Is ultra low-dose CT with tin filtration useful for examination of SI joints? Can it replace X-ray in diagnostics of sacroiliitis?

OBJECTIVES: The first objective of our study was to determine the radiation exposure received by patients during tin-filtrated ultra-low-dose computed tomography (TFULDCT) of sacroiliac joints and to compare those to conventional X-ray doses. For comparison, we added a cohort examined by low-dose CT (LDCT) without tin filtration. The second objective was to compare the results of TFULDCT and X-ray in the detection of sacroiliitis. METHODS: Our retrospective study covered 45 patients, who were examined for suspected axial spondyloarthritis (AxSpA). The first group underwent TFULDCT as well as conventional radiography (CR); the second group underwent LDCT only without tin filtration. Effective doses of TFULDCT, LDCT and CR were calculated by an experienced medical physicist. TFULDCT and CR were independently evaluated by three investigators, who decided on the presence or absence of rheumatoid inflammatory bone changes. The results were statistically evaluated. RESULTS: In our cohort, the median effective dose for TFULDCT was 0.11 mSv, range (0.06-0.40 mSv), for LDCT 0.5 mSv (0.29-0.89 mSv), and for CR 0.25 mSv (0.06-1.87 mSv). We proved that TFULDCT produces a significantly lower percentage of uncertain results (23.3%; 95% CI: 11.3-41.6%) than CR (66.7%; 95% CI: 48.3-81.1%). CONCLUSIONS: Tin filtration helps to reduce CT radiation exposure to values lower than those resulting from CR. TFULDCT offers better overall diagnostic performance than CR. Our results prove that TFULDCT can replace CR in the diagnosis of sacroiliitis in the radiographical stage of AxSpA.

Myocardial Involvement Detected Using Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis: A Prospective Observational Study.

INTRODUCTION AND OBJECTIVES: Cardiac involvement in systemic sclerosis (SSc) patients affects mortality. Cardiac magnetic resonance (CMR) is capable of detecting structural changes, including diffuse myocardial fibrosis that may develop over time. Our aim was to evaluate myocardial structure and function changes using CMR in patients with SSc without known cardiac disease during a 5-year follow-up and find possible correlations with selected biomarkers. METHODS: A total of 25 patients underwent baseline and follow-up CMR examinations according to a pre-specified protocol. Standard biochemistry, five biomarkers (hsTnI, NT-proBNP, galectin-3, sST2, and GDF-15), and disease-specific functional parameters enabling the classification of disease severity were also measured. RESULTS: After five years, no patient suffered from manifest heart disease. Mean extracellular volume (ECV) and T1 mapping values did not change significantly (p ≥ 0.073). However, individual increases in native T1 time and ECV correlated with increased galectin-3 serum levels (r = 0.56; p = 0.0050, and r = 0.71; p = 0.0001, respectively). The progression of skin involvement assessed using the Rodnan skin score and a decrease in the diffusing capacity of the lungs were associated with increased GDF-15 values (r = 0.63; p = 0.0009, and r = -0.51; p = 0.011, respectively). CONCLUSIONS: During the 5-year follow-up, there was no new onset of heart disease observed in patients with SSc. However, in some patients, CMR detected progression of sub-clinical myocardial fibrosis that significantly correlated with elevated galectin-3 levels. GDF-15 values were found to be associated with disease severity progression.

Uricemia in the acute phase of myocardial infarction and its relation to long-term mortality risk.

Aim: Although uric acid has antioxidant effects, hyperuricemia has been established as an indicator of increased cardiovascular mortality in various patient populations. Treatment of asymptomatic hyperuricemia in patients with acute myocardial infarction (MI) is not routinely recommended, and the efficacy of such treatment in terms of cardiovascular risk reduction remains doubtful. Materials & methods: In a prospective cohort study, we followed 5196 patients admitted for a MI between 2006 and 2018. We assessed the relationship between baseline uricemia and the incidence of all-cause death and cardiovascular mortality and the effect of long-term allopurinol treatment. Hyperuricemia was defined as serum uric acid >450 µmol/l in men and >360 µmol/l in women. Results: In the entire cohort, the 1-year all-cause and cardiovascular mortality rates were 8 and 7.4%, and the 5-year rates were 18.3 and 15.3%, respectively. Using a fully adjusted model, hyperuricemia was associated with a 70% increased risk of both all-cause death and cardiovascular mortality at 1 year, and the negative prognostic value of hyperuricemia persisted over the 5-year follow-up (for all-cause death, hazard risk ratio = 1.45 [95% CI: 1.23-1.70] and for cardiovascular mortality, hazard risk ratio = 1.52 [95% CI: 1.28-1.80], respectively). Treatment of asymptomatic hyperuricemia with allopurinol did not affect mortality rates. Conclusion: Hyperuricemia detected in patients during the acute phase of an MI appears to be independently associated with an increased risk of subsequent fatal cardiovascular events. However, hyperuricemia treatment with low-dose allopurinol did not prove beneficial for these patients.

