Evaluation of acquired and hereditary risk factors for the development of thromboembolism in patients with systemic lupus erythematosus.

Although the contribution of antiphospholipid antibodies (aPL) to thrombolembolism in systemic lupus erythematosus (SLE) is well known, there is not enough data on the contribution of various hereditary thrombophilic factors. In this study, we aimed to determine acquired and hereditary thrombophilic factors in adult patients with SLE. A total of 93 SLE patients (87 women and 6 men) were included. Data on clinical, demographic and laboratory characteristics, and disease activity scores (SLEDAI) of the patients were evaluated. The patients were analyzed with a screen, including lupus anticoagulant, anticardiolipin antibodies (aCL), antithrombin III, protein C, protein S, and homocysteine levels; factor V Leiden ( FVL ), methylenetetrahydrofolate reductase ( MTHFR ) and prothrombin G20210A gene mutations. A total of 23 thromboembolic events were reported in 17 (18.3%) of the patients. The frequency of pregnancy complications and SLEDAI scores were significantly higher in SLE patients who had a thromboembolism event ( P  < 0.05). Thromboembolism was detected in 12 (32.4%) of 37 patients with positive aPL antibody and 5 (8.9%) of 56 patients with negative aPL antibody ( P  = 0.006). In addition, thromboembolism developed in 11 (32.3%) of 34 lupus anticoagulant-positive patients and 6 (10.1%) of 59 lupus anticoagulant-negative patients ( P  = 0.012). Moreover, protein C levels were significantly lower in patients who developed thromboembolism ( P  < 0.05). Patients with and without thromboembolism were similar in terms of genetic thrombophilia factors ( MTHFR A1298C, MTHFR C677T, FVL and Prothrombin G20210A ) ( P  > 0.05). In conclusion, in the current study, some acquired (aPL, lupus anticoagulant and cCL IGG) and hereditary (protein C deficiency) thrombophilic factors were shown to be associated with the development of thrombosis in SLE patients. However, the effect of other hereditary factors on the development of thromboembolism could not be demonstrated. According to the data of this study, genetic screening seems inappropriate in terms of the risk of thromboembolism in patients with SLE.

Derivation and validation of adult Still Activity Score (SAS).

OBJECTIVES: Adult-onset Still's disease (AOSD) is a multi-systemic, autoinflammatory disorder. Several activity scores have been proposed but none of them have been adopted universally. Our aim was to create a clinician-friendly activity scoring system by using simple clinical and laboratory parameters. METHODS: AODS patients, according to Yamaguchi criteria, were included in this cross-sectional, multicenter study. Derivation and validation cohorts were constituted. Demographic, clinical, and laboratory evaluation at the study visit; patients' and physicians' global assessments of disease activity (both VAS/Likert scale) were recorded. To develop the score, an ordinal logistic regression model was used to determine independent predictors of physicians' global assessments of disease activity. Clinically and statistically significant variables were weighted according to regression coefficients. Then, performance of the score was tested on the validation cohort. RESULTS: A total of 197 consecutive AOSD patients (125 in derivation, 72 in validation cohorts) were included. Final Still Activity Score was fever (2 points), arthralgia (2 points, plus 1 point if arthritis was present in≥2 joints), neutrophilia≥65% (1 point) and ferritin≥350ng/mL (1 point) (maximum of 7 points). The SAS yielded an AUC value of 0.98 (0.96-1.00) in the derivation cohort and 0.91 (95%CI: 0.85-0.98) in the validation cohort to discriminate high AOSD activity from moderate-inactive AOSD. The correlation of SAS with PGA was 83% for the derivation cohort and 76% for the validation cohort. CONCLUSIONS: SAS has shown a good test performance to distinguish active AOSD patients from others. SAS may be a useful method for evaluating the disease activity of AOSD patients in daily practice.

The frequency of synovitis and calcium pyrophosphate deposition with ultrasound is increased in transfusion-dependent beta-thalassaemia patients: effect of iron accumulation?

