Ophthalmological Manifestations and Tear Investigations in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. There are only few reports available concerning ophthalmological complications in the course of SSc, although ocular manifestations, e.g., dry eye syndrome (DES), occurs frequently and decreases the quality of life of these patients. Vascular endothelial growth factor (VEGF), the major pro-angiogenic factor, plays a key role in the pathomechanism of SSc. Although elevated levels of VEGF in sera have already been demonstrated, VEGF analysis in tears of patients with SSc has not been performed in previous studies. VEGF in the tears of patients with SSc was found to be decreased by 20%, compared to healthy controls. The reason why the VEGF levels are not elevated in the tears of patients with SSc needs further investigations, as does the sera of the same patients. The cytokine array results revealed a shift in the cytokine profile characterized by the predominance of inflammatory mediators. Our current data depict a group of cytokines and chemokines, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc with ocular manifestations

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course

High circulating osteoprotegerin levels are associated with non-zero blood groups

Background: Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients. Methods: Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data. Results: OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002). Conclusions: OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF: CB might have functional importance in an atherothrombosis-prone biological environment

Follow-up of thrombin generation after prostate cancer surgery: global test for increased hypercoagulability.

Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual's hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events

Membrane array and multiplex bead analysis of tear cytokines in systemic sclerosis

Although serious ocular manifestations of systemicsclerosis (SSc) have been described, tear analysis ofpatients with SSc has not been performed in previousstudies. Our aim was to measure a wide panel of cytokinesand chemokines in tears of patients with SSc and to assessthe most significant molecules with a more sensitive andspecific method. Unstimulated tear samples were collectedfrom nine patients with SSc and 12 age- and gender-matchedhealthy controls. The relative levels of 102 differentcytokines were determined by a cytokine array, and thenabsolute levels of four key cytokines were determined by amagnetic bead assay. Array results revealed shifted cytokineprofile characterized by predominance of inflammatorymediators. Of the 102 analyzed molecules, nine weresignificantly increased in tears of patients with SSc. Basedon the multiplex bead results, C-reactive protein, interferon-c-inducible protein-10, and monocyte chemoattractant protein-1 levels were significantly higher in tears of patients with SSc. Our current data depict a group of inflammatory mediators, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc patients with ocular manifestations

Specific test results of patients before and following radical prostatectomy.

1<p>Results are given as mean and ±SD or median and 25–75 percentile values, depending on the normality of the test results. P values are also calculated according to the distribution of the given data series and the option of pairing. Preoperative data were compared to controls and the results of the postoperative samples were compared to the preoperative ones (day-1).</p>2<p>limit of detection.</p>3<p>No LMWH therapy.</p><p>Bold letters indicate significant differences.</p

Thrombin generation parameters: Whiskers: 5–95 percentile graphs of peak thrombin (A), area under the curve (B), lag time (C) and peak time (D).

<p>Labels of significance: *p<0.05, **p<0.01, ***p<0.001.</p

Routine test results of patients before and following radical prostatectomy.

1<p>Results are given as mean and ±SD or median and 25–75 percentile values, depending on the normality of the test results. P values are also calculated according to the distribution of the given data series and the option of paring: i.e. “preoperative results” to the “results of the controls” with unpaired t test (with Welch’s correction or Mann Whitney test); “postoperation results” to the “preoperative results” with Paired t test (and Wilcoxon signed rank test). Preoperative data were compared to controls and the results of the postoperative samples were compared to the preoperative ones (day-1).</p>2<p>reference range of the method applied.</p>3<p>mean±2SD of pooled control samples (n = 20) in the period of the study.</p>4<p>ND = not determined.</p><p>Bold letters indicate significant differences.</p