tbuckley/cabot-search huggingface dataset:
Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis
Authors: Mark A Little, Peter Nightingale, C A Verburgh, Thomas Hauser, Kirsten De Groot, Caroline Savage, David Jayne, Lorraine Harper
Journal: Annals of the Rheumatic Diseases (2009)

Objective To contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods This study assessed the outcome and adverse events in patients prospectively recruited to four European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were included. The burden of adverse events was quantified using a severity score for leucopenia, infection and other adverse events, with an additional weighting for follow-up duration. A ‘combined burden of events’ (CBOE) score was generated for each patient by summing the individual scores. Vasculitis severity was quantified using the Birmingham vasculitis activity score and glomerular filtration rate (GFR). Results 1-year mortality probability was 11.1%; 59% and 14% of deaths were caused by therapy-associated adverse events and active vasculitis, respectively. Using Cox regression analysis, infection score (p&lt;0.001), adverse event score (p&lt;0.001), leucopenia score (p&lt;0.001) and GFR (p=0.002) were independently associated with mortality. The risk of 1-year mortality remained low (5%) with CBOE scores less than 7, but increased dramatically with scores above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI 8.4 to 24.8). Age and GFR were independent predictors of CBOE score. Conclusions The greatest threat to patients with AAV in the first year of therapy is from adverse events rather than active vasculitis. The accumulation of adverse events, monitored using this scoring method, should prompt increased awareness that the patient is at high risk of death.
Mobilized Endothelial Progenitor Cells by Granulocyte-Macrophage Colony-Stimulating Factor Accelerate Reendothelialization and Reduce Vascular Inflammation After Intravascular Radiation
Authors: Hyun-Jai Cho, Hyo-Soo Kim, Myoung-Mook Lee, Dae-Hee Kim, Hyun-Ju Yang, Jin Hur, Kyoung-Kook Hwang, Seil Oh, Young-Jin Choi, In-Ho Chae, Byung-Hee Oh, Yun-Shik Choi, Kenneth Walsh, Young-Bae Park
Journal: Circulation (2003)

Background— Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy. Methods and Results— One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 μg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81±13% in the GM-CSF radiation [n=7] versus 30±11% in the control radiation [n=9] at 2 weeks, P &lt;0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14±0.11 in the GM-CSF radiation [n=5] versus 0.36±0.07 in the control radiation [n=5] at 4 weeks, P &lt;0.01). Conclusions— GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.
Postactivation potentiation: role in performance
Authors: D Sale
Journal: British Journal of Sports Medicine (2004)

<h3>Objective</h3> This study aims to evaluate the presenting characteristics, management, outcomes and complications for paediatric traumatic hyphaema in Western Australia. <h3>Methods and Analysis</h3> A retrospective review of medical records was conducted for consecutive patients ≤16 years of age admitted for traumatic hyphaema to Princess Margaret Hospital for Children (Perth, Australia) between January 2002 and December 2013 (n=82). From this sample, a cohort whose injury occurred ≥5 years prior attended a prospective ocular examination (n=16). Hospital records were reviewed for patient demographics, injury details, management, visual outcomes and complications. The prospective cohort underwent examination for visual and structural outcomes. <h3>Results</h3> Most injuries (72%) resulted from projectile objects. Angle recession was present in 53% and was associated with projectiles (p=0.002). Most eyes (81%) achieved a final visual acuity of 0.3 logarithm of the minimum angle of resolution (logMAR) (20/40) or better. Age ≤5 years and posterior segment injury were significant predictors of final visual acuity poorer than 0.3 logMAR. At ≥5 years post-trauma, injured eyes had greater intraocular pressure (IOP) (p=0.024) and anterior chamber depth (ACD) (p=0.022) compared with sound eyes. IOP asymmetry was associated with angle recession (p=0.008) and ACD asymmetry (p=0.012). <h3>Conclusion</h3> Poorer visual outcomes are associated with younger age at injury and posterior segment injury. Angle recession and ACD asymmetry are associated with IOP asymmetry 5–12 years after injury.
CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells
Authors: Martin A. Schneider, Josef G. Meingassner, Martin Lipp, Henrietta D. Moore, Antal Rot
Journal: The Journal of Experimental Medicine (2007)

CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3+ CD4+ CD25+ regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3+ T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel disease.
Azacitidine in patients with WHO-defined AML – Results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group
Authors: Lisa Pleyer, Reinhard Stauder, Sonja Burgstaller, Martin Schreder, Christoph Tinchon, Michael Pfeilstocker, Susanne Steinkirchner, Thomas Melchardt, Martina Mitrovic, Michael Girschikofsky, Alois Lang, Peter Krippl, Thamer Sliwa, Alexander Egle, Werner Linkesch, Daniela Voskova, Hubert Angermann, Richard Greil
Journal: Journal of Hematology & Oncology (2013)

The Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios.The sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed.In this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001).In this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.
Antibiotic treatment and factors influencing short and long term outcomes of acute exacerbations of chronic bronchitis
Authors: R Wilson
Journal: Thorax (2006)

<b>Background:</b> The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research. <b>Methods:</b> Outpatients aged ⩾45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7–10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). <b>Results:</b> In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV<sub>1</sub>) &lt;50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and ⩾4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age ⩾65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV<sub>1</sub>&lt;50% predicted (HR 1.27; 95% CI 1.05 to 1.53), ⩾4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged ⩾65 years. <b>Conclusion:</b> Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.
Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations.
Authors: C P Larsen, S C Ritchie, T C Pearson, P S Linsley, R P Lowry
Journal: The Journal of Experimental Medicine (1992)

Whereas dendritic cells (DC) are known to be potent activators of T cells both in vitro and in vivo, the critical costimulatory molecules expressed on DC are not well characterized. Using immunocytochemical and molecular techniques we find that splenic DC express B7/BB1, the counter-receptor for CD28. Moreover, expression of B7/BB1 is upregulated on epidermal Langerhans cells (LC) during their functional maturation into potent T cell stimulators. In blocking experiments, we find that participation of B7/BB1 is required for optimal proliferation of unprimed, allogeneic T cells in DC-driven, primary mixed leukocyte reactions. These data demonstrate that the regulated expression of B7/BB1 on DC may be important in the initiation of a primary T cell response.
Cost Effectiveness of Intraperitoneal Compared With Intravenous Chemotherapy for Women With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Laura J. Havrilesky, Angeles Alvarez Secord, Kathleen M. Darcy, Deborah K. Armstrong, Shalini Kulasingam
Journal: Journal of Clinical Oncology (2008)

Purpose To determine the cost effectiveness of intraperitoneal versus intravenous regimens for adjuvant treatment of optimally resected stage III ovarian cancer. Patients and Methods A decision model was developed to compare the cost effectiveness at 7-, 11.5-, and 35-year horizons of intravenous carboplatin and paclitaxel (IV-CARBO/PAC), intravenous cisplatin and paclitaxel (IV-CIS/PAC), or intravenous paclitaxel followed by intraperitoneal cisplatin and paclitaxel (IP-CIS/PAC). Survival data were from women participating in representative Gynecologic Oncology Group (GOG) protocols. Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database were used to estimate costs for treatment regimens and grade 3 to 4 adverse effects, respectively. Results Median predicted survival was 66, 57, 51, and 48 months for IP-CIS/PAC, IV-CARBO/PAC, IV-CIS/PAC (GOG 172), or IV-CIS/PAC (GOG 158), respectively. Across a range of analyses, IV-CIS/PAC was more costly and had lower life expectancy than IV-CARBO/PAC. Compared with IV-CARBO/PAC, IP-CIS/PAC had an incremental cost-effectiveness ratio (ICER) of $180,022 per quality-adjusted life year (QALY) saved at a 7-year time horizon, $71,835/QALY at 11.5 years, and $32,053/QALY over a lifetime. Extending the survival advantage of IP-CIS/PAC over 11.5 years and a lifetime results in ICERs of $26,249 and $23,973, respectively. Assuming IP-CIS/PAC and IV-CIS/PAC were equally effective when administered on an outpatient basis, the ICER of IP-CIS/PAC compared with IV-CARBO/PAC was $26,311. Conclusion Inpatient IP-CIS/PAC, while not cost effective compared with IV-CARBO/PAC at 7 years, becomes cost effective if a longer time horizon is modeled and/or a survival benefit can be assumed to persist longer than currently available data. Outpatient IP-CIS/PAC may also be cost effective compared with IV-CARBO/PAC if proven as effective as inpatient IP-CIS/PAC.
Heparin decreases activator protein-1 binding to DNA in part by posttranslational modification of Jun B.
Authors: Y P Au, G Dobrowolska, D R Morris, A W Clowes
Journal: Circulation Research (1994)

