Depression/anxiety symptoms in axial spondyloarthritis and psoriatic arthritis patients in Serbia: a pilot study.

To assess prevalence and change of depression/anxiety symptoms in spondyloarthritis patients and feasibility of depression/anxiety questionnaires. 43 Patients with axial spondyloarthritis (axSpA) and 27 patients with psoriatic arthritis (PsA) were consecutively recruited. There were 34 patients on biologics and 36 patients on nonbiologics. Patients were not previously treated for depression. The demographic variables, pain, patient global assessment, laboratory, clinical findings, diseases activity scores, Beck Depression Inventory (BDI) and Depression Anxiety and Stress Scale-short version (DASS-21) were collected. The study visits were at the beginning, after 1 month, after 3 and after 6 months. In axSpA and PsA patients on biologics, BDI and DASS-21 were significantly lower compared to nonbiologics group during time. The axSpA patients on biologics had significantly lower BDI and depression severity by BDI at each time point and lower DASS-21 after 1, 3 and 6 months. BDI in PsA patients who received biological therapy was significantly lower after 3 and 6 months. In biologics groups, BDI significantly decreased after 3 months in axSpA patients and after 1 month in PsA patients. In axSpA patients, there was a medium correlation between BDI and axial pain, patient global assessment and disease activity scores. The biological therapy significantly affected the depression/anxiety symptoms in axSpA and PsA during time. BDI moderately correlated with pain and disease activity in axSpA. BDI and DASS-21 are easy to use in daily practice.

Matrix Metalloproteinases-3 Baseline Serum Levels in Early Rheumatoid Arthritis Patients without Initial Radiographic Changes: A Two-Year Ultrasonographic Study.

OBJECTIVE: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. METHODS: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. RESULTS: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23-18.9], p = 0.024; OR 1.17 [0.320-4.26], p = 0.816 respectively). CONCLUSION: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.

Construct validity and sensitivity to change of Belgrade Ultrasound Enthesitis Score in patients with spondyloarthritis: a pilot study.

The objective of this study was to determine the construct validity and sensitivity to change of Belgrade Ultrasound Enthesitis Score (BUSES) in spondyloarthritis patients. Seventy-six spondyloarthritis patients with enthesitis were included in this pilot, prospective, double-blinded ultrasound study. Thirty-four patients received biological and forty-two patients received non-biological therapy. BUSES was determined at the beginning, after 1, 3, and 6 months. Spearman's correlation coefficient was calculated between BUSES and baseline characteristics. Brunner-Langer mixed non-parametric ANOVA was used to examine sensitivity to change of BUSES and effect of biological therapy on BUSES. Effect of time on the presence of each of the ultrasound enthesitis signs (increased thickness, hypoehogenicity, Power Doppler, enthesophytes, and erosions) was assessed using Cochran Q test. There was a weak, positive correlation between BUSES and disease duration, clinical enthesitis score, BASFI, BASDAI, and ASDAS-ESR/CRP. BUSES was higher at the beginning than after 1 month (p = 0.004), after 3 months (p < 0.001) and after 6 months (p < 0.001), as well as BUSES was higher after 1 month than after 3 months (p < 0.001) and after 6 months (p = 0.002). There is no difference in efficiency between non-biological and biological therapies on BUSES. Increased thickness, hypoechogenicity, and Power Doppler have decreased on Achilles tendon's and plantar fascia's enthesis over time. BUSES has a certain degree of construct validity because of the weak, positive correlation with parameters referring to severity of spondyloarthritis. BUSES demonstrated sensitivity to change over time due to decreasing of ultrasound acute enthesitis signs in treated spondyloarthritis patients. BUSES could be useful for monitoring the progression of enthesitis and effectiveness of the treatment.

Systemic sclerosis impacts right heart and cardiac autonomic nervous system.

AIM: To evaluate the influence of systemic sclerosis (SSc) on right ventricular (RV) remodeling by two- and three-dimensional echocardiography (2DE and 3DE) and heart rate variability (HRV). METHODS: Forty-five SSc patients and 35 age- and gender-matched healthy controls underwent clinical examination, 24-h Holter monitoring, and comprehensive 2DE and 3DE. RESULTS: 2DE RV global and RV free wall longitudinal strains, as well as 2DE RV endocardial, mid-myocardial, and epicardial longitudinal strains were lower in SSc subjects, who exhibited greater 3DE RV volumes but lower 3DE RV ejection fraction than controls. HRV indices were impaired in SSc subjects. These differences in RV global and free wall longitudinal strain, layer-specific strains, and ejection fraction, were associated with HRV indices independently of demographic, clinical, and echocardiographic parameters. Modified Rodnan Skin Score, clinical indicator of skin involvement in SSc, was associated with HRV parameters, RV layer-specific mechanics, and RV ejection fraction. CONCLUSION: SSc affects RV function and mechanics of all myocardial layers, as well as cardiac autonomic nervous function. HRV indices are significantly associated with RV function, RV deformation, and skin involvement in SSc patients.

