tbuckley/cabot-search huggingface dataset:
THU0559 Comparative Efficiency of Four Rehabilitation Programs for Patients with Early Rheumatoid Arthritis:
Authors: E. Orlova, D. Karateev, L. Denisov, A. Kochetkov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) requires long term management by drug treatments, rehabilitation techniques and cooperation of the multidisciplinary team [1–3]. <h3>Objectives</h3> To compare the efficacy of four rehabilitation programs for patients with early RA within 6 months. <h3>Methods</h3> 128 patients with early RA (85,9% females, age of 18 to 63 years, disease duration of 2 to 19 months) were included. 34 patients (group 1) underwent drug therapy and complex rehabilitation program (hospital stage for 2 weeks: local air cryotherapy (−60°C, Criojet Air C600) for hand, knee or ankle joints for 15 min, 45-min therapeutic exercises for joints under the supervision of a trainer, 45-min occupational therapy (joint protection strategies, use of assistive devices and adaptive equipment), 10 sessions, education program (4 daily 90-min lessons) and outpatient stage for 6 months: 45-min home exercises 3 times a week, orthoses (functional wrist and knee orthoses, individual orthopedic insoles)). At hospital stage 31 patients (group 2) received local air cryotherapy, therapeutic exercises and occupational therapy; the home-based exercises lasted for 6 months 3 times a week. At hospital stage 15 patients (group 3) underwent 10 high-intensity dynamic exercises using gym apparatus Enraf-Nonius for 45–60 min (aerobic part (En-Cardio) and 18–20 muscle-strengthening exercises (En-Dynamic Track)), 18 patients (group 4) – 10 therapeutic exercises for 45 min, at outpatient stage the both exercise programs lasted for 6 months 3 times a week. 30 patients (control) received only drug therapy. Tender and swollen joint count, ESR, joint pain on 100-mm VAS, DAS28, HAQ, RAPID3, hand grip strength, the average powers of knee extension and ankle flexion by the EN-TreeM movement analysis were evaluated at baseline and at 6 months. <h3>Results</h3> At baseline there were no statistically significant differences in all parameters between the 5 groups (p&gt;0,05). After 6 months there were the best achievements of most parameters in the group 1 (p&lt;0,05). <h3>Conclusions</h3> Individual complex rehabilitation program, including different elements of the multidisciplinary service (physiotherapy, physical exercises, occupational therapy, education program and orthoses), provides the maximum positive effect on functional ability, motion activity, quality of life and diseases activity in patients with early RA within 6 months. <h3>References</h3> Forestier R, et al. Joint Bone Spine 2009;76(6):691–8. Luqmani R, et al. Rheumatology 2006;45(9):1167–9. Hurkmans EJ, et al. Acta Reumatol Port 2011;36(2):146–58. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3821
SAT0373 Safety of Allopurinol Compared with Other Urate-Lowering Drugs in Patients with Gout: A Systematic Literature Review and Meta-Analysis
Authors: I. Castrejon, E. Toledano, M. P. Rosario, E. Loza, F. Perez-Ruiz, L. Carmona
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Allopurinol is the most widely used urate-lowering drug (ULD). Drug safety helps, with efficacy and cost, making treatment decisions. <h3>Objectives</h3> To analyze the safety of allopurinol in comparison to other ULD <h3>Methods</h3> The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library. Selection criteria: a) Patients&gt;18, b) Gout by the ACR criteria or evidence of urate crystal in synovial fluid, c) Comparator (placebo or other ULD), and d) RCTs, cohorts, or meta-analysis. Primary outcomes were: rate of adverse events and death. Quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. <h3>Results</h3> From 