tbuckley/cabot-search huggingface dataset:
AB1294 Psoriatic arthritis - a follow-up study applying dynamic MRI, conventional MRI and clinical measures:
Authors: R.P. Poggenborg, P. Bøyesen, C. Wiell, S.J. Pedersen, I.J. Sørensen, O.R. Madsen, O. Slot, J. Møller, M. Boesen, H. Bliddal, O. Kubassova, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) has been validated in rheumatoid arthritis for measuring inflammation, but has rarely been studied in psoriatic arthritis (PsA). <h3>Objectives</h3> To evaluate changes in DCE-MRI parameters of inflammation in patients with PsA in an investigator-initiated trial, during adalimumab therapy. <h3>Methods</h3> Anti-TNF-naïve patients with PsA according to Moll and Wrights criteria, ≥3 swollen joints, ≥3 tender joints, hand involvement (swelling and/or dactylitis) and clinical indication for anti-TNF therapy were included. Conventional and DCE-MRI (0.6 T) was performed at baseline, and after 6 and 48 weeks. All patients received adalimumab 40 mg eow. The PsA MRI scoring system (PsAMRIS) was used for analyzing conventional MRIs, and Dynamika software (Image Analysis Ltd., Leeds, UK) for DCE-MRIs. Regions of interest (ROIs) were drawn around the 2.-5. MCP joints, excluding large blood vessels. The ROIs were used for computing the number of pixels with plateau and washout pattern (N<sub>p+w</sub>), the initial rate of enhancement (IRE), and the maximum enhancement. PsAMRIS total was calculated by adding the components of synovitis, flexor tenosynovitis, periarticular inflammation and bone marrow oedema. <h3>Results</h3> Patient characteristics (n=9) were: 5 males (56%), median (range) age 39 (25-63) years, joint/skin disease duration 7 (2-59)/12 (2-59) years, 76-swollen joint count (SJC) 20 (6-32), 78-tender joint count (TJC) 41 (9-71), HAQ-score 1.3 (1.1-2.1) and dactylitis count 6 (0-13). Five patients discontinued the trial between 3 and 7 month after inclusion due to lack of efficacy (1 patient), adverse events (2 patients), or violation of study protocol (2 patients). Significant reductions in N<sub>p+w</sub>were observed between baseline and follow-up in the entire patient group (n=9, see table). DCE-MRI scans were also available for 12 patients who did not have D-MRI performed at inclusion (total 21 patients). For these 21 patients N<sub>p+w</sub>, IRE and ME*N<sub>p+w</sub> correlated with PsAMRIS synovitis (Spearman's rho 0.52, -0.51, 0.53, all P&lt;0.05), and with PsAMRIS total (Spearman's rho 0.60, -0.57, 0.61, all P&lt;0.05). We found no statistical significant correlation between dynamic parameters and DAS28, SJC or TJC. <h3>Conclusions</h3> In active PsA patients treated with adalimumab, dynamic MRI parameters decrease significantly as assessed by the Dynamika software, and are associated with findings on conventional MRI. DCE-MRI might be a valuable method for measuring joint inflammation in PsA. <h3>Disclosure of Interest</h3> None Declared
FRI0488 Ultrasound detects joint damage and bleeding in haemophilic arthropathy: the utility of a score.
Authors: D. Melchiorre, S. Linari, M. Morfini, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Haemarthrosis is the trigger of haemophilic arthropathy (HA), because bleeding starts soon synovitis, damages cartilage, and leads to loss of function and disability. <h3>Objectives</h3> To investigate the capacity of ultrasonography (US) to detect bleeding and joint damage in HA. <h3>Methods</h3> The joints of 82 patients (pts) with Haemophilia A or B were consecutively evaluated and scored (score ranging from 0 to 21) for effusion (E), bone remodelling (BR), cartilage damage (CD), synovial hypertrophy (SH), haemosiderin (H), osteophytes (O), haemarthrosis (Hae), erosion (Er) and fibrotic septa (FS) with US. X-rays [Pettersson Score (PXS)] were performed in 81 pts and clinical evaluation [World Federation Haemophiliac orthopaedic score (WFHO)] was done in all pts. Power Doppler US (PDUS) was performed in all patients on the knee, ankle and elbow joints. <h3>Results</h3> A total of 103 joints were studied (60 knees; 22 elbows and 21 ankles). US showed effusion in 77 joint, bone remodelling in 82, cartilage damage in 74, synovial hypertrophy in 65, haemosiderin in 49, osteophytes in 46, haemarthrosis in 34, erosion in 25 and fibrotic septa in 12. In haemophiliacs 44 out of 103 joints showed US score ≤5, and 59 US score &gt;5. Joints with US score ≤ 5 had a low PXS (SRCC=0.375, P &lt; 0.01) and joints with US score &gt; 5 showed a high PXS (SRCC=0.440, P&lt;0,01). A significant correlation between US score and PXS for bone remodelling [Spearman's rho Correlation Coefficient (SRCC)] =0.429 p&lt;0,01 and for osteophytes (SRCC= 0.308 p&lt;0,05) was found. The correlation between the US score and number of bleedings in 103 joints was very significant (SRCC=0.375, P &lt; 0.01). A total of 34 bleeding joints were identified and verified with aspiration of haematic fluid. <h3>Conclusions</h3> US may detect bone and cartilage alterations and synovitis. Indeed PDUS identified bleeding also in asymptomatic joints and was able to show different entity of haemarthrosis. US may be a feasible and reliable tool to evaluate joint modifications in HA. <h3>Disclosure of Interest</h3> None Declared
Decreased Activity of Hepatic Uroporphyrinogen Decarboxylase in Sporadic Porphyria Cutanea Tarda
Authors: George H. Elder, Geoffrey B. Lee, John A. Tovey
Journal: New England Journal of Medicine (1978)

To investigate the role of uroporphyrinogen decarboxylase in the pathogenesis of the sporadic form of porphyria cutanea tarda, we measured this enzyme in liver, erythrocytes and cultured skin fibroblasts, and also measured coproporphyrinogen oxidase and the total iron concentration in liver. The mean uroporphyrinogen decarboxylase activity was lower in liver from seven male patients (9.0 pmol of coproporphyrin per minute per milligram of protein) than in 12 controls, including seven with alcoholic liver disease (22.3 pmol per minute per milligram; P less than 0.05). Coproporphyrinogen oxidase activities were the same in each group. Liver iron concentrations were lower during remission, but uroporphyrinogen decarboxylase activities were not related to clinical activity for uroporphyrin excretion. Erythrocyte and fibroblast enzyme activities were the same as in normal subjects. A hepatic uroporphyrinogen decarboxylase defect is a prerequisite for the development of porphyria cutanea tarda, but other factors, which probably do not alter uroporphyrinogen decarboxylase activity, determine the clinical onset. In sporadic porphyria cutaneous tarda, the enzyme defect appears to be restricted to the liver.
EFFICACY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS FOR CARDIAC FUNCTION IN DIABETIC PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Daisuke Kitano, Tadateru Takayama, Rikitake Kogawa, Shunichi Yoda, Satoshi Kunimoto, Yuji Kasamaki, Takafumi Hiro, Atsushi Hirayama
Journal: Journal of the American College of Cardiology (2015)
Abstract 440: The sublethal dose radiation induces cellular senescence and potent bystander effects through c-Myc oncogene.
