tbuckley/cabot-search huggingface dataset:
The responsiveness of joint counts, patient-reported measures and proposed composite scores in hand osteoarthritis: analyses from a placebo-controlled trial
Authors: I. K. Haugen, B. Slatkowsky-Christensen, J. Lessem, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To evaluate the responsiveness of joint counts, patient-reported measures and proposed composite scores in hand osteoarthritis (HOA). <h3>Methods</h3> Data were used from a previously reported study in which 83 patients with HOA were randomly assigned to CRx-102 or placebo. CRx-102 consists of prednisolone (3 mg/day) and dipyridamole (400 mg/day), and was shown to be superior to placebo. Assessments were performed at baseline and after 7, 14, 28 and 42 days, and included the Australian/Canadian osteoarthritis hand index (AUSCAN), visual analogue pain subscale (VAS) pain and patient global, and counts of distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal and carpometacarpal (CMC) joints (tenderness, soft tissue swelling, bony enlargement, limited motion). Various combinations of patient-reported outcomes and joint counts were computed as composite scores (similar to clinical disease activity index) and tested for responsiveness. For each measure, mean change from baseline to day 42, treatment effect, standardised response mean (SRM) and relative efficiency compared with AUSCAN pain were calculated. <h3>Results</h3> The SRM were largest for VAS patient global (0.92), VAS pain (0.77) and AUSCAN pain (0.68), whereas the responsiveness of tender (0.46) and swollen joint counts (0.51) (18 joint assessment of DIP, PIP, CMC) was similar to AUSCAN stiffness (0.53) and physical function (0.37). Composite scores showed similar responsiveness as patient-reported pain and global. <h3>Conclusion</h3> Patient-reported pain and patient global assessment were the most responsive outcomes, whereas joint counts had similar responsiveness to patient-reported stiffness and physical function. Composite scores were as responsive as VAS pain, and these results encourage further elaboration and validation of composite scores in HOA in larger studies.
Adenosine monophosphate and histamine induced bronchoconstriction: repeatability and protection by terbutaline
Authors: E. Egbagbe, I. D. Pavord, P. Wilding, J. Thompson-Coon, A. E. Tattersfield
Journal: Thorax (1997)

BACKGROUND: Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies. METHODS: The response to histamine and AMP challenges and the protection afforded by terbutaline (500 micrograms) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement. RESULTS: Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (delta PD20 = 2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to -3.5 and from 3.78 to -4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD20 histamine and PD20 AMP values after placebo were similar, being from 3.73 to -3.72 DD after allowing for the 17.8-fold higher PD20 values for AMP compared with histamine. CONCLUSIONS: Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD20 values was similar to the agreement between repeat histamine or repeat AMP PD20 values suggests that, within an asthmatic population, PD20 AMP may not be providing different information from that provided by PD20 histamine.
The influence of inflammation in the development of subclinical atherosclerosis in psoriatic arthritis: comment on ‘Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review’ by Jamnistki<i>et al</i>
Authors: Miguel A González-Gay, Carlos González-Juanatey, Javier Llorca, Santos Castañeda
Journal: Annals of the Rheumatic Diseases (2014)

We read with great interest the elegant systematic review on cardiovascular (CV) comorbidities by Jamnitski et al , in patients with psoriatic arthritis (PsA) published in the February 2013 issue of ARD .1 Overall, we agree that there is an increased CV risk in patients with PsA similar to that observed in patients with rheumatoid arthritis (RA).2 Therefore, adequate CV risk stratification is also required in PsA patients.