544 studies, 7 met the eligibility criteria and were included. All RCT with low power for safety. Participants were similar among studies (all RCTs included a mixed population-gout and hyperuricemia). Allopurinol (max. dose 300mg), was compared to febuxostat (40-240mg) in 5 RCTs, benzbromarone and probenecid in 2 RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26%), followed by allopurinol (11%), and benzbromarone (4%). The incidence of adverse events was similar between allopurinol (range 38.6 to 85) and febuxostat (range 41.8 to 80). Six patients on febuxostat and 3 on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95% CI: 0.98, 1.11) (Fig. 1). <h3>Image/graph</h3> <h3>Conclusions</h3> Allopurinol is a reasonable safe option, similar or slightly better than other ULDs; although the doses studied may be considered low for some patients. <h3>Disclosure of Interest</h3> I. Castrejon: None Declared, E. Toledano: None Declared, M. P. Rosario: None Declared, E. Loza: None Declared, F. Perez-Ruiz Consultant for: Menarini, Ardea Biosciences, Novartis Pharmaceutical Corporation, Savient, L. Carmona: None Declared
A8.10 MAPK-Activated Protein Kinase-3 (MK3) Regulates Osteoclast Differentiation and Bone Homeostasis
Authors: Tobias Braun, Gisela Ruiz Heiland, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> MAPK-activated protein kinase-2 (MK2) plays a key role in bone homeostasis. MK2 deficient mice have increased bone mineral density associated with reduced number of osteoclasts. Osteoclast differentiation is impaired due to reduced DNA binding activity of the transcription-factors c-fos and NFATc1. MK3 is besides MK2 an important downstream target of MAPK p38. MK3 plays together with MK2 an important role in regulation of cytokine secretion and inflammation. Aim of our study is to determine the role of MK3 and MK3/MK2 interaction in bone homeostasis. <h3>Materials and Methods</h3> We analysed trabecular bone structure of the tibia of 12 week old wild type, MK3 deficient, MK2 deficient and MK2/3 deficient mice by micro CT. Tibiae were decalcified and paraffin sections were stained with tartrate-resistant acid phosphatase (TRAP) to determine osteoclast number/bone perimeter and osteoclast surface/bone surface by histomorphometry. Bone marrow cells of wild type, MK3 deficient, MK2 deficient and MK2/3 deficient mice were simulated with M-CSF and RANKL and stained for TRAP after four days to investigate osteoclast differentiation ex vivo. <h3>Results</h3> Analysis of trabecular bone structure showed increased trabecular volume, increased trabecular number and decreased trabecular separation of MK3 deficient, MK2 deficient and MK2/3 deficient mice compared with wild type. MK3 deficient bones have lower trabecular number and higher trabecular separation than MK2 deficient bone while MK2/3 deficient bones showed the same phenotype than MK2 deficient bones. Number of osteoclasts was reduced in MK3 deficient, MK2 deficient and MK2/3 deficient bones in vivo compared with wild type. Number of osteoclasts was higher in MK3 deficient bones than in MK2 bones, MK2/3 deficient bones showed the same number of osteoclasts than MK2 deficient bones. Ex vivo osteoclast differentiation assay showed reduced osteoclasts number using MK3, MK2 and MK2/3 deficient cells compared with wild type cells. <h3>Conclusions</h3> MK3 deficient mice showed increased trabecular bone volume than wild type mice, but trabecular volume was less increased than in MK2 deficient mice. MK2/3 deficient mice showed no additional effect compared to MK2 deficient mice. Increased trabecular volume was associated with reduced number of osteoclasts due to impaired osteoclast differentiation. Thus MK3 regulated osteoclast differentiation and bone homeostasis but there is no additional effect to MK2.