Authors: Chia-Chien Lo, Yen-Ting Chou, Su-Jun Chiu, Jeng-Jung Hwang, Yi-Jang Lee
Journal: Cancer Research (2013)

Abstract The sublethal dose radiation may induce cellular senescence and promote secondary maligancy during radiotherapy. However, the molecular mechanisms are unclear. It has been reported that a variety of early response oncogenes can be up-regulated by the low dose radiation. Because oncogene-induced senescence (OIS) has been considered important for tumor development, we are interested in investigating whether the sublethal dose radiation also raises OIS to affect the malignancy. To this end, human diploid fibroblasts WI-38 cells and human non-small lung cancer H1299 cells were exposed to less than 2Gy of X-rays delivered by the RS2000 X-rays machine. Both cell types exhibited senescent phenotypes within a dose-dependent manner using the senescence-associated β-galactosidase (SA-β-gal) staining. Subsequently, we investigated the expression of c-Myc and c-Ras oncogenes, and the results showed that sublethal dose radiation could induce c-Myc, but not c-Ras, in both transcriptional and translational levels. Additionally, up-regulated c-Myc exhibited transcriptional activity as demonstrated by the promoter-based reporter gene assys. Although the sublethal dose radiation caused cellular senescence and growth delay in exposed cells, the collected culture medium could increase the motility of non-irradiated H1299 cancer cells using the wound healing assay. Interestingly, the culture medium obtained from irradiated H1299 cancer cells caused higher motility in non-irradiated cells than that from irradiated WI-38 fibroblasts. Furthermore, the sublethal dose radiation induced senescent phenotype was suppressed in cells treated with siRNA against c-Myc. Meanwhile, the motility of non-irradiated cells was not increased by the cultured medium obtained from irradiated c-Myc silenced cells. Taken together, the current data suggest that the sublethal dose radiation causes a c-Myc oncogene induced senescence, and this event may promote the bystandard effects that influence the motility of non-irradiated cancer cells. Citation Format: Chia-Chien Lo, Yen-Ting Chou, Su-Jun Chiu, Jeng-Jung Hwang, Yi-Jang Lee. The sublethal dose radiation induces cellular senescence and potent bystander effects through c-Myc oncogene. [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 440. doi:10.1158/1538-7445.AM2013-440 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
SP0124 Infections and rheumatic diseases: What is new?
Authors: A. Silman
Journal: Annals of the Rheumatic Diseases (2013)

There has been a long-standing belief that both rheumatoid arthritis and other types of inflammatory arthritis may be a consequence, either directly or indirectly, of infection. Although there is no evidence of a single organism or group of organisms responsible for a significant proportion of otherwise idiopathic cases, there are still increasing and intriguing reports of inflammatory arthritis following several viral, bacterial and other infecting microorganisms. More importantly, patients with rheumatoid arthritis and related diseases are at an increased risk of infection independent of their drug treatment, which in its turn can cause the arthritis to worsen. There are attempts to develop risk scores to predict which patients are more likely to develop a serious infection but their value in clinical practice is uncertain. Much work has shown a number of immunological biomarkers are risk indicators and these data need to be pursued. The greatest interest in infections has resulted from concerns following the introduction of biological agents with their pathway blocking activity in reducing inflammation, also enhancing the risk of potentially serious infections. Reactivation of TB infection following TNF monoclonal use is well known but with the increasing use of these agents, there are more case reports of infections with unusual organisms. Such reports do help guide clinicians when attempting to diagnose an unknown infection in a recently treated patient. Currently much interest is centred on the less well-documented data on use of drugs such as Abatacept, Anakinra, Tociluzimab and Rituximab, as well as the newer agents that are likely to receive their license in the near future. <h3>Disclosure of Interest</h3> None Declared
P13 Identifying patients who had surgical resection for non-small cell lung cancer using large datasets: Abstract P13 Table 1.
Authors: HA Powell, LJ Tata, RA Stanley, DR Baldwin, RB Hubbard
Journal: Thorax (2013)

<h3>Introduction</h3> Surgical resection rates have become an important indicator of NHS Trust performance and efforts to increase them are on-going with the aim of improving overall survival. The National Lung Cancer Audit (NLCA) has collected data on primary lung cancer since 2004 and has now been linked with Hospital Episode Statistics (HES) for research into inequalities in access to treatment. How well these two large datasets capture surgical data is not known. <h3>Methods</h3> We used the NLCA to identify all cases of NSCLC, excluding stage IIIB or IV, diagnosed between January 2004 and March 2010. We calculated the proportion of cases with a procedure date in the NLCA, and the proportion with a code in HES, for potentially curative surgery less than 6 months after or 3 months before diagnosis. We looked at the age, lung function, performance status, stage and survival according to where surgery was recorded. Given the increase in NLCA case ascertainment from approximately 19% in 2004 to 98% in 2009 we also looked for changes in our results over time. <h3>Results</h3> There were 60,196 people in the NLCA who met the inclusion criteria; 8,535 (14%) had a record of surgery in both databases. An additional 2,568 (4%) had a record of surgery in HES and 795 (1%) in the NLCA. The features of people who had surgery in HES only or the NLCA only were similar, however median survival was shorter, and the proportion that died soon after surgery was higher, in the NLCA only group compared with those with surgery records in both databases (table 1). The proportion with HES only records of surgery decreased from 6% (n = 215) in 2004 to 3% (n = 367) in 2009; the patterns of survival each year were similar to the overall results. <h3>Conclusion</h3> The proportion of people who had potentially curative surgery differed according to the database used to identify surgical procedures. There are many possible explanations for our results; however use of either database alone is likely to under-estimate the proportion of people who had surgery and this should be taken into account in studies investigating access to surgery.
