Assessment of Takayasu arteritis in routine practice with PETVAS, an 18F-FDG PET quantitative scoring tool.

BACKGROUND: The aim of this study was to evaluate the value of the PET vascular activity score (PETVAS) during the follow-up of patients with Takayasu arteritis. METHODS: Takayasu arteritis patients who underwent 18F-Fluorodeoxyglucose (FDG) PET imaging were evaluated retrospectively. In 8 patients both 1 and 2-h imagings were also performed prospectively. For PETVAS, 9 arterial areas were scored between 0-3 according to the FDG uptake. RESULTS: Forty-six images of 34 patients were evaluated. PETVAS was higher in patients with clinically active disease (p = 0.03) and in the C-reactive protein (CRP) elevated group among clinically inactive patients (p = 0.0015). PETVAS correlated with CRP (p = 0.003, r = 0.53) and erythrocyte sedimentation rate (p = 0.005, r = 0.41), whereas age, disease duration, immunosuppressive, and glucocorticoid (GC) treatments were not associated with PETVAS. First vs. 2nd-h PETVAS was similar in patients who had both 1st and 2nd h PET scans (p = 0.67). DISCUSSION: We observed higher PETVAS in patients with active disease and elevated acute phase reactants. Although scores in our study (performed at one-h) were lower compared to the original PETVAS study performed at two h, PETVAS seems to be a reliable tool to quantify FDG PET scores in routine practice.

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

PURPOSE: Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients. METHODS: Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated. RESULTS: MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m2, p 0.004]. ROC curve analysis showed NT-pro-BNP > 58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536-0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010-1.370), p 0.039] and NT-pro-BNP > 58 pg/ml [OR (95% CI): 5.5 (1.02-30.1) p 0.047] were independent predictors of MetS in AAV patients. CONCLUSION: MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

Nationwide Experience With Off-Label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients.

OBJECTIVE: Approximately 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. METHODS: In 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. RESULTS: In 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. CONCLUSION: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

Impaired quality of life, disability and mental health in Takayasu's arteritis.

OBJECTIVE: Patient-reported outcomes (PROs) are increasingly accepted to be among the major tools for outcome assessment in rheumatic disorders. In this study we aimed to assess quality of life (QoL), disability, anxiety and depression in patients with Takayasu's arteritis (TAK). METHODS: Patients followed with the diagnosis of TAK (n = 165) and healthy controls (HCs) (n = 109) were enrolled to the study. The 36-item Short Form Health Survey (SF-36) and hospital anxiety and depression scales (HADS) were used to assess QoL and mental status together with HAQ for disability. RESULTS: In SF-36 subscale assessment, all items were observed to be statistically lower in TAK patients; similarly HAQ scores were also higher (P < 0.001) in this group. In mental assessment, anxiety was found to be more common in TAK patients [90 (54.5%) vs 38 (34.9%), P = 0.001]. Depression also tended to be higher in TAK patients [70 (66.7%) vs 35 (33.3%)], without reaching significance (P = 0.086). Most of the SF-36 subgroup parameters were lower in TAK patients with active disease. Patients having anxiety and depression or with high HAQ scores reported worse SF-36 scores. In multivariate analysis, HADS-A, HADS-D and HAQ were associated with most SF-36 subscales. CONCLUSION: PROs demonstrate that not only general health but also physical and social functioning with physical role limitations and mental health parameters were impaired in TAK. Our results, especially in active disease, suggest that PROs such as SF-36 can be core domains of disease assessment in TAK, similar to ANCA-associated vasculitides.

Vascular endothelial function assessed by a noninvasive ultrasound method and serum asymmetric dimethylarginine concentrations in mild-to-moderate plaque-type psoriatic patients.

OBJECTIVES: Our aim was to evaluate vascular endothelial function assessed by serum asymmetric dimethylarginine (ADMA) concentrations and noninvasive ultrasonographic parameters such as flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) in mild-to-moderate plaque-type psoriatic patients, as rated by the Psoriasis Area and Severity Index. DESIGN AND METHODS: Plaque-type psoriatic patients (n = 29) diagnosed with clinical and/or histopathological findings and control subjects (n = 25) without skin and systemic metabolic diseases were included in the study. RESULTS: There was no statistically significant difference between patients and control subjects in respect to FMD (p = 0.441), NID (p = 0.557), or serum ADMA concentrations (p = 0.225). Also, among the acute-phase reactants, serum C-reactive protein and plasma fibrinogen levels were moderately higher in patients when compared to control subjects (p = 0.008 and p = 0.011, respectively). CONCLUSIONS: Mild-to-moderate plaque-type psoriatic patients with low-to-medium grade systemic inflammation did not have evidence of vascular endothelial function.

Evaluation of ventricular functions using tissue Doppler echocardiography in patients with subclinical hypothyroidism.

