tbuckley/cabot-search huggingface dataset:
SAT0596 Efficacy of epidural steroid injection in lumbar spinal stenosis is not related to the degree of severity by mri
Authors: ES Elsayad, MA Mortada, T Abd El Samad Elhawala, ESA Abd El Hady, A Hijab
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lumbar spinal stenosis (LSS) is a common degenerative disease. Treatment modalities for LSS vary and include medication, exercise, interventional techniques, and surgery. Epidural steroid injection has been used for the treatment of LSS with variable results. The relationship between severity of lumbar spinal stenosis and efficacy of lumbar epidural steroid injection is still undetermined. <h3>Objectives</h3> The aim of our study was to determine the relationship between the severity of LSS using MRI grading system and the response to lumbar epidural steroid injection. <h3>Methods</h3> Thirty patients with degenerative LSS were enrolled in this prospective study. All subjects underwent lumbar spine MRI (T2-weighted axial images). LSS was graded using MRI grading system (grade 1 = mild stenosis with separation of all cauda equine; grade 2 = moderate stenosis with some cauda equine aggregated; grade 3 = severe stenosis with none of the cauda equine separated). All fluoroscopy guided transforaminal epidural steroid injections (FG- TFESI) were performed in the procedure room. Outcome measures were obtained using the visual analogue scale (VAS) for both back and leg pain, Oswestry disability index (ODI), Roland 5-point pain scale, walking tolerance and patient9s satisfaction scale at 2 and 8 weeks post-treatment. <h3>Results</h3> Thirty LSS patients treated with FG- TFESI, who were completely followed up, were included in this study, the injection rate was one injection per patient. The patients were followed at 2 weeks and 8 weeks. Fifty-six percent of patients at 2 weeks and 70%% at 8 weeks had a successful outcome, reporting at least a &gt;50% reduction between pre-injection and post-injection visual analogue pain scores.Roland 5 point pain scale showed pain reduction in 50% of patients by (26%) at 2 weeks and in 70% of patients by50%pain reduction at 8 weeks. Oswestry low back pain disability questionnaire (ODI) scores showed statistically significant improvement from initial scores to 2 weeks and from to 8 weeks in 70% of patients. Walking tolerance showed improvement at 2 weeks in 50% of patients and at 8 weeks in 70% of patients. The outcome was statistically significant even in severe stenotic patients when comparing initial scores of moderate and severe stenosis at 2 weeks and 8 weeks scores in walking tolerance (<i>P</i>=0.006), Back VAS (<i>P</i>=0.717), Leg VAS (<i>P</i>=0.139), ODI (0.139), and Roland (<i>P</i>=0.001). <h3>Conclusions</h3> FG-LESI may reduce pain and improve walking tolerance in the short term for the treatment of patients with LSS for a period of 8 weeks. The outcome does not seem to correlate with the degree of lumbar spinal stenosis. Patients with severe LSS may have the same chance to get benefits from FG-LESI as patients with moderate LSS. <h3>Disclosure of Interest</h3> None declared
Response to Comment on Jackson et al. Insulitis in Autoantibody-Positive Pancreatic Donor With History of Gestational Diabetes Mellitus. Diabetes Care 2017;40:723–725
Authors: Jessica Jackson, Amanda Posgai, Martha Campbell-Thompson, Irina Kusmartseva
Journal: Diabetes Care (2017)

We greatly appreciate the interest of Marchand et al. (1) in our article (2), which we indeed hoped would stimulate interest regarding gaps in knowledge of diabetes during pregnancy. In some cases, gestational diabetes mellitus (GDM) could certainly represent previously undiagnosed/presymptomatic type 1 or type 2 diabetes secondary to β-cell stress during pregnancy.

Indeed, both the case presented in our original article and the example case described by the Thivolet group (1) highlight the need for further studies of GDM to determine the role of type 1 diabetes–associated autoantibodies during pregnancy and postpartum. Our intention was to highlight an interesting presentation of insulitis and autoantibody positivity …
Comparative health system performance in six middle-income countries: cross-sectional analysis using World Health Organization study of global ageing and health
Authors: Riyadh Alshamsan, John Tayu Lee, Sangeeta Rana, Hasan Areabi, Christopher Millett
Journal: Journal of the Royal Society of Medicine (2017)

Objective To assess and compare health system performance across six middle-income countries that are strengthening their health systems in pursuit of universal health coverage. Design Cross-sectional analysis from the World Health Organization Study on global AGEing and adult health, collected between 2007 and 2010. Setting Six middle-income countries: China, Ghana, India, Mexico, Russia and South Africa. Participants Nationally representative sample of adults aged 50 years and older. Main outcome measures We present achievement against key indicators of health system performance across effectiveness, cost, access, patient-centredness and equity domains. Results We found areas of poor performance in prevention and management of chronic conditions, such as hypertension control and cancer screening coverage. We also found that cost remains a barrier to healthcare access in spite of insurance schemes. Finally, we found evidence of disparities across many indicators, particularly in the effectiveness and patient centredness domains. Conclusions These findings identify important focus areas for action and shared learning as these countries move towards achieving universal health coverage.
GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome
Authors: Peng Li, Evan Wuthrick, Jeff A. Rappaport, Crystal Kraft, Jieru E. Lin, Glen Marszalowicz, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Scott A. Waldman
Journal: Cancer Research (2017)

