tbuckley/cabot-search huggingface dataset:
FRI0139 Spinal Mobility Gets Impaired in A Fixed Order in Patients with Ankylosing Spondylitis: 12-Year OASIS Results
Authors: S. Ramiro, R. Landewé, D. van der Heijde, C. Stolwijk, M. Dougados, F. van den Bosch, A. van Tubergen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Spinal mobility is impaired in patients with ankylosing spondylitis (AS) compared to normal subjects. However, the extent of impairment and the relative contribution of different measures are unknown. <h3>Objectives</h3> To investigate which spinal mobility measures are most frequently impaired in patients with AS and whether a hierarchy for the impairment of the measures could be established. <h3>Methods</h3> Patients from the Outcome in AS International Study (OASIS) were followed-up for up to 12 years in which spinal mobility was regularly measured (measures detailed in Table). From a previous study in normal subjects (1), percentile curves (2.5th to 97.5th) were obtained for each of the spinal mobility measures (Figure). We added 4 parallel curves representing z-scores of 2.5, 3, 3.5 and 4 respectively (helplines a to d) to be able to plot impaired measures. For every observation, and taking patient9s age into account, each of the spinal mobility measures was defined as impaired if the measurement fell below each of the cutoffs (2.5th percentile and each of the 4 helplines). The proportion of observations and also of patients (using baseline observation) in which each of the spinal mobility measures was impaired according to each of the cutoffs was calculated. Analyses were repeated in strata according to gender, symptom duration (median and tertiles) and baseline number of syndemophytes (0 vs ≥1 and &lt;5 vs≥5). <h3>Results</h3> A total of 216 patients were included (70% males, mean (SD) age 44 (13) years, mean symptom duration 21 (12) years and 85% HLA-B27 positive). Lateral spinal flexion (LSF) was always the most frequently impaired measure, sequentially followed by Schober9s, tragus-to-wall, cervical rotation, intermalleolar distance (IMD) and chest expansion (CE) (Table). This order was strikingly similar at both the observation-level and the patient-level (baseline observations only) as well as for all cutoffs (with the only exception being the 2.5th percentile, for which CE was slightly more impaired than IMD). Even with stratifications did this hierarchy in general persist. <h3>Conclusions</h3> LSF and Schober9s are the most frequently impaired mobility measures in AS, reflecting an earlier involvement of lumbar spine in spinal mobility impairment, followed by the involvement of the thoracic and cervical spine. This fixed order of involvement of the spine persists across different patient groups. <h3>References</h3> Ramiro et al. Arthritis &amp; Rheumatism 64(12):4173-4174. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1841
Prednisolone and<i>Mycobacterium indicus pranii</i>in Tuberculous Pericarditis
Authors: Bongani M. Mayosi, Mpiko Ntsekhe, Jackie Bosch, Shaheen Pandie, Hyejung Jung, Freedom Gumedze, Janice Pogue, Lehana Thabane, Marek Smieja, Veronica Francis, Laura Joldersma, Kandithalal M. Thomas, Baby Thomas, Abolade A. Awotedu, Nombulelo P. Magula, Datshana P. Naidoo, Albertino Damasceno, Alfred Chitsa Banda, Basil Brown, Pravin Manga, Bruce Kirenga, Charles Mondo, Phindile Mntla, Jacob M. Tsitsi, Ferande Peters, Mohammed R. Essop, James B.W. Russell, James Hakim, Jonathan Matenga, Ayub F. Barasa, Mahmoud U. Sani, Taiwo Olunuga, Okechukwu Ogah, Victor Ansa, Akinyemi Aje, Solomon Danbauchi, Dike Ojji, Salim Yusuf
Journal: New England Journal of Medicine (2014)

Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer.In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).
