Characteristics of the complement system gene expression deficiency in patients with symptomatic pulmonary embolism

Introduction

Pulmonary embolism (PE) is a disease with a high mortality and morbidity rate, and the pathogenesis of PE remains still unclear. We aimed to investigate the gene expression differences of the complement system in peripheral blood mononuclear cells (PBMCs) from patients with symptomatic PE and controls.

Methods

Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study. Human cDNA microarray analysis was used to detect the gene expression difference of the complement system between the two groups.

Results

1). Expression of twenty-one genes encoding complement components was detected. In PE patients, expression of the genes encoding C1qα, C1qβ, C4b, C5 and Factor P was significantly greater (P < 0.05) than controls, while C6, C7, C9, mannose-binding lectin (MBL) and mannan-binding lectin serine peptidase 1 (MASP1) mRNAs were lower (P < 0.05) than controls. 2). Expression of seven genes encoding complement receptors was examined. In PE patients, CR1, integrin αM, integrin αX and C5aR mRNAs were significantly up-regulated (P < 0.01) compared with controls. 3). Seven genes encoding complement regulators were examined. The mRNA expression of CD59 and CD55 was significantly up-regulated (P < 0.05), whereas Factor I mRNA was significantly down-regulated (P < 0.05) in PE patients than controls.

Conclusions

In PE patients, the mRNA expressions of complement components, receptors and regulators were unbalanced, suggesting dysfunction and/or deficiency of the complement system, which leads to decreased function of MAC-induced cell lysis in PE patients finally.     

Atorvastatin favorably modulates proinflammatory cytokine profile in patients following deep vein thrombosis

Background

Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients.

Materials and Methods

Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood.

Results

The VTE patients displayed higher C-reactive protein (p = 0.013), IL-1b (p = 0.03), IL-8 (p = 0.03) and vWF (p < 0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p = 0.0003), IL-8 (p = 0.003) and P-selectin (p < 0.0001), but increased IL-10 (p = 0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p = 0.01), IL-6 (p = 0.03) and P-selectin (p = 0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p < 0.05).

Conclusion

A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.     

Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents

Objective

Increased impulsivity seems to be present across all phases of bipolar disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it is also found among normal individuals at high genetic risk for mood disorders. In this study, we assessed impulsivity across four different groups of children and adolescents: patients with BD, major depressive disorder (MDD) patients, unaffected offspring of bipolar parents (UO), and healthy controls (HC).

Subjects and Methods

52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait impulsivity.

Results

UO displayed significantly higher total BIS-11 impulsivity scores than HC (p = 0.02) but lower scores than BD patients (F = 27.12, p < 0.01). Multiple comparison analysis revealed higher BIS-11 total scores among BD patients when compared to HC (p < 0.01) and UO (p < 0.01). MDD patients had higher BIS-11 scores when compared to HC (p < 0.01). Differences between MDD patients and UO, as well as between MDD and BD patients, were not statistically significant.

Conclusion

Our findings suggest that trait impulsivity is increased among children and adolescents with mood disorders, as well as in unaffected individuals at high genetic risk for BD.     

Hemarthrosis in hemophilic mice results in alterations in M1-M2 monocyte/macrophage polarization

Introduction

Joint bleedings result in iron-mediated synovitis and cartilage destruction. Monocyte/macrophage polarization affects their role in iron homeostasis. This study evaluates the effects of hemarthrosis on monocyte/macrophage polarization.

Materials and methods

Using a murine hemophilia model of acute joint bleeding and flow cytometry, we evaluated monocyte/macrophage polarization in blood, spleen, synovium, and knee lavage at day 1, 2, and 7 following the induction of hemarthrosis.

Results

Induction of hemarthrosis resulted in a transient shift of blood monocytes towards a M1 type (control 13 vs. 1847 counted cells at day 1; p < 0.01), a temporary decrease of spleen M1 monocytes (control 2841 vs. 1086 counted cells at day 1; p = 0.02), and a sustained decrease of spleen M2 red pulp macrophages (control 1853 vs. 673 counted cells at day 7; p = 0.01). In addition, an increase in M1 (control 119 vs. 592 counted cells at day 1; p = 0.04) and M2 (control 247 vs. 650 counted cells at day 1; p = 0.02) synovial macrophages was noted. In the joint lavage, a temporary increase in M1 monocytes (control 20 vs. 125 counted cells at day 1; p = 0.04) and a more sustained increase in M2 monocytes (control 73 vs. 186 counted cells at day 2; p < 0.01) was observed.

