tbuckley/cabot-search huggingface dataset:
SAT0432 Effectiveness of oral corticosteroid on gait in patients with narrow lumbar canal syndrome: Randomized, controlled, double-blind study
Authors: L.C.L. Rodrigues, J. Natour
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Lumbar canal stenosis mainly affects adults in the 5th decade of life and has a negative impact on quality of life. One of the most frequent complaints is claudication during gait. <h3>Objectives</h3> Assess the effectiveness of orally administered systemic corticosteroids on gait in patients with narrow lumbar canal syndrome <h3>Methods</h3> Sixty-one patients aged 50 to 75 years were randomized. The patients and examiner were blinded. The study received approval from the local ethics committee. Clinical diagnosis: lower limb complaints (pain, weakness, sensation of burning or tingling) that improved with the cessation of ambulation, with or without the presence of low back pain. The radiological diagnosis was based on stenosis of the lumbar canal with an area less than 100 mm<sup>2</sup>, One group took prednisone (corticosteroid) at an initial daily dose of 1mg per kg of weight, with weekly decreasing. The control group received a placebo in the morning. Evaluations were performed on the initial session and after three, six and twelve weeks. <h3>Results</h3> Among the patients having taken the corticosteroid, the mean distance traveled on the walk text was 367 m (88-553 m) on the initial evaluation, 379 m (168-568 m) after three weeks, 346 m (176-498 m) after six weeks and 352 m (206-572 m) on the final evaluation. Among those who took the placebo, the mean distance traveled was 388 m (176-575 m) on the initial evaluation (p=0.3728), 391 m (178-581 m) after three weeks (p=0.6453), 389 m (181-607 m) after six weeks (p=0.0746) and 395 m (260-572 m) on the final evaluation (p=0.0496). Figure 1: Results regarding improvement (Likert scale): 1 = much worse; 2 = worse; 3 = unaltered; 4 = better; 5 = much betterThe patients submitted to the corticoid steroid exhibited a greater improvement between the first evaluation and second evaluation. <h3>Conclusions</h3> The use of an oral corticoid steroid with a progressive reduction in dose over a three-week period proved effective in the initial phase of treatment, but no differences were found in relation to patients having taken a placebo over 12 weeks of follow up <h3>References</h3> Hamanishi C, Matukura N, Fujita M, Tomihara M, Tanaka S: Crosssectional area of the stenotic lumbar dural tube measured from the transverse views of MRI. J Spinal Dis 1994, 7:388-393. <h3>Disclosure of Interest</h3> None Declared
AB0929 The Serum Levels of Cholinesterase and Total Cholesterol PREDICT the Existence or Latency of Multiple Organs' Involvements in Japanese Patients with Igg4-Related Disease
Authors: Y. Taniguchi, K. Ode, K. Hirose, Y. Shimamura, K. Ogata, K. Inoue, T. Horino, M. Hyodo, S. Fujimoto, Y. Terada
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is the new entity, which is a multisystem and fibroinflammatory condition. It is characterized by progressive scarring and dysfunction of affected organs and tissues including the pancreas, hepatobiliary tree, kidneys, salivary glands, retroperitoneum and lungs, etc. New diagnostic imaging methods for IgG4-RD have been sought. Recent several reports showed that FDG-PET/CT scans accurately, and safely identifies the multiple organs9 involvements in IgG4-RD patients. <h3>Objectives</h3> To evaluate clinical characteristics, including laboratory and FDG-PET/CT findings, of Japanese patients with IgG4-RD. <h3>Methods</h3> The clinical symptoms, laboratory, pathological and FDG-PET/CT findings of Japanese patients with IgG4-RD (n=14) were assessed. Several laboratory data of IgG4-RD with multiple organs9 involvements (n=7), IgG4-RD with limited organ9s involvement (n=7) and, one of hyper-IL-6 syndromes, ANCA-associated vasculitis (n=10) were comparatively examined. All data are presented as mean ± SD. <h3>Results</h3> IgG4-RD patients (mean age 68±11; male/female 10/4) had xerostomia and bilateral submandibular glands enlargement. As complication, 3 had bronchial asthma, 2 had chronic thyroiditis and 1 had ulcerative colitis. FDG-PET/CT imaging revealed enlargement and increase of FDG accumulation of the bilateral submandibular glands, mediastinal lymph node, lung, spleen, kidney, periaorta and prostate. Interestingly, a part of these organs was asymptomatic. Follow-up FDG-PET/CT after steroid treatment, with no symptoms, showed a significant decrease in FDG accumulation in IgG4-RD lesions. The serum IgG4 level was 847±711 mg/dl (normal 8-135 mg/dl). Four cases with hypocomplementemia and elevated immunocomplex of 14 IgG4-RD cases revealed renal involvements (tubulointerstitial nephritis), and moreover, these 4 cases also had interstitial lung involvements. Notably, cholinesterase (ChE) and total cholesterol (T-cho) levels in IgG4-RD cases with multiple organs9 involvements (n=7) significantly decreased from these levels in IgG4-RD with limited organ9s involvement (n=7) and ANCA-associated vasculitis (n=10) (<i>p</i>&lt;0.05). <h3>Conclusions</h3> When we diagnose IgG4-RD, it is important to differentiate hyper-IL-6 syndrome. FDG-PET/CT imaging and measuring serum ChE and T-cho levels might help us not only to evaluate widespread lesions and monitor disease activity in IgG4-RD, but also to differentiate other disorders. <h3>Acknowledgements</h3> No funding support <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4250
Abstract 3104: HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway.
