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).

An open-source platform for interactive collision prevention in photon and particle beam therapy treatment planning.

We present an open-source platform to aid medical dosimetrists in preventing collisions between gantry head and patient or couch during photon or particle beam therapy treatment planning. This generic framework uses the native scripting interface of the particular planning software to import STL files of the treatment machine elements. These are visualized in 3D together with the contoured or scanned patient surface. A graphical dialog with sliders allows the interactive rotation of the gantry and couch, with real-time feedback. To prevent a future replanning, treatment planners can assess in advance and exclude beam angles resulting in a potential risk of collision. The software platform is publicly available on GitHub and has been validated for RayStation with actual patient plans. Furthermore, the incorporation of the complete patient geometry was tested with a 3D surface scan of a full-body phantom performed with a handheld smartphone. With this study, we aim at minimizing the risk of replanning due to collisions and thus of treatment delays and unscheduled consumption of manpower. The clinical workflow can be streamlined at no cost already at the treatment planning stage. By ensuring a real-time verification of the plan feasibility, the script might boost the use of optimal couch angles that a planner might shy away from otherwise.

Clinical predictors of complications in patients with left-sided infective endocarditis: A retrospective study of 206 episodes.

PURPOSE: Early identification of specific patient subgroups at high risk of developing life-threatening infective endocarditis (IE) complications is of paramount importance. Better stratification may allow more intensive treatment of these patients and positively influences clinical outcomes. METHODS: We carried out a retrospective survey of consecutive left-sided IE adult patients, admitted over a 15-year period to two main tertiary care centres in the Czech Republic. RESULTS: Among a group of 196 patients (155 males; median age 64 years), a total of 206 left-sided IE episodes were identified. Perivalvular extension of infection was most frequently seen in prosthetic aortic valve endocarditis (OR 6.706, p<0.0001). Valve prolapse/perforation during IE episodes was significantly associated with mitral valve IE (OR 2.136, p=0.026) and vegetation length (OR 1.055, p=0.009). Septic shock was significantly related to two main risk factors: S. aureus infection (OR 8.459, p=<0.0001) and smoking (OR 8.403, p=0.001). Mitral valve IE with a vegetation length ≥13 mm was the strongest risk factor for this complication (OR 3.24, p=0.001), followed by S. aureus infection (OR 3.59, p=0.002). Finally, septic shock (OR 6.000, p=0.001) represented the most important risk factor of in-hospital mortality. CONCLUSIONS: This study provides the most detailed profile of complication predictors related to left-sided IE in Central Europe. Early individual stratification of IE related occurrence of complications might help to decrease extremely high morbidity and mortality of this disease (Tab. 5, Ref. 37).

A Monte Carlo based radiation response modelling framework to assess variability of clinical RBE in proton therapy.

The clinical implementation of a variable relative biological effectiveness (RBE) in proton therapy is currently controversially discussed. Initial clinical evidence indicates a variable proton RBE, which needs to be verified. In this study, a radiation response modelling framework for assessing clinical RBE variability is established. It was applied to four selected glioma patients (grade III) treated with adjuvant radio(chemo)therapy and who developed late morphological image changes on T1-weighted contrast-enhanced (T1w-CE) magnetic resonance (MR) images within approximately two years of recurrence-free follow-up. The image changes were correlated voxelwise with dose and linear energy transfer (LET) values using univariable and multivariable logistic regression analysis. The regression models were evaluated by the area-under-the-curve (AUC) method performing a leave-one-out cross validation. The tolerance dose TD50 at which 50% of patient voxels experienced toxicity was interpolated from the models. A Monte Carlo (MC) model was developed to simulate dose and LET distributions, which includes variance reduction (VR) techniques to decrease computation time. Its reliability and accuracy were evaluated based on dose calculations of the clinical treatment planning system (TPS) as well as absolute dose measurements performed in the patient specific quality assurance. Morphological image changes were related to a combination of dose and LET. The multivariable models revealed cross-validated AUC values of up to 0.88. The interpolated TD50 curves decreased with increasing LET indicating an increase in biological effectiveness. The MC model reliably predicted average TPS dose within the clinical target volume as well as absolute water phantom dose measurements within 2% accuracy using dedicated VR settings. The observed correlation of dose and LET with late brain tissue damage suggests considering RBE variability for predicting chronic radiation-induced brain toxicities. The MC model simulates radiation fields in patients precisely and time-efficiently. Hence, this study encourages and enables in-depth patient evaluation to assess the variability of clinical proton RBE.

Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?

OBJECTIVES: Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. METHODS: This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. RESULTS: Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 ± 9% and 32 ± 9% in patients with a venous allograft bypass and 46 ± 10% and 22 ± 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 ± 7%, 72 ± 8% and 63 ± 9%, and in the autologous group 91 ± 6%, 76 ± 9%, and 65 ± 13%, with no difference between groups (p = .69). CONCLUSIONS: Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage.

A comparison of secondary prevention practice in poststroke and coronary heart disease patients.

OBJECTIVES: It is evident that patients with atherosclerotic vascular disease (AVD) benefit from appropriate secondary prevention. In clinical reality, the secondary prevention in AVD patients other than those with coronary heart disease (CHD) is often overlooked. Therefore, we compared the adherence to secondary prevention principles between poststroke and CHD patients. STUDY DESIGN: Descriptive (cross-sectional) study with prospective mortality follow-up. METHODS: We examined 1729 chronic patients with AVD (mean age 65.9 (±SD 9.6) years), 964 with CHD, and 765 poststroke (pooled data of Czech samples of EUROASPIRE III, IV, and the ESH stroke survey). The interview was performed 6-36 months after the coronary event/revascularization or the first ischemic stroke, while the mortality follow-up 5 years after this interview. RESULTS: Poststroke patients had a significantly higher risk of persistent smoking, blood pressure ≥140/90 mmHg and LDL ≥2.5 mmol/L than CHD patients [odds ratios adjusted for age, gender and survey were 1.63 (95% CI: 1.13-2.33), 1.38 (95% CI: 1.13-1.69) and 2.26 (95% CI: 1.84-2.78), respectively]. In contrast, poststroke patients showed a lower risk of inappropriate glucose control and hypertriglyceridemia [0.66 (95%CI: 0.54-0.82) and 0.74 (95%CI: 0.61-0.91), respectively]. The prescription rates of antiplatelets/anticoagulants, antihypertensives and statins were also significantly lower in poststroke than in CHD patients (89.4 vs 93.7, 85.9 vs 97.5, and 57.7 vs 89.8, respectively). Mortality analysis was performed in a subsample of 815 subjects interviewed in 2006/07. The 5-year all-cause mortality rates were 25.8% and 13.3% in poststroke and coronary patients, respectively (P = 0.0023); the hazard ratio for stroke adjusted for major risk factors was 1.85 (95% CI: 1.31-2.63). CONCLUSIONS: Compared to CHD patients, poststroke patients are strongly handicapped in terms of poor adherence to secondary prevention target, prescription of basic pharmacotherapies and mortality risk.

Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population.

Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.

Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: consecutive survivors and population-based controls.

OBJECTIVE: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking. METHODS: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism. RESULTS: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype. CONCLUSIONS: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.

Endothelial dysfunction expressed as endothelial microparticles in patients with end-stage heart failure.

Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies.

Reinforced aneurysmorrhaphy for true aneurysmal haemodialysis vascular access.

OBJECTIVE: In 2008, a new technique of reinforced aneurysmorrhaphy with a polyester mesh tube for salvaging true aneurysmal arteriovenous (AV) haemodialysis access was described by us. In this study, the long-term patency and complication rates associated with this procedure were analysed, and the effect of reinforced aneurysmorrhaphy on high-flow vascular access was assessed. METHODS: This was a retrospective non-randomised study with prospectively collected data performed at a single centre. Patients with true aneurysmal haemodialysis AV access who underwent aneurysmorrhaphy with external mesh prosthesis between March 2007 and October 2012 were included. Clinical assessment and duplex ultrasound were performed preoperatively, 1, 3, and 12 months postoperatively, and annually thereafter. RESULTS: Data from 62 patients (median age 60 years, range 28-81 years; 63% men) were analysed. The commonest indication was high-flow vascular access associated with the risk of high output cardiac failure (24 patients, 39%). The mean follow-up time was 14.66 ± 12.80 months. Primary patency rates at 6 and 12 months were 86% and 79% respectively. Assisted primary patency rates at 6 and 12 months were 89% and 80% respectively. In 23 patients (96%) operated on for high-flow vascular access, decreased vascular access flow was observed after the procedure. The average flow reduction after aneurysmorrhaphy was 2,197 mL/minute. Postoperative bleeding and infection necessitating surgical revision occurred in three (4.8%) and three (4.8%) patients respectively. CONCLUSIONS: Reinforced aneurysmorrhaphy with an external mesh prosthesis is an effective method for treating true aneurysmal haemodialysis AV access, with excellent long-term patency and minimal complications due to infection.