Conclusions

This study demonstrates alterations in monocyte/macrophage polarization following hemarthrosis resulting in a blood monocyte M1 phenotype and a combined M1-M2 monocyte/macrophage phenotype in the joint. Based on the different capabilities of M1 and M2 cells, modulating polarization of distinct monocyte/macrophage populations might represent interesting prophylactic or therapeutic approaches for joint bleedings.     

Pulmonary embolism in elderly patients: Prognostic impact of the Cumulative Illness Rating Scale (CIRS) on short-term mortality

Background

Pulmonary embolism (PE) is associated with high short-term mortality in elderly patients, even when hemodynamically stable.

Methods

One hundred and seventy hemodynamically stable patients with confirmed PE (41 < 65 years and 129 ≥ 65 years) were prospectively followed for one month in order to assess whether comorbidities can predict short-term mortality in elderly patients. Upon admission, patients’ clinical characteristics (including instrumental and laboratory parameters) were evaluated, and two clinical scores were calculated: the Cumulative Illness Rating Scale (CIRS), commonly used to evaluate comorbidities in elderly patients, and the Pulmonary Embolism Severity Index (PESI).

Results

Fifteen patients (all elderly) died within one month from their PE diagnosis (mortality rate = 8.8%; 95%CI:4.6-13.1%). In these non survivors, arterial partial oxygen pressure (p < 0.0001) and saturation (p < 0.0001), pH (p = 0.001) and systolic blood pressure (p = 0.017) at admission were significantly lower than in survivors, whereas their respiratory rate (p < 0.0001), white blood cells (p < 0.0001), lactate dehydrogenase (p < 0.0001), troponin T (p = 0.001) and D-dimer (p = 0.023) were significantly higher. CIRS correlated with PESI (rho = 0.54, p < 0.0001), and was higher in non-survivors (p = 0.002). The age- and sex-adjusted odds ratio of 1-month mortality was 1.91 (95%CI:1.24-2.95) for every 1-point increase in CIRS. The AUC was 0.78 (95%CI:0.67-0.89) for the logistic model containing CIRS, and 0.88 (95%CI:0.79-0.96) for that containing PESI (p = 0.059).

Conclusions

In elderly patients with PE, CIRS demonstrated a fairly good performance in predicting short-term mortality. Its easiness and suitability for use in common clinical practice make CIRS a potentially useful prognostic score for short-term mortality in these patients.     

The relationship between impulsivity and lipid levels in bipolar patients: does temperament explain it?

Background

The aim of this study was to investigate whether there was a relationship between impulsivity and lipid levels in patients with bipolar disorder (BD) and to examine the correlation of impulsivity and lipid levels with temperament subtypes.

Methods

For this purpose, one hundred patients who were admitted to our out-patient unit for routine controls, had been in remission for at least 8 weeks, and diagnosed as BD according to the DSM-IV were evaluated consecutively. Impulsivity and temperament were evaluated with the BIS-11 and the TEMPS-A. Blood samples were obtained to measure levels of lipids (cholesterol, triglyceride, high density lipoprotein-HDL, low density lipoprotein-LDL).

Results

A weak correlation was found between impulsivity scores and triglyceride levels (r = 0.190, p = 0.050). Correlation was found between impulsivity scores and depressive, anxious, cyclothymic, and irritable temperaments (r = 0.371, p < 0.001; r = 0.458, p < 0.001; r = 0.541, p < 0.001; r = 0.530, p < 0.001), while triglyceride levels were only related with depressive and anxious temperaments (r = 0.485, p = 0.001 and r = 0.391, p = 0.006).

Conclusions

Temperament is an important mediator of the relationship between lipid levels and trait impulsivity in patients with BD.     

Do sleep,stress, and illness explain daily variations in fatigue? A prospective study

Objective

Fatigue is related to a number of serious diseases, as well as to general well-being. It is also a major cause of sickness absence and use of health facilities. Still, the determinants of variations in fatigue are little investigated. The purpose of present study was to investigate the relationships between the daily variations of fatigue with sleep during the previous night, stress or disease symptoms during the same day — across 42 consecutive days of normal life.

Methods

50 individuals participated and gave diary reports and used an actigraph across the 42 days. The data was analyzed using a multilevel approach with mixed model regression.

