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Objective. To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. Methods. Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. Results. Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. Conclusion. The new 2012 EULAR/ ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

Background: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. Methods: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritic, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. Results: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. Conclusion: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD. (C) 2016 Elsevier Ltd. All rights reserved.

Purpose Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is, 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. Patients and Methods A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. Results In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. Conclusion Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival. (C) 2016 by American Society of Clinical Oncology

Background/Aim: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. Materials and Methods: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. Results: There were marked increases in the CC genotype (94.7% vs 81.8%, p

Congress of the European-Academy-of-Allergy-and-Clinical-Immunology -- JUN 06-10, 2015 -- Barcelona, SPAIN Bavbek, Sevim/0000-0002-7884-0830 WOS: 000369950701148 … European Acad Allergy & Clin Immunol

WOS: 000208898501295, …

Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-α and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals.

Objective. Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods. Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results. We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 x 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 x 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 x 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 x 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 x 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion. Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Vascular involvement is one of the major causes of mortality and morbidity in Behcet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n-936, female/male: 347/589, mean age: 37.6 ± 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired. VBD was observed in 27.7% (n - 260) of the patients during followup. In 57.3% of the VBD patients, vascular involvement was the presenting sign of the disease. After the first vascular event, ISs were given to 88.8% and AC treatment to 59.8% of the patients. Median duration of AC treatment was 13 months (1-204) and ISs, 22 months (1-204). Minor hemorrhage related to AC treatment was observed in 7 (4.7%) patients. Asecond vascular event developed in 32.9% (n=86) of the patients. The vascular relapse rate was similar between patients taking only ISs and AC plus IS treatments after the first vascular event (29.1% vs 22.4%, P=0.28) and was significantly higher in group taking only ACs than taking only ISs (91.6% vs 29.1%, P

In a penciling-induced epilepsy model, Wistar rats (16 males, 16 females) were i.p. administered by an extract of Salvia miltiorrhiza (SmE; total dose 50mg/kg) once a day, during 15 days. The rats were divided into four equal groups, control and SmE-treated for each sex. After the treatment period, an epilepsy model was produced by penicillin G (500 IU) injection into the motor cortex; the electrocorticogram (EcoG) was recorded for 120 min, and statistical analysis was performed. In the male control group with penicillin-induced epilepsy, the spike frequency was significantly (P < 0.05) higher than that in the female control group. The frequency values have been significantly (P < 0.01) increased within the observation period in the female SmE-treated group, while the respective values significantly (P < 0.05) decreased in the analogous male group. There were insignificant differences in the amplitude values and latency to onset of the spike/wave events between female/male SmE and female/male control groups (P > > 0.05). Thus, the SmE exerts anticonvulsant effects in the male rat group, while its effect should be characterized as proconvulsant in the female group in penicillin-induced epilepsy model. The difference (related to the presence of estrogen analogs in the SmE) is determined by dissimilar hormonal backgrounds in males and females. The SmE may be considered the base for development of anticonvulsant drugs for clinical therapy of epilepsy in the future. В умовах моделювання епілептичної активності (індукція інтракортикальним уведенням пеніциліну) щурам лінії Вістар (16 самців і 16 самиць) уводили екстракт шавлії (Salvia miltiorrhiza extract, SmE, загальна доза 50 мг/кг, щоденні ін’єкції протягом 15 діб). Щури були поділені на чотири рівні групи – контрольні та піддані ін’єкціям SmE самці та самиці. Після періоду введень екстракту епілептиформна активність індукувалась уведенням (500 МО) пеніциліну G у моторну кору, після чого відводили електрокортикограму (EКoГ) протягом 120 хв та піддавали її статистичному аналізу. В контрольній групі самців частота в ЕКоГкомплексах пік–хвиля була вірогідно вищою (P < 0.05), ніж така в контрольній групі самиць. Значення частоти істотно зростали (P < 0.01) у групі самиць котрим уводили SmE, тоді як відповідні значення в аналогічній групі самців вірогідно зменшувалися (P < 0.05). Не було виявлено істотних відмінностей між середніми значеннями амплітуд комплексів пік–хвиля та латентних періодів виникнення таких комплексів у групах самиць та самців, котрим уводили SmE, та аналогічних контрольних груп самиць і самців (P > 0.05). Отже, SmE проявляє протисудомні впливи в умовах пеніцилінової моделі епілепсії в групі самцівщурів, тоді як у групі самиць ефекти мають кваліфікуватись як просудомні. Різниця в характері впливів, зумовлена наявністю аналогів естрогенів у SmE, визначається різним гормональним фоном у самиць і самців. SmE може розглядатись як основа для розробки антиконвульсантних засобів для терапії епілепсії в майбутньому.

Vascular involvement is one of the major causes of mortality and morbidity in Behcet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n = 936, female/male: 347/589, mean age: 37.6 +/- 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired.