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Tezcan, Mehmet Engin/0000-0002-1753-4936; TUFAN, Abdurrahman/0000-0001-6244-9362; SARI, Ismail/0000-0001-7737-4180; YILMAZ, Sedat/0000-0002-4691-3417 WOS: 000436403100017 PubMed: 28992387 ObjectiveApproximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients. MethodsIn all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed. ResultsIn total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced. ConclusionAnti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

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 × 10−9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10−8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 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 × 10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 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.

WOS: 000434417500008, PubMed ID: 29879318, ObjectiveThe potential side effects of biological agents may increase the anxiety levels of patients and influence not only their desire to use these therapies but also their concordance to treatment. This study aimed to determine the level and prevalence of drug-related concern in patients treated with biological agents and to acquire additional information regarding the related causes. Materials and MethodsA total of 1134 patients who were using biological agents for at least 3months with a diagnosis of rheumatic diseases were enrolled. General anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI). ResultsThe most common cause for drug-related concerns was the potential side effects of the drugs (59.5%). Among the potential side effects, cancer risk was the most common cause for concern (40.1%), followed by the risk of tuberculosis activation (30.7%). Anxiety levels were higher in patients who experienced side effects than in other patients, and this difference was statistically significant (P

Vemurafenib is an inhibitor of the BRAF V600E mutation which is associated with tumor responses in patients with metastatic melanoma. Although it is generally well tolerated, common side effects of vemurafenib have been reported. Arthralgia is one of the more common adverse event associated with vemurafenib. We herein report a 49-year-old woman diagnosed with metastatic melanoma harboring the BRAF V600E mutation with severe polyarthritis associated with vemurafenib after 7 days of treatment. Sonographic examination of affected joints revealed synovitis and the patient's articular symptoms were improved by analgesic and anti-inflammatory treatment, including corticosteroids. During therapy with selective BRAF inhibitors, arthritis represents a new adverse event that can require dose reduction. In case of this adverse event, treatment with anti-inflammatory drugs, such as ibuprofen and prednisone, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression.

BACKGROUND Obesity is associated with heart failure, cardiovascular morbidity, and mortality. A direct effect of weight on left ventricle (LV) structure and myocardial function is not well-established. AIM The aim of our study is to determine the effect of obesity on LV morphology and systolic function by using LV standard Doppler echocardiographic indices, myocardial Doppler imaging and strain/strain rate imaging indices. METHODS We studied 33 obese and 34 age, sex-adjusted control subjects who had no other pathological conditions. Standard transthoracic Doppler echocardiographical measurements, reconstructed spectral pulsed wave tissue Doppler velocities, strain and strain rate imaging of six different myocardial regions were obtained. Peak systolic velocity (SR), peak systolic strain (I), peak systolic strain rate (SR) for each region and as a global systolic longitidunal LV function mean of peak systolic strain of six myocardial regions (glsca) were compared. RESULTS Age, body surface area, blood pressure, and heart rate were comparable between the two groups. Obese subjects had significantly increased LV end-diastolic volume, septal wall thickness, left atrial diameter, and decreased transmitral early to late diastolic velocity ratio. In obese subjects, reconstructed spectral pulsed-wave tissue Doppler analysis showed significantly decreased basal lateral peak systolic (Sm) velocity (6.68 +/- 1.89 vs. 8.08 +/- 2.50, P < 0.05), mid lateral Sm (5.01 +/- 2.17 vs. 6.78 +/- 3.22, P < 0.05). Differences in regional strain rate (mid septal SR, 1.45 +/- 0.23 vs. 1.63 +/- 0.18, P < 0.05), regional strain (basal septum I, 19.13 +/- 3.83 vs. 22.09 +/- 4.60, P < 0.05; mid-septum I, 18.03 +/- 2.91 vs. 20.25 +/- 4.77, P < 0.05; radial I, 27.50 +/- 7.32 vs. 35.53 +/- 9.48, P < 0.05), and global strain (glsca, 19.38 +/- 1.34 vs. 21.24 +/- 2.82, P < 0.05) were identified between obese and the referent subjects. CONCLUSIONS Obesity is associated with morphologic alterations in left ventricle and left atrium and subclinical changes in left ventricle systolic function which can be detected by strain and strain rate imaging even without overt heart disease.