Results

The analyses showed that the day-to-day variation in fatigue was related to (poor) sleep quality (p < .001) and (reduced) sleep duration (p < .01) the previous night, as well as to higher stress (p < .05), and to the occurrence of a cold or fever (p < .001) during the same day as the fatigue rating. Fatigue was also strongly related to poorer subjective health (p < .001) and sleepiness (p < .001) during the same day.

Conclusion

The results indicate that prior sleep (and sleepiness) as well as stress and illness are consistently connected to how fatigue is experienced during normal living conditions.     

Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers

Objective

Serotonin modulates human behavior and emotion. Recent evidence implies that a higher level of serotonergic activity could be associated with a higher level of perceived social support. This study aimed to examine the correlation between serotonin transporter (SERT) availability and perceived social support scores in healthy volunteers.

Methods

111 healthy participants, 50 males and 61 females, were enrolled from the community and completed the Measurement of Support Function questionnaire. Single photon emission computed tomography (SPECT) with [¹²³I] ADAM was performed to examine SERT availability.

Results

Perceived social support was positively correlated with SERT availability (Spearman's ρ = 0.29, p < 0.01; χ² = 7.57, p < 0.01), particularly in males (Spearman's ρ = 0.37, p < 0 .01; χ² = 11.77, p < 0.01). Censored regressions indicated that these associations are not influenced by a ceiling effect and remained significant after controlling the effect of age.

Conclusions

This result confirmed the correlation between perceived social support and central serotonergic activity. However, this correlation was present only in males.     

Sustained high plasma plasminogen activator inhibitor-1 levels are associated with severity and mortality in septic patients

Background

Higher plasma plasminogen activator inhibitor-1 (PAI-1) levels have been reported in septic patients. However, some questions remain unanswered, such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality, and inflammation state during the first week.

Methods

Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units of 260 patients with severe sepsis. Circulating levels of PAI-1 and tumour necrosis factor (TNF)-α were measured at day 1, 4 and 8. End-point was 30-day mortality.

Results

Nonsurviving septic patients (n = 89) presented higher PAI-1 levels than surviving (n = 171) at day 1 (58.4 (33.3-83.8) vs 36.5 (21.1-62.5) ng/mL; p < 0.001), 4 (34.0 (14.7-53.3) vs 16.2 (10.2-27.4) ng/mL; p < 0.001) and 8 (30.6 (16.2-47.8) vs 18.9 (10.4-29.5) ng/mL; p = 0.004). We found a positive correlation of PAI-1 levels with SOFA, lactic acid, aPTT, INR and TNF-α, and negative with platelet count at day 1, 4 and 8. Logistic regression analyses showed that PAI-1 levels at day 1 (p < 0.001), 4 (p < 0.001) and 8 (p = 0.001) were associated with 30-day mortality. On ROC curve analysis to predict 30- day survival, the area under the curve of PAI-1 levels at day 1, 4 and 8 were 0.65 (95% CI = 0.58-0.72; p < 0.001), 0.69 (95% CI = 0.60-0.78; p < 0.001) and 0.65 (95% CI = 0.54-0.75; p = 0.005) respectively.

Conclusions

The most interesting findings of our study, to our knowledge the largest series reporting PAI-1 levels during follow-up in septic patients, were that plasma PAI-1 levels during the first week were associated with inflammation, severity and mortality.     

Residual perfusion defects in patients with pulmonary embolism are related to impaired fibrinolytic capacity

Background

Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE).

Objective

To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnormalities.

Patients and methods

We studied 71 consecutive patients with a prior episode of PE, who were examined after one year of the incident embolic event, and at least one month after anticoagulation withdrawal. They underwent lung scintigraphy to assess the recovery of pulmonary perfusion, echocardiography and chest radiography to look for signs of pulmonary hypertension. Clot formation and lysis were evaluated by two turbidimetric methods: Clot and Lysis Assay and Clot Lysis Time. We also measured the in vitro plasmin-mediated lysis of fibrin from purified fibrinogen, and the circulating levels of fibrinolytic inhibitors. The sample was split in two categories based on the extent of residual perfusion defects: < 10% (n = 53), ≥ 10% (n = 18).

Results

Patients with perfusion defects > 10% had significantly longer lysis time (p < 0.05), and higher levels of plasminogen activator inhibitor-1 (p < 0.01) than those with perfusion defects < 10%. The time interval between symptoms onset and PE diagnosis (time-to-diagnosis) was significantly longer in patients with perfusion defects > 10% than in the others (p = 0.005). In multivariate logistic regression, both lysis time and time-to-diagnosis were independently associated with perfusion defects > 10% (p < 0.001). None of the sampled patients had echocardiographic or radiologic signs of pulmonary hypertension.

