tbuckley/cabot-search huggingface dataset:
FRI0061 The Concomitance of Inflammatory Bowel Disease with Incident Rheumatoid Arthritis and Ankylosing Spondylitis in Finland
Authors: K. Puolakka, V. Rantalaiho, H. Kautiainen, M. Färkkilä
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Association between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well established. Some reports have suggested increased concomitance of rheumatoid arthritis (RA) with IBD, as well. <h3>Objectives</h3> To examine the prevalence of IBD among incident patients with RA and AS in Finland <h3>Methods</h3> Finland has a general sickness insurance covering the entire population. Patients with certain chronic diseases (e.g., RA, AS IBD, etc.) are entitled to special reimbursement of medications if their condition meets defined criteria. The reimbursement decisions are recorded in the national registry of the Social Insurance Institution. From this registry all incident cases of RA (ICD-10 code M05 for RF/anti-CCP positive and M06 for seronegative RA) and AS (ICD-10 code M45) between 1 Jan 2004 and 31 Dec 2007 were identified. From the same source prevalent cases of IBD (colitis ulcerosa, morbus Crohn; ICD-10 codes K50 and K51) were gathered and any coexistence recorded. <h3>Results</h3> A total of 7209 incident patients over 17 years of age with RA (68% female, 65% RF positive, age 57±15) and 1436 with AS (40% female, age 38±11) were identified. Of the patients with RA, 35 individuals (0.49%; 95% CI: 0.34 to 0.67), 24 (0.49%) female and 11 (0.47%) male, already had IBD at the index day of reimbursement decision for antirheumatic medication. Age-adjusted rate ratio (RR) of women compared to men was 1.04 (95% CI: 0.50 to 2.19). Compared to the general population, the age and sex–adjusted standardized rate ratio (SRR) was 0.74 (95% CI: 0.51 to 1.03); for RF positive patients it was 0.69 (0.43 to 1.05) and for RF negative ones 0.83 (0.45 to 1.39). Of the incident patients with AS, 29 individuals (2.0%; 95% CI: 1.4 to 2.9), 11 (1.93%) female and 18 male (2.08%), had concomitant IBD. Age-adjusted rate ratio (RR) of women compared to men was 1.07 (95% CI: 0.51 to 2.26). Age-and sex-adjusted SRR was 2.73 (1.83 to 3.92). <h3>Conclusions</h3> Co-occurrence of incident RA with IBD was not increased compared to the general population. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5122
A Multi Centre Prospective Longitudinal Study Establishing Level II Evidence of Health Related Quality of Life after Types of Immediate Latissimus Dorsi (LD) Breast Reconstruction.
Authors: Z. Winters, J. Mills, J. Haviland, A. Reece-Smith, M. Greenslade, J. Benson, M. Galea, P. MacMannus, S. Nicholson, E. Weiler-Mithoff, Z. Rayter, H. Thomson
Journal: Cancer Research (2009)

Abstract Introduction: NICE recommends that the majority of women undergoing mastectomy should be offered immediate breast reconstruction with its potential benefits to improve health related quality of life (HRQL). A systematic review shows poor and conflicting evidence with a lack of 'hard' data to best inform both clinicians and their patients. Our aim was to evaluate the effects of implant-assisted LD (LDI) versus autologous LD (ALD) breast reconstruction on HRQL over 36 months. Recently, with the exception of the USA Breast-Q module there is a lack of a validated Breast reconstruction questionnaire.Methods: An MREC approved prospective longitudinal cohort study involving 6 centres commenced in early 2007. Serial patient reported outcome measures using the EORTC C30 (global QoL, physical functioning, fatigue, pain), BR-23 (breast and arm symptoms), 10 item Body Image Scale (BIS) and HADS, were completed pre-operatively and at 3, 6, 12, 24 and 36 months after surgery. Overall cosmetic satisfaction of the breast reconstruction was measured by a study-specific question on a 5 point Likert scale. Generalised estimating equations were used to assess change over time and differences between treatment groups.The Spearman's rank correlation coefficient was used to assess associations between patient reported cosmetic satisfaction with BIS and breast symptoms.Results: 118 patients (65 – ALD, 53 – LDI) were recruited to the study with a mean age of 50 years (range 22-70). Compliance with questionnaires at all time points was between 85-90%. There were no significant differences in HRQL domains between LDI and ALD, except a tendency for worse pain with ALD (p=0.06). Significant improvements over time were seen for overall HRQL (p&amp;lt;0.001), fatigue (p&amp;lt;0.001), breast symptoms (p=0.04), arm symptoms (p=0.001), as well as anxiety (p=0.017) and depression (p&amp;lt;0.001). Preliminary data shows that overall cosmetic satisfaction was significantly correlated with better body image and fewer breast symptoms. The study is ongoing in terms of 24 and 36 months follow-up and the evaluation of RT.Conclusion: There is an important need for cumulative clinical evidence in this field on which to base patient informed consent and clinical recommendations. Further analyses will assess whether there is an independent effect of RT on HRQL. A validated EORTC breast reconstruction module is in development. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3106.
Senior managers quit Tameside Hospital amid questions over outcomes
Authors: J. Wise
Journal: BMJ (2013)

Both the chief executive and the medical director of Tameside Hospital NHS Foundation Trust in Greater Manchester have resigned, after reports of poor patient care and mounting public pressure.

The trust is expected to face heavy criticism in a report into 14 hospitals in England with high death rates. The report, led by the NHS’s medical director, Bruce Keogh, is due out on 16 July.1

On 2 July the Guardian published the findings of two reviews that had found problems …
Abstract 3189: Aggressive renal cancer cell behavior is partly mediated by CD98hc
Authors: Marina Poettler, Wazlawa Kalinowska, Martin Susani, Andrea Haitel, Christoph Zielinski, Gerald W. Prager
Journal: Cancer Research (2010)

Abstract CD98, a heteromeric transmembrane protein, consists of a heavy subunit (4F2hc, SLC3A2), extracellular linked to a light subunit. The light chains provide amino acid transport activity of CD98. Recently, we could show that CD98hc directly interacts with a conserved motif in integrin beta subunits, thereby mediating outside - in signaling. A genetic knockout of CD98hc in animals is embryonic lethal, whereas overexpression of CD98hc in somatic cells leads to malignant transformation. Recently, we reported that high CD98hc expression is a novel and reliable diagnostic marker for the more malignant subtype II papillary renal cell cancer marker (pRCC). Thereby, CD98hc expression directly correlated with grade of differentiation. In the present study, we identified the functional role of CD98hc in clear cell renal cell cancer (ccRCC) behavior. First, we generated stable low CD98hc ccRCCs by the use of a shRNA lentiviral construct and compared tumor cell behavior with high CD98hc expressing mock infected ccRCCs. We found that downregulation of CD98hc led to an altered tumor cell behavior including tumor cell survival, migration and proliferation. Expression of a silent mutation - lacking shRNA binding motif - reconstituted CD98hc expression in lowCD98hc ccRCC, thereby restoring aggressive tumor cell behavior. By introducing CD98hc mutations either lacking integrin binding capacities or light chain interactions, we could identify the functional role of leucine amino acid transport in tumor cell proliferation, as affected C14-leucine uptake was directly correlated with tumor cell proliferative activity. In contrast, mutants lacking interaction sites for integrins showed defects adhesion-induced FAK phosphorylation and c-src activation, leading to reduced tumor cell adhesion and spreading. A biological relevance of the in vitro finding was confirmed in in vivo tumor xenotransplant assays, whereby stable low CD98hc/ccRCCs either reconstituted with wild type CD98hc or with mutated CD98hc were used. Only wild type reconstitution was capable to restore full aggressiveness of tumor growth and metastasis formation. From our data we conclude that CD98 partially mediates functional activity of renal cancer cell behavior. Thus, CD98hc-mediated tumor cell behavior may offer a potential novel therapeutic target for the treatment of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3189.
THU0516 The Unequal Pattern of Colchicine-Induced Neutrophil F-Actin Dynamics in Familial Mediterranean Fever
Authors: N. Mkrtchyan, T. Davtyan, L. Petrosyan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To examine neutrophil actin cytoskeleton dynamics during neutrophil chemoattractant-dependent activation in patients with Familial Mediterranean Fever (FMF), in an effort to understand the mechanisms that regulate switch of neutrophil activation program and therapeutic effect of colchicine (Col). <h3>Methods</h3> Whole blood neutrophils obtained from 37 FMF patients and 15 healthy donors, without MEFV mutations (ND), were activated with chemoattractant peptide N-formyl-Met-Leu-Phe (FMLP), and cellular F-actin content determined by flow cytometry before and after exposure to Col. <h3>Results</h3> We found that while a non-stimulated neutrophil shows an increased overall F-actin content in patients with FMF, the activation-dependent F-actin dynamics in the presence of chemoattractant peptide FMLP are significantly reduced. Colchicine causes reduction of overall F-actin content and shows a distinctively unequal effect on chemoattractant-activated neutrophil F-actin dynamics in FMF patients compared with healthy donors. <h3>Conclusions</h3> Impaired neutrophil F-actin cytoskeleton dynamics that tightly regulate switch of neutrophil activation program during its encounter with chemoattractants might be a potential pathogenic mechanism causing aberrant resolution of inflammation and could represent a potential target for Col therapy during FMF. MEFV-mutated neutrophils showed a unique sensitivity to Col, which causes the re-organization of the actin cytoskeleton with a reduction of overall F-actin. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3733
Concomitant Presence of Tumor-Specific Cytotoxic and Inhibitor Lymphocytes in Patients with Osteogenic Sarcoma
Authors: Alice Yu, Hugh Watts, Norman Jaffe, Robertson Parkman
Journal: New England Journal of Medicine (1977)