[Chronic pain therapy in inflammatory rheumatic diseases]. / Lécba chronické bolesti u zánetlivých revmatických onemocnení.

Chronic pain is a common health problem related to most of inflammatory rheumatic disorders. It is pain that has persisted for at least 3 month and cannot be fully relieved by standard pain medication. 40-60 % of patients do not have adequate relief of their pain. Paramount in the management of chronic pain patients is assessment of the pain and its impact on physical and psychosocial functioning. Multidisciplinary and multimodal approach is of vital importance. Non-steroidal anti-rheumatic drugs (NSA) have been used mainly due to their strong analgesic effect, especially in the treatment of acute pain as well as their anti-inflammatory effect in the treatment of chronic i pain. Long-term systemic administration of NSA may be associated with a number of serious side effects, which significantly limit NSA use in long term therapy. Due to opiophobia, opioids are insufficiently used treatment modality. Knowledge about pain and its management, as well as an awareness of barriers to effective pain therapy, are important not only for pain specialists but also primary care physicians.Key words: chronic pain - non-steroidal antirheumatic drugs - opiophobia - opioids - pain assessment - paracetamol - rheumatoid arthritis.

Mapping Quality of Life (EQ-5D) from DAPsA, Clinical DAPsA and HAQ in Psoriatic Arthritis.

BACKGROUND: Clinical trials and observational studies lacking measures of health-related quality of life (QoL) are often inapplicable when conducting cost-effectiveness analyses using quality-adjusted life-years (QALYs). The only solution is to map QoL ex post from additionally collected clinical outcomes and generic QoL instruments. Nonetheless, mapping studies are absent in psoriatic arthritis (PsA). METHODS: In this 2-year, prospective, multicentre, non-interventional study of PsA patients, EQ-5D and key clinical parameters such as Disease Activity in PsA (DAPsA), clinical DAPsA (cDAPsA; DAPsA without C-reactive protein [CRP]), and Health Assessment Questionnaire disability index (HAQ) were collected. We employed a linear mixed-effect regression model (ME) of the longitudinal dataset to explore the best predictors of QoL. RESULTS: A total of 228 patients were followed over 873 appointments/observations. DAPsA, cDAPsA and HAQ were stable and highly significant predictors of EQ-5D utilities in both cross-sectional and longitudinal analyses. The best prediction was provided using a linear ME with HAQ and cDAPsA or DAPsA. A HAQ increase of 1 point represented a decrease in EQ-5D by -0.204 or -0.203 (p < 0.0001); a one-point increase in cDAPsA or DAPsA dropped EQ-5D equally by -0.005 (p < 0.0001). The ME revealed steeper and more accurate association compared with cross-sectional regressions or non-linear models/transformations. CONCLUSIONS: This is the first mapping study conducted in PsA and we hope that our study will encourage further mapping studies in PsA. The results showed that in cases where CRP is absent, cDAPsA provides similar results to DAPsA in predicting QoL.

Myocardial fibrosis detected by magnetic resonance in systemic sclerosis patients - Relationship with biochemical and echocardiography parameters.