AB1166-HPR Evaluation of Work-Related Musculoskeletal Disorders in Office Workers
Authors: D. Tarakci, E. Tarakci, S.N. Baydogan, A. Razak Ozdincler
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Musculoskeletal disorders are injuries or disorders of the muscles, nerves, tendons, joints, cartilage, and spinal discs. Work-related musculoskeletal disorders are conditions in which the work environment and performance of work contribute significantly to the condition; and/or the condition is made worse or persists longer due to work conditions. <h3>Objectives</h3> To evaluate the musculoskeletal problems, which may be encountered in various professional groups who spend most of their work hours on desk jobs and using computer. <h3>Methods</h3> 35 architects, 44 banker and 27 secretaries, with ages between 20 and 45 were included to the study. The participants9 socio-demographical information, total year of employment, average number of daily work hours, time spent sitting at the desk, computer usage period and their pains during working and resting hours were investigated. Their risk degrees associated with their postures during work were evaluated through the Ovako Working-Posture Analysis System – (OWAS). <h3>Results</h3> The total year of employment was 9.22±3.02 in architects, 14.3±5.12, in bank employees and 7.18±2.43 in secretaries. Architects stated they spend 5.23±1.12 hours of a day at desk and 3.44±0.60 hours at the construction site; banker stated they spend 7.68±0.80 hours of a day performing desk jobs and secretaries stated they spend 9.52±2.14 hours performing desk jobs. Of the architects, 37% stated they have neck pains, 23% stated they have low back pains, and 39% stated they have wrist pains; of the banker, 44% stated they have neck pains, 52% stated they have low back pains and 38% stated they have wrist pains; and of the secretaries, 27% stated they have neck pains, 48% stated they have low back pains and 36% stated they have wrist pains. It was determined that while 58% of the architects have risky postures which have to be controlled at regular intervals, 43% of the banker and 52% of the secretaries have risky postures which have to be immediately treated. <h3>Conclusions</h3> Our study revealed that musculoskeletal problems are frequently encountered in various professional groups using computer, due to bad working postures and non-ergonomic working environments. We believe that studies in our country on musculoskeletal system disorders and on ergonomics are insufficient and that these disorders negatively affect employees and the economy by restricting the physical and psychosocial functions. By courtesy of ergonomics trainings which shall be initiated at early periods and which would prevent the problems which may occur in employees performing desk jobs, would provide significant contributions to the field of protective rehabilitation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6061
Replacement Therapy for Alpha<sub>1</sub>-Antitrypsin Deficiency Associated with Emphysema
Authors: Mark D. Wewers, M. Anthony Casolaro, Stephanie E. Sellers, Sonia C. Swayze, Kathleen M. McPhaul, Janet T. Wittes, Ronald G. Crystal
Journal: New England Journal of Medicine (1987)

In patients with alpha1-antitrypsin deficiency, the development of emphysema is believed to be caused by the unchecked action of proteases on lung tissue. We evaluated the feasibility, safety, and biochemical efficacy of intermittent infusions of alpha1-antitrypsin in the treatment of patients with alpha1-antitrypsin deficiency. Twenty-one patients were given 60 mg of active plasma-derived alpha1-antitrypsin per kilogram of body weight, once a week for up to six months. After a steady state had been reached, the group had trough serum levels of alpha1-antitrypsin of 126±1 mg per deciliter as compared with 30±1 mg per deciliter before treatment, and serum anti-neutrophil elastase capacities of 13.3±0.1 μM as compared with 5.4±0.1 μM. The alpha1-antitrypsin level in the epithelial-lining fluid of the lungs was 0.46±0.16 μM before treatment, and the anti-neutrophil elastase capacity was 0.81 ±0.13 μM. Six days after infusion, alpha1-antitrypsin levels (1.89±0.17 μM) and anti-neutrophil elastase capacities (1.65±0.13 μM) in the lining fluid were significantly increased (P<0.0001). Because of the chronicity of the disorder and the lack of sensitive measures of lung destruction, the clinical efficacy of this therapy could not be studied rigorously. No changes in lung function were observed in our patients over six months of treatment. The only important adverse reactions to the 507 infusions were four episodes of self-limited fever. This study demonstrates that infusions of alpha1-antitrypsin derived from plasma are safe and can reverse the biochemical abnormalities in serum and lung fluid that characterize this disorder. Together with lifetime avoidance of cigarette smoking, replacement therapy with alpharantitrypsin may be a logical approach to long-term medical treatment. (N Engl J Med 1987; 316:1055–62.)
