Characteristics, management, and outcome of infective endocarditis in the Czech Republic: prospective data from the ESC EORP EURO-ENDO registry.

INTRODUCTION: Data describing contemporary profile of infective endocarditis (IE) in the Czech Republic are lacking. The aim of this study was to describe the current profile and outcomes of IE patients. METHODS: Prospectively collected data on consecutive patients admitted for IE diagnosis between April 2016 and March 2018 to 11 main tertiary care cardiac centers in the Czech Republic were used for this analysis. RESULTS: Among 208 patients, 88 patients (42.3 %) had native valve IE (NVIE), 56 patients (26.9 %) had prosthetic valve IE (PVIE), and 57 patients (27.4 %) had intracardiac device-related IE (CDRIE). The mean age was 61.66±15.54 years. Staphylococcus aureus was the most common etiological agent of IE (27.4 %), whereas Culture negative IE was present in 26.4 % patients. Surgery was performed during hospitalization in 112 (53.8 %) patients. In-hospital death occurred in 21.2 % patients, while 1-year mortality was 40.3 %. In patients, who had an indication for surgery, but the procedure was not performed, mortality was significantly higher (p=0.002). CONCLUSION: High proportion of culture negative IE and IE related to artificial intra-cardiac materials calls for action. Furthermore, we show that cardiac surgery should be more often contemplated, especially in the presence of risk factors as septic shock and congestive heart failure (Tab. 6, Fig. 1, Ref. 32).

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors]. / Pirrozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy II. cast. Receptory TLR, význam polymorfizmu receptoru pro nebezpecné vzory.

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part 1: identification of danger signals by innate immunity]. / Prirozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy I. cást: Prirozená imunita, rozlisení signálu nebezpecí.

Cellular and humoral components of innate immunity are able to identify danger signals both of the exogenous and endogenous origin. Exogenous danger signals are evolutionary conserved mosaics of danger patterns which are frequent in pathogenic microbes. Endogenous danger signals are raised during damage of self structures, by oxidative stress and/or by chemical modification of self molecules. Danger signals are identified by several families of molecules which are expressed on the surfaces of innate immunity cells. Among them the TLR receptors family which is associated with intracellular signaling pathway NF-kappaB is one of the most important. The inflammatory response is induced via activated NF-kappaB transcription factor.

Rapid onset of ICAM-1 expression is a marker of effective macrophages activation during infection of Francisella tularensis LVS in vitro.

Francisella tularensis is capable to modulate immunobiological activities of the host cells. We focused on the expression of ICAM-1 (CD54) on J774.2 mouse macrophage cell line infected by F. tularensis live vaccine strain (LVS) in vitro as a putative marker of subsequent elimination of infection. J774.2 cell line cells were infected by F. tularensis LVS strain (multiplicity of infection, 1:100). Cell cultures were stimulated either 3 h before infection or 3 h after infection by either lipopolysaccharide (LPS) or interferon γ (IFN-γ). The expression of ICAM-1 was determined by flow cytometry 6 h after infection. The intensity of ICAM-1 expression after 6 h of J774.2 macrophage cells infection by F. tularensis is very sensitive indicator of the effective macrophages stimulation resulting in the elimination of F. tularensis infection. The mean fluorescence intensity MFI = 49.8 is set-up by our experiments as a reliable threshold of the effective elimination of F. tularensis experimental infection with 83.3% sensitivity and 96.7% specificity, respectively. Simultaneous stimulation of J774.2 macrophage cells by LPS and IFN-γ was essential to elicit the elimination of F. tularensis infection. The ICAM-1 expression determined by flow cytometry can be considered to be highly sensitive and specific approach to predict elimination of F. tularensis infection by J774.2 macrophages.

J774 macrophage-like cell line cytokine and chemokine patterns are modulated by Francisella tularensis LVS strain infection.

Mutual interactions were investigated between intracellular parasitic bacterium Francisella tularensis (F.t.; highly virulent bacterium responsible for tularemia, replicating within the host macrophages) and murine macrophage-like cell line J774. Recombinant murine lymphokine INF-gamma and/or LPS derived from E. coli were determined to stimulate in vitro antimicrobial activity of macrophage-like J774 cell line against the live vaccine strain (LVS) of F.t. through their ability to produce proinflammatory cytokines and chemokines. F.t. infection up-regulated IL-12 p40 production and down-regulated TNF-alpha production by stimulated macrophages; on the other hand, F.t. infection did not affect the production of IL-8, IL-6, MCP-5, and RANTES by stimulated macrophages. This showed that F.t. infection modulates the cytokine synthesis by J774 macrophage cell line.