INTENSITY OF STATIN THERAPY AND CLINICAL OUTCOME AFTER ACUTE MYOCARDIAL INFARCTION FROM THE KOREAN ACUTE MYOCARDIAL INFARCTION REGISTRY
Authors: Jang Hoon Lee, Jae Hee Kim, Se Yong Jang, Sun Hee Park, Myung Hwan Bae, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae
Journal: Journal of the American College of Cardiology (2015)
Abstract 3362: Tumor initiating cells are sensitive to paclitaxel encapsulated in polymeric nanoparticles
Authors: Suresh Kumar Swaminathan, Udaya Toti, Jayanth Panyam
Journal: Cancer Research (2012)

Abstract Tumor initiating cells (TICs) represent a small fraction of tumor cells, and are considered to be key drivers of tumor growth, drug resistance and recurrence. TICs are highly resistant to conventional chemotherapy, possibly due to overexpression of drug efflux transporters and other protective mechanisms. Because drug resistance and tumor relapse are significant problems, approaches to eliminate TICs are urgently needed. Recent studies show that tumor populations that are depleted of TICs demonstrate a return of the TIC sub-population 1 suggesting the possibility of de-differentiation of non-TICs to TICs. We hypothesized that sustained delivery of a cytotoxic agent to the tumor population could potentially reduce TIC fraction and consequently increase the therapeutic effectiveness of chemotherapy. To test this hypothesis, we encapsulated paclitaxel, a microtubule stabilizing agent, in PLGA nanoparticles formulated using an FDA-approved polymer, poly (lactide-co-glycolide). Our previous studies have shown nanoparticles can sustain the intracellular delivery of encapsulated drugs like paclitaxel 2. The effectiveness of nanoparticle-encapsulated paclitaxel in reducing TIC fraction was investigated by standard cancer stem cell assays- mammosphere formation and anchorage-independent growth on soft agar in MCF-7, an ER+ luminal breast cancer cell line. Results obtained in these studies show that drug encapsulated PLGA formulations effectively decreased mammosphere formation and soft-agar colony formation when compared to free drug treatment. In mammosphere assays, paclitaxel solution treatment did not significantly affect the mammosphere formation relative to untreated controls, whereas paclitaxel loaded PLGA nanoparticles treatment decreased the number of mammospheres to 50 ± 33% of untreated controls. In soft-agar colony formation assay, paclitaxel solution treatment increased the number of colonies to 122 ± 10% of untreated controls. In contrast to this, paclitaxel loaded PLGA nanoparticles treatment decreased the number of colonies to 66 ± 8% of untreated controls. Future studies will investigate the effectiveness of these formulations on TICs in mouse models of breast cancer. References 1 Gupta, P. B. et al., Cell 146 (4), 633; Chaffer, C. L. et al., Proc Natl Acad Sci U S A 108 (19), 7950. 2 Patil, Y. B. et al., Biomaterials 31 (2), 358. 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 3362. doi:1538-7445.AM2012-3362
A2.10 The isotype and subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients
Authors: MAM van Delft, MK Verheul, D van der Woude, TWJ Huizinga, REM Toes, LA Trouw
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The presence of auto-antibodies is an important hallmark in Rheumatoid Arthritis (RA). In RA, auto-antibodies can be detected that target post-translationally modified proteins. Next to the well-known anti-citrullinated protein antibodies (ACPA) we have recently identified anti-carbamylated protein antibodies (anti-CarP antibodies). These anti-CarP antibodies are present in 45% of the RA patients and are associated with radiological damage. Anti-CarP is present years before disease onset and predicts the progression to RA in arthralgia patients and healthy blood donors. For better understanding of the antibody response, we determined the anti-CarP isotype and IgG subclass usage in RA patients. <h3>Methods</h3> To investigate the presence of anti-CarP IgM, IgA IgG isotypes and IgG subclasses, serum samples of 373 unselected RA patients, 196 healthy controls and 120 disease controls were collected. ACPA data was available for almost all RA patients The presence of anti-CarP antibodies was determined by ELISA. <h3>Results</h3> Within RA patients, anti-CarP IgM is present in 16.4% of the subjects, while 49.2% and 40.8% are positive for anti-CarP IgG or IgA, respectively. Interestingly, 24% of ACPA negative RA patients display anti-CarP IgA reactivity. Furthermore, we observed reactivity for all anti-CarP IgG subclasses with 50.7% of patients positive for anti-CarP IgG1, 27.1% for IgG2, 8.0% for IgG3 and 27.3% for IgG4. Moreover, we find that the number of anti-CarP isotypes and IgG subclasses in RA patients is associated with anti-CarP antibody levels. In ACPA and anti-CarP double positive patients we observed that the distribution of isotype and subclass usage differs between the two autoantibody reactivities. In addition also the number of anti-CarP isotypes and IgG subclasses is not obviously related to the number of ACPA isotypes and IgG subclasses in IgG double positive patients. <h3>Conclusions</h3> These data show that the anti-CarP antibody response uses a broad spectrum of isotypes and IgG subclasses in RA patients. These data are of relevance for the potential pathological effector mechanisms that can be recruited by the anti-CarP antibody response and possibly the clinical associations associated therewith.