Authors: Shou Liu, Hongmei Zhang, Hexin Chen
Journal: Cancer Research (2013)

Abstract Our previous studies have shown that overexpression of Hoxb7 delays tumors onset, but promotes tumor progression and metastasis in oncogene Her2/neu-induced mammary tumorigenesis, which is reminiscent of the dual role of TGF-β in breast cancer. To investigate whether HOXB7 directly or indirectly regulates the TGF-β signaling, we examined the phosphorylation levels of SMAD3, an important mediator of TGF-beta signaling, in primary mammary tumors derived from the Hoxb7 and Her2/neu double-transgenic mice and the Her2/neu mono-transgenic mice. Phosphorylation of SMAD3 is detected in a higher percentage of primary tumor tissues from double transgenic mice than that from Her2/neu mono-transgenic mice (69.2% versus 15.4%, p &amp;lt; 0.05), suggesting that Hoxb7 may activate TGF-β/Smad signaling in breast tumor tissues. In line with this finding, overexpression of HOXB7 induces expression of TGF-β ligands in both mouse and human breast cancer cell lines, leading to increased cell motility and invasiveness. The acquainted phenotypes in HOXB7-overepressing cells can be reversed by pharmacologic inhibition of TGF-β signaling. Promoter deletion analysis and Chromotin-immunprocipiration assay further demonstrated that HOXB7 can directly bind to and activate the promoter of TGFβ2. More importantly, expression of HOXB7 and TGFβ2 is strongly correlated in primary breast cancer tissues and associated with advanced stages of tumor progression and reduced survival rate. Taken together, our results suggest that HOXB7 may promote tumor migration, invasion and possibly metastasis through activation of the TGF-β signaling pathway. Citation Format: Shou Liu, Hongmei Zhang, Hexin Chen. HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2013-3104 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
P980 AN EXTERNAL VALIDATION OF THE HEPATOMA ARTERIAL-EMBOLISATION PROGNOSIS (HAP) SCORE: THE LIVERPOOL EXPERIENCE
Authors: O. Noorullah, V.P. Lekharaju, I.U. Din, J. Klcova, T. Cross, J. Evans, R. Sturgess, D. Palmer, P. Kumar, E. O'Grady, N. Stern
Journal: Journal of Hepatology (2014)
PMO-152 Characterising the immune status of HBV-specific CD4+ and CD8+ T-cells producing IL-17 in patients with chronic hepatitis B (CHB) virus infection
Authors: H Cooksley, A Riva, M Simonova, K Katzarov, S Chokshi
Journal: Gut (2012)

<h3>Introduction</h3> Virus specific CD4+ and CD8+T-cells are essential in the control of HBV infection and their functions are tightly regulated by immune homeostatic control mechanisms, such as the programmed death (PD1) pathway, Tim3 and CD244. These pathways maintain the equilibrium between efficient control of viral replication and unnecessary inflammatory/immunopathological damage. Recent studies have described a unique subset of T-cells which produce IL-17. Preliminary studies suggest that IL-17-producing T-cells maybe involved in inflammation and liver damage but largely the role of HBV-specific IL-17 producing CD4+(Th17) and CD8+(Tc17) T-cells during chronic HBV infection remains elusive. Moreover, the impact of immunoregulatory signatures on these T-cells are unknown. The aim of this study was to characterise the role and immune status of virus-specific CD4+ Th17 and CD8+ Tc17 cells in CHB patients. <h3>Methods</h3> Peripheral blood mononuclear cells were collected from ten treatment naïve HBeAg+ CHB patients and ten healthy controls. PBMC9s were stimulated