The lack of detectable tumor-specific cytotoxicity by the peripheral blood lymphocytes of patients with cancer may be due to a lack of cytotoxic lymphocytes or the presence of suppressor lymphocytes that inhibit cytotoxic cells. Unfractionated peripheral blood lymphocytes from 12 of 28 patients with osteogenic sarcoma were cytotoxic to osteogenic sarcoma cells in vitro (P less than 0,001). When the peripheral blood lymphocytes from patients whose lymphocytes were not cytotoxic underwent fractionation, a tumor-specific cytotoxic subpopulation was isolated from 11 of 13 patients (P less than 0.0001). Lymphocytes that inhibited cytotoxic activity of autologous tumor-specific cytotoxic lymphocytes were found in four of 10 patients with osteogenic sarcoma but not in six normal controls. Inhibitor lymphocytes form rosettes with sheep erythrocytes and adhere to nylon, whereas cytotoxic lymphocytes have a receptor for C3 but no surface immunoglobulin. The lack of tumor-specific lymphocytotoxicity in some patients can be due to inhibitor lymphocytes.
A Prospective Study of Dietary Calcium and Other Nutrients and the Risk of Symptomatic Kidney Stones
Authors: Gary C. Curhan, Walter C. Willett, Eric B. Rimm, Meir J. Stampfer
Journal: New England Journal of Medicine (1993)

A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones. However, a high intake of calcium can reduce the urinary excretion of oxalate, which is thought to lower the risk. The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination.We conducted a prospective study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones. Dietary calcium was measured by means of a semiquantitative food-frequency questionnaire in 1986. During four years of follow-up, 505 cases of kidney stones were documented.After adjustment for age, dietary calcium intake was inversely associated with the risk of kidney stones; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 (95 percent confidence interval, 0.43 to 0.73; P for trend, < 0.001). This reduction in risk decreased only slightly (relative risk, 0.66; 95 percent confidence interval, 0.49 to 0.90) after further adjustment for other potential risk factors, including alcohol consumption and dietary intake of animal protein, potassium, and fluid. Intake of animal protein was directly associated with the risk of stone formation (relative risk for men with the highest intake as compared with those with the lowest, 1.33; 95 percent confidence interval, 1.00 to 1.77); potassium intake (relative risk, 0.49; 95 percent confidence interval, 0.35 to 0.68) and fluid intake (relative risk, 0.71; 95 percent confidence interval, 0.52 to 0.97) were inversely related to the risk of kidney stones.A high dietary calcium intake decreases the risk of symptomatic kidney stones.
Nasopharyngeal carcinoma with esophageal metastasis presenting with progressive dysphagia
Authors: S.-Y. Yang, C.-Y. Chien
Journal: Endoscopy (2013)

A 49-year-old man attended our department complaining of progressive difficulty in swallowing over a period of 2 weeks. He reported no other discomfort. His medical history revealed that he had been diagnosed with nasopharyngeal carcinoma (cT3N3bM0; WHO Type III) in September 2008 and had undergone chemotherapy and radiotherapy concurrently. A complete response was achieved initially, but regional recurrence in the right side of his neck required him to undergo neck dissection in June 2010. Progressive dysphagia brought him to our department 4 months later. Imaging studies of the head and neck region produced negative findings, but an esophagogram revealed narrowing in the middle third of his esophagus.
The Promise and Problems of Meta-Analysis
Authors: John C. Bailar
Journal: New England Journal of Medicine (1997)