Heparin is a potent inhibitor of the proliferation and migration of vascular smooth muscle cells. This agent selectively inhibits the transcription of tissue-type plasminogen activator and interstitial collagenase, probably by decreasing the binding of activator protein-1 (AP-1) to phorbol ester-responsive elements in the promoters of these genes. Decreased AP-1 binding is not due to a direct inhibition by heparin, since heparinase digestion of nuclear extracts prepared from heparin-treated smooth muscle cells does not restore AP-1 binding activity. Treatment of cells with heparin suppresses the expression of Jun B, one of the components of AP-1. The major effect of heparin is at the level of posttranslational modification of Jun B. Results from pulse-chase labeling experiments show that the newly synthesized Jun B is rapidly converted to a higher-molecular-weight form and that conversion is suppressed by heparin. Evidence is presented suggesting that the heparin-inhibited event is phosphorylation of Jun B.
Involved-Field Radiotherapy Is Equally Effective and Less Toxic Compared With Extended-Field Radiotherapy After Four Cycles of Chemotherapy in Patients With Early-Stage Unfavorable Hodgkin’s Lymphoma: Results of the HD8 Trial of the German Hodgkin’s Lymphoma Study Group
Authors: Andreas Engert, Petra Schiller, Andreas Josting, Richard Herrmann, Peter Koch, Markus Sieber, Friederike Boissevain, Maike de Wit, Jörg Mezger, Eckhart Dühmke, Normann Willich, Rolf-Peter Müller, Bernhard F. Schmidt, Helmut Renner, Hans Konrad Müller-Hermelink, Beate Pfistner, Jürgen Wolf, Dirk Hasenclever, Markus Löffler, Volker Diehl
Journal: Journal of Clinical Oncology (2003)

To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy.Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B).Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm.Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.
Vitamin D Supplementation and the Risk of Colds in Patients with Asthma
Authors: Loren C. Denlinger, Tonya S. King, Juan Carlos Cardet, Timothy J. Craig, Fernando Holguin, Monica Kraft, Stephen P. Peters, Kristie R. Ross, Kahura Sumino, Homer A. Boushey, Daniel J. Jackson, Michael E. Wechsler, Mario Castro, Pedro C. Avila
Journal: Journal of Allergy and Clinical Immunology (2015)
Unlocking the "PAD" lock on rheumatoid arthritis
Authors: P J Utz
Journal: Annals of the Rheumatic Diseases (2004)

Perhaps a panel of antigens containing citrulline may explain RA: many questions remain

Rheumatoid arthritis (RA) affects about 1% of the world population, yet the driving antigen(s) remain unidentified. A number of different antigens have been proposed to have a fundamental role in RA, including antibodies bound by rheumatoid factor (RF), collagen, BiP, Sa, and many others (reviewed by Rantapaa-Dahlqvist et al 1). The field has been revolutionised by the discovery that antigens containing arginine residues that have been deiminated to form citrulline are prominent targets of autoantibodies in RA.2,3 Their detection forms the basis of several assays that are now standard diagnostic tests in rheumatology clinics world wide. The goal of this editorial is to provide a brief history of the discovery of citrullinated antigens in RA, a review of what is known about the enzymes (peptidylarginine deiminases, PADs) involved in the catalysis of a reaction that forms citrulline, and a roadmap of future areas for research.

The history of citrullinated antigens is one that is particularly important for students of rheumatology to review, because the initial discovery was largely overlooked and rediscovered on several different occasions over the ensuing four decades. In 1964, in the Annals of the Rheumatic Diseases , a search for cell and tissue substrates containing antigens that could be bound by autoantibodies from patients with RA found that granules from differentiating buccal mucosal cells expressed such an autoantigen. The autoantibody system was termed “antiperinuclear factor”.4 A similar screen performed 15 years later showed that rat oesophagus was an ideal and more easily studied substrate for detection of these serum autoantibodies, and these were named “antikeratin antibodies”.5 This work went largely unnoticed until nearly another 20 years had passed, when two European groups independently demonstrated that the target of both antiperinuclear …
Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis
Authors: J Braun, J Brandt, J Listing, A Zink, R Alten, G Burmester, E Gromnica-Ihle, H Kellner, M Schneider, H Sörensen, H Zeidler, J Sieper
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor α, for the treatment of patients with ankylosing spondylitis (AS). <b>Methods:</b> Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). <b>Results:</b> Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. <b>Conclusions:</b> Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.
Gastrointestinal endoscopy: past and future
Authors: M V Sivak
Journal: Gut (2005)

The former editor of <i>Gastrointestinal Endoscopy</i> reflects on the history of endoscopy, which reveals much about the mechanisms whereby innovation occurred, and attempts to forecast the future. Endoscopic technological development in most industrialised countries will be determined largely by various combinations of many external factors together with the further development of virtual imaging