Abstract High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095–106. ©2017 AACR.
THU0658 WNT/β-catenin pathway is affected in primary sjÖgren's syndrome
Authors: Z Omercikoglu, A Karatas, O Catak, B Oz, F Erman, K Sahin, AF Dagli, N Gozel, SS Koca
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Sjögren9s syndrome (SS) is a chronic autoimmune disease that causes salivary and lacrimal gland dysfunction, resulting in oral and ocular dryness. The pathogenesis of SS is still unknown. The Wingless (Wnt)/β-catenin pathway has been recently shown to play an important role in inflammation. <h3>Objectives</h3> The aim of the present study was to determine serum and salivary levels of <i>Dickkopf-related protein 1</i> (DKK1) and sclerostin those are inhibitor of Wnt/β-catenin signaling pathway and to evaluate the expression of Wnt-1 and Wnt-3a in the salivary gland, in patients with primary SS. <h3>Methods</h3> 30 patients with primary SS, 30 patients with systemic lupus erythematosus (SLE) and 29 healthy controls were enrolled in the study. Fasting blood and saliva samples were obtained from the participants. Serum and salivary levels of DKK1 and sclerostin were measured by enzyme-linked immunosorbent assay. Wnt-1 and Wnt-3a expression were also immunohistochemically assessed in salivary gland. EULAR SS Disease Activity Index (ESSDAI), and EULAR SS Patient Reported Index (ESSPRI) in the SS group and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the SLE group were recorded. <h3>Results</h3> Serum DKK1 and sclerostin levels were decreased in the SS and SLE groups compared to the controls (Table 1) (p&lt;0.001 for both). Salivary sclerostin levels were similar among the study groups (p&gt;0.05 for all). Salivary DKK1 levels were higher in the SS group compared to the control and SLE group (p=0.004 and p=0.009, respectively). Moreover, serum DKK1 level was higher in the SS group than in the SLE group (p=0.046). Serum DKK1 level was positively correlated with serum sclerostin level in the SS, SLE and control groups (r=0.677; p&lt;0.001, r =0.783; p&lt;0.001, and r=0.829; p&lt;0.001, respectively). ESSPRI was negatively correlated with serum DKK1 and sclerostin levels (r=-0.363; p=0.049 and r=-0.416; p=0.022, respectively) in the SS group. Moreover, in the salivary gland tissues, the positivities of Wnt-1 (71.4% vs. 46.2%, p=0.182) and Wnt-3a (71.4% vs. 53.8%, p=0.345) were relatively higher in the SS group compared to the control group, respectively. <h3>Conclusions</h3> According to the best of our knowledge, this study is the first study evaluating the activity of Wnt/β-catenin pathway in the primary SS. The altered serum levels of DKK1 and sclerostin in primary SS and SLE is suggest that Wnt/β-catenin pathway is affected in these inflammatory diseases. Salivary DKK1 level is increased in primary SS in contrast to SLE. On the other hand, Wnt-1 and Wnt-3a expressions on the salivary gland are increased in primary SS. Therefore, it may be concluded that Wnt/β-catenin pathway acts pathogenic roles on the glandular inflammation. <h3>Disclosure of Interest</h3> None declared
Abstract 127: Phosphorylation of Serum Responsive Factor by p90 Ribosomal S6 Kinase 3 Promotes Concentric Growth of Cardiac Myocytes
Authors: Jinliang Li, Eliana C Martinez Valencia, Catherine L Passariello, Hrishikesh Thakur, Michael Kapiloff
Journal: Circulation Research (2016)

