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Central retinal artery occlusion (CRAO) is an emergency state characterized by sudden, painless vision impairment. Patients with CRAO have an increased risk of cardiovascular events, including stroke, likely related to vascular endothelial damage. Therefore, we investigated flow-mediated dilatation (FMD) of the brachial artery as a marker of endothelial dysfunction, intima-media complex thickness (IMT) of the common carotid artery, pointing to the arterial wall atherosclerotic alteration, and transthoracic echocardiographic parameters in 126 consecutive CRAO patients (66 men [52.4%], median age 55 years) and 107 control participants (56 men [52.3%], matched by age, sex, and body mass index). Most CRAO patients (n = 104, 82.5%) had at least one internal medicine comorbidity, mainly hypercholesterolemia and hypertension, which coexisted in one-fourth of them. Furthermore, they had a 38.2% lower relative increase of FMD (FMD%) and a 23.1% thicker IMT compared to the controls (p < 0.001, both, also after adjustment for potential confounders). On echocardiography, the CRAO group was characterized by increased dimensions of the left atrium and thicker left ventricular walls, together with impaired left ventricular diastolic function. CRAO is related to vascular endothelial damage, atherosclerosis, and left ventricular diastolic cardiac dysfunction. Thus, non-invasive ultrasound assessments, such as FMD%, IMT, and echocardiography, may be helpful in screening patients with increased CRAO risk, particularly those with other comorbidities.

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

BACKGROUND Monocyte subsets are involved in atherosclerotic vascular disease and its thromboembolic complications. Moreover, the role of monocytes has been suggested in the pathogenesis of venous thromboembolism (VTE). OBJECTIVES We hypothesized that pro-inflammatory non-classical and intermediate monocytes are increased in the first months following VTE. MATERIAL AND METHODS We enrolled 70 patients aged 18-65 years (mean age 41.6 ±11.6) with the firstever provoked (n = 32; 45.7%) or unprovoked (n = 38; 54.28%) VTE episode, and 46 healthy controls. The exclusion criteria were: acute infection, cancer, autoimmune disorders, previous myocardial infarction (MI), or stroke. Monocyte subsets were assessed 12 (8.5-21.5) months after VTE using flow cytometry and were defined as classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). RESULTS Patients with VTE had higher intermediate and non-classical monocyte counts compared to the control group (16.8 ±9.3 vs 10.4 ±4.0 cells/μL, and 64.1 ±25.2 vs 44.1 ±19.2 cells/μL, respectively, both p < 0.001). Increased non-classical monocyte counts were observed in patients who experienced a VTE incident within 12 months prior to enrollment (71.5 ±27.4 vs 56.03 ±20.6 cells/μL; p = 0.01) and those with unprovoked VTE (70.2 ±4.1 vs 58.8 ±4.3 cells/μL; p = 0.06). There were no differences in monocyte subsets related to the current anticoagulation. CONCLUSIONS Our data has shown for the first time that VTE is associated with an increased number of nonclassical and intermediate monocytes, which may indicate the involvement of monocyte-related mechanisms in the pathophysiology of this disease.

Plasmapheresis is a therapeutic method based on removal of high molecular weight particles from blood. It is used in a variety of clinical entities in which pathogenic role of such particles has been proven e.g. ANCA-associated vasculitides (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]). Efficacy of plasmapheresis in ANCA antibodies removal and its impact on disease activity has not been adequately investigated so far. Influence of antibodies levels on disease activity also remains unknown.Analysis of plasmapheresis effect on serum ANCA levels in patients with ANCA-associated vasculitides.Seven patients with diagnoses of ANCA-associated vasculitides were enrolled in the study between November 2015 and April 2016. All of them underwent plasmapheresis procedures. Serum ANCA levels were measured before and after plasmaphereses using fluoroimmunoenzymatic assay (FEIA). Disease activity was assessed using Birmingham Activity Vasculitis Score; BVAS ver. 3 before first plasma exchange procedure.Patients in disease exacerbation (BVAS 5-10) with positive ANCA antibodies were enrolled in the study: 2 patients with GPA and 5 patients with MPA. Number of performed plasmapheresis procedures ranged from 5 to 7 (median=7). Decrease of serum antibodies concentration was observed in all patients (mean decrease of 88.3% (±10.1%)) with statistically significant difference in mean antibodies concentration before and after plasmapheresis procedures (113.0 vs 15.4; p=0.014).Plasmapheresis is an effective method of ANCA antibodies removal in patients in disease exacerbation.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the presence of antiphospholipid antibodies and subsequent arterial or venous thrombosis or pregnancy morbidity. Individuals with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. The aim of this systematic review was to assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thromboembolism, particularly ischemic stroke, in people diagnosed with APS. We searched several electronic databases up to February 2017 and supplemented them by searching several ongoing trials registers, checking the reference lists of included studies, systematic reviews, and practice guidelines, and contacting experts in the field. We included randomized controlled trials that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thromboembolism among patients with APS diagnosed according to the criteria valid when the …