Abstract 4433: RB mediates TGF-β effects on growth inhibition and invasion in pancreatic cancer cells
Authors: Jesse Gore, Murray Korc
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that arises from precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN). PDAC's aggressiveness derives from its advanced stage when patients present clinically, the high frequency of driver mutations (KRAS, INK4A, TP53 and SMAD4) and the heterogeneous distribution of low frequency driver mutations. To study the potential role of RB in PDAC pathobiology, we generated a novel mouse model with pancreatic RB deletion and oncogenic Kras expression (Rb/K mice). These mice rapidly developed highly proliferative PanIN that progress to PDAC with high frequency, underscoring RB's tumor suppressive role in the pancreas. RB deletion alone, however, did not alter pancreatic histology. Previously, we have demonstrated that Smad7-induced loss of TGF-β-mediated growth inhibition is due to functional inactivation of RB. To further examine RB's role in TGF-β action, we established pancreatic cancer cell lines from the Rb/K model. These cells were resistant to TGF-β1-mediated growth inhibition, whereas growth of murine cell lines that retained RB was markedly inhibited. RB loss also abolished TGF-β-induced cell invasion, but did not alter Smad-dependent TGF-β1 signaling since TGF-β1 induced Smad2 phosphorylation, Smad3/4 nuclear translocation, and transactivation of TGF-β1-dependent reporters. By contrast, RB loss did not affect TGF-β1-induced epithelial-to-mesenchymal transition. Array analysis revealed marked alterations in the gene expression profile of Rb/K cells. These data suggest that RB loss contributes to the dysregulation of TGF-β actions in PDAC and suggest that delineation of these perturbations may yield novel therapeutic approaches in this malignancy. 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 4433. doi:1538-7445.AM2012-4433
Extracellular vesicles and infectious diseases: new complexity to an old story
Authors: Jeffrey S. Schorey, Clifford V. Harding
Journal: Journal of Clinical Investigation (2016)

Exosomes and other extracellular microvesicles (ExMVs) have important functions in intercellular communication and regulation. During the course of infection, these vesicles can convey pathogen molecules that serve as antigens or agonists of innate immune receptors to induce host defense and immunity, or that serve as regulators of host defense and mediators of immune evasion. These molecules may include proteins, nucleic acids, lipids, and carbohydrates. Pathogen molecules may be disseminated by incorporation into vesicles that are created and shed by host cells, or they may be incorporated into vesicles shed from microbial cells. Involvement of ExMVs in the induction of immunity and host defense is widespread among many pathogens, whereas their involvement in immune evasion mechanisms is prominent among pathogens that establish chronic infection and is found in some that cause acute infection. Because of their immunogenicity and enrichment of pathogen molecules, exosomes may also have potential in vaccine preparations and as diagnostic markers. Additionally, the ability of exosomes to deliver molecules to recipient cells raises the possibility of their use for drug/therapy delivery. Thus, ExMVs play a major role in the pathogenesis of infection and provide exciting potential for the development of novel diagnostic and therapeutic approaches.
P08.28 * AN INTERNET-BASED REGISTRY FOR THE DOCUMENTATION OF NEOPLASTIC MENINGITIS
Authors: H. M. Strik, H. Rock
Journal: Neuro-Oncology (2014)

Neoplastic involvement of cerebrospinal fluid (CSF) and meninges is a relatively rare and highly heterogeneous disease. Only few randomized studies investigated different treatment strategies and achived no conclusive results. New prospective studies with homogeneous entities are difficult to establish and some initiatives failed recently. Therefore, an open, multicentric registry may be an adequate alternative for a prospective documentation and analysis of a large number of cases of neoplastic meningitis from different primary neoplasms. To enable an easy multicentric access, an internet-based database was chosen. Secutrial is a professional database which enables pseudonymized registration of clinical courses and meets all reuqirements for the protection of personal data. Predefined routines allow for an immediate analysis of data like survival or toxicity including the most recently documented data. The internet-based access enables a multicentric, international documentation of cases of neoplastic meningitis. Analysis of these data may allow conclusions on efficacy and toxicity of different treatment strategies in the separate tumor entities. The configuration of the database allows for a separate documentation of the course of primary neoplasm, systemic and solid central nervous system metastases as well as neoplastic meningitis. Also, complications of the disease and toxicity of treatment can be documented. By such, the database is able to discriminate between different causes of clinical deterioration and death. Operative, medical treatment and radiotherapy can be assessed as well as results of radiological, histological and cytological examniations including diagnostic and prognostic markers. The system is flexible enough to enable the addition of newly established items like biomarkers if needed. Dicomm data of radiological examniations can be upoaded and shared if needed and biobanking organized. The results of tumor boards can be documented as well. Since multicentric prospective trials are difficult to perform for this rare and heterogeneous disease, an internet based registry appears to be an adequate alternative to collect data on treatment results. We think that the structure and content of the database presented here provides an adequate tool to collect and analyse a large number of cases with neoplastic meningitis.
