tbuckley/cabot-search huggingface dataset:
THU0667 A qualitative and quantitative comparison of synovial biopsy techniques during clinical trials of inflammatory arthritis
Authors: F Humby, S Bugatti, A Filer, S Kelly, A Manzo, E Souza, V Romao, V Rocher, R Hands, M Wechalekar, J Fonseca, C Montecucco, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Synovial tissue is an attractive area of research for biomarkers of disease outcome in RA. Currently acquisition of synovial tissue using an arthroscopic approach in clinical trials is recommended though two US-guided techniques have been described, a portal and forceps (P&amp;F) approach and an adaptation using a quick core needle (NB). However before US-guided biopsy techniques are widely adopted into clinical trials validation of performance against arthroscopy is required. <h3>Objectives</h3> To evaluate whether there were significant differences in synovial sampling quality and quantity between arthroscopic, US-P&amp;F and US-NB procedures within the context of clinical trials. <h3>Methods</h3> This was a multicentre retrospective analysis of inflammatory arthritis patients recruited to clinical trials utilizing US-guided NB (Barts Health NHS Trust), US-guided P&amp;F (ICRSS Policlinico San Matteo and University Hospital Birmingham) and arthroscopic biopsy (Repatriation General Hospital). Paraffin embedded synovial sections from each procedure underwent H&amp;E staining and sections examined for intact cell lining layer (graded sections). Biopsy procedures were segregated into large (knee) and small joint procedures (wrist/MCP) for analysis. Proportion of samples yielding graded tissue per procedure was recorded. Using CellSens Dimensions software the mean area of synovial tissue obtained per procedure was determined. In addition the degree of synovitis was assessed using semi-quantitiative scoring (0–9). <h3>Results</h3> 78 patient procedures were evaluated, 22 on small joints (11 US-NB, 11 US P&amp;F) and 56 on large joints (11 US-NB, 35 US-P&amp;F, 10 arthroscopic). 47 patients had RA, 11 undifferentiated arthritis and 10 psoriatic arthritis. Arthroscopic sampling resulted in a significantly higher area of tissue retrieved per procedure than US P&amp;F or US-NB. There were no significant differences in proportion of graded samples per procedure suggesting quality of synovial tissue was preserved between techniques. Finally no significant differences in degree of histological synovitis were demonstrated between sampling techniques. <h3>Conclusions</h3> The results suggest that US-guided biopsy provides a reliable method for sampling synovial tissue of comparable quality to that obtained from arthroscopy. However when sampling large joints arthroscopic techniques, and when sampling small joints US-P&amp;F yield a significantly higher quantity, though not quality, of tissue per procedure than US-NB. These results may influence choice of biopsy technique when designing clinical trial protocols in inflammatory arthritis. <h3>Disclosure of Interest</h3> None declared
If We Are Smart Enough to Stop HIV From Replicating, Why Can’t We Help People to Stop Smoking?
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Genomic Activation of <i>PPARG</i> Reveals a Candidate Therapeutic Axis in Bladder Cancer
Authors: Jonathan T. Goldstein, Ashton C. Berger, Juliann Shih, Fujiko F. Duke, Laura Furst, David J. Kwiatkowski, Andrew D. Cherniack, Matthew Meyerson, Craig A. Strathdee
Journal: Cancer Research (2017)

The PPARG gene encoding the nuclear receptor PPARγ is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene, which encodes the heterodimeric partner of PPARγ. Here, we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer. Cancer Res; 77(24); 6987-98. ©2017 AACR.
