Molecular Aspects of MAFLD-New Insights on Pathogenesis and Treatment.

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications.

Primary antiphospholipid syndrome as a cause of impaired left ventricular diastolic function: experience from a Serbian cohort.

OBJECTIVES: Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). METHODS: We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. RESULTS: LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was signi cantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. CONCLUSIONS: Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS.

Humoral Response of Different Types of SARS-CoV-2 Vaccines in Patients with Autoimmune Rheumatic Diseases: Experiences from a Serbian Cohort.

BACKGROUND: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD). OBJECTIVES: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity. METHODS: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured. RESULTS: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose. CONCLUSIONS: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients.

Objective: The potential contribution of asymmetric dimethylarginine (ADMA) and high-sensitivity C reactive protein (hsCRP) to endothelial dysfunction in APS patients has not been studied in detail, until now. The study involved 105 APS patients (59 diagnosed with primary APS (PAPS) and 46 APS associated with systemic lupus erythematosus (SAPS)) who were compared to 40 controls. Endothelial dysfunction was assessed by measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate dilatation (NMD) of the brachial artery. ADMA (micromol/L) was analyzed by ELISA. Results: FMD in patients with APS was significantly lower than that of the controls (p < 0.001), with no difference between the PAPS and the SAPS groups. ADMA and hsCRP concentrations were significantly higher in the patient cohort than in the control group (p < 0.001, p = 0.006, respectively), as was the case with the SAPS group as compared to the PAPS group (p < 0.001, p = 0.022, respectively). FMD impairment correlated to ADMA (ρ 0.472, p < 0.001) and to hsCRP (ρ 0.181, p = 0.033). In the regression model, the ADMA concentration confirmed the strength of its association (B 0.518, SE 0.183, Wald 8.041, p = 0.005, Exp(B) 1.679, 95% CI 1.174−2.402) to FMD impairment. The synergistic probability model of ADMA and hsCRP caused FMD impairment when the positivity of ß2GPIIgG was added. ADMA may be used as a simple and low-cost tool for verifying the presence of endothelial dysfunction in APS patients. According to the results of the study, we could presume that hsCRP, together with aPL, has a preparatory effect on the endothelium in causing endothelial dysfunction.

Analysis of Serbian Primary Antiphospholipid Syndrome Patients Confirmed a Strong Association Between Livedo Reticularis and Arterial Thrombosis: A National Cross-Sectional Cohort Study.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPLs) associated with thrombosis (arterial and/or venous) and/or obstetrical manifestations. However, various manifestations, which are considered to be noncriteria manifestations, are frequently found in APS. AIM: The purpose of this study was to evaluate whether noncriteria manifestations may be found more frequently in subjects with thrombotic and/or obstetrical APS ("criteria" manifestations) in a population of patients with primary APS (PAPS). This study presents the results from our national cohort. PATIENTS AND METHODS: This is a cross-sectional study of 360 PAPS patients. Data regarding the presence of thrombocytopenia, livedo reticularis, chorea, and valvulopathy were analyzed. The aPL analysis included the detection of anticardiolipin antibodies (aCLs: immunoglobulin G [IgG]/IgM), anti-ß 2 glycoprotein I (IgG/IgM), and lupus anticoagulant positivity. RESULTS: In our cohort, livedo reticularis was significantly related to arterial thromboses in the same way as valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) ( p = 0.0001, p = 0.013, respectively). Age was strongly related to all the noncriteria manifestations analyzed. Thrombocytopenia was significantly related to ß 2 glycoprotein I IgG and lupus anticoagulant positivity ( p = 0.043, p = 0.030, respectively), as well as to double and triple aPL positivity ( p = 0.041, p = 0.013 respectively). Moreover, in a multivariate model, livedo reticularis was strongly and independently related to arterial thrombosis in our cohort (odds ratio, 2.010; confidence interval, 1.229-3.288; p = 0.005). CONCLUSION: This cross-sectional analysis of a large cohort of Serbian PAPS patients confirmed a strong relationship between livedo reticularis and arterial thrombosis, suggesting a more cautious approach regarding the presence of noncriteria manifestations, especially livedo reticularis, in APS.