OBJECTIVES: To determine the frequency of synovitis and calcium pyrophosphate deposition (CPDD) with ultrasound (US) in the wrists of transfusion dependant (TD) beta-thalassaemia patients and to investigate the associated factors with these pathologies. METHODS: Eighty-seven beta-thalassaemia patients (46 thalassaemia major and 41 thalassaemia minor patients) were grouped into two as TD and transfusion non-dependent (TND)-thalassaemia patients. Under bilateral wrist US the presence of synovial hypertrophy (SH), power Doppler signal (PD) combined synovitis (SH+PD), tenosynovitis, and triangular fibrocartilage complex (TFC)-cartilage calcification (CC) were examined. SH, PD, and combined synovitis in the US were classified as Grade-0 (no), Grade-1 (minimal), Grade-2 (moderate), and Grade-3 (severe). RESULTS: The incidence of moderate/severe SH, PD, and combined synovitis with US was 34.8%, 17.4%, and 34.8% in TD-thalassaemia patients, respectively, but none in TND patients (p<0.001, p=0.006, p<0.001). The frequency of TFC-CC with US was 32.6% in TD and 2.4% in TND-thalassaemia patients (p<0.001). Ferritin level was positively correlated with SH (r=0.414, p<0.001), PD (r=0.279, p=0.009) and combined synovitis scores (r=0.402, p<0.001). Ferritin level (OR:1.001, CI:1.000-1.002) and the presence of TFC-CC (OR:25.048, CI:5.187-120.951) were determined as to be associated with moderate/severe combined synovitis. CONCLUSIONS: The presence of synovitis and TFC-CC with the US is common in patients with beta-thalassaemia who have had recurrent blood transfusions. Iron overload in beta-thalassaemia patients may cause CPDD and synovial inflammation.

Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity.

OBJECTIVES: We aimed to compare thiol/disulfide hemostasis and serum ischemia-modified albumin (IMA) levels, which are indicators of oxidative stress (OS), in patients with systemic lupus erythematosus (SLE), with the healthy control (HC) group and to evaluate the relationship of these parameters with disease activity and major organ involvement. MATERIAL-METHODS: Eighty-four SLE patients and 96 HCs were included in this study. The disease activity of SLE patients was calculated using The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Patients with SLEDAI-2K ≤ 5 were classified as low disease activity (LDA) and those with SLEDAI-2K > 6 as high disease activity (HDA). Thiol/disulfide hemostasis was evaluated using a new automated method and natural thiol (NT), total thiol (TT), disulfide (SS) levels, SS/NT, SS/TT, NT/TT ratios, and serum IMA levels were recorded. RESULTS: NT and TT levels were significantly lower (490.11 ± 123.61 vs 536.96 ± 86.05, p = 0.003) (532.56 ± 125.80 vs 565.72 ± 89.82, p = 0.046), SS level (21.22 ± 11.75 vs 13.37 ± 9.31, p < 0.001) was higher, and SS/TT (4.64 ± 2.93 vs 2.52 ± 1.82, p < 0.001) and SS/NT (4.12 ± 2.33 vs 2.35 ± 1.59, p < 0.001) ratios were significantly higher in SLE patients compared to HCs. IMA values were not different between the two groups (p = 0.920). NT (449.84 ± 136.98 vs 520.32 ± 104.11, p = 0.012) and TT levels (492.01 ± 138.45±562.97 ± 107.09, p = 0.013) were significantly lower and serum IMA levels (0.802 ± 0.089 vs 0.764 ± 0.040, p = 0.023) were significantly higher in SLE patients with HDA than in LDA patients. There was a weak negative correlation between NT (r = -0.284, p=0.009) (r = -0.291, p = 0.007) and TT levels (r = -0.281, p = 0.010) (r = -0.289, p = 0.008) and a weak positive correlation between IMA levels (r = 0.279, p = 0.011) (r = 0.263, p = 0.016) and SLEDAI-2K, and major organ involvement. CONCLUSION: It is thought that thiol/disulfide hemostasis and IMA levels may be used as ideal biomarkers of OS in SLE patients and may reflect the disease activity and major organ involvement.

Evaluation of subclinical retinal microvascular changes in systemic lupus erythematosus patients using optical coherence tomography angiography and its relationship with disease activity.

OBJECTIVE: This study aimed to investigate subclinical retinal microvascular changes with optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) and healthy controls (HCs), and to evaluate the relationship between OCTA findings and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). MATERIALS AND METHODS: In this study, 47 eyes of SLE and 41 eyes of healthy control (HC) were evaluated. The SLE patients were divided into two subgroups: low disease activity (LDA) (SLEDAI≤5) and high disease activity (HDA) (SLEDAI>6). The results of OCTA were compared between SLE patients and HCs as well as the SLE subgroups. The relationship between OCTA results and SLEDAI-2K was evaluated. RESULTS: There were no differences in foveal avascular zone (FAZ) areas between the SLE patients and HCs. Central foveal thickness (CFT) was lower in SLE patients (p = .046). Superficial capillary plexus (SCP) vessel density (VD) in SLE patients was significantly lower only in the foveal area compared to that in HCs (p = .006). Deep capillary plexus (DCP) VD in SLE patients was significantly lower in all areas except the temporal parafoveal area compared to that in the HCs. There was no statistically significant difference between SLE groups with LDA and HDA in FAZ or any of the other areas, including SCP and DCP. When the correlation between OCTA findings and SLEDAI-2K was examined, both SCP and DCP VD were found to be negatively correlated. CONCLUSIONS: It was observed that DCP VDs were affected in SLE patients with LDA, and SCP VDs were also affected in addition to DCP with HDA. This suggests that DCP may be the first capillary plexus to be comprised in SLE. VDs were negatively correlated with disease activity. It was concluded that OCTA can be a useful tool in assessing subclinical retinal microvascular pathology and disease activity in patients with SLE.

