (BMP), a group of over 450 practitioners, is evaluating a division based pilot program for VC that, while it includes wRVUs, also includes other important performance metrics. QOPI is emerging nationally as a comprehensive method for assessing quality across oncology practices. We describe the use of QOPI measures as part of a financial incentive plan for a hospital-based oncology division. Methods: A nine member QOPI certified Oncology Division participated in a pilot VC plan with group specific targets selected based on prior below average performance. 20 overall weighting percent (10% weight per category) of the overall VC framework was linked to success in two QOPI categories; “completion of treatment summaries (RxS) within 90 days of end of chemo” and “assessment of patients’ emotional well being by second office visit.” Three tiers of achievement were set for each goal. For RxS completion, Tiers I, II and III were defined as completion of 15, 25, and 40% of charts respectively as measured by an internal audit. For assessment of patient emotional well being tiers were at the 75 th , 80 th , and 85 th percentiles of national QOPI participants. A formula combining VC goals into year-end VC payout was driven by three levels of percent base salary: 8, 12, and 24% respectively. The probability of achievement of each goal was expected to be 90, 50, and 10% respectively. Educational discussions with BMP leadership were held to teach about QOPI validity in the oncology community. Results: BMP fiscal year ends September 30, thus final numbers are pending. With systems based improvements, Tier I achievement for emotional well being and Tier II achievement for RxS completion is expected. The division is interested in using different QOPI measures for VC next year with the goal of continuous improvement in QOPI scores. Conclusions: QOPI metrics can be used as a quality incentive for oncologists in the setting of a VC plan. Non-oncologists can appreciate the strength of QOPI as a quality tool. With time, the combination of a QOPI program through ASCO and use of various QOPI metrics can drive continuous improvement in an oncology group.
Erratum to: The real cost of sequencing: scaling computation to keep pace with data generation
Authors: Paul Muir, Shantao Li, Shaoke Lou, Daifeng Wang, Daniel J. Spakowicz, Leonidas Salichos, Jing Zhang, George M. Weinstock, Farren Isaacs, Joel Rozowsky, Mark Gerstein
Journal: Genome biology (2016)

After the publication of this work [1], the authors noticed an error in Fig. 4. The error occurred on the y-axis, instead of running from 0 to 20 it just has 20 at each point. The publisher apologises for the error and any inconvenience caused. The corrected figure is given below:



Fig. 4

The number of faculty position hires at 51 US universities in 3-year bins. The recent increase in hiring coincides with the explosion in sequencing data. Data were obtained from http://jeffhuang.com/computer_science_professors.html
3-day mortality in hospitalised community-acquired pneumonia: frequency and risk factors
Authors: Martin Kolditz, Torsten T. Bauer, Thomas König, Gernot Rohde, Santiago Ewig
Journal: European Respiratory Journal (2016)

Mortality of hospitalised patients with community-acquired pneumonia (CAP) continues to be high and efforts have been made to characterise a subgroup of patients with an emergency presentation defined by a high risk of early clinical deterioration or death in order to target initial management interventions to patients with a high potential of prognosis improvement [1–3]. However, the actual magnitude of an emergency presentation in CAP remains unclear as the most severely affected patients are frequently underrepresented in prospective studies [1, 3]. Additionally, early mortality within 3 days in CAP only rarely has been studied so far [3–5]. The aim of the present analysis was to characterise patients dying within 3 days after hospitalisation for CAP using the unique database of the German nationwide mandatory quality assurance programme, which requests all hospitals in Germany to document all cases hospitalised with CAP according to a pre-specified electronic data sheet. 3-day mortality from CAP corresponds to 33% of in-hospital deaths; the CRB-65 criteria are independent predictors <http://ow.ly/XFMlB> The authors thank all physicians and technicians working for and with the quality control initiative for community acquired pneumonia and the AQUA Institute, Gottingen, Germany.
TCTAP C-245 Usefulness of Reverse Wire Technique for Septal Branch Selection During Percutaneous Transluminal Septal Myocardial Ablation
Authors: Tatsuya Shigematsu, Hideki Okayama, Go Kawamura, Tatsunori Takahashi, Masaki Kinoshita, Yoshitaka Kawata, Go Hiasa, Tadakatsu Yamada, Hideaki Shimizu, Shuntaro Ikeda, Yukio Kazatani
Journal: Journal of the American College of Cardiology (2016)
Preclinical evaluation of an endoscopic electroporation system
Authors: Patrick F. Forde, Mira Sadadcharam, Michael G. Bourke, Thomas A. Conway, Shane R. Guerin, Marcel de Kruijf, Gerald C. O’Sullivan, Joseph Impellizeri, Anthony J. P. Clover, Declan M. Soden
Journal: Endoscopy (2016)

Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment. The aim of the preclinical studies described here was to investigate the efficacy and safety of this nonthermal ablation system in the treatment of gastrointestinal cancer models.Murine, porcine, and canine gastrointestinal tumors and tissues were used to assess the efficacy and safety of electroporation delivered through the special device in combination with bleomycin. Tumor cell death, volume, and overall survival were recorded.Murine tumors treated with electrochemotherapy showed excellent responses, with cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of the system in canine gastrointestinal cancers demonstrated successful local endoluminal tumor resolution, with no safety or adverse effects noted.Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.
Abstract 406: Effects of an RGD peptide in osteoclast maturation and behavior as a therapeutic option for metastatic bone disease
Authors: Gerald Prager, Daniela Bianconi, Anastasia Chillà, Alexandra Dorda, Nisha Geetha, Matthias Unseld, Despoina Sykoutri, Marina Poettler, Kurt Redlich, Christoph Zielinski
Journal: Cancer Research (2015)

Abstract Metastatic bone disease is a common feature of many types of cancer and has a severe impact on the quality of life of patients. Hence, specific therapeutic strategies inhibiting tumor induced osteolysis are urgently needed. In this study, we aimed to interfere with integrin adhesion receptors, which are central players of the bone resorption process, including osteoclastogenesis as well as osteoclast/bone matrix interaction. For this purpose, we used a cyclic RGD peptide which blocks integrin áVâ3 and áVâ5-ligand binding. Our results revealed that the RGD peptide blocked osteoclast maturation in a dose-dependent manner. In detail, pre-osteoclasts treated with the RGD peptide exhibited reduced cell spreading, migration and adhesion on RGD-containing matrix proteins, such as osteopontin and fibrinogen, which are ligands of integrin áVâ3. The activation of the most upstream signal transduction molecules of the integrin receptor-initiated pathway, such as FAK and c-Src, were consistently blocked by the RGD peptide. First evidence has suggested that the RGD peptide might interfere with metastatic bone disease in vivo and the evidence presented herein describes the underlying mechanisms of the inhibitory effect of the RGD peptide on áV-integrin expressing pre-osteoclasts by blocking integrin ligand binding and interfering with osteoclast maturation and cell behavior. In conclusion, our findings suggest that using an RGD peptide to interfere with áV-integrins on osteoclasts may represent a novel therapeutic strategy in the treatment of malignant bone disease. Citation Format: Gerald Prager, Daniela Bianconi, Anastasia Chillà, Alexandra Dorda, Nisha Geetha, Matthias Unseld, Despoina Sykoutri, Marina Poettler, Kurt Redlich, Christoph Zielinski. Effects of an RGD peptide in osteoclast maturation and behavior as a therapeutic option for metastatic bone disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 406. doi:10.1158/1538-7445.AM2015-406
FRI0183 Characteristic Changes in Histopathology of Synovial Tissues from Patients with Rheumatoid Arthritis Treated with Tocilizumab
Authors: S. Hirohata, A. Abe, A. Murasawa, T. Tomita, H. Yoshikawa
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of synovial tissues, leading to the destruction of joint structures. TNF inhibitors, including anti-TNF-α antibodies and soluble TNF receptors, have been shown to result in characteristic discoid fibrosis in the deep lining layer of the synovium, probably by their action on synovial cells thereof. Tocilizumab, anti-IL6 receptor antibody, also has comparable beneficial effects in the treatment of RA. However, detailed mechanism actions of tocilizumab have not been fully understood. <h3>Objectives</h3> The current studies were therefore designed to determine the characteristic features of synovial tissues of RA patients treated by tocilizumab. <h3>Methods</h3> Synovial tissues were obtained during the joint surgical operations from 13 RA patients who had been treated with tocilizumab for at least 4 months (4-47months), 7 of whom had been previously received TNF inhibitors. As a control, synovial tissues were similarly obtained