The authors confirmed that subclinical atherosclerosis and CV risk factors are increased in patients with PsA when compared with controls.1 It is well known that inflammation promotes endothelial cell activation in patients with chronic inflammatory rheumatic diseases like RA.3 The presence of a chronic inflammatory state is responsible for the development of subclinical atherosclerosis and increased incidence of CV events …
Evidence for an Important Role of CIDEA in Human Cancer Cachexia
Authors: Jurga Laurencikiene, Britta M. Stenson, Elisabet Arvidsson Nordström, Thorhallur Agustsson, Dominique Langin, Bengt Isaksson, Johan Permert, Mikael Rydén, Peter Arner
Journal: Cancer Research (2008)

Abstract Loss of fat mass in cancer cachexia is linked to increased adipocyte lipolysis; however, the fate of the excess fatty acids (FA) generated by lipolysis is not known. We investigated if the adipocyte-specific gene cell death–inducing DNA fragmentation factor-α–like effector A (CIDEA) could be involved. CIDEA mRNA expression was assessed in s.c. white adipose tissue from 23 cancer cachexia patients, 17 weight-stable cancer patients, and 8 noncancer patients. CIDEA was also overexpressed in adipocytes in vitro. CIDEA expression was increased in cancer cachexia (P &amp;lt; 0.05) and correlated with elevated levels of FAs and reported weight loss (P &amp;lt; 0.001). CIDEA overexpression in vitro increased FA oxidation 2- to 4-fold (P &amp;lt; 0.01), decreased glucose oxidation by 40% (P &amp;lt; 0.01), increased the expression of pyruvate dehydrogenase kinase (PDK) 1 and PDK4 (P &amp;lt; 0.01), and enhanced the phosphorylation (inactivation) of the pyruvate dehydrogenase complex (PDC). Inactivation of PDC facilitates FA oxidation by favoring the metabolism of FAs over glucose to acetyl-CoA. In accordance with the in vitro data, PDK1 and PDK4 expression correlated strongly with CIDEA expression in white adipose tissue (P &amp;lt; 0.001). We conclude that CIDEA is involved in adipose tissue loss in cancer cachexia and this may, at least in part, be due to its ability to inactivate PDC, thereby switching substrate oxidation in human fat cells from glucose to FAs. [Cancer Res 2008;68(22):9247–54]
Incidence, Risk Factors and Prevention Strategies for Work-Related Assault Injuries: A Review of What Is Known, What Needs To Be Known, and Countermeasures for Intervention
Authors: Jess F. Kraus, Bonnie Blander, David L. McArthur
Journal: Annual Review of Public Health (1995)

