We demonstrate autosomal-recessive Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in a patient with relapsing C. albicans meningoencephalitis. We identified a novel, hypomorphic mutation with intact Th17 responses, but impaired GM-CSF responses. We report complete clinical remission with adjunctive GM-CSF therapy, suggesting that a CARD9/GM-CSF axis contributes to susceptibility to candidiasis.
IntroductionHeart perforation is a rare complication of pacemaker (PM)/implantable cardioverter-defibrillator (ICD) implantation.Material and methodsIn our clinic in 2005–2010, 6 patients with heart perforation were hospitalized (3 women, 3 men), mean age 58.6 ±20.8 years (17 to 73 years). The indication to PM/ICD implantation was tachy-brady syndrome in 3 cases, second-degree atrioventricular block, advanced with losses of consciousness, vaso-vagal syndrome type II B with asystole lasting 12 s and recurrent non-sustained ventricular tachycardia in 1 patient. We analyzed patient's medical records, X-rays, echocardiography, computed tomography (CT) and procedure protocols.ResultsThe incidence of heart perforation was 0.09%. Symptoms developed 4 to 990 days (mean 186.3 ±394.3) after PM/ICD implantation. The perforation site was found in the right atrial wall in 1 cases and the right ventricular wall in 6 cases. The TTE revealed an accumulation of fluid in the pericardium over 10 mm behind the posterior wall of the left ventricle in all patients. The CT scan confirmed perforation of the heart chambers (atrium and in 6 cases ventricle). In 5 cases the whole device was removed by direct traction or percutaneous lead extraction with pericardiocentesis when necessary (pericardium drainage in 3 cases) while in 1 case cardiac surgery was needed.ConclusionsThe perforating lead may be removed by direct traction in the operating room with cardiosurgical, anesthesiological and echocardiographical backup. In case of the lead perforation outside the pericardial sac or its atypical location, cardiac surgery is a safer method. The most important diagnostic method remains computed tomography.
Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.
IntroductIon Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is associated with a prothrombotic state reflected by elevated thrombin generation markers, including F1 + 2 prothrombin fragments, or D-dimer. 1,2 It has also been shown that increased levels of plasminogen activator inhibitor 1 (PAI-1) occur in patients with AF. 3 Other hypercoagulability markers detected in permanent AF involved increased levels of plasma fibrinogen, von Willebrand factor, and soluble P-selectin. 4 It is well known that AF is associated with an increased risk of stroke and arterial thromboembolism, which can be effectively reduced by anticoagulation. 5,6 In AF patients aged 75 years or older taking adjusted-dose of warfarin, the stroke rate per year was nearly half lower compared with AF patients on aspirin. 7 AF is also associated with an increased risk of myocardial infarction (MI). 8 Moreover, vascular endothelial cell damage is observed in AF patients as evidenced by elevated soluble thrombomodulin (sTM). 9 TM, an integral
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