Relation of central and brachial blood pressure to left ventricular hypertrophy. The Czech Post-MONICA Study.

Central blood pressure (BP) has been shown to be a better predictor of target organ damage and cardiovascular events than brachial BP. Whether central BP is a better predictor of left ventricular hypertrophy (LVH) determined by electrocardiography (ECG) is not known. Radial applanation tonometry and ECG were performed in 728 subjects from the Czech Post-MONICA Study (a randomly selected 1% population sample). LVH was determined using the Sokolow-Lyon index and Cornell product; central pressure was derived from radial pulse. Of 657 subjects included in the analysis, 17 (9.4%) below 45 years and 43 (9%) over 45 years had LVH. In multiple linear regression analysis, the Sokolow-Lyon index in younger individuals was only associated with male sex and low BMI, with no association with BP found. In older individuals, LVH was associated with higher central and brachial BP. In separate binary logistic regression analyses adjusted for covariates, the odds ratio for central systolic pressure was higher than those for brachial systolic and pulse pressure in LVH prediction. Noninvasively determined central pressure in subjects over 45 years is more strongly related to ECG LVH than brachial pressure. This further supports a closer association of central pressure with target organ damage. Voltage criteria of LVH are not independently associated with central or brachial BP in younger individuals.

A novel oscillometric device for peripheral arterial disease screening in everyday practice. The Czech-post MONICA study.

AIM: Ankle brachial index (ABI) is a diagnostic tool for peripheral arterial disease (PAD) and a cardiovascular risk stratification tool. Despite this evidence and guidelines recommending its use in everyday practice, ABI is not widely used. Automatic ABI measurement may lower the barrier to incorporate ABI measurement into everyday practice. The aim of this study was to validate a novel automatic oscillometric ABI device (BOSO ABI) against a gold standard-Doppler device in an epidemiological setting. METHODS: In 839 patients from the Czech post-MONICA study (a randomly selected representative population sample aged over 25 years), mean age 54.3±13.8 years (47% of men), ABI measurement was performed using the BOSO ABI device and a handheld Doppler device in a random fashion. The two techniques were carried out by different investigators each blinded to the findings of the other. Analyses were conducted as proposed by Bland and Altman. RESULTS: The mean ABI difference between the two methods was 0.1±0.11, with 95% limits of agreement ranging from -0.11 to 0.30. The difference between Doppler and oscillometric ABI increased significantly with increasing mean ABI (r=0.29; P<0.001). When considering Doppler the gold standard, automated oscillometric measurement had a 76.9% sensitivity, 97.9% specificity, and 37% positive and 99.6% negative predictive values in diagnosing ABI <0.9. CONCLUSION: The BOSO ABI device cannot be used interchangeably for standard Doppler ABI measurement in diagnosing PAD. However, its high negative predictive value allows using it as a screening tool for PAD.

Fetuin-A early after renal transplantation.