Phase I Trial of Targeted Alpha-Particle Therapy Using Actinium-225 (225Ac)-Lintuzumab (Anti-CD33) in Combination with Low-Dose Cytarabine (LDAC) for Older Patients with Untreated Acute Myeloid Leukemia (AML)
Authors: Joseph G Jurcic, Farhad Ravandi, John M. Pagel, Jae H Park, B. Douglas Smith, Dan Douer, Elihu H. Estey, Hagop M. Kantarjian, Richard L. Wahl, Dennis Earle, Dragan Cicic, David A. Scheinberg
Journal: Blood (2014)
AB0453 Off-label use of mycophenolate in patients with systemic lupus erythematosus in a rheumatology center in colombia
Authors: K Mendez, D Buitrago-Garcia, P Santos-Moreno, J Urrego
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immunosuppressants such as mycophenolate are widely used in people with systemic lupus erythematosus (SLE), but not all are specifically licensed by FDA, EMA (1) and in the case of Colombia the Regulatory Agency for Food and Drugs (INVIMA) has not approved it for this indication, only for the prevention of the rejection of some transplants. Mycophenolate mofetil was found to be associated with a lower risk of toxic adverse events such as ovarian failure, alopecia and leucopenia, compared with cyclophosphamide (1). <h3>Objectives</h3> To describe the population of patients with SLE receiving mycophenolate during a five year period. <h3>Methods</h3> We conducted a retrospective observational study, extracting information from a database in our rheumatic diseases center; we reviewed the clinical record of each patient with diagnosis of SLE and receiving mycophenolate. Descriptive epidemiology was performed for each variable presented. <h3>Results</h3> 1989 patients were diagnosed with Systemic Lupus Erythematosus (SLE) during 2011 and 2016 and 287 were receiving mycophenolate. Regarding demographic characteristics 94% were woman and 6% men, mean age was 49 years ± 15. 41% of patients were employed, 40% were housekeepers, 11% students and 8% retired. The indication for mycophenolate was mainly for lupus nephritis 62%, SLE in overlapping with systemic sclerosis 30% and only for SLE in 8% of cases. 36% of patients received a daily dose of 2000 mg, 30% 1500 mg, 20% 1000 mg, 8% 3000 mg, 3.5% 4000 mg and 1.5% 6000 mg and 1% 500mg. The mean value for 24 hour urine protein was 792 mg/dl ± 140 and for creatinine was 0.84 mg/dl ± 0.36. In our population patients were taking mycophenolate during a median of 24 months with a minimum of 6 and a maximum of 132. In combination with mycophenolate 28% of the patients were taking corticoids, 21% hydroxichloroquine, 20% chloroquine, 17% antihypertensive drugs, 7% other medications and only 4% were taking the mycophenolate alone. <h3>Conclusions</h3> Despite of the absence of a license for mycophenolate for the management of Systemic Lupus Erythematosus, the use off-label of this drug continues to be frequently as an alternative and effective treatment in patients with lupus nephritis and other conditions associated to SLE. <h3>References</h3> National Institute for Health Care Excellence. NICE. Systemic lupus erythematosus: oral mycophenolate. England: NICE 2014. <h3>Disclosure of Interest</h3> None declared
THU0406 Serum uric acid lowering treatment appears unnecessary during hemodialysis
Authors: M Andrés, R Soriano, E Oliveira, C Trigo, MD Arenas, E Pascual
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout patients often suffer from renal disease, some ultimately developing end-stage renal disease (ESRD) and requiring hemodialysis (HD) replacement therapy. Though some reports suggested that tophi disappear after HD, urate-lowering agents are frequently continued, often based on persistent high SUA levels before HD. Also, the impact of SUA levels in the survival of patients on hemodialysis (HD) is under discussion. <h3>Objectives</h3> To assess the SUA reduction achieved under HD and analyze the kinetics of SUA in a week of intermittent HD. <h3>Methods</h3> SUA levels were determined before and after HD sessions in consecutives 96 patients with end-stage renal disease (ESRD), and compared through paired samples Student9s t test. Variables related to HD were analyzed whether associated with SUA reductions ≥80% using Student9s t test or ANOVA. Also, a kinetics study on selected 10 patients with hyperuricemia (SUA before HD&gt;6.8 mg/dL) throughout intermittent HD sessions in a week period was performed; differences in SUA levels were analyzed by repeated measures ANOVA. <h3>Results</h3> Patients were mean aged 66.5 years (SD±13.8), 62 males (64.6%). Mean time on HD replacement was 7.1 years (±7.2). Before starting HD, 43.0% had hyperuricemia and 21.6% reported gout. Sixteen (16.4%) continued on urate-lowering agents after HD. Mean SUA levels before and after HD session was 5.2mg/dL (± 1.0) and 1.0mg/dL (±0.4), respectively. Mean SUA reduction following HD was 80.2% (95% CI 78.4–82.0); 51 patients (56.7%) showed SUA reduction ≥80%. HD-related variables Kt/v&lt;1.3 (p=0.006) and blood efflux&lt;400mL/min (p=0.004) significantly associated with achieving SUA reduction ≥80%. Figure shows the SUA kinetics study: SUA significantly reduced all over the period and persisted below hyperuricemia threshold (p=0.015). <h3>Conclusions</h3> Under HD replacement therapy SUA levels effectively reduced and persisted below saturation point, suggesting that urate-lowering therapy appears unnecessary for patients with gout and ESRD. <h3>Disclosure of Interest</h3> None declared