Abstract 2361: The role of thrombomodulin in bladder cancer
Authors: Ann-ann Ding, Wen-Pin Su, Wen-Horng Yang
Journal: Cancer Research (2011)

Abstract Bladder cancer is one of the most common cancers in the United States and Taiwan. We have discovered that thrombomodulin (TM) is up-regulated in bladder cancer patients and cancer cell lines but not in normal cells. TM is an exclusive endothelial cell surface glycoprotein and an important vascular protective molecule that has anticoagulant, anti-inflammatory and anti-apoptotic properties. TM immunohistochemical analysis of tissue microarray from bladder cancer patients of the United States was performed, and we found that TM staining was more pronounced in high grade and muscle invasive cancers. TM expression by western blot have been examined in 10 bladder cancer tissues from Taiwan in comparison to 3 normal bladder tissues, 80% (8/10) of the cancer group were over-expressed while none showed in normal bladder tissues. In a cell model, we knocked down the TM expression in BFTC905 bladder cancer cells (which was a cell line from invasive TCC) by siRNA. The two stable TM knocked-down cells (C6 and E2) showed a lower proliferation rate than BFTC905 wild type cells and vector control cells (D3). TM knocked-down cells (C6 and E2) also had lower migration and invasion abilities than control cells. Furthermore, TM knocked-down cells have a decreased colony number and size in tumor formation assays. By contrast, SV-HUC-1(immortalized human normal urothelial cell line) enhanced the migration and invasion ability by transient over-expression with TM plasmid. In an animal model, the RT-PCR analysis of the ascites from mice with peritoneal inoculation of MBT-2 cells (mouse bladder tumor cell line), we found that TM expression has higher in the group with tumor formation than the group without. These findings suggest that TM may be involved in the tumor progression of bladder cancer. Thus TM could be a bladder cancer prognosis biomarker and also be a therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2361. doi:10.1158/1538-7445.AM2011-2361
Myocardial Salvage after Intracoronary Thrombolysis with Streptokinase in Acute Myocardial Infarction
Authors: John E. Markis, Michael Malagold, J. Anthony Parker, Kenneth J. Silverman, William H. Barry, Ann V. Als, Sven Paulin, William Grossman, Eugene Braunwald
Journal: New England Journal of Medicine (1981)

Nine patients with acute myocardial infarction had cardiac catheterization and intracoronary infusions of streptokinase 2.3 to 4.3 hours (mean, 3.5) after the onset of symptoms. Occluded coronary arteries were opened within approximately 20 minutes in all patients, but reocclusion occurred in one patient. The immediate effect of thrombolysis on myocardial salvage was assessed with the intracoronary injection of thallium-201. Improved regional perfusion, indicating myocardial salvage after recanalization, was observed in seven of the nine patients. One patient, who had also sustained a nontransmural infarction one week before, had no change after thrombolysis. In the ninth patient, recanalization of a coronary artery was followed by reocclusion and worsening of the myocardial-perfusion defect. Intracoronary thallium-201 studies two weeks and three months after streptokinase infusion in two patients were unchanged in comparison with scintiscans performed 1.5 hours after thrombolysis. These short-term observations suggest that recanalization of obstructed coronary arteries after intracoronary thrombolysis can salvage jeopardized myocardium. However, evaluation of the long-term effects of this procedure on survival and myocardial function will require controlled clinical trials. (N Engl J Med. 1981; 305:777–82.)