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both), and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence of APS is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. OBJECTIVES: To assess the effects of antiplatelet (AP) or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with APS. SEARCH METHODS: We last searched the MEDLINE, Embase, CENTRAL, Cochrane Stroke Group Trials Register, and ongoing trials registers on 22 November 2019. We checked reference lists of included studies, systematic reviews, and practice guidelines. We also contacted experts in the field. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated any anticoagulant or AP agent, or both, in the secondary prevention of thrombosis in people with APS, according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently worked on each step of the review, following Cochrane methods. We summarized the evidence using the GRADE approach. MAIN RESULTS: We identified eight studies including 811 participants that compared different AP or anticoagulant agents. NOAC (non‐VKA oral anticoagulant: rivaroxaban 15 or 20 mg/d) versus standard‐dose VKA (vitamin K antagonist: warfarin at moderate International Normalized Ratio [INR] ‐ 2.5) or adjusted [INR 2.0‐3.0] dose): In three studies there were no differences in any thromboembolic event (including death) and major bleeding (moderate‐certainty evidence), but an increased risk of stroke (risk ratio [RR] 14.13, 95% confidence interval [CI] 1.87 to 106.8; moderate‐certainty evidence). One of the studies reported a small benefit of rivaroxaban in terms of quality of life at 180 days measured as health state on Visual Analogue Scale (mean difference [MD] 7 mm, 95% CI 2.01 to 11.99; low‐certainty evidence), but not measured as health utility on a scale from 0 to 1 (MD 0.04, 95% CI ‐0.02 to 0.10; low‐certainty evidence). High‐dose VKA (warfarin with a target INR of 3.1 to 4.0 [mean 3.3] or 3.5 [mean 3.2]) versus standard‐dose VKA (warfarin with a target INR of 2.0 to 3.0 [mean 2.3] or 2.5 [mean 2.5]): In two studies there were no differences in the rates of thrombotic events and major bleeding (RR 2.22, 95% CI 0.79 to 6.23, low‐certainty evidence), but an increased risk of minor bleeding in one study during a mean of 3.4 years (standard deviation [SD] 1.2) of follow‐up (RR 2.55, 95% CI 1.07 to 6.07). In both trials there was evidence of a higher risk of any bleeding (hazard ratio [HR] 2.03 95% CI 1.12 to 3.68; low‐certainty evidence) in the high‐dose VKA group, and for this outcome (any bleeding) the incidence is not different, only the time to event is showing an effect. Standard‐dose VKA plus a single AP agent (warfarin at a target INR of 2.0 to 3.0 plus aspirin 100 mg/d) versus standard‐dose VKA (warfarin at a target INR of 2.0 to 3.0): One high‐risk‐of‐bias study showed an increased risk of any thromboembolic event with combined treatment (RR 2.14, 95% CI 1.04 to 4.43; low‐certainty evidence) and reported on major bleeding with five cases in the combined treatment group and one case in the standard‐dose VKA treatment group, resulting in RR 7.42 (95% CI 0.91 to 60.7; low‐certainty evidence) and no differences for secondary outcomes (very low‐ to low‐certainty evidence). Single/dual AP agent and standard‐dose VKA (pooled results): Two high‐risk‐of‐bias studies compared a combination of AP and VKA (aspirin 100 mg/d plus warfarin or unspecified VKA at a target INR of 2.0 to 3.0 or 2.0 to 2.5) with a single AP agent (aspirin 100 mg/d), but did not provide any conclusive evidence regarding the effects of those drugs in people with APS (very low‐certainty evidence). One of the above‐mentioned studies was a three‐armed study that compared a combination of AP and VKA (aspirin 100 mg/d plus warfarin at a target INR of 2.0 to 2.5) with dual AP therapy (aspirin 100 mg/d plus cilostazol 200 mg/d) and dual AP therapy (aspirin 100 mg/d plus cilostazol 200 mg/d) versus a single AP treatment (aspirin 100 mg/d). This study reported on stroke (very low‐certainty evidence) but did not report on any thromboembolic events, major bleeding, or any secondary outcomes. We identified two ongoing studies and three studies are awaiting classification. AUTHORS' CONCLUSIONS: The evidence identified indicates that NOACs compared with standard‐dose VKAs may increase the risk of stroke and do not appear to alter the risk of other outcomes (moderate‐certainty evidence). Using high‐dose VKA versus standard‐dose VKA did not alter the risk of any thromboembolic event or major bleeding but may increase the risk of any form of bleeding (low‐certainty evidence). Standard‐dose VKA combined with an AP agent compared with standard‐dose VKA alone may increase the risk of any thromboembolic event and does not appear to alter the risk of major bleeding or other outcomes (low‐certainty evidence). The evidence is very uncertain about the benefit or harm of using standard‐dose VKA plus AP agents versus single or dual AP therapy, or dual versus single AP therapy, for the secondary prevention of recurrent thrombosis in people with APS (very low‐certainty evidence).