with recombinant HBcAg/HBsAg and PMA/Ionomycin. The frequency of total and virus-specific CD4 and CD8 T-cell producing IL-17/IFNg and the expression of T-cell immunoregulatory molecules PD1, Tim3 and CD244 was analysed by flow cytometry. <h3>Results</h3> Total number of CD8+ T-cells producing IL-17 was not different between chronic HBV patients and healthy controls. However HBV-specific Tc17 cells were significantly higher in CHB-patients compared to controls (p=0.007). Total Th17 were also higher in CHB-patients compared to controls (p=0.03) however the difference was more pronounced in HBV-specific CD4+ Th-17 (p=0.003). Upon analysis of the immune-homeostatsis signatures we found a higher expression of PD1 and CD244 on HBV-specific CD4+ and CD8+ T-cells producing IFNg (p&lt;0.001 and p=0.026 respectively) in CHB patients. No expression of Tim3 was found on these cells. However, HBV-specific Th17 cells in the CHB patients did not express PD1 or CD244 but had levels of Tim3 significantly lower than healthy controls (p=0.027). <h3>Conclusion</h3> This study reveals the involvement of virus-specific Th17 and Tc17 in the pathogenesis of chronic HBV infection. Interestingly, we observe differential patterns of immunoregulatory signatures operational within the populations of virus-specific T-cells producing IFNg and IL-17 which may influence their role in HBV disease. <h3>Competing interests</h3> None declared.
The impact of team familiarity and surgical experience on operative efficiency: a retrospective analysis
Authors: Mahiben Maruthappu, Antoine Duclos, Charlie D Zhou, Stuart R Lipsitz, John Wright, Dennis Orgill, Matthew J Carty
Journal: Journal of the Royal Society of Medicine (2016)

The independent impact of individual surgical experience and team familiarity on surgical performance has been widely studied; however, the interplay of these factors and their relative, quantified, contributions to performance is poorly understood. We determined the impact of team familiarity and surgeon, and cumulative team experience on operative efficiency in total knee replacement.Retrospective analysis of all total knee replacements conducted at the host institution in 1996-2009. Multivariate generalised-estimating-equation regression models were used to adjust for patient risk and clustering.Tertiary care academic hospital.All patients undergoing TKR at the host institution in 1996-2009.Operative efficiency.A total of 4276 total knee replacements were completed by 1163 different surgical teams. The median experience level was 17.6 years for consultant surgeons and 3.7 years for trainee surgeons. After patient-risk adjustment, consultant surgical experience (p < 0.0001), trainee surgical experience (p < 0.05), cumulative team operative experience (p < 0.0001) and team familiarity (p < 0.0001) were associated with significant reductions in operative time. Surgical experience and team familiarity demonstrated concave and linear relationships with operative time, respectively. For a consultant surgeon, the expected reduction in operative time after 25 years in practice was 51 min, compared to a 21-min reduction over the span of 40 collaborations with the same team members.Surgical experience and team familiarity display important and distinct relationships with operative time in total knee replacement. Appreciation of this interplay may serve to guide implementation and allocation of procedure-specific quality improvement strategies in surgery.