BACKGROUND: Fetuin-A is a major inhibitor of ectopic calcium phosphate precipitation and an acute phase reactant. Its deficiency, common in end-stage renal disease, has been suggested to be associated with cardiovascular complications. The aim of this study was to monitor fetuin-A levels in the early period after renal transplantation. METHODS: 30 deceased donor kidney recipients treated with calcineurin inhibitor-based immunosuppression were followed prospectively for the first 3 months and the association of fetuin-A levels with clinical and laboratory parameters was evaluated. RESULTS: Despite a correlation of fetuin-A levels with creatinine clearance (r = 0.348, p < 0.01) and estimated GFR (r = 0.331, p < 0.01), no significant increase in fetuin-A levels over the first 3 months was observed. Moreover, a significant decrease in serum fetuin-A levels was noted at 2 weeks (p < 0.001). Subsequently, fetuin-A levels increased (p < 0.001) reaching pretransplant values at month 3. CONCLUSIONS: In this study there was no increase of fetuin-A levels during the first 3 months, but a decrease 2 weeks after transplantation was observed.

[Experimental use of the peritoneal graft as a vascular prosthesis]. / Vyuzitie peritoneálneho stepu ako cievnej náhrady v experimente.

INTRODUCTION: The parietal peritoneum appears to be a suitable material for the vascular system reconstructions. AIM: The aim was to assess and compare thrombogenicity and ability for endothelization of the mesothelial and submesothelial side of the parietal peritoneum in the canine venous system. EXPERIMENTAL ANIMALS: canis familiaris (n = 13), half-breeds of both sexes, aged between 1 and 2 years, weighting 15-25kgs, underwent authological transplantations of the peritoneal grafts with the mesothelial side in the lumen- the group M (n = 5) and with the submesothelial side in the lumen the group S (n = 5). In the control group K (n = 3) a part of the venous wall was used as a graft and was affixed back to its original place. The bioptic samples collected on the 10th, 20th, 30th and 40th postoperative day (POD) were stained using the HE staining, NADPH-d and imunohistochemically on the intermedial filaments. The endothelization rate of the peritoneal graft was measured using morphometry and the trombogenicity was assessed peroperatively. RESULTS: In none of the trial groups a presence of thrombi was detected peroperatively. In the first trial group (group M), the onset of the peritoneal graft epithelization (reaching 20%) was recorded on the 10th POD. The endothelization process was completed on the 30th POD in this trial group. In the second trial group (group S), the peritoneal graft epithelization reaching 10% was recorded on the 10th POD. The process was completed on the 40th POD. In the third trial group K, no endothelial changes were recorded during the experiment. CONCLUSION: Both sides of the peritoneum do not show signs of thrombogenicity and possess ability for endothelization.

[Histologic changes in the jejunal wall after autotransplantation in a dog]. / Histologické zmeny v stene jejuna po jeho autotransplantácii u psa.

INTRODUCTION: Damages to the small intestinal wall resulting from ischemic-reperfusion changes, represent common complications of the clinical transplantation of the small intestine. AIM: Evaluation and quantification of the histological changes in the jejunal wall following its autotransplantation in a dog using the scale according to Park. MATERIAL AND METHODS: In dogs (n = 8), mongrel of both sexes, aged from 6 months to 2 years, weighting from 10 to 25 kgs, a resection of the jejunum followed by its autotransplantation was performed. At the time of the jejunal harvest, then after one-hour-long cold ischemia, 20 minutes after its reperfusion and then the 10th and the 20th day after the transplantation, bioptic samples of the whole jejunal wall were taken to be examined histologically. After being stained with hematoxyllin-eosine, the samples were evaluated according to the Park grading system. STATISTICS: The severity of the jejunal wall damage at the respective biopsy samples collection times was evaluated using the t-test for two dependent samples. RESULTS: After an hour-long cold ischemia, signs of increasing damage to the intestinal wall were observed, when compared to the peroperative sample (0 +/- 0) up to the degree 0.68 +/- 0.5 of the Park grading schema (p < 0.05). This damage degree increased 20 minutes after the reperfusion up to the value of 4 +/- 0 (p < 0.05). On the 10th and the 20th day a practically normal histological picture of the jejunal wall was observed. The histological changes in both cases were graded 0.38 +/- 0.5 (p < 0.05). CONCLUSION: Maximum histological changes following the autotransplantation of the small intestine with an hour-long cold ischemia were observed 20 minutes after the reperfusion. After 10 postoperative days, a practically normal histological picture of the small intestinal wall structure was observed. It remained unchanged even on the 20th postoperative day.