A Lower Level of Post-Vaccinal Antibody Titer against Influenza Virus A H1N1 May Protect Patients with Autoimmune Rheumatic Diseases from Respiratory Viral Infections.

Background and Objectives: The concentration of antibodies against virus influenza A H1N1 in the titer (≥1:32) positively correlates with resistance to flu in healthy persons. In elderly and immune-compromised patients, an influenza vaccine may be less immunogenic. Hypothesis: A lower post-vaccinal antibody titer (≥1:16) may be sero-protective against respiratory viral infections in patients with autoimmune rheumatic diseases. Materials and Methods: Fifty patients with autoimmune rheumatic diseases (Systemic Lupus Erythematosus-24; Rheumatoid Arthritis-15; and Sjögren's Syndrome-11), who were at least 65 years old or whose relative disease duration (disease duration/age) was greater than 1/8, were examined. Thirty-four of them were vaccinated with a trivalent inactivated non-adjuvant influenza vaccine. The antibody concentration against influenza virus A H1N1 was measured using the standardized hemagglutination inhibition test and patients who got any respiratory viral infection were registered. To test the hypothesis, a correlative analysis was applied, followed by a binary logistic regression that included potential confounding variables, such as age, disease duration and therapy (personal/health-related conditions). Results: Vaccinated patients were significantly less affected by respiratory viral infections (21% vs. 75%). The lower titer considered (≥1:16) was significantly present more often among vaccinated patients (68% vs. 6%). The correlation between its presence/absence and that of respiratory viral infections was -0.34 (p < 0.05). The binary logistic regression evidenced the relevance of this correlation, confirming the hypothesis. Vaccination was associated with the 87.3% reduction in the likelihood of getting respiratory viral infections, whereas the lower antibody titer (≥1:16) was associated with the 77.6% reduction in the likelihood of getting respiratory viral infections. The vaccine was well tolerated by all patients and after vaccination no exacerbation of the underlying disease was observed. Conclusions: A lower antibody titer (≥1:16) against influenza virus A H1N1 could be protective against respiratory viral infections for certain autoimmune rheumatic diseases patients, which confirms the clinical effectiveness of influenza vaccination.

Summary of the 12th Meeting of the European Forum on antiphospholipid antibodies ONLINE.

As a result of the current COVID-19 pandemic, the 12th meeting of the European Forum on Antiphospholipid Antibodies was held in a digital format on 26th March 2021. Even experienced for the first time in a virtual set-up, it kept its strength in continuation of the opportunity for more than 200 physicians from all continents and 20 countries to meet the experts in the field. Contemporary research in the area of antiphospholipid syndrome was presented, and proposals for the new research projects, as a distinguishing feature of the meeting, made a major contribution. Despite challenging times, this meeting enabled the highest number of registered participants to have interactive communication with presenters. This report summarizes major studies and new research projects presented during the online forum meeting.

The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.

Relationship between cerebrovascular and valvular manifestations in a Serbian cohort of patients with antiphospholipid syndrome.

OBJECTIVES: Antiphospholipid syndrome (APS) may manifest itself as a primary (PAPS) or secondary disease, most commonly in the context of systemic lupus erythematosus (SLE) with various neurological and cardiac manifestations in its occurrence. The objective of this study was to investigate the relationship between cerebrovascular (stroke and transient ischaemic attack (TIA)) and valvular manifestations in a Serbian cohort of APS patients. METHODS: This is cross sectional study of 508 APS patients: 360 PAPS and 148 APS patients associated with SLE (SAPS). aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and LA. RESULTS: The prevalence of valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) in our cohort was significantly higher in SAPS group. (28.4% vs. 8.6%, p=0.0001). Age was strong predictor for stroke and TIA occurrence in both groups as well as gender (stroke more likely occurred in male SAPS and TIA in male PAPS patients). Presence of ß2GPI IgG in SAPS patients was significantly related to stroke (p=0.018), whereas ß2GPI IgG negative PAPS patients were more prone to TIA. Valvular manifestations were significantly related to TIA in both groups of patients and were independent risk factors for TIA in PAPS (OR 3.790 CI 1.597-8.998 p=0.003). CONCLUSIONS: In this cross-section analysis of a large cohort of Serbian APS patients, there was a strong relationship between valvular and cerebrovascular manifestations, suggesting a more cautious approach regarding neurological symptoms, especially in PAPS patients with valvular vegetations present.