Tocilizumab-induced intestinal injury
Authors: K. Hagiwara
Journal: Endoscopy (2011)

I read with great interest the article by Dr. Iwasa and colleagues about the patient who developed multiple ulcers in the intestines during therapy for rheumatoid arthritis with tocilizumab, a monoclonal antibody against human interleukin-6 (IL-6) receptor [1]. The temporal relationship between unexpected re-administration of tocilizumab and recurrence of hematochezia is convincing. Recently, I treated a 62-year-old woman with a 7-year history of refractory rheumatoid arthritis, who developed massive hematochezia 1 day after the first administration of tocilizumab. Endoscopic examination revealed bleeding from multiple diverticula in the large intestine. Similarly, the patient experienced recurrence of hematochezia after unexpected re-administration of tocilizumab.
Tc-99m DTPA Renal Scintigraphy Using Deconvolution Analysis With Six Functional Images of the Mean Time to Evaluate Acute Pyelonephritis
Authors: M Poropat, D Batinić, M Basić, L J Nizić, D Dodig, D Milosević, A Votava-Raić, S Tezak, K Vrljicak, D Huić, M Medvedec
Journal: Clinical Nuclear Medicine (1999)

In 38 children with proved P-fimbriated Escherichia coli acute pyelonephritis, Tc-99m DTPA dynamic renal scintigraphy in the zoom mode using deconvolution analysis was performed, and the results were compared with those of Tc-99m DMSA scans. From the dynamic study, six functional images of the mean time were generated. Each functional image was analyzed separately to search for focal areas of increased mean time within the kidney contour, especially over the kidney parenchyma. Time-activity curves from these areas were generated and analyzed. Tc-99m DMSA scintigraphy showed generalized or focal decreased uptake in 32 (41.8%) kidneys, and deconvolution analysis of Tc-99m DTPA scintigraphy revealed pathologic renographic curves in 58 (77.6%) kidneys. Prolonged whole-kidney and normal renal parenchymal transit times (dilatation without obstruction) were found in 38 (50%) kidneys, whereas prolonged whole-kidney and renal parenchymal transit times (dilatation with obstruction) were observed in 20 (27.6%) kidneys. Separate analysis of each of the six functional images of the mean time showed focal areas of increased mean time in the kidney parenchyma of 11 kidneys. In five cases, time-activity curves from these areas showed a sharp increase of activity on the descending part of the curve, which might reflect the return of urine from the collecting system into kidney cortex (i.e., intrarenal reflux). These results showed that in a urinary tract with acute pyelonephritis, urodynamic changes may lead to obstructive nephropathy and intrarenal reflux. Tc-99m DTPA renal scintigraphy in the zoom mode using deconvolution analysis with six functional images of the mean time has proved to be a valuable method to evaluate acute pyelonephritis, thus allowing dynamic and morphologic analysis of the urinary tract at the same time.