This review organizes available data to address current epidemiological understanding of injuries from workplace assaults. We describe the incidence and general populations at risk for fatal and nonfatal work-related injury, and assess available information on risk factors and countermeasures considered important in reducing injury occurrence. Overall rates of occurrence of workrelated homicides and nonfatal injuries are estimated, and those factors that appear to be consistent across studies are explored. Much of what is known about occupations at high risk for assaults and injuries comes from a small number of documents and special studies within subsets of workplaces. Unfortunately, the potency of specific countermeasures for prevention of violence-related injury in work settings continues to be largely unknown. Numerous fundamental questions remain to be answered: Critical is a full assessment of risk, identification of situations and circumstances amenable to intervention, and evaluations to demonstrate effectiveness.
Altered Expression of FAS System Is Related to Adverse Clinical Outcome in Stage I-II Breast Cancer Patients Treated with Adjuvant Anthracycline-Based Chemotherapy
Authors: Claudio Botti, Simonetta Buglioni, Maria Benevolo, Diana Giannarelli, Paola Papaldo, Francesco Cognetti, Patrizia Vici, Franco Di Filippo, Franca Del Nonno, Franco Maria Venanzi, Pier Giorgio Natali, Marcella Mottolese
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To determine the prognostic value of Fas receptor and Fas ligand (FasL) as apoptosis-related biomarkers in the context of chemoresponsiveness in breast cancer (BC) patients submitted to anthracycline-based adjuvant therapy. Experimental Design: Fas and FasL were investigated by immunohistochemistry in surgical samples collected from 167 stage I-IIa-b BC patients enrolled in a prospective clinical trial using epirubicin plus cyclophosphamide in the adjuvant setting. Results: Fas and FasL were significantly associated with tumor stage (P &amp;lt; 0.0001). Multivariate analysis indicated that stage, loss of Fas (relative risk, 8.5 and 9.12; P &amp;lt; 0.0001) and FasL up-regulation (relative risk, 2.38 and 2.88; P = 0.01) were independent prognostic variables influencing both disease-free survival (DFS) and overall survival (OS). A Cox analysis using a four-category Fas/FasL phenotype (+/−, +/+, −/+, −/−) as a stratification factor evidenced a highly positive association between Fas/FasL phenotype and the cumulative hazard of relapse and death in the entire series of patients. We also estimated the DFS and OS for different combinations of the pathological-tumor-node-metastasis (TNM) stage and Fas/FasL by using the K sample log-rank exact test demonstrating that significantly shorter DFS and OS were observed in Fas-negative and FasL-positive patients in both stage I-IIa and IIb. Conclusions: Data presented herein demonstrated that, according to a number of in vitro studies, the prognosis for BC patients receiving adjuvant anthracycline-based chemotherapy strongly depends on the Fas/FasL status. Therefore, a concomitant altered pattern of Fas/FasL expression seems to configure an aggressive tumor phenotype linked to disease progression.
COPD and microalbuminuria: a 12-year follow-up study
Authors: Solfrid Romundstad, Thor Naustdal, Pål Richard Romundstad, Hanne Sorger, Arnulf Langhammer
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD), low lung function independent of diagnosis and markers of inflammation are all associated with increased morbidity and mortality. Microalbuminuria, reflecting endothelial dysfunction, could be a relevant inflammatory marker of potential systemic effects of COPD. We hypothesised that there was a positive association between microalbuminuria and mortality in individuals with COPD. We conducted a 12-year follow-up study of 3129 participants in the second survey of the Nord-Trøndelag Health Study (HUNT), Norway. At baseline, albuminuria was analysed in three urine samples and spirometry was performed. Among the participants, 136 had COPD and microalbuminuria, defined as a urinary albumin/creatinine ratio between 2.5 and 30.0 mg·mmol(-1). The main outcome measures were hazard ratio of all-cause mortality according to microalbuminuria. Compared to those with COPD without microalbuminuria, the adjusted hazard ratio for all-cause mortality in those with COPD and microalbuminuria was 1.54, 95% CI 1.16-2.04. This result was similar after excluding cardiovascular disease at baseline. Classifying COPD severity by Global Initiative for Chronic Obstructive Lung Disease, there was a positive association trend with increasing severity stages. Microalbuminuria is associated with all-cause mortality in individuals with COPD and could be a relevant tool in identification of patients with poor prognosis.
A systematic approach to therapeutic target selection in oesophago-gastric cancer
Authors: Anna L Paterson, Nicholas B Shannon, Pierre Lao-Sirieix, Chin-Ann J Ong, Christopher J Peters, Maria O'Donovan, Rebecca C Fitzgerald
Journal: Gut (2012)

<h3>Objective</h3> The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas. <h3>Design</h3> Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46). <h3>Results</h3> MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p&lt;0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs. <h3>Conclusions</h3> The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs. Molecular phenotyping can inform a rational choice of targeted therapy.
Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities
Authors: T. Grosser
Journal: Journal of Clinical Investigation (2005)

Inhibitors selective for prostaglandin G/H synthase-2 (PGHS-2) (known colloquially as COX-2) were designed to minimize gastrointestinal complications of traditional NSAIDs — adverse effects attributed to suppression of COX-1–derived PGE2 and prostacyclin (PGI2). Evidence from 2 randomized controlled-outcome trials (RCTs) of 2 structurally distinct selective inhibitors of COX-2 supports this hypothesis. However, 5 RCTs of 3 structurally distinct inhibitors also indicate that such compounds elevate the risk of myocardial infarction and stroke. The clinical information is biologically plausible, as it is compatible with evidence that inhibition of COX-2–derived PGI2 removes a protective constraint on thrombogenesis, hypertension, and atherogenesis in vivo. However, the concept of simply tipping a “balance” between COX-2–derived PGI2 and COX-1–derived platelet thromboxane is misplaced. Among the questions that remain to be addressed are the following: (a) whether this hazard extends to all or some of the traditional NSAIDs; (b) whether adjuvant therapies, such as low-dose aspirin, will mitigate the hazard and if so, at what cost; (c) whether COX-2 inhibitors result in cardiovascular risk transformation during chronic dosing; and (d) how we might identify individuals most likely to benefit or suffer from such drugs in the future.
Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial
Authors: Anthony V Moorman, Hannah M Ensor, Sue M Richards, Lucy Chilton, Claire Schwab, Sally E Kinsey, Ajay Vora, Chris D Mitchell, Christine J Harrison
Journal: The Lancet Oncology (2010)
Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds
Authors: N Mori, Y Horie, M E Gerritsen, D C Anderson, D N Granger
Journal: Gut (1999)