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

AIM: To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). METHODS: This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). RESULTS: The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). CONCLUSIONS: In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

Antiphospholipid-mediated thrombosis: interplay between type of antibodies and localisation of lung, and cardiovascular incidences in primary antiphospholipid syndrome.

OBJECTIVES: The aim of this study was to analyse prevalence and type of pulmonary manifestations in patients with primary antiphospholipid syndrome (PAPS), their association to antiphospholipid antibody (aPL) type and localisation of peripheral vascular thrombosis, and possible relationship to existing cardiac manifestations. METHODS: Our cross-sectional study comprised 318 PAPS patients, enrolled in the study as the Serbian APS Registry. aPL analysis included detection of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA, served to evaluate associations with cardiac and pulmonary manifestations. RESULTS: In patients with pulmonary embolism and infarction, we observed significant prevalence of myocardial infarction (p=0.044), unstable angina pectoris (p=0.001), venous thrombosis (p=0.007) arterial thrombosis (p=0.0001), deep venous thrombosis of the low extremities (p=0.008), and superficial thrombophlebitis of the low extremities (p=0.023). Patients with primary pulmonary hypertension were more prone to unstable angina pectoris (p=0.009), while patients with secondary pulmonary hypertension were more prone to venous thrombosis (p=0.04) and deep venous thrombosis of the inferior extremities (p=0.04). Patients with pulmonary microthrombosis were more prone to unstable angina pectoris (p=0.026), arterial thrombosis (p=0.002), venous thrombosis (p=0.001), deep venous thrombosis of the inferior extremities (p=0.001), and superficial thrombophlebitis of the inferior extremities (p=0.001). The presence of LA was significantly higher in patients with pulmonary embolism and infarction (p=0.001), secondary pulmonary hypertension (p=0.032), and pulmonary microthrombosis (p=0.001). CONCLUSIONS: Presence of LA was associated with distinct pulmonary manifestations in the Serbian APS cohort. There is a strong link between some cardiovascular and pulmonary manifestations in PAPS patients, suggesting complexity and evolutionary nature of PAPS.

Physical Activity Program Is Helpful for Improving Quality of Life in Patients with Systemic Lupus Erythematosus.

Given the crucial events in systemic lupus erythematosus (SLE) such as joint and muscle pain, fatigue, depression, obesity and osteoporosis, the very thought of exercising can be challenging. This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women performed isotonic exercises (to stretch and lengthen muscles and improve the range of motion) for 30 minutes, 3 times per week during the same period. Fatigue Severity Scale (FSS), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. At baseline FSS score was 53.8 ± 5.7 and after the physical activity FSS score was 29.1 ± 7.8 (FSS ≥ 36; fatigue is present). The largest number of patients (66.7%) was in a moderate depressed state at the baseline, while after physical activities 61.7% of patients, had a mild mood disturbance. There were significant differences (p < 0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. The type of physical activity had no influence in FSS and BDI values. Continuous physical activity, regardless of its type, significantly improved quality of life of SLE patients. We recommend regular physical activity as an integral part of modern therapeutic approach in this patient population.

Does the presence of secondary antiphospholipid syndrome in patients with systemic lupus erythematodes accelerate carotid arteries intima-media thickness changes?