Conclusion

Prolonged time-to-diagnosis and fibrinolysis imbalance are independent predictors of incomplete perfusion recovery after acute PE.     

Facial emotion recognition in male antisocial personality disorders with or without adult attention deficit hyperactivity disorder

Objective

We aimed to investigate facial emotion recognition abilities in violent individuals with antisocial personality disorder who have comorbid attention deficient hyperactivity disorder (ADHD) or not.

Method

The photos of happy, surprised, fearful, sad, angry, disgust, and neutral facial expressions and Wender Utah Rating Scale have been performed in all groups.

Results

The mean ages were as follows: in antisocial personality disorder with ADHD 22.0 ± 1.59, in pure antisocial individuals 21.90 ± 1.80 and in controls 22.97 ± 2.85 (p > 0.05). The mean score in Wender Utah Rating Scale was significantly different between groups (p < 0.001). The mean accurate responses to each facial emotion between groups were insignificant (p > 0.05) excluding disgust faces which was significantly impaired in ASPD + ADHD and pure ASPD groups. Antisocial individuals with attention deficient and hyperactivity had spent significantly more time to each facial emotion than healthy controls (p < 0.05) while pure antisocial individual had more time to recognize disgust and neutral faces than healthy controls (p < 0.05).

Conclusion

Study of complex social cognitive abilities in adults with ADHD and violent behaviors is lacking. This study is the first, investigating the differences according to social cognition cues in violent individual that revealed no significance within pure antisocial individuals and antisocial individuals with ADHD.     

Weight-adjusted LMWH Prophylaxis Provides More Effective Thrombin Inhibition in Morbidly Obese Pregnant Women

Introduction

Low molecular weight heparin (LMWH) prophylaxis has been recommended for morbidly obese pregnant women (> 40 kg/m²). There is very little data on the anticoagulant effects of LMWH in this group. We investigated two different dosing regimens; fixed dose and weight-adjusted dose on the anticoagulant effects of the LMWH tinzaparin used for thromboprophylaxis in obese pregnant women.

Materials and Methods

Twenty morbidly obese pregnant women were started on a fixed dose of tinzaparin (4,500 iu/day) at 32 weeks gestation and then changed to a weight-adjusted dose (75iu/kg/day) for the remainder of their pregnancy. Four-hour post LMWH, venous bloods were taken after each initial dose and repeated every two weeks until delivery. Twenty normal weight women who did not receive LMWH at the same gestation were used as controls.

Results

Prior to LMWH prophylaxis, tissue factor pathway inhibitor (TFPI) levels in the obese group at 32 weeks were significantly lower (p < 0.001) and endogenous thrombin potential (ETP) and peak thrombin levels in obese group were significantly higher, compared with controls (p < 0.0001; p < 0.001).There was no significant difference between ETP levels before and after fixed LMWH. However, ETP levels were significantly lower post weight-adjusted dose compared with post fixed dose. There was a significant effect of LMWH on TFPI levels, (p < 0.0001). ETP correlated positively with total body weight prior to LMWH (r = 0.631) (p < 0.05) and at fixed dose (r = 0.578) (p < 0.05).

Conclusion

Morbidly obese pregnant women have increased thrombin generation and reduced natural anticoagulant in third trimester. This prothrombotic state was more effectively attenuated by weight-adjusted than fixed LMWH doses.     

Association of costs with somatic symptom severity in patients with medically unexplained symptoms

Objective

To analyse the association of direct and indirect costs in patients with medically unexplained symptoms (MUS) with somatic symptom severity (SSS).

Methods

A cross-sectional cost analysis for retrospective 6 months was conducted in 294 primary care patients with MUS. Health care utilisation and loss of productivity were measured by questionnaires. SSS was measured using the “Patient Health Questionnaire 15” (PHQ-15). Direct and indirect costs and the association of costs with SSS were analysed via multiple linear regression analysis.

Results

Patients with MUS had average 6-month direct costs of 1098 EUR and indirect costs of 7645 EUR. For direct costs, outpatient physician visits were the most expensive single cost category (36%), followed by pharmaceuticals (25%) and hospital stays (19%). Indirect costs were predominantly caused by productivity reduction at work (56%) followed by early retirement (29%) and acute sickness absence (14%). As compared to mild SSS, moderate SSS was not significantly associated with direct, but with indirect costs (+ 2948 EUR; p < .001); severe SSS was associated with increased direct cost (+ 658 EUR; p = .001) and increased indirect costs (+ 4630 EUR; p < .001). Age was positively associated with direct cost (+ 15 EUR for each additional year; p = .015) as well as indirect cost (+ 104 EUR for each additional year; p < .001).