TEMPORAL TRENDS OF INFECTIVE ENDOCARDITIS EPIDEMIOLOGY FROM 2007-2013 IN OLMSTED COUNTY, MINNESOTA
Authors: Daniel DeSimone, Imad Tleyjeh, Daniel Correa de Sa, Nandan Anavekar, Brian Lahr, Muhammad Sohail, James Steckelberg, Walter Wilson, Larry Baddour
Journal: Journal of the American College of Cardiology (2015)
AB0291 Changes of mineral bone density in patients with rheumatoid arthritis treated with metotrexat after one-year application of etanercept
Authors: T. Jankovic, J. Zvekic-Svorcan, M. Lazarevic, B. Erdeljan, S. Subin-Teodosijevic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The reduction of mineral bone density (BMD) in rheumatoid arthritis (RA), starts early during the disease and progresses rapidly, with interleukin 1(IL-1), tumour necrosis factor (TNF) and other proinflammatory cytokines playing an important role in its emerging, activating osteoclasts, which accelerate bone resorption. <h3>Objectives</h3> To determine the effect of etanercept on BMD in patients with RA treated with metotrexat (MTX) after one-year application. <h3>Methods</h3> The study was conducted in the period of one year in 100 patients with RA, 86 women and 14 men, median age 57, with mean disease duration of 8.9 years, who had been treated with MTX for at least 3 years in the average weekly dose of 12,5mg. Patients were monitored and divided into two groups. The first group consisted of 44 patients, 38 women and 6 men in whom beside MTX, Etanercept was included in the weekly dose of 50mg. The other group included 56 patients, 48 women and 8 men who continued taking MTX. The use of glucocorticoids was the excludingcriterion for further monitoring. All patients at baseline and after one year had osteodensitometric examination (DEXA) done using LUNAR review. Mineral bone density (BMD) was measured at the lumbar spine (LS) and hips, expressed in absolute values (g/cm2). Statistical analyses were done in Statistical Package for The Science 20.0 program. <h3>Results</h3> In the first group of patients the received initial value of BMD and DEXA control finding, located on the LS(1.08g/cm2, 1.04g/cm2) and hip(0.868g/cm2, 0.846g/cm2), showed statistical difference(t=4.43, p=0.000) and(t=4.14, p=0.000). In the second group of patients the received BMD values at LS (0.997g/cm2, 0.960g/cm2) were statistically significant (t=5.29, p=0.000) as well as those obtained athip (0.834g/cm2, 0.815g /cm2) (t=5.33, p=0.000). Comparing changes in BMD in both groups of patients, patients who were only on MTX had a statistically significant decrease in BMD values. <h3>Conclusions</h3> Changed BMD values in patients treated only with metotrexat, after a year, was higher and showed a statistically significant difference, as well as when compared with the change in BMD in patients treated in combination with etanercept, where this change was on the level of statistical significance. <h3>References</h3> Strand V, Kavanaugh AF. The role of interleukin-1 in bone resorption in rheumatoid arthritis. Rheumatology (Oxford) 2004; Suppl 3:43. <h3>Disclosure of Interest</h3> None Declared
GW25-e3383 Correlation of CHADS2 and CHA2DS2-VASc scores with left atrial thrombus in Chinese patients with nonvalvular atrial fibrillation
Authors: J. Huang, Ym. Xue, Xz. Zhan, Xh. Fang, Hw. Feng, Sl. Wu
Journal: Journal of the American College of Cardiology (2014)
Renal-Cell Cancer — Targeting an Immune Checkpoint or Multiple Kinases
Authors: David I. Quinn, Primo N. Lara
Journal: New England Journal of Medicine (2015)

Therapy for advanced renal-cell cancer has evolved considerably in the past decade, with new agents greeted like “buried treasure,” although these agents come with substantial costs to both patients and the health system. Before 2005, the widely used systemic agents were cytokines — interferon alfa and interleukin-2, which yielded modest efficacy and substantial toxicity. Nevertheless, underlining the immunogenic nature of renal-cell cancer, durable complete responses occur in some patients who receive interleukin-2; these patients are mostly cured.1 After 2005, angiogenesis and mammalian target of rapamycin (mTOR) pathway inhibitors displaced cytokine therapy.2,3 Although the most effective sequence of therapies is . . .