Patients with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. The aim of our study was to evaluate the importance of secondary antiphospholipid presence (SAPS) in light of carotid artery intima-media thickness (CIMT) changes in SLE patients. Our study included 120 patients with SLE (46.02 ± 13.16 years), 108 women and 12 men divided into two groups: 58 patients with SAPS and 62 SLE patients without SAPS taken as a control group. All patients underwent assessment of CIMT of right and left common carotid artery (CCA) and left and right internal carotid artery (ICA) by Doppler ultrasonography. In SAPS group, 48.3 % patients had significant changes of carotid arteries comparing to 16.1 % patients in control group (p = 0.008). Average CIMT values in left and right CCA and right ICA were significantly higher in SAPS group. No significant relationship between antiphospholipid antibody type and CIMT changes was established. Multivariate regression analysis revealed SAPS as a significant predictor of CIMT changes in SLE patients (p = 0.025). Presence of SAPS in SLE patients is associated with significant CIMT changes. Additional autoimmune burden leads to a need for a more aggressive education and prevention considering standard risk factors in this group of patients.

Association between cardiac manifestations and antiphospholipid antibody type and level in a cohort of Serbian patients with primary and secondary antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS, also known as Hughes syndrome) may manifest itself as a primary or secondary disease, most commonly with systemic lupus erythemathosus (SLE) and various cardiac manifestations. OBJECTIVES: To report the first results from the Serbian National Cohort study, which was started in January 2000. METHODS: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), beta2-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected. RESULTS: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations. CONCLUSIONS: Patients with secondary APS had a higher prevalence ofvalvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.

Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid syndrome.

OBJECTIVES: The aim of this study was to investigate the association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipd syndrome (APS), as well as their connection with type and level of antiphospholipid antibodies. METHODS: Our prospective study comprises 333 patients: 218 with primary and 115 with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL(IgG/IgM), ß2GPI(IgG/IgM) and LA and served to evaluate associations with distinct neurological manifestations. RESULTS: The presence of aCL IgG was more common (p=0.001) in SAPS and LA in PAPS patients (p=0.002). High ß2GPI IgM levels (>100PLU/ml) were more common in epilepsy (p=0.00001) in PAPS, and in transient ischaemic attack (p=0.029) in SAPS. High ß2GPI IgG levels (>100PLU/ml) were more common in epilepsy (p=0.035) in SAPS. Chorea, migraine and epilepsy occurred more often in SAPS and headache and depression in PAPS. We found statistical significance considering the presence of aCL IgG and acute ischaemic encephalopathy in SAPS, aCL IgM and epilepsy in SAPS, aCL IgM and migraine in PAPS, ß2GPI IgG and chorea in SAPS and ß2GPI IgM and TIA and epilepsy in PAPS. LA was linked to depression, transient global amnaesia and migraine in PAPS. Patients with non-stable angina pectoris were more likely to develop TIA in both PAPS and SAPS, epilepsy and transient global amnaesia in PAPS and acute ischaemic encephalopathy in SAPS. Patients with valve vegetations were more prone to epilepsy and depression. CONCLUSIONS: Certain aPL type and levels are associated with distinct neurological non-thrombotic manifestation, suggesting their predictive role. There is strong link between some non-thrombotic neurological and cardiac manifestations in APS patients, suggesting the complexity and evolutionary nature of APS.

Association between systemic non-criteria APS manifestations and antibody type and level: results from the Serbian national cohort study.

