Cardiovascular risk in myositis patients compared with the general population.

OBJECTIVES: We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. METHODS: Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. RESULTS: Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. CONCLUSION: Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

Today's view of hereditary thrombophilia.

Venous thromboembolism (VTE) is still a serious medical problem with the non-decreasing incidence of new cases despite prophylaxis in risky situations. It is a multifactorial disease, in which the hereditary component is also significantly involved. The aim of the current research is to search for new polymorphisms that are involved in thrombogenesis in addition to classical thrombophilia (deficiency of natural coagulation inhibitors and FVL and FII prothrombin mutations). The article provides an overview of the results of already performed genome-wide association studies of VTE and their use for the calculation of the so-called polygenic risk score, which could be used for individualized prevention of VTE after standardization of the method.

Optimizing clinical approaches to COVID-19 patients in primary care.

There is insufficient evidence from medical studies for clinical approaches to patients with COVID-19 in primary care. Patients often urge the therapeutic use and preventive administration of various medicines, often controlled by studies insufficiently or completely unverified. The aim of the project, commissioned by the Committee of the Society of General Practice of the Czech Medical Association JEP, was to compensate for this deficiency by interdisciplinary consensus and thus provide general practitioners (GPs) with a basic support in accessing patients with COVID-19. Representatives of GPs identified the most common questionable diagnostic or therapeutic approaches and formulated 17 theses, taking into account their own experience, existing Czech and foreign professional recommendations. The RAND/UCLA Appropriateness Method, modified for the needs of pandemic situation, was chosen to seek consensus. Representatives of 7 medical specialties accepted the participation in the 20-member panel. The panel evaluated in 2 rounds, with the comments and opinions of others available to all panelists before the second round. The outcome of the evaluation was agreement on 10 theses addressing the administration of vitamin D, inhaled corticosteroids in patients with COPD and bronchial asthma, acetylsalicylic acid, indications for D-dimer levels examination, preventive administration of LMWH, importance of pulse oximetry, indication for emergency services, indication for antibiotics and rules for distant contact. The panel disagreed on 6 theses recommending the administration of ivermectin, isoprinosine, colchicine and corticosteroids in patients with COVID-19 in primary care. One thesis, taking into account the use of D-dimers in primary care was evaluated as uncertain. The most discussed theses, on which there was also no agreement, were outpatient administration of corticosteroids and the importance of elevation of D-dimers levels or their dynamic increase in a symptomatic patient with COVID-19 as an indication for referral to hospital. The results of the consensus identified topics that need to be further discussed and on which it is appropriate to focus further research.

Determination of Circulating Endothelial Cells and Endothelial Progenitor Cells Using Multicolor Flow Cytometry in Patients with Thrombophilia.

BACKGROUND/AIMS: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Therefore, it is essential to use standardized methods for their identification and quantification. METHODS: In this study, we used multicolor flow cytometry to analyze the number of EPCs and CECs in patients with thrombophilia with or without a history of thrombosis. Patients with hematological malignancies after high-dose chemotherapy and patients with acute myocardial infarction were used as positive controls. RESULTS: EPC and CEC immunophenotypes were determined as CD45dim/-CD34+CD146+CD133+ and CD45dim/-CD34+CD146+CD133-, respectively. Increased levels of endothelial cells were observed in positive control groups. No significant changes in the number of EPCs or CECs were detected in patients with thrombophilia compared to healthy controls. CONCLUSION: Our optimized multicolor flow cytometry method allows unambiguous identification and quantification of endothelial cells in the peripheral blood. Our results support previous studies showing that elevated levels of CECs could serve as an indicator of endothelial injury or dysfunction. Normal levels of CECs or EPCs were found in patients with thrombophilia.

Role of Dipyrone in the High On-Treatment Platelet Reactivity amongst Acetylsalicylic Acid-Treated Patients Undergoing Peripheral Artery Revascularisation.

OBJECTIVE: To evaluate the effects of dipyrone on sensitivity to aspirin (acetylsalicylic acid [ASA]) in patients who underwent peripheral artery vascular reconstruction. SUBJECTS AND METHODS: Impedance aggregometry and light transmission aggregometry were used to determine the effects of dipyrone on ASA treatment in 21 patients. Blood samples were drawn in a 7-day period after the surgery. The cut-off value for high on-treatment platelet reactivity (HTPR) was set at < 65% of aggregation inhibition for impedance aggregometry. For light transmission aggregometry the cut-off value for arachidonic acid-induced aggregation was set at > 20% of aggregating platelets, and the cut-off value for epinephrine-induced aggregation was > 44% of aggregating platelets. The cut-off value for each method was derived from a large number of patients treated with a daily dose of 100 mg of ASA. RESULTS: We found HTPR in 14 (67%) of the 21 patients. None had primary resistance to ASA, i.e., after the addition of ASA in vitro all samples showed antiplatelet efficacy. Regression analysis showed a possible correlation between lower efficacy of ASA treatment and higher daily doses of dipyrone (p = 0.005 for impedance aggregometry, p = 0.04 for light transmission aggregometry), higher platelet count (p = 0.005 for impedance aggregometry), and shorter time from surgery (p = 0.03 for impedance aggregometry). CONCLUSION: HTPR occurs in 67% of ASA-treated patients after lower limb vascular surgery. The occurrence of HTPR correlates with the daily dose of dipyrone. Therefore, dipyrone should not be used as a postoperative analgesic in ASA-treated patients after peripheral artery revascularisation due to its influence on the effectiveness of ASA.