Conclusions

MUS are associated with relevant direct and even much higher indirect costs that strongly depend on SSS.     

Tumour expresion of tissue factor and tissue factor pathway inhibitor in ovarian cancer- relationship with venous thrombosis risk

Introduction

Ovarian cancer is known to display a particular association with venous thromboembolism (VTE) with reports up to 42% of patients developing thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of this study was to measure tumour derived TF and TFPI and to investigate their potential role in VTE in ovarian cancer patients.

Methods

TF and TFPI mRNA expression was measured using TaqMan real time PCR in 99 ovarian tumour samples. Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and TFPI protein levels were measured using ELISA and immunohistochemistry was used to localize TF expression. The role of TF expression on overall survival was also determined.

Results

TF mRNA and protein expression was increased in tumours from patients with clear cell carcinoma (p < 0.001). TF protein expression was also increased in endometroid carcinoma (P < 0.01) compared with benign tumours. TFPI mRNA expression was increased in clear cell carcinoma (P < 0.01). TF mRNA and antigen level was increased in malignant tumours of patients who developed VTE compared with matched malignant õtumours of patients who remained thrombosis free (P < 0.01). There was no difference in TFPI expression between the two groups.

Conclusion

TF expression in ovarian cancer is significantly higher in patients who develop VTE. TF expression was increased in clear cell ovarian cancer and endometroid cancer and this may explain the higher risk of VTE in these subgroups. TF derived from these tumours may be the trigger for VTE in ovarian cancer.     

Which psychological factors exacerbate irritable bowel syndrome? Development of a comprehensive model

Objective

There is evidence that psychological factors affect the onset, severity and duration of irritable bowel syndrome (IBS). However, it is not clear which psychological factors are the most important and how they interact. The aims of the current study are to identify the most important psychological factors predicting IBS symptom severity and to investigate how these psychological variables are related to each other.

Methods

Study participants were 286 IBS patients who completed a battery of psychological questionnaires including neuroticism, abuse history, life events, anxiety, somatization and catastrophizing. IBS severity measured by the IBS Severity Scale was the dependent variable. Path analysis was performed to determine the associations among the psychological variables, and IBS severity.

Results

Although the hypothesized model showed adequate fit, post hoc model modifications were performed to increase prediction. The final model was significant (Chi² = 2.2; p = 0.82; RMSEA < .05) predicting 36% of variance in IBS severity. Catastrophizing (standardized coefficient (β) = 0.33; p < .001) and somatization (β = 0.20; p < .001) were the only two psychological variables directly associated with IBS severity. Anxiety had an indirect effect on IBS symptoms through catastrophizing (β = 0.80; p < .001); as well as somatization (β = 0.37; p < .001). Anxiety, in turn, was predicted by neuroticism (β = 0.66; p < .001) and stressful life events (β = 0.31; p < .001).

Conclusion

While cause-and-effect cannot be determined from these cross-sectional data, the outcomes suggest that the most fruitful approach to curb negative effects of psychological factors on IBS is to reduce catastrophizing and somatization.     

Reduced ANXA5 mRNA and protein expression in pregnancies complicated by preeclampsia

Introduction

The placental anticoagulant protein Annexin A5 (ANXA5) is a multifunctional protein that is highly expressed on the apical surfaces of syncytiotrophoblasts, and plays an important role in haemostatic regulations, maintaining blood fluidity of the placenta. The aim of this study was to investigate the expression of ANXA5 in pregnancies complicated by preeclampsia (PE).

Materials and Methods

Placental tissue samples were collected from 23 pregnancies with PE and 34 normal pregnancies. ANXA5 mRNA levels were measured by quantitative Real-Time PCR (qPCR), while ANXA5 protein expression was measured by Western Blot (WB) and immunohistochemistry.