The effects of the renin-angiotensin-aldosterone system blockers on serum ischemia-modified albumin levels in autosomal dominant polycystic kidney disease.

BACKGROUND: Among one of the common hereditary causes of chronic kidney disease is autosomal-dominant polycystic kidney disease (ADPKD), and its incidence rate is reported as one between 500 and 1.000 individuals. The most common complications of ADPKD are hypertension (HT) and end-stage renal disease (ESRD). HT occurring in the early stage of ADPKD leads to deteriorations in renal function. AIMS: It was aimed to investigate the ischemia-modified albumin (IMA) levels and the effect of renin-angiotensin-aldosterone system (RAAS) blockers on serum IMA levels in patients with ADPKD. METHODS: One hundred and fifteen patients were included as ADPKD (n = 50), HT (n = 35), and healthy control (HC) groups (n = 30). Patients with ADPKD and HT were divided into two subgroups as RAAS blocker-users and non-users. RESULTS: Serum IMA levels were detected as 0.42 (0.17-0.80) in ADPKD and 0.28 (0.04-0.51) in HT and 0.36 (0.22-0.56) in HC groups as absorbance units (ABSU), and the highest serum IMA level was seen in Group ADPKD. Serum IMA levels were 0.33 ± 0.14 in RAAS blocker-users and 0.41 ± 0.11 ABSU in non-users with ADPKD. Serum IMA levels were witnessed to be significantly lower in RAAS blocker-users in Groups ADPKD (p = 0.038) and HT (p = 0.004), compared to non-users. Given basal and 6-month values of those with ADPKD, the levels of serum IMA within 6 months were significantly lower (p = 0.002). CONCLUSIONS: We consider that serum IM levels should be assessed in oxidative stress (OS)-related conditions, such as ADPKD, and RAAS blockers may be effective in reducing serum IMA levels in ADPKD and HT patients.

Rheumatology patients' attitude regarding Ramadan and fasting.

OBJECTIVE: Fasting may lead to some problems in patients who have to use drugs on a regular and continuous basis. The objective of this study is to identify rheumatology patients' attitudes toward Ramadan and fasting. METHOD: The descriptive and cross-sectional study was conducted with 374 patients. The study data were collected using a questionnaire form. SPSS was used and percentage and Chi-square analyses were performed. RESULTS: It was determined that 56.1% fasted during Ramadan. When asked about the effect of fasting on the disease, 88.4% of those who fasted answered "it had no effect", and 80.1% of those that did not fast said "it affected negatively" (P < .05). It was determined that 41.9% of the fasting patients did not visit the doctor during Ramadan, 52.9% continued using their drugs without any change, and 73.3% did not ask for information on fasting. The rate of patients who were informed by the doctor without any request for information was found to be only 9% (P < .05). CONCLUSION: It was determined that more than half of the rheumatology patients fasted, the majority of these patients thought that it would not affect their disease, and the rate of request for information from the doctor was low. It is considered that a drug program could be prepared for fasting individuals who are willing to fast, in which drugs are taken between the Iftar and Suhur times, and patients can safely fast without any additional risk to their disease.

Methotrexate intoxication: Beyond the adverse events.

AIM: Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug in rheumatoid arthritis (RA). However, this anchor may cause some side effects that may range from nausea to mortality. The clinical features of MTX toxicity are under-researched. In this study, we aimed to find out the potential predisposing factors and outcomes of the MTX toxicity (n = 31). METHODS: The data were collected from 31 patients whose ages ranged from 25 to 81 years, who were suffering from immune-mediated inflammatory diseases and major MTX-related toxicity. RESULTS: Out of 31 patients, six (19.4%) used MTX every day, and 13 (41.9%) patients had renal insufficiency who were admitted to the hospital because of mucositis (90.3%) and fever (71%). While using MTX, 27 patients (87.1%) were discharged after the treatment and four patients (12.9%) died. CONCLUSIONS: Although MTX has high efficacy for the toxicity ratio, wrong use and dosage of MTX may be harmful to patients. Thus, patients should be informed about the proper use of MTX.