THU0245 Mammalian target of rapamycin pathway might contribute the minor salivary gland changes in both sjogren's syndrome and systemic sclerosis patients
Authors: ZZ Gumus, F Cakalagaoglu, Z Soypacaci, M Ozmen, D Solmaz, S Gucenmez, O Gercik, S Akar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The <i>Mammalian Target of Rapamycin</i> (mTOR), a multiprotein complex, controls cell growth, proliferation, survival and plays an important role in immunity and inflammation. <i>Transforming Growth Factor-β1</i> (TGF- β1) leads to an increase in mTOR levels by protein kinase B (PKB or Akt) pathway. <i>Phosphatase and tensin homolog</i> (PTEN) affects mTOR pathway by inhibiting Akt. Recently, increased activities of TGF-β1 and mTOR were established in a mouse model of SSc. However the role of mTOR pathway, which might be a potential treatment target, in the human salivary gland inflammation is not evaluated systematically before. <h3>Objectives</h3> Therefore, we aimed to examine the activity of mTOR pathway and TGF-β1 in human minor salivary gland biopsies of Sjogren9s Syndrome (SjS) and systemic sclerosis (SSc) patients. <h3>Methods</h3> Immunohistochemical technique was used to analyze the expression of mTOR, PTEN and TGF-β1 in human minor salivary gland biopsies of SjS, SSc and SjS-SSc overlap patients. Immunohistochemical staining was evaluated by light microscopy and staining intensity was scored semi-quantitatively (Figure 1). The biopsy specimens were also examined for the degree of fibrosis. <h3>Results</h3> Formalin fixed sections of minor salivary gland biopsies of 58 SjS (57 female [98.3%]), 14 SSc (13 female [92.8%]) and 23 SjS-SSc overlap patients (all female) were included in the study. All biopsy specimens of SjS and overlap patients had a focus score of ≥1. There is no significant difference regarding mTOR expression between groups (<i>P</i>=0.622). mTOR expression was found in 94.4% in SjS group, 100% in overlap and 90% in SSc patients. PTEN protein was expressed in 87.2% of patients with SjS, 57.9% of overlap and 100% of SSC patients and the difference was statistically different (<i>P</i>=0.023). Although ductal epithelial TGF-β1 expression was similar between groups (<i>P</i>=0.345), acinar cell expression is more frequent in SSc (72.7%) and overlap patients (85.7%) in comparison with SjS (58.2% and <i>P</i>=0.004). Additionally, most of the acinar TGF-β1 staining was strong positive in SSC patients (45.5% vs 19.0% and 3.6%). <h3>Conclusions</h3> The results of our study showed that mTOR may be one of the common pathways for the pathology/inflammation observed in both SjS and SSc. Thus, there may be a room for mTOR inhibitors for the treatment of both diseases. Additionally PTEN and TGF-β1 expression, in particular acinar TGF-β1 might be a distinctive feature of SSc. <h3>Disclosure of Interest</h3> None declared
THU0592 Do junior doctors prescribe disease modifying anti rheumatic drugs safely?
Authors: MK Nisar, H Weller
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatic diseases occupy over 50,000 bed days annually in the National Health Service. Adverse drug events are major causes of harm to patients in hospitals and are associated with prolonged length of stay with higher costs. National Patient Safety Agency has issued several alerts regarding DMARDs and Methotrexate overdose remains a "never event". Prescribing medications, including DMARDs for rheumatology patients, is one of the chief responsibilities of junior doctors. <h3>Objectives</h3> We undertook a pilot survey of junior doctors and medical students to understand their level of prescribing confidence with an aim to develop a teaching program. <h3>Methods</h3> Following a focus group discussion based on NPSA safety alerts and BSR DMARD monitoring guidelines, ten items were unanimously identified as core knowledge required for safe prescribing. A questionnaire was created based on these elements. Junior doctors and final year medical students were surveyed at our academic institution. Replies were compiled to ascertain their understanding of safe prescribing and troubleshooting DMARD related issues. <h3>Results</h3> 41 junior doctors of all grades and nine medical students contributed to the survey. Only 6/50 (12%) felt confident in prescribing whereas 16/50 (32%) had borderline confidence and remaining 56% felt it was beyond their expertise. Of the 41 junior doctors, 19 (46%) had never even prescribed DMARD despite encountering such patients on the wards. Principal reasons for this included lack of confidence (40%), paucity of knowledge (15%) and no formal education (32%). Questions pertaining to safe prescribing were confidently answered by only 4/50 (8%) participants. <h3>Conclusions</h3> To our knowledge, this is the first survey to demonstrate that there are serious shortcomings in junior doctors9 understanding of safe DMARD prescribing. Inadequate training and hence poor confidence among front line medical staff remains the main cause of this issue. Despite consistent evidence suggesting that rheumatology teaching in medical schools has historically been poor and active measures taken in recent past to identify better ways to address the issues, this study highlights major knowledge gaps among everyday and future prescribers. Focused strategy and better training of junior doctors, both during and after graduation, are pivotal to providing better care for patients prescribed DMARDs during inpatient hospital stay. <h3>Disclosure of Interest</h3> None declared