Left atrial phasic function and heart rate variability in patients with systemic sclerosis: A new part of the old puzzle.

OBJECTIVE: We aimed to research left atrial (LA) phasic function and heart rate variability (HRV), as well as their relationship, in subjects with uncomplicated systemic sclerosis (SSc). METHODS: The investigation involved 44 SSc patients and 33 age-matched healthy controls. All participants underwent clinical examination, serological tests, 24-hours Holter monitoring, and echocardiographic examination including strain analysis. RESULTS: Maximum, minimum, and pre-A LA volumes and volume indices were higher in the SSc patients than in the controls. The total emptying fraction, the parameter of the LA reservoir function, as well as passive LA emptying fraction, which represents the LA conduit function, were significantly lower in the SSc patients compared to the controls. Active LA emptying fraction, the parameter of the LA booster pump function, was significantly higher in the SSc participants. There was no difference in LA reservoir function between the diffuse and the limited SSc form. LA conduit function was significantly decreased, whereas LA booster pump function was compensatory increased in the diffuse SSc form compared to the limited SSc form. Similar results were obtained by LA strain analysis. HRV indices were significantly decreased in the SSc patients. Modified Rodnan skin score, the parameter of skin involvement in SSc, and HRV indices correlated well with LA phasic function in SSc. CONCLUSION: Left atrial (LA) phasic function, assessed by both volumetric and strain method, as well as cardiac autonomic nervous function is significantly deteriorated in SSc patients. Skin score and HRV indices correlate with LA phasic function parameters.

The relationship between left ventricular deformation and heart rate variability in patients with systemic sclerosis: Two- and three-dimensional strain analysis.

OBJECTIVE: We sought to investigate left ventricular (LV) function and deformation, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). METHODS: The study included 49 SSc patients and 38 age-matched healthy subjects. All patients underwent clinical examination, serological tests, 24-h Holter monitoring, and comprehensive two- and three-dimensional echocardiography (2DE and 3DE). RESULTS: 2DE and 3DE LV global longitudinal and circumferential strain, as well as 3DE area strains are significantly reduced in SSc patients comparing with controls. 2DE and 3DE LV radial strains are similar between the observed groups. 2DE LV layer-specific longitudinal and circumferential strains are also significantly affected by SSc. Parameters of cardiac autonomic nervous system, assessed by HRV indices, SDNN, SDANN, rMMSD, p50NN, 24-h HF, LF and TP are significantly lower in SSc group. HRV indices (24-h HF and LF) are associated with 2DE LV global, 2DE LV layer-specific and 3DE LV mechanics independently of main demographic, clinical and echocardiographic parameters of the study population. Additionally, Modified Rodnan Skin Score, clinical parameter of skin involvement in SSc, is significantly associated with HRV (24-h HF and LF), 2DE and 3DE LV deformation. CONCLUSION: SSc significantly impacts LV deformation, all myocardial layers, and cardiac autonomic nervous function. A significant association between cardiac autonomic nervous system function, skin involvement and LV mechanics is revealed in SSc patients. These findings should encourage detailed cardiac assessment and further cardiac follow-up of the SSc patients with higher skin involvement, even when traditional echocardiographic parameters are within normal range.

Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis.

BACKGROUND: Dipeptidyl peptidase IV (DPPIV/CD26) plays an important role in T cell activation and immune regulation, however the role of this enzyme in early rheumatoid arthritis (eRA) has not been clearly defined. The aim of this study was to determine the serum activity of DPPIV, its expression on peripheral blood mononuclear cells (PBMC) and to examine possible correlations with disease activity (DAS28) in untreated patients with eRA. METHODS: The study included 50 patients newly diagnosed with RA, who had not received any corticosteroid or disease modifying antirheumatic drugs (DMARD) therapy and whose conventional radiographs of hands and feet showed no structural damage. The control group consisted of 40 healthy volunteers. Also, 30 patients with chronic RA (cRA) were examined. The serum activity of DPPIV was determined by the direct photometric method, while expression of CD26 on PBMC was determined using flow cytometry. RESULTS: Decreased DPPIV serum activity was detected in patients with eRA and cRA compared to the control group (p=0.024, p<0.0001, respectively). Although, the percentage of overall CD26+ white blood cells (WBC) was significantly decreased in eRA patients (p<0.001), the percentage of CD26+ lymphocytes and monocytes and mean fluorescence intensity of CD26 on these cells in eRA patients showed no significant difference compared to healthy volunteers. DAS28 showed no significant correlation with CD26 expression or DPPIV serum activity, but a significant inverse correlation between the duration of symptoms and DPPIV serum activity was observed. CONCLUSIONS: Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis.