Neutrophil to Lymphocyte Ratio and Mean Platelet Volume as Inflammatory Indicators in Systemic Lupus Erythematosus Nephritis.

OBJECTIVES: This study aims to evaluate the role of neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) as activation and inflammatory markers in systemic lupus erythematosus (SLE) patients with nephritis. PATIENTS AND METHODS: A total of 108 SLE patients (8 males, 100 females; mean age 35.3±10.2 years; range 16 to 64 years) including 78 patients with renal involvement (8 males, 70 females; mean age 33.9±10.6 years; range 16 to 64 years) (SLEn+ group) and 30 patients without renal involvement (30 females; mean age 39.1±8.2 years; range 22 to 55 years) (SLEn- group) were included in this retrospective study. All patients' clinical characteristics and laboratory data which include erythrocyte sedimentation rate, C-reactive protein, white blood counts, neutrophil counts, lymphocyte counts, platelet counts, and MPV levels were obtained from medical records. The laboratory data at the highest proteinuria periods of the patients with renal involvement were recorded. RESULTS: Mean MPV (SLEn+ =9.1±2.2, SLEn- =7.9±1.2, p=0.001) and NLR (SLEn+ =5.9±5.9, SLEn- =2.6±2.5, p<0.001) values were significantly higher in lupus nephritis group. Besides, a positive correlation between NLR and C-reactive protein was found in lupus nephritis group (r=1.97, p=0.045). Based on receiver operating characteristic curve with area under the curve of 0.76, cutoff NLR value of 1.93 had 83% sensitivity and 54% specificity [95% confidence interval, 0.66-0.85] in differentiating SLE patients with or without nephritis. CONCLUSION: Neutrophil to lymphocyte ratio and MPV may be discriminative for lupus nephritis. Also, NLR may be a predictor of lupus nephritis. Both MPV and NLR values may be affected by a great number of factors; therefore, further prospective studies are needed to evaluate the use of these parameters in SLE.

Prolonged Tpeak-Tend interval in anti-Ro52 antibody-positive connective tissue diseases.

Patients with connective tissue diseases (CTDs) may have prolonged corrected QT interval which indicates increased risk for ventricular arrhythmias. However, a more sensitive measure of ventricular repolarization, T-peak-to-end (Tpe) interval, has not been studied in CTDs. We aimed to investigate the relationship between ventricular repolarization abnormalities and anti-Ro52-positivity in subjects with connective tissue diseases (CTDs). We enrolled patients with anti-Ro52-positive CTDs, ANA-positive CTDs, and healthy subjects in this cross-sectional study. We excluded conditions potentially affecting the QT interval. We compared the ECG measures between the groups and performed analyses to define factors associated with ventricular repolarization measures. 15 ANA and anti-Ro52-positive, 39 ANA-positive and anti-Ro52-negative, and 22 healthy subjects were enrolled. None of the subjects had rhythm or conduction disturbances. Corrected QT intervals were similar between the groups. Tpe (84, 77.3, and 69.4 msn, respectively) and QT-dispersion (40, 27.2, and 20.1 msn, respectively) were higher in anti-Ro52-positive subjects compared with the ANA-positive and healthy subjects. Anti-Ro52 titers were correlated with Tpe and QT-dispersion (r = 0.52 and p < 0.001 for each). ANA and anti-Ro52-positivity were independently associated with higher Tpe (OR = 7.7, p = 0.001 and OR = 6.9, p = 0.001, respectively), corrected Tpe (OR = 11.3, p = 0.001 and OR = 8.4, p = 0.003, respectively), QT dispersion (OR = 7, p = 0.008 and OR = 13, p < 0.001, respectively), and QTc dispersion (OR = 9.1, p = 0.001 and OR = 14.1, p < 0.001, respectively). This study provides evidence that ANA positivity, especially when concomitant anti-Ro52-positivity is present, significantly deteriorates ventricular repolarization. The aforementioned ventricular repolarization abnormalities may render these subjects susceptible to serious rhythm or conduction disorders in the setting of predisposing conditions.

Correlation between arterial stiffness and inflammatory markers in autosomal dominant polycystic kidney disease patients with preserved renal function.