The objective of our study was to evaluate the T-helper (Th) and regulatory T (Treg) cell profile in ANCA-positive granulomatosis with polyangiitis (GPA) and its relation to disease activity. In a prospective study, we studied two groups of GPA patients: (i) disease flare (active-GPA, BVAS>6, n = 19), (ii) sustained remission (≥ 1-year prior enrollment, inactive-GPA, BVAS = 0, n = 18). 24 age-sex matched healthy subjects served as controls. Active-GPA patients were followed for 6 months and reevaluated during remission (early remission; n = 13). We analyzed subsets of Th-cells (flow cytometry), production of signature cytokines by in vitro stimulated lymphocytes, and broad spectrum of serum cytokines (Luminex). In all GPA patients we observed expansion of effector Th17 cells, and increased production of IL-17A by in vitro stimulated T cells, as compared to controls. Disease flare was characterized by marked reduction in Treg cells, whereas in sustained remission we showed expansion of both Treg and Th2 subset. Finally, analyzing the cytokine profile, we identified CCL23 and LIGHT, as potential biomarkers of active disease. We conclude that in GPA, expansion of Treg and Th2 lymphocytes in parallel to increased Th17 response is a characteristic feature of sustained remission. In contrast, Treg cells are markedly decreased in disease flare.

Purpose: There is a need to develop predictive tests that would allow identifying cancer patients with a high risk of developing side effects to radiotherapy. We compared the predictive value of three functional assays: the G0 aber ration assay, the G2 aberration assay and the alkaline comet assay in lymphocytes of breast cancer and gynaecological cancer patients. Material and methods: Peripheral blood was collected from 35 patients with breast cancer and 34 patients with gy naecological cancer before the onset of therapy. Chromosomal aberrations were scored in lymphocytes irradiated in the G0 or G 2 phase of the cell cycle. DNA repair kinetics was performed with the alkaline comet assay following irradiation of unstimulated lymphocytes. The results were compared with the severity of early and late side effects to radiotherapy. Results: No correlation was observed between the results of the assays and the severity of side effects. Moreover, each assay identified different patients as radiosensitive. Conclusions: There is no simple correlation between the in vitro sensitivity of lymphocytes and the risk of developing early and late side effects. J Contemp Brachyther 2012; 4, 4: 219‐226 DOI: 10.5114/jcb.2012.32556