OBJECTIVES: We evaluated right (RV) and left (LV) ventricle functions by tissue Doppler imaging (TDI) in patients with subclinical hypothyroidism (SH). STUDY DESIGN: Twenty-seven patients (24 women, 3 men; mean age 35.4±11.4 years) with newly diagnosed SH and 22 age- and sex-matched healthy subjects (20 women, 2 men; mean age 34.8±8.6 years) were evaluated by standard echocardiography and TDI. The diagnosis of SH was based on increased serum thyrotropin (TSH) level in the presence of normal free T3 and free T4 levels. The following TDI-derived parameters were measured: isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (S), and diastolic indices including peak early (E') and late (A') diastolic velocities, E'/A' and E/E' ratios, and myocardial performance index. RESULTS: Compared to healthy controls, patients with SH had higher LV mitral A velocity (p=0.022), lower E/A ratio (p=0.021), lower E' velocity (p=0.019), and higher E/E' ratio (p=0.017), suggesting significant LV diastolic dysfunction. The patient group also had lower IVV (p=0.004) and IVA (p<0.001), and higher isovolumic contraction time (p=0.012), suggesting LV subclinical systolic dysfunction. For RV parameters, decreased E/A ratio (p=0.014) and E' velocity (p=0.028) and increased isovolumic relaxation time (p=0.003) in SH patients were consistent with RV diastolic dysfunction, whereas parameters of RV systolic function were similar in the two groups. Myocardial performance indices of both ventricles were also significantly higher in the patient group (p<0.05). CONCLUSION: Our data suggest that SH is associated with biventricular systolic and diastolic dysfunction.

Evaluation of the effect of L-thyroxin therapy on cardiac functions by using novel tissue Doppler-derived indices in patients with subclinical hypothyroidism.

OBJECTIVES: Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (fT4), free T3 (fT3) levels and increased serum thyroid stimulating hormone (TSH) levels.The aim of this study was to assess the validity of tissue Doppler imaging (TDI) in evaluating cardiac effects of SH and to demonstrate the improving effects of L-thyroxin(L-T4) on TDI parameters. METHODS: Twenty-seven patients with SH and 22 healthy controls were evaluated by standard echocardiography and TDI. TDI-derived systolic velocities [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IW), peak systolic velocity during ejection period (Sa)] and diastolic indices (peak early (Ea) and late diastolic (Aa) velocities, Ea/Aa, E/Ea ratios and Tei index) were measured. After restoring euthyroidism, all measurements were repeated. RESULTS: At baseline, left ventricular (LV) systolic velocities (IW and IVA) and diastolic indices were significantly impaired in the SH group. After L-T4 therapy, left ventricular systolic and diastolic functions were improved. Right ventricular (RV) systolic velocities were similar between the study group and the healthy controls but diastolic functions were impaired in the SH group, at baseline. Tei index of the RV was improved after L-T4 therapy. RV IVA remained unchanged after hormone replacement therapy. CONCLUSIONS: SH is associated with biventricular systolic and diastolic dysfunction. IVA which is an accurate estimate of subclinical systolic dysfunction, was significantly impaired in the left ventricle and had improved after L-T4 therapy. We found that IVA is able to detect early effects of subclinical hypothyroidism on LV systolic functions and L-T4 therapy can improve ventricular functions.

Evaluation of oxidative stress, the activities of paraoxonase and arylesterase in patients with subclinic hypothyroidism.

INTRODUCTION: In subclinical hypothyroidism (SH), serum lipid and lipoprotein concentrations are frequently changed. Compared to the normal population, the levels of oxidized low-density lipoprotein (LDL) cholesterol are higher and the levels of high density lipoprotein (HDL) cholesterol are lower. In SH patients, the mechanism of atherosclerosis may be attributed to the lipid abnormalities. There is evidence showing that, oxidation plays an important role during the process of atherosclerosis, preventing the lipid peroxidation of paraoxonase 1 and thereby, acting against the atherosclerosis. In this study, we evaluated the activity of paraoxonase and arylesterase in subclinical hypothyroidism and investigated its relation with oxidative stress. METHOD: The study enrolled 25 cases with SH and 20 healthy controls. The patient group and the control group were compared in terms of the activity of paraoxonase and arylesterase and the oxidative stress index. RESULTS: Between two groups, no significant difference was found in terms of age, gender, total cholesterol, low-molecular weighted lipoprotein, high-molecular weighted lipoprotein. In SH group, the activity ofparaoxonase was significantly lower than that observed in the control group (p=0.01). Also, the activity of arylesterase was significantly lower in the group with subclinical hypothyroidism (p=0.03). Oxidative stress index was found to be significantly higher in the group with subclinical hypothyroidism compared to the healthy controls (p<0.01). Oxidative stress index showed a strong positive correlation with the levels of TSH in all cases (r=0.60, p<0.01. CONCLUSION: Consequently, in SH, the activity of paraoxonase and arylesterase were significantly low and oxidative stress was significantly high. Lower activities ofparaoxonase and arylesterase indicated increased oxidative damage in SH. This may be useful to elucidate the mechanism of atherosclerosis in SH. In addition, these findings suggested that the activities of paraoxonase and arylesterase may be used for the determination of therapeutical response and during the follow-up. (www.actabiomedica.it).