28 day post-operative persisted hypercoagulability after surgery for benign diseases: a prospective cohort study.

BACKGROUND: Surgery for benign disease is associated with a low-risk of developing venous thromboembolism (VTE). Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period. We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge. METHODS: Prospectively, patients who underwent surgery for benign disease were included. Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients. Prevalence of VTE in postoperative period was observed. Markers of systemic inflammatory response (IL-6, CRP, α-1-acid glycoprotein, transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer) were measured before surgery, on 7-10th postoperative day and on 28-30th postoperative day. RESULTS: Clinically apparent deep vein thrombosis was diagnosed in only one patient - 0.46%. Statistically significant elevation of inflammatory markers IL-6, CRP and α-1-acid glycoprotein (p < 0.001; all) were proved in both groups of patients on 7-10th postoperative day. Statistically significant elevation of coagulation markers PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer (p < 0.001; all) were proved in LC and HS groups on 7-10th postoperative day. No statistical difference was observed in IL-6, CRP and α-1-acid glycoprotein levels a month after surgery as compared with preoperative levels within each group. Statistically significant elevation of fibrinogen and prothrombin fragment F1 + 2 levels (p < 0.001; both) persisted on 28-30th postoperative day in both groups. Persisted elevation of D-dimer levels was proved only in HS group (p < 0.001), not in LC group (p = 0.138), a month after surgery. CONCLUSIONS: Activated systemic inflammatory response and hypercoagulable condition were verified in patients after laparoscopic cholecystectomy and hernia surgery after their hospital discharge. Hypercoagulability persisted even a month after surgery. Nevertheless, we observed very low prevalence of clinically apparent VTE in patients with in-hospital postoperative VTE prophylaxis. TRIAL REGISTRATION: Trials of the Czech Ministry of Health No. RVO-VFN64165 and NT 13251-4 .

[Guidelines of Czech Association for Thrombosis and Haemostasis of the Czech Medical Association of J. E. Purkyne for safety treatment with new oral anticoagulants (NOAC) - dabigatran etexilate, apixaban and rivaroxaban]. / Doporucení Ceské spolecnosti pro trombózu a hemostázu Ceské lékarské spolecnosti J. E. Purkyne pro bezpecnou lécbu novými perorálními antikoagulancii (NOAC) - dabigatran etexilátem, apixabanem a rivaroxabanem.

There are presently new oral anticoagulants (NOAC) for prevention and the treatment of thromboembolic diseases and they are registered in CZ. It concerns of orally direct inhibitors of thrombin (dabigatran etexilate), inhibitors of factor Xa (apixaban, rivaroxaban), respectively, with advantage of some properties not being seen in "classical" anticoagulants. In the use of new anticoagulants, however, are some problems - such as laboratory monitoring in urgent situations of effective treatment and the absence of specific antidote - resolved. The text below brings indications, dosage of the drugs, their elimination, follow-up of efficacy of the treatment or risk of the bleeding as well as the therapy of bleeding complications.Key words: apixaban - dabigatran etexilate - NOAC - rivaroxaban.

[Comparison of the overall stress during large bowel operations in senior patients (laparoscopy versus open surgery)]. / Porovnání stupne záteze pri operacích na tlustém streve u senioru (laparoskopie versus otevrené výkony).

BACKGROUND: Colorectal surgery particularly as a treatment option for colorectal cancer comprises considerable and ever expanding spectrum of surgical procedures. Seniors (over 65 years of age) form the majority of patients operated for benign or malignant colon disease. High age in general poses one of the significant risks of the operation. The study analyses overall stress caused to patients by laparoscopy and laparotomy surgical procedures. METHODS: Literature analysis of surgical stress in patients and prospective study of our patients' data collected over the period of four years. Comparable indicators: objectification of pre-operative stress and risks, per-operative cardiac and circulatory parameters, course of the lesion healing process, laboratory reactions of acute phase proteins, morbidity and lethality related to the surgery treatment. RESULTS: Comparable results of tissue response examinations demonstrated no fundamental difference between laparoscopic and laparotomic operations performed on otherwise healthy younger individuals. Laparoscopic surgery, however, appears to be fully appropriate treatment modality in majority of patients suffering from colorectal disease, even in senior age. In advanced or complicated stages of the disease the open-section surgery still remains more efficient. CONCLUSION: Age itself cannot be generally denoted as a fundamental risk factor. Co-morbid conditions, however, represent considerable risk, especially in high age patients. Laparoscopic surgery may well be applied even in senior age patients with no contra-indications. Yet, its application requires perfectly mastered laparoscopic technique and rational approach. Success of the operation in high-risk patients depends on close interdisciplinary cooperation, especially with anaesthetists.