Meta-analysis has acquired a substantial following among both statisticians and clinicians. The technique was developed as a way to summarize the results of different research studies of related problems. Meta-analysis may be applied even when the studies are small and there is substantial variation in the specific issues studied, the research methods applied, the source and nature of the study subjects, and other factors that may have an important bearing on the findings. In this issue of the Journal, LeLorier et al.1 compare the findings of 12 large randomized, controlled trials with the results of meta-analyses of the same problems. . . .
P628 INTEGRATIVE MICRORNA AND GENOMIC ANALYSIS IDENTIFIES miR-21, miR-100 AND miR-192 AS NEW REGULATORY ELEMENTS OF HEPATIC STELLATE CELL ACTIVATION
Authors: M. Coll, A. El Taghdouini, L. Perea, I. Mannaerts, J.J. Lozano, R. Bataller, P. Ginés, L.A. van Grunsven, P. Sancho-Bru
Journal: Journal of Hepatology (2014)
Abstract 16108: Mutations in the Lamin A/C Gene Play a Major Role in Sudden Arrhythmic Death Syndrome
Authors: Daniel V Moller, Elijah R Behr, Paula Hedley, Petros Syrris, Perry M Elliott, William J McKenna, Michael Christiansen
Journal: Circulation (2010)

Introduction: Sudden arrhythmic death syndrome (SADS) is identified in at least 5% of sudden deaths, when no underlying cause of death is revealed. In about half of the SADS cases a comprehensive c...
SRC-1 Promotes Breast Cancer Metastasis by Activating MAPK Pathway.
Authors: L. Qin
Journal: Cancer Research (2009)