from 13 RA patients who had been received TNF inhibitors and from 10 RA patients who had not been given any biological agents. Synovial tissues were fixed in formaldehyde and embedded in paraffin. The sections were evaluated by hematoxylin and eosin stain and Masson trichrome stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities were quantitated under microscopy. <h3>Results</h3> The most prominent changes in the synovium from RA patients with TNF inhibitors are degeneration of synovial cells and discoid fibrosis in the deep lining layer. By contrast, perivascular fibrosis with decreased vasculatures in the deep sublining layer and marked degeneration of the lining layer appeared to be typical changes in the synovium from RA patients treated with tocilizumab irrespective of the previous use of TNF inhibitors. Notably, microvessel densities in patients treated with tocilizumab with or without previous TNF inhibitors were significantly decreased compared with those in patients with TNF inhibitors alone or in patients with non-biological DMARDS (figure). <h3>Conclusions</h3> These results suggest that inhibition of vascularization is a primary action of tocilizumab, leading to the marked degeneration of synovial cells in the lining layers. <h3>Acknowledgements</h3> The authors thank Dr. Masahisa Kyogoku for helphul advice. <h3>Disclosure of Interest</h3> None declared
Increased expression of fractionated radiation response genes of PC3 cells after valproic acid treatment
Authors: David Cerna, Molykutty John-Aryankalayil, Sanjeewani Palayoor, C. Norman Coleman
Journal: Cancer Research (2008)

430   Prostate carcinoma currently is the most common malignant tumor in men with greater than 230,000 new cases diagnosed in 2005. Radiation therapy is one method of treating early stage prostate cancer, however it is still not 100 percent effective as the cellular response to radiation variables (low, high, single or fractionated dose) is still unclear. To test our hypothesis that fractionated radiation can induce or modulate  molecular targets and thereby make tumors more susceptible to molecular-targeted therapy, we treated the androgen receptor-negative PC3 cell line with two different irradiation schemes, single (10 Gy) and fractionated (1 Gy X 10). Cells were harvested 24 hours after radiation treatment and mRNA isolated.  Focusing on molecular targeting agents that are already in clinical use or under development, we explored the effects of the histone deacetylase inhibitor, valproic acid (VPA), on PC3 radiation induced molecular targets, as it has become evident that VPA possesses antitumor properties.   Results:  Gene expression analysis by microarray revealed that fractionated radiation altered significantly more genes compared to the single dose radiation. The data also revealed significant modulation in several interferon related genes in fractionated irradiated cells. Up regulated genes include IFI27, OSAL, OSA1, IFI44, and TNFAIP2. Up regulation of STAT1, STAT2, and STAT4 were also present in cells treated with fractionated radiation. Down regulated genes in fractionated radiation samples included cell cycle dependent genes, E2F transcription factor 2 and 8, Aurora Kinase, Polo-Like Kinase 1, Cyclin A2, E2, and B1. Cells treated with VPA alone increased gene expression of fractionated radiation induced mRNAs and the magnitude of fold change was also more in comparison to single dose radiation. Verification was performed on genes of interest by RT-PCR or Western analysis.   Conclusion:  Our data indicate that VPA may enhance the radiation-inducible and -suppressible gene profile and might be an important addition to the radiation-inducible molecular targeted therapy. Additional  experiments are planned to determine if VPA can enhance radiosensitivity in combination with fractionated irradiation compared to a single dose treatment within the PC3 cell line. We are also currently in the process of identifying other additional radiation-induced targets for molecular-targeted drug therapy.  This work was supported by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health.
ZIO-201 (isophosphoramide mustard; IPM) is an orally active anti-cancer agent
Authors: Philip Komarnitsky, John Amedio, Brian Schwartz, Barbara Wallner
Journal: Cancer Research (2007)