SAT0280 A ten-year survival analysis of filipino patients with systemic lupus erythematosus at the national kidney and transplant institute (philippines)
Authors: EML Yap, CC Bermudez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is increasingly being diagnosed in our country. Despite the increasing number of patients, there are no studies describing their clinical profile at the time of diagnosis at the National Kidney and Transplant Institute (NKTI). This study aims to describe patients9 initial clinical presentations, outcomes, and their survival rate within ten years. <h3>Objectives</h3> To determine the ten-year survival rate and presenting clinical manifestations of Filipino patients first diagnosed with SLE at the National Kidney and Transplant Institute (NKTI) <h3>Methods</h3> This is a retrospective cohort study using chart review of patients first diagnosed with SLE in 2004 followed up in the next ten years. <h3>Results</h3> Eighty-five patients were first diagnosed with SLE wherein their average age was 28.10 years old ±12.03, 34.12% had hypertension, and 74.12% with renal involvement. The patients9 cumulative 10-year survival was 75% with average survival time of 9.84 years. Moreover, biopsy- proven lupus nephritis had significantly longer survival time (mean=10.57 years, p=0.006) while those with cardiopulmonary manifestations had shorter survival (mean=0.71 years, p=0.030) as well as those on hemodialysis (mean=8.82 years, p=0.040). Lastly, eleven patients (12.94%) expired during the study period with active diseases and infections as the common causes of mortality. <h3>Conclusions</h3> The 10-year survival rate of patients with systemic lupus erythematosus was 75% which was comparable to the findings from several countries. Although renal involvement was the most common initial manifestation, it did not significantly affect survival similar to prominent studies. <h3>Disclosure of Interest</h3> None declared
Eradication of large orthotopic breast tumors and metastasis by combined nab-paclitaxel and bevacizumab therapy
Authors: Lisa Volk, Christopher Bivens, Alan Stutzman, Neil Desai, Vuong Trieu, Sophia Ran
Journal: Cancer Research (2008)

4021    Introduction:  Metastasis is the main cause of mortality from cancer. Treatments to prevent or eradicate metastasis will sustain long-term remissions and significantly improve patients’ survival. We have previously shown that reactionary angiogenesis induced by chemotherapy correlated with increased VEGF production in tumors (Trieu et al., AACR 2007, #4636). The combined therapy of ABX and anti-VEGF-A antibody (bevacizumab, Avastin) has superior efficacy against both primary tumors and metastasis than either of these drugs used alone in medium-sized MDA-MB-231 tumors (~230 mm 3 ) (Ran et al., AACR 2007, #2201). In this study, to verify the effect of ABX and Avastin combination on metastasis, we optimized dosage of  nab -paclitaxel and the timing of Avastin administration to achieve sustainable regressions of large-sized primary tumors (average size 450 mm 3 ) as well as lymphatic and lung metastases.     Methods:  Luciferase-tagged MDA-MB-231-Luc +  human breast carcinoma cells were implanted into mammary fat pads of  nu/nu  mice and allowed to reach an averaged size of 450 mm 3  (range 350-600 mm 3 ). Mice were treated with ABX at 10 or 30 mg/kg on the qdx5 schedule for 1, 2 or 3 cycles separated by one week. In combination groups, Avastin (4mg/kg) was administered either concurrently with ABX or post-ABX treatment; and either continued for the duration of the experiment or discontinued after cessation of ABX therapy. Tumor growth was monitored for ~100 days after implantation, and organs were analyzed for luciferase activity representing metastatic spread.   Results:  No toxicity was observed in any of the treated mice. Complete regressions were achieved in 100% of mice bearing large orthotopic MDA-MB-231-Luc +  tumors after treatment with 2 cycles of Abraxane and Avastin given concurrently at 30 mg/kg and 4 mg/kg, respectively. All cured mice were free of metastasis as determined by measuring luciferase activity in lymph nodes and lungs. Three cycles of combined therapy with Abraxane at 10 mg/kg resulted in 80% regressions and 98% reduction in averaged metastatic burden. Avastin effect was optimal when administered concurrently with Abraxane and continued for the duration of the experiment. Avastin administered sequentially after Abraxane delivered no benefits of the combined therapy. The antitumor and antimetastatic efficacy of the combined therapy was diminished with lower ABX dose, reduction in number of treatment cycles, and early discontinuation or delayed application of Avastin.      Conclusions:  Our data show that large-sized (up to 600 mm 3 ) orthotopic tumors and lymphatic and systemic metastases can be eradicated using repetitive cycles of  nab -paclitaxel at 30 mg/kg given concurrently with bevacizumab at 4 mg/kg. The suppression of paclitaxel-induced reactionary angiogenesis by Avastin can significantly enhance the antitumor and antimetastatic efficacy of Abraxane.