p90 Ribosomal S6 Kinase 3 (RSK3) is required for the induction of concentric hypertrophy in hearts subjected to pressure overload and catecholamine infusion, as well as in a model for Noonan Syndrome-associated hypertrophic cardiomyopathy. Serving important roles in both cardiac development and adult function, the transcription factor Serum Responsive Factor (SRF) regulates genes expression involved in myocyte growth and sarcomeric assembly. It has been reported that SRF can be phosphorylated by RSK protein kinases on residue Ser-103, but the function of that post-translational modification has remained uncertain. We now show that SRF is a substrate for RSK3 associated with muscle A-Kinase-Anchoring-Protein (mAKAP) scaffold in cardiac myocytes, contributing to the regulation of concentric myocyte growth. By co-immunoprecipitation assay, SRF and RSK3 were both associated with the mAKAP scaffold in heart extracts, such that a ternary complex could be detected when recombinant proteins were expressed in cells. Silencing RSK3 or mAKAP expression by siRNA transfection reduced phenylephrine-induced SRF(S103) phosphorylation in neonatal cardiac myocytes. Similar results were acquired following expression of a peptide comprising the mAKAP RSK3-binding domain (RBD) that competed the binding of the kinase to the scaffold. Overexpression of either a SRF S103A phosphoablative mutant or the RBD peptide diminished the increase in width of adult cardiac myocytes stimulated by phenylephrine. In contrast, overexpression of RSK3 or a SRF S103D phosphomimetic mutant promoted adult cardiac myocyte concentric hypertorphy in vitro. While baseline SRF S103 phosphorylation in the heart was inhibited by mAKAP or RSK3 gene knock-out in mice, acute transverse aortic constriction significantly increased SRF S103 phosphorylation in the heart. Based upon these results, we porpose that RSK3 phosphorylation of SRF at mAKAP signalosomes is an important regulator of concentric cardiac myocyte growth. These results are consistent with additional findings that an adeno-associated virus gene therapy vector that expresses RBD in the cardiac mycoyte attenuates pathological hypertrophy and prevents heart failure in response to pressure overload.
AB0406 Stable efficacy and safety after switching from tocilizumab intravenous to subcutaneous in rheumatoid arthritis: results of a cohort of 200 patients
Authors: L Joffres, E Ricard, C Pereira Gillion, M Herbette, C Lucas, JB Cren, E Bergeal, Y Maugars, C Saillot, P Goupille, A Saraux, A Perdriger, B Bouvard, E Solau Gervais
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Intravenous tocilizumab has been used since 2009 in Europe for the treatment of active rheumatoid arthritis. Since 2015, a subcutaneous formulation is available. The switch from a monthly, intravenous, with dose adjusted for bodyweight treatment to a weekly, subcutaneous, fixed dose, leads to various questions about efficacy and toxicity. <h3>Objectives</h3> The objectives were to evaluate the efficacy maintenance (maintenance rate and DAS28 variation), the safety, the dose variation after the switch and the characteristics of patients switching to the subcutaneous form respect to those following with the intravenous tocilizumab. <h3>Methods</h3> Multicenter and retrospective study was performed from a cohort of 203 patients undergoing intravenous tocilizumab from the rheumatology unit of 7 university hospitals between September 2015 and May 2016. Assessment has been done on the records, effectiveness was assessed using the DAS28, adverse events and reasons for staying on IV form were reported. <h3>Results</h3> On the 203 records analyzed, 3 were secondarily excluded. Of the 200 patients, 77 have switched for the subcutaneous form. Mean age of the 200 patients was 58 years (+/- 13.3) with 155 women (78%) and the mean duration of rheumatoid arthritis was 14 years (+/- 10.4). 72% of patients received a standard intravenous dose (8mg/kg/month) at baseline. At the first visit after the prescription of the subcutaneous treatment, 58 patients on 65 (89%) maintained the treatment. The mean DAS28 was 1.53 (+/-1.00) at baseline and 1.19 (+/-0.78) at T1 (45 patients). Three patients received a reduced subcutaneous dose of 162mg/2 weeks following a reduced IV dose (&lt;8 mg/kg/month) and maintained the subcutaneous treatment. About safety, there was no new case of neutropenia&lt;1000/mm<sup>3</sup>. One severe adverse effect occurred (gastro intestinal perforation). Regard to the dose variation, for the 77 patients switching, the mean difference between intravenous and subcutaneous dose was + 29mg/week (+/-35mg) with the subcutaneous tocilizumab. Reasons for staying on IV form were essentially: the subcutaneous tocilizumab was not proposed in 55% of the cases and 17% of patients refused the subcutaneous form. <h3>Conclusions</h3> 89% of patients maintained the subcutaneous treatment after 4 months; efficacy was maintained in patients who received a reduced subcutaneous dose. Despite the higher dose after the switch (+29mg/week), there was no new case of neutropenia. <h3>Disclosure of Interest</h3> None declared
MiR-205/YAP1 in Activated Fibroblasts of Breast Tumor Promotes VEGF-independent Angiogenesis through STAT3 Signaling
Authors: Yan-E Du, Gang Tu, Guanglun Yang, Genyou Li, Dan Yang, Lei Lang, Lei Xi, Kexin Sun, Yanlin Chen, Kunxian Shu, Huadong Liao, Manran Liu, Yixuan Hou
Journal: Theranostics (2017)