OBJECTIVES: The aim of this study was to investigate the importance of aPL type and level for non-criteria-related events in APS patients. METHODS: Our study included 374 patients: 260 with PAPS and 114 with APS associated with systemic lupus erythematosus (SLE). RESULTS: We discovered significant connection between migraine and LA absence, livedo reticularis and aCL-IgG, skin ulcerations with aCL-IgG and anti-ß2GPI-IgM, pseudovasculitis lesions with aCL-IgG, aCL-IgM and anti-ß2GPI-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG and anti-ß2GPI-IgG. Thrombocytopenia occurred more frequently in patients with more than one aPL. In PAPS, epilepsy correlated with ß2GPI-IgM, migraine with aCL-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG, anti ß2GPI-IgG and LA. Skin ulcerations occurred more frequently in IIc category patients and in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Livedo reticularis was more prominent in PAPS with high levels of aCL-IgG. Significantly higher prevalence of thrombocytopenia was observed in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Epilepsy was related to high levels of anti ß2GPI-IgM and thrombocytopenia in the SAPS was correlated with aCL-IgG. Skin ulcerations were more prevalent in aCL-IgM positive SAPS patients and epilepsy more frequently in SAPS patients with high levels of anti ß2GPI-IgG. CONCLUSIONS: Our study showed that certain aPL type with certain level correlated with non-criteria manifestations, suggesting their predictive role.

Influenza vaccination in autoimmune rheumatic disease patients.

Patients suffering from autoimmune rheumatic diseases have significantly higher risk of developing various infections compared to the healthy population. Our study included patients suffering from systemic lupus erythematosus (n = 30), rheumatoid arthritis (n = 37) or Sjögren's syndrome (n = 32), with stable underlying diseases status. In November 2010, 47 patients, including 35 subjects vaccinated annually during 2006-2010, received immunization against influenza with trivalent inactivated split vaccine, whereas 52 patients did not accept proposed vaccination in that period. The presence of viral (primarily influenza) and bacterial infections, parameters of disease activity (from the date of vaccination until April 2011), and titers of antibodies against A H1N1 were then monitored in vaccinated and unvaccinated patients. We have identified the importance of predisposing factors for influenza occurrence (i.e. previous respiratory infections and vaccinations in last five years, age, sex, type of disease and duration, medications, smoking) in those groups of patients. The incidence of influenza or bacterial complications (bronchitis) among vaccinated patients was significantly lower, compared to the non-vaccinated group. Importantly, there was no case of exacerbation of the underlying disease. The last vaccination in 2010 reduced the risk of influenza by 87%, but previous bacterial infections (bronchitis and pneumonia) increased influenza risk significantly. In the present study, we have shown the efficiency, sufficient immunogenicity and safety of modern influenza vaccine application in patients suffering from systemic lupus erythematosus, rheumatoid arthritis or Sjögren's syndrome.

Chronic or Changeable Infarct Size after Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) could be the cause of acute myocardial infarction (AMI) and sudden cardiac death. Clinical presentations can vary considerably, but the most common is the elevation of cardiac biomarkers associated with chest discomfort. Different pathological etiology in comparison with Type 1 AMI is the underlying infarct size in this population. A 42-year-old previously healthy woman presented with SCAD. Detailed diagnostical processing and treatment which were performed could not prevent myocardial injury. The catheterization laboratory was the initial place for the establishment of a diagnosis and proper management. The management process can be very fast and sometimes additional imaging methods are necessary. Finding predictors of SCAD recurrence is challenging, as well as predictors of the resulting infarct scar size. Patients with recurrent clinical symptoms of chest pain, ST elevation, and complication represent a special group of interest. Therapeutic approaches for SCAD range from the "watch and wait" method to complete revascularization with the implantation of one or more stents or aortocoronary bypass grafting. The infarct size could be balanced through the correct therapeutical approach, and, proper multimodality imaging would be helpful in the assessment of infarct size.

Pathophysiology of spontaneous coronary artery dissection: hematoma, not thrombus.

Spontaneous coronary artery dissection (SCAD) accounts for 1.7%-4% of all acute coronary syndrome presentations, particularly among young women with an emerging awareness of its importance. The demarcation of acute SCAD from coronary atherothrombosis and the proper therapeutic approach still represents a major clinical challenge. Certain arteriopathies and triggers are related to SCAD, with high variability in their prevalence, and often, the cause remains unknown. The objective of this review is to provide contemporary knowledge of the pathophysiology of SCAD and possible therapeutic solutions.