Urea-Cycle Enzyme Deficiencies and an Increased Nitrogen Load Producing Hyperammonemia in Reye's Syndrome
Authors: Philip J. Snodgrass, G. Robert DeLong
Journal: New England Journal of Medicine (1976)

Assay of urea-cycle enzymes in liver tissue showed ornithine transcarbamylase activities of 18 to 72 per cent of the normal mean in eight patients with Reye's syndrome, below the range of normal in seven of eight, and, in six cases, as low as those in females with X-linked deficiency of this enzyme. Carbamyl phosphate synthetase activities were less than 32 per cent of controls in two patients. Argininosuccinate synthetase and lyase activities were normal in seven patients. Arginase was normal in two biopsy specimens, but below normal in four of five autopsy specimens. The Km's for ornithine and carbamyl phosphate, pH optimum, and heat lability of ornithine transcarbamylase were normal. Two patients excreted 0.64 and 0.58 g per kilogram per day of urinary nitrogen at the peak of hyperammonemia, in spite of peritoneal dialysis. The hyperammonemia of Reye's syndrome apparently results from excess waste nitrogen that overwhelms the ability of reduced ornithine transcarbamylase (and occasionally carbamyl phosphate synthetase) to detoxify the ammonia load.
SP0153 Pathophysiology and Management of Glucorticoid Induced Osteoporosis
Authors: G. Bianchi
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Glucorticoid treatment is the most common cause of secondary osteoporosis in men and women. One of the most important side effects of glucocorticoids is bone loss, which is biphasic, with a rapid reduction of bone mineral density (BMD) during the first year (6% to 12%), followed by a slower annual loss of about 3% for as long as glucocorticoids are administered. The relative risk of fracture increases more rapidly (up to 75% within the first 3 months), and fragility fractures often occur before a significant decline in BMD become evident, indicating that the use of corticosteroids does has an effect on fracture risk also independently of the effects on bone density. In fact the detrimental actions of glucocorticoids on the skeleton are the direct consequences of their interaction with the bone cells, produce a decrease in osteoblastogenesis and an increase in osteoblasts apoptosis, leading to a continual decrease of cancellous osteoblasts, synthetic ability and bone formation. On the other hand, osteoclasts survival is improved by glucocorticoids, producing an increase of cancellous osteoclasts and bone resorption. A relevant effect on osteocytes has been also described, with increased osteocyte apoptosis and decreased canalicular circulation, leading to an alteration of bone quality. General measures for fracture prevention in patients receiving glucocorticoids are excellent nutrition, appropriate calcium intake, physical exercise and avoid detrimental lifestyle factors (e.g., smoking cessation). Vitamin D supplementation should be always considered in order to attain and maintain an adequate vitamin D level (25-hydroxy-vitamin D &gt;30 ng/ml), due to its implication for bone health and falls prevention. Finally, in patients at risk of falls, intervention to prevent falls by improving balance and strength should be implemented. In RCTs of men and women receiving glucocorticoids, bisphosphonates and teriparatide showed significant beneficial effects in preserving and/or improving the bone mineral density. Some of these pharmacological agents also demonstrated to reduce the risk of vertebral fractures. Teriparatide represents the rational approach to glucocorticoid-induced osteoporosis, as it directly counteracts the detrimental effects of glucocorticoids on osteoblasts. Although these data support the use of bisphosphonates and teriparatide in the management of glucocorticoid-induced osteoporosis their anti-fracture and long-term efficacy has not been fully clarified mainly due to the small samples studied and to the short-term follow-up of RCTs. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6173