Tumor microenvironment contributes to tumor angiogenesis. However, the role of the activated cancer associated-fibroblasts (CAFs) in angiogenesis is still unclear. Here we report that miR-205/YAP1 signaling in the activated stromal fibroblasts plays a critical role in VEGF-independent angiogenesis in breast tumor. Methods: miR-205 expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR); YAP1 expression by qRT-PCR, western blotting and immunohistochemistry; IL11 and IL15 expression by qRT-PCR, western blotting and ELISA. Tube formation and three-dimensioned sprouting assays in vitro, and orthotopic Xenografts in vivo were conducted as angiogenesis experiments. The mechanism of miR-205/YAP1-mediated tumor angiogenesis was analyzed via overexpression and shRNA, siRNA, or antibody neutralization experiments in combination with anti-VEGF antibody or Axitinib. Results: miR-205/YAP1 signaling axis activates breast normal fibroblasts (NFs) into CAFs, promotes tubule formation and sprouting of Human Umbilical Vein Endothelial Cells (HUVECs). Rescue of miR-205 in CAFs blunts angiogenesis processes. YAP1, a target of miR-205, does not regulate VEGF expression but specifically enhances IL11 and IL15 expressions, maintaining tumor angiogenesis even in the presence of Axitinib or after exhaustion of VEGF by neutralizing VEGF antibody. IL11 and IL15 released from CAFs activate STAT3 signaling in HUVECs. Blockage of IL11 and IL15 expression in CAFs results in the inactivation of STAT3-signaling in HUVECs and repression of the CAF-induced angiogenesis. The blunt angiogenesis halts the invasion and metastasis of breast cancer cells in vivo. Conclusions: These results provide a novel insight into breast CAF-induced tumor angiogenesis in a VEGF-independent manner.
THU0454 Role of physical exercise in patients with hip arthroplasty for aseptic necrosis of the femoral head
Authors: RI Marcu, S Patru, AC Bighea, D Matei
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Necrosis of the femoral head has a slow but progressive evolution, increasing degradation of the joint, worsening instability, with permanent pain and reduced walk perimeter. In the advanced stages of the disease, the only effective treatment is replacement of the joint (hip arthroplasty). <h3>Objectives</h3> The objective of our study was to examine the effects of a two weeks kinetic program on pain and functional status in patients with hip arthroplasty for aseptic necrosis of the femoral head. <h3>Methods</h3> We conducted an observational, prospective, randomized study on a sample of 47 patients with hip arthroplasty for aseptic necrosis of the femoral head. Patients were randomly assigned to a control group (23 patients) who received only analgesics and NSAID9s when needed (group 1) and a study group (24 patients) whose therapeutic program included daily physical exercise (group 2). Patients were initially evaluated and after two weeks of rehabilitation treatment. The clinical and functional parameters assessed were: pain on a visual analogue scale (100 mmVAS), physical impairments (muscular strength and mobility of hip joint) and disabilities (Tinetti Gait Scale, D9Aubigné Scale and movement capacity). <h3>Results</h3> The scores for functional parameters improved: pain- 42.6% (group 2) and 33.4% (group 1) (p=0.000054); physical impairments: muscular strength- 8.3% (group 2), without improving by group 1, mobility: 41.8% (group2) and 21.4% (group 1); disabilities: Tinetti Gait Scale- 33.6% (group 2) and 22.1% (group 1), D9Aubigné Scale- 35.8% (group 2) and 22.4% (group 1), movement capacity- 55.8% (group2) and 31.9% (group 1). The results were statistic significant (p&lt;0.05). <h3>Conclusions</h3> Improvement of pain, physical impairments and disabilities for the study group certifies the efficacy of the rehabilitation program including physical exercise in patients with hip arthroplasty for aseptic necrosis of the femoral head and motivates the continuation of the study on a longer period of time and on a larger number of patients. Rehabilitation program must begin right after patients underwent surgery for hip replacement. <h3>Disclosure of Interest</h3> None declared
Chromosome Constitution of Cells in Effusions of Cancer Patients&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Takaaki Ishihara, George E. Moore, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1961)

The chromosome constitution was determined in 18 effusions from patients with cancer and in 13 benign effusions. In contrast to the sharp modes of 46 in nonmalignant effusions, there was a considerable spread in the chromosome numbers of the neoplastic fluids examined, only about 30 percent of the cells in the latter having the modal number. Eleven fluids had modes ranging from 44 to 56 chromosomes, 2 had a mode from 62 to 64, and the remaining effusions had unbalanced polyploid modes of 78 to 112. Karyotype analysis revealed a characteristic chromosomal profile for each effusion. On a morphologic basis, most of the chromosomes in malignant effusions could be grouped superficially into the normal categories of human chromosomes, but the total set was extremely unbalanced, even in pseudodiploid cells. “New” marker chromosomes were present in most effusions, including an unusual case with a pseudodiploid chromosome constitution characterized by the presence of 3 marker chromosomes. Therapy did not seem to affect the chromosomal constitution of the effusions studied.