P460Anti-collagen type IV IgM serum antibodies levels are associated with development of microangiopathy in diabetic patients with uncomplicated essential hypertension
Authors: A Nikolov, I Tsinlikov, G Nicoloff, I Tsinlikova, A Blazhev, A Garev
Journal: Cardiovascular Research (2014)

Purpose: Thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. Patients with diabetes mellitus and arterial hypertension are at higher risk of vascular disease. Methods: To monitor the metabolism of the basement membrane protein collagen type IV (CIV) in type 2 diabetes mellitus (T2DM), serum levels of antibodies to CIV (ACIV) IgG, IgM and IgA were measured using an ELISA method in 93 patients with type 2 diabetes mellitus and arterial hypertension (AH) (mean age 61,4±11,3 years, diabetes duration 9,88±3,12 years; hypertension duration 9,28±4,98). These values were compared to serum antibodies to CIV in 42 age and sex matched controls. Diabetics were divided in two groups according to presence- Group 1 (n=67) or absence- Group 2 (n=26) of microangiopathy. Results: Patients with T2DM and AH showed statistically significantly higher ACIV IgM antibodies than healthy controls 0,178 (0,145÷0,220) vs. 0,142 (0,118÷0,173) (KW=6,31; p=0,01). Group 1 (patients with microvascular complications) showed significantly higher levels of ACIV IgM in comparison with control group 0,180 (0,136÷0,223) vs. 0,142 (0,118÷0,173) (KW=5,03; P=0.02). Patients from Group 2, were with higher ACIV IgM levels than controls 0,176 (0,151÷0,202) vs. 0,142 (0,118÷0,173) (KW=6,15; p=0,01). Group 1 showed the highest values of ACIV IgM. ACIV IgM showed correlation with microalbuminuria (r=0.18); (p=0.05), and BMI (r=0.19); (p=0.04). Serum ACIV IgG and IgA levels in patients with T2DM and AH were lower than these in controls, but the differences are not statistically significant. Conclusions: Our study showed a relationship between elevation of serum levels of ACIV IgM in diabetics and development of microangiopathy.
SP0109 Rheumatic and Musculoskeletal Diseases (RMDS)
Authors: S. Bevan
Journal: Annals of the Rheumatic Diseases (2015)

Rheumatic and musculoskeletal diseases (RMDs) are serious non-communicable diseases, representing the primary cause of sickness absence and years lived with disability in Europe. RMDs affect as many Europeans as the population of Germany, Belgium and Austria added together (100 million), curtailing ability to work, labour productivity and employment status. Every year, RMDs diminish the European economy by € 240bn. This lecture will examine the clinical, economic and social impact of RMDs among Europeans of working age and will put forward evidence that early interventions which focus on work as a clinical outcome of care and on work-focused rehabilitation can be cost-effective and reduce productivity losses. <h3>Disclosure of Interest</h3> None declared
Abstract 1846: Cyr61 a therapeutic target for breast carcinomas
Authors: Chandra Mohan Kurapaty Venkatapoorna, Ingrid Espinoza, Cheol-Hong Park, Robert Busby, Elizabeth Wiley, Alfred Rademaker, Ruth Lupu
Journal: Cancer Research (2012)

Abstract Background: Cyr61, also known as CCN1, is a survival and pro-angiogenic factor overexpressed in invasive breast tumors that promotes tumorigenicity. We investigated whether Cyr61 plays important roles in breast cancer and evaluated its potential role as a chemotherapeutical target. Methods: We analyzed Cyr61 expression in a tissue microarray from breast cancer patients consisting of primary breast carcinomas and recurrences. Cyr61 was silenced in the metastatic MDA-MB-231 cells using a Cyr61-specific short hairpin RNA (Cyr61-shRNA). The effect of Cyr61 silencing on anchorage dependent- and independent growth, migration and invasiveness was characterized in vitro. The mechanism by which Cyr61 mediates the proliferation effects was investigated. The effect of Cyr61 in tumor growth was investigated in a subcutaneous orthotopic tumor xenograft model and the histological and immunohistochemical analysis ware performed. All statistical tests were two-sided. Results: Cyr61 is highly expressed in about 47% of the metastatic breast cancer patients analyzed. The expression is higher in the recurrences than in the primary tumors. Silencing Cyr61 inhibits cell proliferation, prevents anchorage-dependent and -independent growth, and suppresses the invasive potential of the cells by inhibiting migration in vitro. We also found that silencing Cyr61 decreases the expression of its own receptor αvβ3, and decreases its signaling activities. Remarkably, the in vivo studies showed that after silencing Cyr61 the tumor burden is significantly decreased and there is poor vascularized compared to control tumors. Conclusions: Our findings provide the proof of concept that Cyr61 is a key promoter of breast cancer tumorigenicity. It should be considered as a potential target for developing therapies to breast cancers patients that overexpress Cyr61. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1846. doi:1538-7445.AM2012-1846