Action potentials of the rabbit, guinea pig, dog and albino rat working ventricular myocardium under interpolated extrasystole conditions during postnatal ontogenesis.

Experiments were carried out on the working myocardium of the right heart ventricle of newborn and adult rabbits, guinea-pigs, dogs and albino rats. In the dog, the guinea-pig and the rabbit, after ten action potentials (AP) elicited with 1 Hz frequency we always interpolated an extrasystole at an interval (TE) of 100-900 ms. In albino rats we used a basic frequency of 2 Hz and a TE of 30-370 ms from the last regular AP. Using glass microelectrodes, we recorded the extrasystolic AP (EAP) and the next subsequent AP (2AP). The results were evaluated by constructing graphs of the correlations of the duration of the plateau phase (D0) to TE and of the duration of repolarization to -60 mV level (D60) to the TE. In the myocardium of newborn rabbits, guinea-pigs and dogs, with short TE both D0 and D60 of the EAP are shorter than in the steady state (SS), while for the 2AP the same parameters are influenced only a little. As the TE lengthens, the EAP gradually acquire a length corresponding more to the SS. With TE longer than half the duration of the cycle in the steady state the EAP return to normal, while the 2AP become shorter. The effect of extrasystole on the rat EAP and 2AP diminished with advancing age. In the myocardium of adult rabbits and adult guinea-pigs, and slightly in the myocardium of adult dogs and newborn rats, we observed that the duration of the EAP, with certain TE, was greater than in the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of a period of inactivity on the duration of post-rest action potentials of the mammalian working ventricular myocardium in correlation to the preceding stimulation frequency.

Experiments were carried out on the working right ventricular myocardium of adult cats, guinea-pigs and rabbits. Membrane voltage was recorded by the glass microelectrode technique and the preparations were stimulated with frequencies of 5, 1 and 0.2 Hz. After a steady state had been reached, a pause (TP) lasting 10-600 s was interpolated. The influence of TP on the duration (D) of post-rest action potentials (AP) was studied; the effect of the pause was measured at electric zero level (D0) and at further repolarization levels (-20, -40 and -60 mV, given here as D-20, D-40 and D-60). At 1 and 0.2 Hz frequency, the cat myocardium displayed lengthening of the AP proportional to the duration of the pause; at 5 Hz frequency, D0 reacted by lengthening up to TP = 120 s and to further pauses by slight shortening. D-60, at all frequencies, lengthened throughout the whole of the given TP range. The rabbit myocardium, at all the given frequencies, reacted up to TP = 60-120 s by marked shortening of post-rest AP at all repolarization levels; with longer pauses the AP lengthened. At 5 Hz frequency the guinea-pig myocardium reacted similarly to the cat myocardium; at the lower stimulation frequencies, the pause-induced changes in the post-rest AP were less strongly expressed. In all the given types of myocardium, the most pronounced post-rest AP reactions were those at electric zero level (the plateau phase of the AP); towards more negative repolarization values and with lower pre-pause stimulation frequencies they were less strongly expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical and electrical manifestations of the papillary muscles of verapamil-treated adult guinea-pigs under steady state conditions and after a pause.

The authors studied the effect of verapamil in 10(-7) to 10(-4) mol.l-1 concentration on the duration of action potentials (AP) and the corresponding isometric contractions (MG) from the right ventricular papillary muscles of adult guinea-pigs. In the steady state, using stimulation frequencies of 0.1, 1 and 2 Hz, verapamil caused dose- and use-dependent shortening of the AP plateau phase (D0) in 10(-5) and 10(-4) mol.l-1 concentration; lower concentrations did not affect the D0. With all the given concentrations, the MG fell in relation to the dose and the stimulation frequency. The pause regimen was defined by the induction of a steady state at 1 Hz frequency, followed by the interpolation of a pause lasting 5 s to 600 s and its effect was studied on the first and second AP after the pause and on the corresponding MG, without any pharmacological treatment and in the presence of verapamil (10(-5) mol.l-1). In the absence of the drug, slight lengthening of the D0 and weakening of the MG, proportional to the length of the pause, occurred after the pause. In the presence of verapamil, the first post-rest contraction after a 10 s pause attained five-fold the value in the steady state, while the second post-rest contraction was much weaker than the first. The possibility that verapamil acts on intracellular links in calcium metabolism, and of disproportion of its effect on the D0 and on contractility when it is administered in low concentrations, is discussed. The most likely mechanism of this effect is the presence of a negative feedback between calcium release from the sarcoplasmic reticulum and membrane electrogenesis.