Background Inflammatory bowel diseases (IBD) are characterised by an intense infiltration of leucocytes that is mediated by adhesion molecules expressed on the surface of activated endothelial cells. Aims To determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs). Methods The expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds of C57Bl/6J mice was measured using the dual radiolabelled monoclonal antibody technique. Results Lipopolysaccharide (LPS) elicited a profound increase in the expression of all ECAMs in the mesentery, small intestine, caecum, and distal colon. The LPS induced increase in CAM expression was not significantly affected by prior treatment with either MTX or 6-MP. However, pretreatment with either DEX or 5-ASA significantly attenuated LPS induced increases in expression of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caecum and distal colon. DEX, but not 5-ASA, largely abolished the rise in plasma tumour necrosis factor α elicited by LPS. Conclusions These findings suggest that DEX and 5-ASA may exert their beneficial therapeutic action in IBD, at least in part, by inhibiting the expression of ECAMs which mediate leucocyte adhesion and transmigration in the microvasculature.
Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy
Authors: Dick de Zeeuw, Giuseppe Remuzzi, Hans-Henrik Parving, William F. Keane, Zhongxin Zhang, Shahnaz Shahinfar, Steve Snapinn, Mark E. Cooper, William E. Mitch, Barry M. Brenner
Journal: Circulation (2004)

Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention.We analyzed data from Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point (composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria (> or =3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold (95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (<1.5 g/g). Among all available baseline risk markers, albuminuria was the strongest predictor of cardiovascular outcome. The association between albuminuria and cardiovascular outcome was driven by those patients who also had a renal event. Modeling of the initial 6-month change in risk parameters showed that albuminuria reduction was the only predictor for cardiovascular outcome: 18% reduction in cardiovascular risk for every 50% reduction in albuminuria and a 27% reduction in heart failure risk for every 50% reduction in albuminuria.Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.
Enhancing Quality Through Innovation: American Society of Clinical Oncology Presidential Address 2010
Authors: Douglas W. Blayney
Journal: Journal of Clinical Oncology (2010)

Members and guests of the Society, welcome to the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO). It has been an honor for me to serve as ASCO president this year and to oversee preparations for this meeting. I am pleased to share with you this year’s accomplishments and my view of the opportunities and challenges ahead. A meeting of this size and quality cannot happen without the skill and leadership of very special people. My sincere thanks go to Kim Margolin, MD, Chair of the Cancer Education Committee, and to Daniel F. Hayes, MD, Chair of the Scientific Program Committee. They and their colleagues have assembled an exciting scientific and educational program. We received more than 5,100 abstract submissions—a new annual meeting record. We will offer 165 education and 89 scientific sessions, and most will be available for review on our virtual meeting site, which has had spectacular growth and acceptance since its inception in 1999. New this year is the “Trials in Progress” poster session. The session will allow investigators leading phase I and phase II trials to present their unfinished work, including their background data, trial design, and methodology. With this new session, we hope to stimulate interest in the therapeutic entities being tested, to stimulate accruals and addition of study sites to ongoing trials, and to draw new investigators into studying promising compounds.
Treatment of childhood Wilms’ tumor without radiotherapy in Nicaragua
Authors: F. Baez, F. Fossati Bellani, E. Ocampo, V. Conter, A. Flores, T. Gutierrez, A. Malta, G. Mendez, C. Pacheco, R. Palacios, A. Sala, S. Galimberti, F. Cavalli, G. Masera
Journal: Annals of Oncology (2002)