Results

ANXA5 mRNA expression in PE samples was lower than 1% of its expression in normal samples (mean ± SD: 0.002 ± 0.004 vs. 0.55 ± 0.38, p < 0.001), while ANXA5 protein levels in PE samples were approximately at 65% of the average normal expression (mean ± SD: 0.53 ± 0.30 vs. 0.81 ± 0.25, p = 0.001). Immunohistochemical analysis also verified the above results, since PE placentas tended to have low labelling indexes (LIs), in contrast to controls which demonstrated high LIs (p = 0.020). Statistical analysis of the WB data revealed that ANXA5 protein expression was increased in PE smokers vs. PE non-smokers (mean ± SD: 0.64 ± 0.23 vs. 0.41 ± 0.33, p = 0.027).

Conclusions

These results suggest that ANXA5 downregulation could be part of the pathophysiology of PE and the possible impairment in coagulation processes, which are seen in pregnancies that demonstrate PE. Further studies may investigate whether ANXA5 could be used as a biomarker for the early detection of PE and for the prediction of its severity.     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Reduced plasma fibrin clot permeability and susceptibility to fibrinolysis are associated with increased intima-media thickness in patients with primary antiphospholipid syndrome

Introduction

Formation of denser fibrin networks displaying impaired lysability has been reported in subjects at an increased risk of atherosclerosis. Given recent data on prothrombotic fibrin clot phenotype reported in patients with antiphospholipid syndrome (APS), we tested the hypothesis that altered fibrin clot properties are associated with increased intima-media thickness (IMT) observed in PAPS.

Materials and methods

We studied 30 consecutive patients with PAPS and 30 controls matched for age, sex and the type of previous thromboembolism. We assessed plasma fibrin clot permeability (K_s) and clot lysis time (CLT) with their potential determinants. The IMT was measured in 3 segments of the carotid arteries.

Results

Patients with APS had 15.2% lower K_s (p = 0.002) and 9.7% prolonged CLT (p = 0.039) compared with controls. The IMT in the APS group was greater in the common carotid artery (5.7%; p = 0.002), at the bifurcation (17.46%; p < 0.001), and the internal artery (9.26%; p = 0.015). Patients with triple positivity in the antiphospholipid antibody profile (n = 9; 30%) had lower K_s and greater IMT (both, p < 0.05), compared with those with single positivity (n = 13; 43.3%). Multivariate analysis adjusted for potential confounders showed that in APS patients, oxidized low-density lipoproteins (p = 0.019) were the only independent predictor of K_s, while thrombin activatable fibrinolysis inhibitor activity (p < 0.001) predicted CLT. Plasminogen activator inhibitor-1 (PAI-1) was found to be the independent predictor of the IMT in the common carotid artery (p = 0.004), and in the internal carotid artery (p < 0.001).

Conclusions

Reduced K_s and susceptibility to lysis are associated with greater IMT in PAPS, which might contribute to the early atherosclerosis in this disease.     

Positive affect,anhedonia, and compliance with self-care in patients with chronic heart failure

Objective

Optimal self-care is crucial in patients with chronic heart failure (HF). While the focus of research has been on negative mood states, adequate psychological resources may be required to successfully engage in HF self-care. Therefore, the longitudinal associations of multiple positive affect measures in explaining HF self-care including consulting behavior were examined while adjusting for depressive symptoms and potential covariates (e.g., disease severity).

Methods

In this prospective cohort study, 238 patients (mean age: 66.9 ± 8.6 years, 78% men), with chronic HF completed questionnaires at baseline and 1-year follow-up. Positive affect was assessed with the Positive and Negative Affect Schedule (PANAS) and the Global Mood Scale (GMS). Anhedonia, i.e. diminished interest or pleasure, was assessed with a subscale of the Hospital Anxiety and Depression Scale (HADS). The 9-item European Heart Failure Self-care Behaviour scale was completed to assess HF self-care including consultation behavior.

Results

Linear mixed modeling results showed that anhedonia was most strongly associated with both poor self-care (estimate = − .72, P < .001) and consulting behavior (estimate = − .44, P < .001) over time, after adjustment for covariates and depressive symptoms. GMS positive affect was related to better HF self-care adjusting for standard depressive symptoms but not when adjusting for anhedonia. PANAS positive affect was not independently related to self-care.

Conclusion

Anhedonia was associated with worse compliance with self-care among chronic HF patients over time, irrespective of disease severity and depression. Associations between positive affect and self-care were dependent on the measures used in multivariable analyses.     

Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder

Objective

Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism.

Method

Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen’s.

Results

In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106) = 6.095; p < .05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106) = 4.068, p = .046; F(1, 106) = 4.068, p = .046; F(1, 106) = 6.064, p = .016).

Conclusion

According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children.