Cardiac mechanics and heart rate variability in patients with systemic sclerosis: the association that we should not miss.

We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.

Which factors impact myocardial function in systemic sclerosis?

BACKGROUND: The aim of our study was to determine clinical and echocardiographic parameters, which impacted the left (LV) and right ventricular (RV) diastolic and global function in patients with systemic sclerosis (SSc). METHODS: The study included 50 SSc patients and 48 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, and complete two-dimensional echocardiography, which included pulsed and tissue Doppler. We determined the ratio of early diastolic transtricuspid/transmitral and the lateral area of the tricuspid/mitral annulus flow velocities (E/e';(lateral) ). RV and LV global ventricular function was estimated by the Tei index. Pulmonary vascular resistance (PVR) was calculated by using echocardiographic parameters. RESULTS: Tricuspid inflow E/A ratio was decreased in the SSc group (P < 0.001), also as e'/a' ratio (P < 0.001), whereas E/e'(tricuspid) was increased (P = 0.001). The RV Tei index was increased in SSc patients (P < 0.001). PVR was significantly higher than in controls (P < 0.001). The multivariate analysis showed that brain natriuretic peptide (BNP) level (ß= 0.403, P = 0.016), diffusion capacity for carbon monoxide (DLCO; ß= 0.361, P = 0.025), RV systolic pressure (ß= 0.449, P = 0.011), and PVR (ß= 0.507, P < 0.001) were independently associated with RV diastolic function (tricuspid E/e'(lateral) ). Similar results were achieved for the RV Tei index. Multiple regression showed that BNP level (ß= 0.337, P = 0.029), DLCO (ß= 0.405, P = 0.011), and PVR (ß= 0.449, P = 0.022) were independently associated with LV diastolic function (mitral E/e'(lateral) ). Similar results were obtained for the LV Tei index. CONCLUSION: Our study revealed some new noninvasive parameters (BNP, DLCO, and PVR), which are useful for everyday clinical practice for determining of early myocardial involvement in SSc. (Echocardiography, ****;**:1-11).

Pregnancy-associated spinal osteoporosis treated with bisphosphonates: long-term follow-up of maternal and infants outcome.

Pregnancy-associated spinal osteoporosis (PPSO) is a rare condition characterized by severe back pain occurring near the end of the first pregnancy or shortly afterward. The aim of this report is to present a 12-year follow-up of a patient with PPSO. Also, the outcomes of patient's two pregnancies and her infants after long-term treatment with bisphosphonates are assessed. A young woman was referred to our tertiary care hospital aged 30 years, due to intense pain in thoracic and lumbar region that started during the last month of her first pregnancy and got worse after delivery. Bone mineral density (BMD) measurement, clinical, and biochemical parameters were performed. Extremely low lumbar spine BMD, L2-L4: 0.627 g/cm(2), T-score -4.8, Z-score -4.3, 52% young adult indicated severe osteoporosis. Cyclical treatment with etidronate and then pamidronate was started, and a substantial increase in the BMD and the reduction in back pain intensity were observed. An increase in BMD of 44.8% over baseline was observed after 12 years of follow-up. Her two pregnancies were uneventful, and no neonatal adverse effects were observed. Control DXA scan in her girl child aged 6.8 years revealed low BMD at the lumbar spine. As PPSO seems to be an underdiagnosed severe disease, caution is recommended if back pain occurs in the last trimester or early post-partum period. Although pre-pregnancy use of bisphosponates does not pose a substantial fetal risk, their use in women of childbearing age might best be done only when strong clinical indications exist.

Atypical Cogan's syndrome associated with coronary disease / 中华医学杂志(英文版)

Cogan’s syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis. Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS.

Watermelon stomach in a patient with primary Sjögren's syndrome.

INTRODUCTION: Watermelon stomach (WS) or gastric antral vascular ectasia (GAVE) is a rare cause of upper gastrointestinal bleeding described in a variety of autoimmune disorders. Association of watermelon stomach with Sjögren's syndrome is extremely rare. CASE REPORT; We presented a 67-year old female with primary Sjögren's syndrome (SS) who had developed a persistent severe iron-deficiency anemia. An upper gastric endoscopy revealed the presence of gastric antral vascular ectasia (GAVE) as a cause of occult gastrointestinal bleeding. The treatment with argon-plasma coagulation was postponed as the conservative therapy with iron substitution and proton pump inhibitor led to improvement of anemia and hemoglobin levels normalization. CONCLUSION: This is the first report of WS in a patient with primary SS without the presence of coexisting autoimmune disorder. Recognition of this rare, but clinically important, cause of gastrointestinal bleeding may decrease comorbidity in patients with autoimmune disorders including primary Sjögren's syndrome.