INTRODUCTION The factors that determine the level of antibodies against N-homocysteinylated (N-Hcy) proteins have not been established so far. The clinical significance of these antibodies and their effect on cardiovascular (CV) risk in patients with end-stage renal disease (ESRD) are still unknown. OBJECTIVES The aim of this study was to identify the factors that determine the level of antibodies against N-Hcyalbumin and N-Hcy hemoglobin in patients on long-term hemodialysis (HD). PATIENTS AND METHODS The study involved 247 subjects on long-term HD (110 women, 137 men; age range, 23-89 years) and 60 controls matched for age, sex, and CV risk factors (serum creatinine level

BACKGROUND Thrombotic events in antiphospholipid syndrome (APS) involve venous and arterial circulation with the possible involvement of coronary or pulmonary microcirculation. OBJECTIVES To evaluate the influence of antiphospholipid antibodies (aPL) and on myocardial ischaemia assessed by single-photon emission computerized tomography (SPECT), coronary atherosclerosis assessed by multidetector computerized tomography (MDCT) and pulmonary pressure assessed by transthoracic echocardiography (TTE) in patients with primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS TTE, SPECT (Tc 99m sestamibi) and MDCT-based coronary calcium scoring were performed in 26 consecutive PAPS patients (20 females, 6 males, aged 20-61, mean 39.7) without any signs of other autoimmunological disease and without clinical symptoms of heart disease. RESULTS Out of 26 patients, TEE showed normal left and right ventricle function in 25 (96.2%) and elevated (≥ 30 mm Hg) right ventricle systolic pressure in 7 (26.9%) patients. SPECT revealed myocardial perfusion defects in 15 (57.7%) patients: exercise-induced in 6 (23.1%) and persistent in 11 (42.3%). MDCT revealed coronary calcifications in 4 (15.4%) patients. The number of plaques ranged from 1 to 11 (median 2), volume 3-201.7 mm³ (median 7), calcium scores 1.3-202.6 (median 5.7). In the group with perfusion defects or coronary calcifications (n = 15), all the patients showed elevated aCL IgG. CONCLUSIONS In most of the relatively young APS patients, without any symptoms of ischemic heart disease, SPECT showed myocardial perfusion defects, and coronary calcifications in 1/6 of them. Right ventricle systolic pressure was elevated in 1/4 of APS patients. These pathologies, well known as cardiovascular risk markers, were associated with elevated levels of the IgG class of both anti-cardiolipin and antiB2 GPI antibodies. Thus, in a high percentage of APS patients, clinically silent myocardial ischaemia, pulmonary pressure elevation and coronary atherosclerosis are present and related to the presence of antiphospholipid antibodies.

Summary N-homocysteinylated (Nε-Hcy) proteins and corresponding antibodies have recently been discovered in humans and animals. Increased autoimmune response to Nε -Hcy-proteins has been reported in stroke patients. The aim of the present study was to investigate whether antibodies against N-homocysteinylated albumin are associated with coronary artery disease (CAD).We studied 88 male patients aged 50 years or under with angiographically documented CAD and 100 age-matched apparently healthy men as controls. Serum levels of IgG antibodies against Nε-Hcy-albumin were determined using an enzymelinked immunosorbent assay. Seropositivity to anti-Nε -Hcy-albumin antibodies was 5-fold more frequent in CAD patients than in controls (52.3 % vs 10.0 %; p14.5 mM were seropositive compared with 25.5 % of normohomocysteinemic individuals (p=0.048).There was a weak correlation between anti-Nε-Hcy-albumin antibodies and Hcy levels (r=0.16; p=0.03). By multivariate logistic regression analysis, seropositivity to anti-Nε-Hcy-albumin antibodies was an independent predictor of early CAD (OR, 14.82; 95% CI, 4.47 to 49.19; p=0.00002). Interestingly, anti-Nε-Hcy-albumin antibodies were associated with C-reactive protein levels (r=0.24; p=0.002). Seropositivity to anti-Nε-Hcy-albumin antibodies showed no association with the MTHFR C677T polymorphism. Our results suggest that seropositivity to antibodies against Nε-homocysteinylated albumin is associated with early-onset CAD. An autoimmune response to Nε-Hcy-albumin may represent a novel mechanism involved in the early development of CAD.