AIM: To evaluate the association between arterial stiffness and inflammatory markers including C-reactive protein (CRP), pentraxin 3 (PTX3) and neutrophil-to-lymphocyte ratio (NLR) in autosomal dominant polycystic kidney disease (ADPKD) patients with preserved renal function. METHODS: A total of 52 ADPKD patients [mean (SD) age 38.2 (12.8) years, 69.2 % were females] with preserved renal function and 25 healthy volunteers [mean (SD) age 35.5 (6.5) years, 48.0 % were females] were included. Data on patient characteristics, blood biochemistry, inflammatory markers [PTX3 (pg/mL), CRP (mg/dL) and NLR] and arterial stiffness [large artery elasticity index (LAEI) (mL/mmHg × 10) and small artery elasticity index (SAEI) (mL/mmHg × 100)] were recorded in patient and control groups. Correlation between inflammatory markers and arterial stiffness parameters was analysed in patients. RESULTS: Overall, 42.3 % of ADPKD patients were hypertensive and 44.4 % were receiving renin-angiotensin-aldosterone system (RAAS) blockade therapy. Median levels for PTX3 [442.0 (20.0-4140.0) pg/mL vs. 220.5 (14.7-393.0) pg/mL, p < 0.001] and SAEI [4.90 (1.60-11.80) mL/mmHg × 100 vs. 6.45 (2.80-15.70) mL/mmHg × 10, p = 0.013] were significantly higher in ADPKD patients than in controls. PTX3 and CRP were not correlated with arterial elasticity, while NLR was significantly correlated with LAEI negatively (Rho = -0.278, p = 0.042). CONCLUSION: In conclusion, our findings revealed increased PTX3 levels and reduced SAEI in patients as compared with controls, while no correlation between inflammatory markers studied and the small artery elasticity.

Arterial dysfunction in early autosomal dominant polycystic kidney disease independent of fibroblast growth factor 23.

INTRODUCTION: Recent studies report reduced vascular compliance and elevated levels of fibroblast growth factor 23 (FGF23) in patients with autosomal dominant polycystic kidney disease (ADPKD) and preserved kidney function. In the present study, we investigated the relationship between vascular compliance and FGF23 in patients in early phases of ADPKD. MATERIALS AND METHODS: We studied 54 ADPKD patients with preserved kidney function and 24 healthy individuals. All participants underwent noninvasive pulse wave analysis in order to determine large arterial elasticity index (LAEI) and small arterial elasticity index (SAEI) using a modified Windkessel model. Levels of FGF23 in addition to several cardiovascular risk factors were evaluated. Linear regression analyses were performed to determine independent correlates of LAEI, SAEI, and FGF23. RESULTS: In the ADPKD group, 33 patients were hypertensive and the remaining patients were normotensive. Serum FGF23 levels of both ADPKD groups were significantly higher than that in the controls. Both hypertensive and normotensive ADPKD patients had lower LAEI and SAEI levels compared to the controls. There was no significant correlation between vascular compliance parameters and FGF23 levels. Having ADPKD was independently associated with increased FGF23 levels and decreased SAEI. CONCLUSIONS: Fibroblast growth factor 23 was found substantially elevated and arterial compliance was found significantly decreased in early ADPKD patients regardless of hypertension. However, there was no significant correlation between FGF23 levels and arterial function parameters. Additional studies are required to determine possible mechanisms of these disturbances and cardiovascular effects of FGF23 in ADPKD patients.

Neutrophil lymphocyte ratio can be a valuable marker in defining disease activity in patients who have started anti-tumor necrosis factor (TNF) drugs for ankylosing spondylitis.

OBJECTIVE: Neutrophil lymphocyte ratio (NLR) has emerged as a valuable and reliable method for follow-up of systemic inflammatory disease. We herein aimed to evaluate the role of NLR in the clinical follow-up of inflammation and also to compare its relationship with other measures, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). MATERIAL AND METHODS: A total of 35 active ankylosing spondylitis (AS) and 38 healthy volunteers were included in the study. The patient group was enrolled for treatment with one anti-tumor necrosis factor (TNF) drug. Total blood count, ESR, CRP, and BASDAI score were obtained before and 3 months following the treatment. NLR was found with a mathematical calculation of the ratio of neutrophils with lymphocytes. RESULTS: The mean NLR value of the control group and patients was 1.90±0.89 and 2.67±1.17, respectively (p<0.05). After a 3-month course of treatment, the patient group had a mean NLR value of 1.8±0.7, which was significantly lower than pretreatment values (p<0.001). The post-treatment mean ESR, CRP, and BASDAI scores were significantly lower than mean baseline scores (p<0.001, p=0.007, p<0.001, respectively). Also, NLR was found to be correlated with BASDAI, ESR, and CRP (r=0.388, p<0.001; r=0.455, p<0.0001; and r=0.3389, p<0.005, respectively). CONCLUSION: Neutrophil lymphocyte ratio could be a reliable and easily accessible method for follow-up of patients with AS.