OBJECTIVES: Systemic scleroderma (SSc) is a rare connective tissue disease presenting with fibrosis affecting skin and internal organs. Cardiovascular magnetic resonance (CMR) with quantification of extracellular volume (ECV) and T1 mapping might help to detect heart involvement. We aimed to evaluate whether myocardial involvement correlates with functional and laboratory parameters. METHODS: Thirty-three asymptomatic SSc patients (29 women, aged 56.6±12.2years) and 20 controls (10 women, 53.7±13.1years) were examined using CMR, echocardiography, functional pulmonary test and laboratory assessment. RESULTS: SSc patients had higher ECV (27.5±2.8 vs. 22.8±1.9%, P<0.0001) and native T1 values (1258.9±51.2 vs. 1192.2±32.6, P<0.0001) compared to controls. Plasma level of growth differentiation factor 15 (GDF-15) and galectin-3 correlated with ECV (r=0.35; P=0.0076 and r=0.38; P=0.0081) and native T1 (r=0.31; P=0.023 and r=0.35; P=0.012). GDF-15 was also negatively correlated with diffusing capacity of the lung for carbon monoxide (r=-0.58; P=0.0004) and positively correlated with modified Rodnan skin score (r=0.59; P=0.0003). Conventional echocardiography parameters were similar in SSc patients and controls. However, the global longitudinal peak systolic strain (GLPS) was lower in SSc patients compared to controls (18.6±1.6 vs. 21.1±1.2%; P<0.0001). GLPS also negatively correlated with native T1 (r=-0.35; P=0.0097), ECV (r=-0.33; P=0.014), GDF 15 (r=-0.31; P=0.022), and galectin-3 (r=-0.37; P=0.0076). CONCLUSIONS: Asymptomatic heart involvement is common in SSc patients and includes focal and diffuse myocardial fibrosis. GDF-15 and galectin-3 were positively correlated with myocardial fibrosis parameters. Future outcome studies must show whether measurement of GDF-15 and galectin-3 in SSC patients might be may be useful in clinical practice.

Mapping the relationship between clinical and quality-of-life outcomes in patients with ankylosing spondylitis.

AIM: To map health-related quality of life (Qol) with clinical parameters BASFI and ASDAS-CRP measure, and other covariates. METHODS: Our prospective multicenter non-interventional observation study of ankylosing spondylitis (AS) collected data about QoL and clinical outcomes on the initial and four subsequent visits. We employed simple linear regression analysis of a cross-sectional dataset, and fixed effect, random effect and pooled linear regression of a longitudinal dataset. RESULTS: We showed that BASFI and ASDAS-CRP are very strong, robust predictors of EQ-5D utilities in all regression specifications together with sex (female), invalidity, and activity impairment. Additionally, the longitudinal regression analysis showed that a fixed effect model may be a viable alternative to the most commonly used random effect model or pooled linear regression due to the nature of our dataset. CONCLUSION: This is one of the first studies using a fixed effect model in longitudinal patient-level data, although, this method has been widely used in economics.

Relationship between hsTnI and coronary stenosis in asymptomatic women with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a condition associated with accelerated progression of atherosclerosis in affected individuals. Myocardial assessment using exercise testing in such patients, however, is often difficult to perform. Our objective was to determine the factors associated with severe coronary stenosis using computed tomography (CT) angiography of the coronary arteries in asymptomatic patients with RA. METHODS: Forty-four women with RA were examined using CT angiography to detect atherosclerotic involvement and significant coronary stenosis (>50 %). CT findings were correlated with the cardiovascular risk score, and with classical and most recent parameters of atherosclerosis. RESULTS: CT angiography of the coronary arteries revealed severe stenosis (>70 %) in 9 % of patients. High-sensitivity troponin I level was associated with severe coronary stenosis (odds ratio 6.37; 95 % confidence interval 1.53 - 26.48; P = 0.011). Adjustment for confounders did not alter this result (P = 0.039). In contrast, classical and modified Systemic Coronary Risk Evaluation scores had no value in predicting severe stenosis (P ≥ 0.49). CONCLUSION: The present study showed the possible benefits of a coronary CT angiography in women with RA and asymptomatic ischemic coronary heart disease. Increased levels of high-sensitivity troponin I may be a potential indication for this type of examination. However, further studies are needed to confirm these results.

Incidence of severe coronary stenosis in asymptomatic patients with peripheral arterial disease scheduled for major vascular surgery.

BACKGROUND: Peripheral arterial disease (PAD) has the risk equivalent of coronary heart disease. The biochemical parameters associated with functionally significant coronary artery stenosis were investigated in asymptomatic patients with PAD who were scheduled for major vascular intervention. METHODS: A total of 50 PAD patients asymptomatic for coronary heart disease were examined using coronary computed tomography angiography (CTA). A stress myocardial CT perfusion (CTP) test was performed in patients who exhibited coronary stenosis >40%. In patients with stress-induced perfusion defects, the severity of stenosis was assessed using invasive coronary angiography including fractional flow reserve assessment. The CT findings were correlated with both classical and more recently developed parameters of atherosclerosis. RESULTS: According to the combined CT examination (CTA and stress CT perfusion), 36% of patients exhibited significant coronary stenosis. Stress-induced hypoperfusion was observed in 95.7% of severe stenotic lesions. After adjustment for confounders, the level of high-sensitivity troponin I was associated with severe coronary stenosis (OR 1.260 [95% CI 1.054 to 1.505]). Other biochemical parameters did not correlate with coronary stenosis. The annual mortality rate was 4%. CONCLUSIONS: The results of the present study confirm a significant diagnostic contribution of a complex cardiac CT examination in patients scheduled for major vascular surgery. A high prevalence of asymptomatic coronary heart disease was observed in this particular patient group. High-sensitivity measurements of troponin I correlated with the extent of the coronary stenosis.