O1 SAPPHIRE II: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/R/ABT-267, ABT-333, AND RIBAVIRIN IN TREATMENT-EXPERIENCED ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1
Authors: S. Zeuzem, I. Jacobson, T. Baykal, R.T. Marinho, F. Poordad, M. Bourliere, M. Sulkowski, H. Wedemeyer, E. Tam, P. Desmond, D. Jensen, A.M. Di Bisceglie, P. Varunok, T. Hassanein, J. Xiong, B. DaSilva-Tillmann, L. Larsen, T. Podsadecki
Journal: Journal of Hepatology (2014)
PROGNOSTIC SIGNIFICANCE OF TUMOUR BUDDING IN RECTAL CANCER BIOPSIES PRIOR TO NEOADJUVANT THERAPY
Authors: A C Rogers, D Gibbons, A M Hanly, J M P Hyland, P R O'Connell, D C Winter, K D Sheahan
Journal: Gut (2013)

<h3>Introduction</h3> Tumour budding is an increasingly important prognostic feature for pathologists to recognise. The phenomenon has been associated with a negative prognosis in rectal cancer when identified in surgical resection specimens. <h3>Aims/Background</h3> The aim of this study was to correlate intra-tumoural budding (ITB) in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy (nCRT) and with long-term outcome. <h3>Method</h3> Data from a prospectively maintained database was acquired for patients with locally advanced rectal cancer who underwent nCRT. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of ITB. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios (HRs) with 95 per cent confidence intervals (CIs). <h3>Results</h3> Of 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20.2%) exhibited budding in a pre-treatment tumour biopsy. ITB predicted a poor pathological response to nCRT (higher ypT stage, p=0.032; lymph node involvement, p=0.018; lymphovascular invasion, p=0.004; and residual poorly differentiated tumours, p&lt;0.001). No patients with ITB exhibited a TRG 1 or complete pathological response, providing 100% specificity and positive predictive value for non-response to nCRT. ITB was associated with a lower disease-free 5-year survival rate (33.3% vs. 77.5%, p&lt;0.001), cancer-specific 5-year survival rate (61.1% vs. 87.3%, p=0.021) and predicted cancer-specific death (HR 3.51, 95% CI 1.03 - 11.93, p=0.040). Patients with tumor budding in initial biopsy have a significantly lower five-year disease-free survival rate (33.33% vs. 77.46%, p=&lt;0.001) and lower cancer-specific survival rate (61.11% vs. 87.32%, p=0.021). <h3>Conclusion</h3> ITB at diagnosis of rectal cancer identifies those who will poorly respond to nCRT and those with a poor prognosis.
Case 25-2003
Authors: John F. Modlin, P. Ellen Grant, Robert S. Makar, Drucilla J. Roberts, Kalpathy S. Krishnamoorthy
Journal: New England Journal of Medicine (2003)

Presentation of CaseA newborn boy was admitted to a special-care nursery because of petechiae and thrombocytopenia.The boy had been delivered at this hospital at 39 weeks' gestation to a 32-year-old woman who had had premature rupture of the membranes 16 hours before delivery. A single dose of penicillin was administered to the mother before vacuum-assisted delivery. The Apgar score was 9 at one minute and at five minutes. A diffuse petechial rash, most prominent on the face and trunk, was noted at delivery, and the baby was transferred to a newborn nursery.The mother had never smoked, and . . .