FRI0331 Apremilast for the treatment of behçet’s syndrome: a phase ii randomized, placebo-controlled, double-blind study
Authors: G. Hatemi, M. Melikoglu, R. Tunc, C. Korkmaz, B. T. Ozturk, C. Mat, P. A. Merkel, K. T. Calamia, Z. Liu, L. Pineda, R. M. Stevens, H. Yazici, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mucocutaneous manifestations of Behçet's syndrome (BS) can be resistant to conventional treatment and at times disabling. Apremilast (APR), an oral phosphodiesterase 4 inhibitor, modulates inflammatory pathways. <h3>Objectives</h3> To investigate the efficacy of APR in BS patients with active oral ulcers (OU). <h3>Methods</h3> Patients with BS without major organ involvement but ≥2 OU were randomized to APR 30 mg BID or PBO for 12 wks followed by a 12-wk active-treatment period for all patients and a 28-day post-tx observational follow-up. Primary endpoint was number of OU at wk 12. Secondary endpoints included number of genital ulcers (GU) at wk 12, efficacy over time (AUC for OU and and GU, first 12 wks), and AEs. <h3>Results</h3> 111 patients (mean age 34.5±10.1 years, 69% women) were randomized (55 APR, 56 PBO) and 95 completed treatment phase (50 APR, 45 PBO). At wk 12, significantly more patients in APR group had a complete response in OU (71% [39/55], APR; 29% [16/56], PBO; p&lt;0.0001). Mean (±SD) number of OU at wk 12 was 0.5±1.03 with APR and 2.1±2.58 with PBO (p&lt;0.0001). Figure shows the mean number of OU over time. Beneficial effect of APR on OU continued in open phase but disappeared once drug was stopped at wk 24. Improvement in OU pain was significantly higher with APR (-44.7±24.30 vs -16.0±32.54; p&lt;0.0001). In pts with GU at baseline, 10/10 in APR had no GU at wk12 vs 3/6 had no GU in PBO (p= 0.04). Serious AEs were 1 diplegia, transient and not thought to be related to APR, 1 anal fissure, and hemorrhoids with APR while 2 disease flares and 1 fever episode with PBO. <h3>Image/graph</h3> <h3>Conclusions</h3> APR was effective in the treatment of OU, the cardinal manifestation of BS, with an acceptable safety profile. There were also indications of efficacy in treating GU, a highly specific lesion for BS. Further trials are warranted to test the efficacy of APR for other manifestations of BS. <b>Disclosure of Interest</b>: G. Hatemi: None Declared, M. Melikoglu: None Declared, R. Tunc: None Declared, C. Korkmaz: None Declared, B. Ozturk: None Declared, C. Mat Paid instructor for: Celgene, P. Merkel Grant/research support from: Celgene, K. Calamia: None Declared, Z. Liu Employee of: Celgene, L. Pineda Employee of: Celgene, R. Stevens Shareholder of: Celgene, Employee of: Celgene, H. Yazici: None Declared, Y. Yazici Grant/research support from: Celgene, Consultant for: Celgene
Massive Pelvic Lymphadenopathy Due to Recurrent Non-Hodgkin Lymphoma Incidentally Revealed on a 99mTc-MDP Bone Scintigraphy
Authors: Jianmin Huang, Peng Xie
Journal: Clinical Nuclear Medicine (2016)

A 58-year-old man underwent Tc-MDP bone scintigraphy to evaluate the cause of diffuse bone pain. The images did not identify the exact cause of his symptoms. However, a "light bulb"-shaped urinary bladder and diffused increased activity in the scrotal region and left thigh were noted, which suggest a mass effect in the pelvis. A CT scan of the pelvis revealed soft tissue compressing the urinary bladder. A diagnosis of recurrent lymphoma was made.
99mTc-HYNIC-TOC (99mTc-Hydrazinonicotinyl-Tyr3-Octreotide) Scintigraphy Identifying Two Separate Causative Tumors in a Patient With Tumor-Induced Osteomalacia (TIO)
Authors: Hongli Jing, Fang Li, Dingrong Zhong, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2013)

Tumors that cause osteomalacia are generally benign fibroblast growth factor-23 producing mesenchymal tumors which can be detected by octreoscan. A 45-year-old man underwent (99m)Tc-HYNIC-TOC scan to detect a possible culprit causing osteomalacia. The images showed abnormal activity in the left humerus and in the right foot. The lesion of the right foot was confirmed pathologically as phosphaturic mesenchymal tumor. After surgical removal of the tumor in the right foot, the patient's symptoms were promptly improved. However, the improvement was transient due to the unresected tumor in the left humerus.