Incidentally diagnosed melorheostosis of upper limb: case report.

BACKGROUND: Melorheostosis is quite a rare bone disease with still unclear ethiology. Although multifocal affection is highly debilitating with unfavorable prognosis, there is no clear consensus about therapeutical approach. There is still insufficient evidence in the literature for almost a century after the first description. Affected bone has a typical appearance of melting wax. Diagnosis is usually incidental with pain as a leading symptom. Diagnosis itself is relatively easy, routine X-ray examination is sufficient. Even though it could be easily overlooked and mistaken with other diseases. Melorheostosis is incurable, the therapy is mostly focused on maintaining patient quality of life. Presented case is unique in terms of extent of the affection (index finger, metacarp shaft, carpal bones, forearm, humerus and whole scapula) in combination with osteopoikilotic islands in other 3 regions (vertebrae, manubrium sterni and left collar bone). Currently there is only one such a case published in the literature (Campbell), but without osteopoikilotic islands. CASE PRESENTATION: Melorheostosis was diagnosed in 26-year old female after injury as an incidental finding. This was quite surprising as the patient already suffered by limited movement in the upper limb and pain before the injury. Detailed examination were performed to confirm the diagnosis, no family history was found. Pharmacotherapy with bisphosphonates, non-steroidal antirheumatics and vasodilatans/rheologic drugs seemed to be effective to maintain the relatively good quality of patient life and good performance in daily routine. Questionable is further development of patient performance status and sustainability of conservative treatment in the long term follow up. CONCLUSION: Conservative treatment with bisphopshonates and COX-2 inhibitors in combination with naftidrofuryl can delay surgery solution.

Single-dose and steady state pharmacokinetics of CSA and two main primary metabolites, AM1 and AM4n in patients with rheumatic/autoimmune diseases.

BACKGROUND: Cyclosporine A (CsA) is an immunomodulatory agent used in standard immunosuppressive regimens in solid organ transplantations as well as in the treatment of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus and psoriasis. Its immunosuppressive activity is primarily due to parent drug. However, following oral administration, absorption is incomplete and varies between individuals. Further, there is a dearth of pharmacokinetic data for CsA in autoimmune patients compared to transplant recipients. AIM: The goal of this study was to investigate the single-dose and steady state pharmacokinetics of CsA and two main primary metabolites, AM1 and AM4N, in patients with rheumatic/autoimmune diseases. METHODS: Thirty-eight subjects, average age (years± SD) 46.8 (±11.6) years with rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis and undifferentiated SpA were included in an observational open study. The single dose pharmacokinetics (area under the concentration-time curve of CsA and its metabolites (AUC) and other PK parameters) were determined over a 24 h period following oral administration of 1.3 mg/kg oral CsA. Two CsA formulations-Neoral and the Czech generic substitute Consupren®, were used. Pharmacokinetic analysis was performed on all 38 patients after administration of a single dose of CsA (1.34 mg/ kg/day). In 12 patients only, a second series of blood samples was taken to calculate monitored PK parameters under steady state conditions. RESULTS: Pharmacokinetic assessment showed AUC(0-24) 3009.66 ± 1449.78 ng/ml.h and C(max) 827.84 ± 425.84 after administration of a single dose of CSA, AUC(0-24) 3698.50 ± 2147 ng/ml.h and C(max) 741 ± 493 ng/ml after repeated dose. The proportion of the AM1 metabolite (AUC(0-24)) after a single dose of CsA corresponded to 40% of the parent compound and to approximately 35% of the parent compound in steady state conditions. The proportion of AM4N metabolite was low in both conditions and represented only 3 and 4.5% after a single dose and at steady state, respectively. CONCLUSION: The pharmacokinetic data (AUC(CsA), C(max)) for the whole 24 h interval were similar to the published findings, mainly under steady state conditions. The AM1 (AUC(0-24)) after a single dose of CsA and in steady state conditions represented about 40% of the parent drug. The ratio of AM4N metabolite was low in both conditions.

Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid arthritis.

OBJECTIVES: To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. METHODS: Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. RESULTS: Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). CONCLUSIONS: This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of RA.