3200  IPM, a bi-functional DNA alkylator, is the active metabolite of ifosfamide (IFOS). IFOS and the related drug cyclophosphamide (CPA) are widely used anti-cancer drugs. Both are pro-drugs and need to be metabolized to be active. Their clinical use is limited by the toxicity associated with some of their metabolites. IPM has shown efficacy in diverse cancer models, including activity in CPA-resistant osteosarcoma cell lines and xenografts. It has a favorable safety profile since the toxic metabolites of IFOS, acrolein and chloracetaldehyde are absent. The pharmaceutical development of IPM has been hindered so far by its extreme instability in solution. In an effort to find a stabilizing formulation of IPM a series of different IPM-salts were evaluated. A lysine salt of IPM (ZIO-201; IPM-lys) a zwitterionic species, offers several advantages relative to the IPM free acid, such as enhanced solubility and stability over a wide pH range, improved non-deliquescence characteristics and a more favorable dissolution rate. This formulation allowed the development of IPM for intravenous administration. ZIO-201 is currently in Phase II clinical trials for sarcoma. Since an oral formulation of ZIO-201 would significantly increase convenience and flexibility of its use in cancer treatment its activity by oral administration was tested in mouse cancer models.  Oral administration of ZIO-201 to mice bearing P388 leukemia increased life span by 150% compared to vehicle controls, demonstrating not only oral bioavailability of ZIO-201 but also activity against leukemia. Similarly, a comparison of oral and systemic administration of ZIO-201 in MX-1 breast cancer xenografts showed a similar decrease in tumor growth for both routes of administration: 80% for intraperitoneal and 65% for oral. The maximum tolerated dose for oral administration was five times that of intraperitoneal, which also coincided with the maximal efficacious dose. These results show that the stabilized form of IPM is orally active and support a clinical development for oral ZIO-201.
Surgical care practitioners in orthopaedics
Authors: Vivek Gulati, Ashley I. Simpson, Chika Uzoigwe, Matthew Jaggard, Charles Gibbons, Chinmay Gupte, Andrew Williams
Journal: Journal of the Royal Society of Medicine (2016)

In Europe during the Middle Ages, the Church’s control permeated the whole of society including medical and surgical training. Doctors at the time were predominantly members of the clergy. An edict from Pope Innocent III in 1215 forbade members of the clergy from performing surgical procedures.1 Hence, while physicians pursued a university education surgery became primarily the domain of craftsmen, local wise men and barbers. The predecessor of the Royal College of Surgeons was the Guild of Barbers and Surgeons of London. This collaboration was formed by an Act of Parliament ratified by King Henry VIII in 1540. It sought to unite this disparate body of practitioners of surgery as well as legitimatising the profession and maintaining standards. In Europe in the 1700s, surgeons began to engage in formal medical training similar to the system seen today.1 The 21st century has seen a revolution in the provision of healthcare in the Western World. It has witnessed the creation and expansion of the role of surgical care practitioners who, while not being medically qualified, are involved in varying degrees with the provision of surgical services. They are employed in trusts throughout the UK. With this article we explore the role of the surgical care practitioners in orthopaedic surgery.