Abstract 1973: Targeting activated alleles of EGFR derived from glioma and lung cancer: Correlating kinase active-site occupancy with efficacy
Authors: Theodore P. Nicolaides, Krister Barkovich, Sujatmi Hariono, Adam Garske, Qi Wen Fan, Kevan Shokat, William A. Weiss
Journal: Cancer Research (2010)

Abstract Introduction: The Epidermal Growth Factor Receptor (EGFR) features prominently in malignant glioma (MG), yet attempts to exploit this target in patients with MG have been somewhat disappointing. Unlike the highly sensitizing kinase site alleles of EGFR derived from patients with non-small cell lung cancer (NSCLCA), mutationally activated alleles of EGFR derived from patients with MG respond poorly to the currently available reversible clinical EGFR inhibitors. We hypothesize that the anti-tumor effects of EGFR inhibitors in MG-associated alleles of EGFR require more efficient blockade to achieve anti-tumor responses, in comparison with NSCLCA-associated alleles of EGFR, and that thisincreased efficiency can be achieved using irreversible inhibitors. Methods: We generated glioma and fibroblast cell lines that expressed wild-type or tumor-associated alleles of EGFR derived either from MG (EGFRvIII) or NSCLCA (L858R or del 747-753). Using an EGFR affinity probe (an irreversible EGFR inhibitor tethered to a flourophore), we quantified occupancy of the kinase active site in response to erotinib, a clinical reversible inhibitor of EGFR, correlating occupancy with proliferation and apoptosis. Next, we repeated these measurements using the tool compound and irreversible EGFR inhibitor PD-168394. Results: Using the affinity probe in pulse-chase experiments, we quantified active site occupancy of EGFR int response to increasing doses of inhibitors. In cells expressing MG-derived alleles, irreversible EGFR inhibitors were significantly more potent than reversible agents in abrogating signaling downstream of EGFR and in decreasing viability. Using the affinity probe, we found that irreversible inhibitors showed nearly complete occupancy of the active site, whereas treatment with reversible EGFR inhibitors resulted in only partial occupancy. Cells containing NSCLCA-derived EGFR alleles showed similar signaling and growth responses to both reversible and EGFR inhibitors, despite a large difference in EGFR kinase site occupancy with the two types of inhibitors. Flow cytometry studies correlating kinase site occupancy with downstream signaling in individual cells will also be presented. Conclusions: Activated alleles of EGFR derived from MG require significantly higher levels of kinase site blockade to achieve an anti-proliferative threshold, as compared with activated alleles derived from NSCLCA. This higher degree of kinase site blockade can be achieved using irreversible inhibitors of EGFR. These studies support the initiation of clinical trials using irreversible inhibitors of EGFR in MG. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1973.
Case 9-1999
Authors: William J. Schwartz, John L. Niles
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 75-year-old woman was admitted to the hospital because of weakness and a tendency to fall.Eight months earlier, a temporal-artery biopsy, with negative results, had been performed elsewhere because of frequent headaches and an elevated erythrocyte sedimentation rate. Magnetic resonance imaging (MRI) of the brain at that time showed enhancement by gadolinium of the cerebellar tentorium, which was more prominent on the right side, in the posterior middle cranial fossa and posterior fossa, without mass effect or evidence of obstruction. Soon thereafter, esophagogastroduodenoscopic and colonoscopic examinations revealed active gastritis, for which the patient received omeprazole. Two . . .
Abstract 3478: Latent KSHV infection increases the vascular permeability of endothelial cells
Authors: Blossom Damania, Christophe Guilluy, Zhigang Zhang, Keith Burridge
Journal: Cancer Research (2011)

Abstract Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is closely linked to the development of Kaposi's sarcoma (KS). The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Latent KSHV-infected endothelial cells display increased Src kinase activity, increased Rac1 activation and activation of its downstream modulator, p21 activated kinase (PAK1). The KSHV-infected endothelial cells exhibited increases in tyrosine phosphorylation of VE-cadherin and β-catenin, while total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that latent KSHV-infected endothelial cells were more permeable than uninfected endothelial cells. Knockdown of Rac1, as well as inhibition of ROS, resulted in decreased permeability of the KSHV-infected endothelial cells. In sum, KSHV latent infection increases the vascular permeability of infected endothelial cells thereby contributing to the pathogenesis of Kaposi's sarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2011-3478