Abstract Background: Steroid receptor coactivator (SRC-1) was defined as a nuclear receptor coactivator. It interacts with nuclear receptor and other transcriptional factors and promotes target genes expression. In breast cancer, SRC-1 expression correlates positively with HER2 expression, disease recurrence and resistance to endocrine therapy. Our previous work demonstrated that knockout of SRC-1 in mice suppressed breast cancer metastasis without affecting primary tumor initiation and growth in the MMTV-PyMT transgenic mice. However, the molecular mechanism responsible for SRC-1 in breast cancer metastasis is still unclear.Material and Methods: To further study the function of SRC-1 in breast cancer metastasis, we generated transgenic mice with overexpression of human SRC-1 in the mouse mammary epithelial cells. The mammary glands of these mice exhibited normal development. After crossing these mice with MMTV-TVA (avian subgroup A receptor gene, TVA) transgenic mice, we obtained MMTV-TVA/MMTV-hSRC-1 (tester) and MMTV-TVA/WT (control) biogenic mice. RCAS (avian leukosis virus) viruses, which contain MMTV-PyMT expression cassette and can bind to TVA, were injected into mammary gland to induce mammary tumor. Tumor initiation, growth and metastasis were carefully examined with these mice. To investigate mechanism, multiple PyMT tumor cell lines were generated form individual primary tumor with or without SRC-1 and cell migration and invasion were compared with those cells and human breast cancer cells.Results and discuss: No difference in tumor initiation and growth was observed in those mice, but metastasis incidence of breast cancer to lung increased significantly in PyMT/TVA/hSRC-1 mice compared with PyMT/TVA/WT control mice. Tumor metastasis in lung also presented higher index in PyMT/TVA/hSRC-1 mice. In vitro study with PyMT/SRC-1 WT and KO cell lines showed SRC-1 deficiency disturbed cells migration and invasion. WT tumor cells adhered faster to extracellular matrix fibronecetin (FN) and presented high levels of phosphorylated forms of FAK, c-Src, Erk, Jnk and activated Rac1. Western blotting and real-time RT-PCR revealed lower integrin alpha5 and Gem, one of GTP binding protein, levels in SRC-1 deficient tumor cells. In human breast cancer MDA-MB-231 cells, SRC-1 knockdown led to decreased cell migration and invasion. Therefore, SRC-1 may regulate integrin expression and MAPK pathway to promote cancer cell migration and metastasis. Our study provides a possibility to inhibit breast cancer metastasis by targeting SRC-1 function. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6150.
FRI0287 Assessment of anti-TNF therapies in patients with spondyloarthropaties: Gait analysis as alternative
Authors: J.L. Garrido-Castro, E. Collantes, R. Medina, A.M. Galisteo, C. Gonzalez, D. Ruiz, P. Font, E.M. Gomariz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mobility measures have been used to demonstrate the effectiveness of anti-TNF therapies for the treatment of spondyloarthropathies (SpA) but they are not enough sensitive to change in short term. Gait Analysis is a noninvasive method used in certain clinical areas, although not very used in rheumatology. SpA produces stiffness in the back that leads to more cautious gait pattern. Anti-TNF therapies reduces inflammation and therefore improve patient's mobility. <h3>Objectives</h3> To analyze kinematic gait changes in SpA patients produced by treatments based on anti-TNF. <h3>Methods</h3> Gait Analysis on 15 patients diagnosed with SpA was evaluated using a motion capture system (UCOTrack). Tests were performed before receiving anti-TNF treatment (baseline), after 8 and 24 weeks. We analyzed spatio-temporal parameters such as cadence, % of support and speed. Ranges of motion in joints: trunk, pelvis, hip, knee and ankle were measured. BASMI, BASDAI, BASFI and ASQoL were also analyzed. <h3>Results</h3> All joint motions were increased with coefficient of variation (CV) from 3.5% to 22.4%. Significant difference (p&lt;0.05) appeared at 8 weeks in trunk flex/ext and in pelvic obliquity, and at 24 weeks in pelvic rotation and hip flex/ext. A significant improvement was detected in cadence and support at 8 weeks. There were reduction in outcome indexes varying from 0.14 in BASMI (7.3%) to 1.18 in ASQoL (22.6%), although this difference were not statistically significant. The figure shows range of movement recorded before treatment (dot lines) and 24 weeks after (solid lines). <h3>Conclusions</h3> Improvements in pain and inflammation caused a higher cadence and lower support. No significant differences were found in knee and ankle, due to patients were in early stages of the disease. Main differences were detected in coordinating the movement of the pelvis. Responsiveness in conventional assessment methods was poor. Therapy improves the patient's walking ability. Gait Analysis may be an effective tool in assessing the effectiveness of these treatments. <h3>Disclosure of Interest</h3> None Declared
AB0287 Are ALL Parameters of Disease Activity Score Reliable for Assessing Activity of Rheumatoid Arthritis in Tunisian Patients?
Authors: K. Ben Abdelghani, S. Miladi, L. Souabni, S. Kassab, S. Chekili, A. Laatar, L. Zakraoui
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is an inflammatory chronic disease with varying signs and outcomes. A valid, reliable and sensitive assessment tool that is able to assess activity is essential in clinical practice. Currently, to assess the activity of RA a combination of clinical signs, subjective parameters and laboratory tests are used as for the Disease Activity Score (DAS). <h3>Objectives</h3> Our aim from this study was to define which parameter is more correlated to disease activity in RA patients. <h3>Methods</h3> A prospective study of Tunisian patients followed up for RA was conducted. Only patients with DAS 28 joints &lt;5,1 were recruited. They were devised into 2 groups: G1: patients in remission (DAS28 &lt;2,6) and G2: patients with active disease. We compared parameters which were essential to calculate the DAS: number of tender joints (NTJ), number of swelling joints (NSJ), the global assessment of disease activity by the patient (GAP) and the erythrocyte sedimentation rate (ESR). All of these findings were compared between the two groups. Significant difference was considered if the p value was &lt;0,05. <h3>Results</h3> Fifty patients were recruited, aged of an average of 50 years-old. Among them, 30 were in remission (G1) and 20 were not (G2). The mean DAS28 was 2,03 for G1 ranging from 1,13 to 2,6 and was 4,2 ranging from 3,1 to 5,1 for G2. The mean NTJ and NSJ were respectively 0,03 and 0,3 for G1 and 2,5 and 3,4 for G2. The difference was significant between the 2 groups for NTJ and NSJ (p&lt;0,0001 and 0,001 respectively). The GAP was higher for G2 than for G1 (46,5 vs 7,5) but the difference was not significant (p=0,47). The ESR was significantly higher for G2 than for G1 (p=0,0015). <h3>Conclusions</h3> Between parameters of the DAS28, NTJ, NSJ and ESR were well correlated to disease activity. However, the GAP, the only subjective parameter, didn9t differ from RA in remission or in active disease. <h3>References</h3> Moya Alvarado P. Is DAS a Profitable Score to Be Used for Rheumatoid Arthritis Patient Follow Up? Rheumatology 211 Burkhard F. A comparison of patient questionnaires and composite indexes in routine care of rheumatoid arthritis patients. Joint Bone Spine 2009 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5253