[Prevalence of thrombophilic mutations of FV Leiden, prothrombin G20210A and PAl-1 4G/5G and their combinations in a group of 1450 healthy middle-aged individuals in the Prague and Central Bohemian regions (results of FRET real-time PCR assay)]. / Prevalence trombofilních mutací FV Leiden, protrombinu G20210A a PAI-1 4G/5G a jejich vzájemných kombinací v souboru 1450 zdravých osob stredního veku v regionu Praha a strední Cechy (výsledky real-time PCR analýzy FRET).

BACKGROUND: Factor V Leiden (G1691A) and prothrombin gene (FII G20210A) mutations are independent risk factors of venous thrombosis and this risk is further increased by the combined genotype 4G/4G PAI-1. AIM: The primary objective was to identify the frequency of mutations of minor alleles and genotypes of FVL, FII G20210A and PAI-1 4G/5G in healthy Caucasians in the Prague and Central Bohemia regions. The secondary objective was to identify the occurrence of their mutual combinations. METHOD: Genotyping was performed in 1,450 healthy individuals (blood donors, 981 men and 469 women) using robotic DNA isolation and subsequent PCR and melting curve analysis (Light Cycler 480 System, Roche). RESULTS: The minor allele frequencies in FV Leiden and FII G20210A mutations were 4.5% and 1.3% respectively. The frequency of the 4G PAI-1 allele was 55.9%. The genotype frequencies were as follows: GG 91.10%, GA 8.83% and AA 0.07% for FV Leiden; GG 97.38%, GA 2.55% and AA 0.07% for FII G20210A and 4G/4G 30.69%, 4G/5G 50.34% and 5G/5G 18.97% for PAI-1. No differences in these frequencies were found between the genders. The occurrence of the combined heterozygous FII and heterozygous FV Leiden mutations was 0.14%. The PAI-1 4G/4G genotype was combined with the heterozygous FV leiden mutation in 2.83% of cases and with the heterozygous FII mutation in 0.62% of cases. CONCLUSIONS: The found frequencies of genotypes and alleles confirm a relatively high prevalence of hereditary thrombophilia in the Czech Republic.

Adrenal Venous Sampling Could Be Omitted before Surgery in Patients with Conn's Adenoma Confirmed by Computed Tomography and Higher Normal Aldosterone Concentration after Saline Infusion Test.

PURPOSE: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. METHODS: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). RESULTS: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. CONCLUSIONS: AVS could be omitted before surgery in patients with typical Conn´s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT.

Validation of Existing Clinical Prediction Tools for Primary Aldosteronism Subtyping.

The new clinical prediction score (SCORE) has been recently proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). This study aimed to compare that SCORE with previously published scores and their validation using a cohort of patients at our center who had had positive SIT confirming PA and had been diagnosed with either bilateral PA according to AVS or unilateral PA if biochemically cured after an adrenalectomy. Final diagnoses were used to evaluate the diagnostic performance of the proposed clinical prediction tools. Only Kamemura's model (with a maximum score of 4 points) and Kobayashi's score (with a maximum score of 12 points) reached 100% reliability for prediction of bilateral PA; however, with sensitivity of only 3%. On the other hand, the values of SCORE = 3 (with sensitivity of 48%), the SPACE score ≥18 (with sensitivity of 35%), the Kobayashi's score ≤2 (with sensitivity of 28%), and the Kocjan's score = 3 (with sensitivity of 28%) were able to predict unilateral PA with 100% probability. Furthermore, Umakoshi's and Young's models both reached 100% reliability for a unilateral PA with score = 4 and both predictive factors together respectively; however, the sensitivity was lower compared with previous models; 4% and 14%, respectively. None of the clinical prediction tools applied to our cohort predicted unilateral and bilateral subtypes together with the expected high diagnostic performance, and therefore can only be used for precisely defined cases.

Gene Profile of Adipose Tissue of Patients with Pheochromocytoma/Paraganglioma.

Background: Brown adipose tissue (BAT) is a therapeutic target to combat obesity and related disorders. Pheochromocytoma and functional paraganglioma (PPGL) are associated with activated BAT due to catecholamine excess. Our aim was to evaluate BAT activity by gene profile and assess its relation to clinical characteristics and overproduced catecholamine. Methods: mRNA expression of 15 genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was measured via RT-PCR in 25 patients with PPGL and 14 controls undergoing cholecystectomy. Results: We found in VAT of PPGL higher expression of UCP1 (p < 0.001), CEBPB, PPARGC1A (both p < 0.001), PRDM16 (p = 0.069) and DIO2 (p = 0.005). UCP1 expression correlated only with norepinephrine levels and its metabolite. UCP1 expression, among others, correlated negatively with BMI, age and positively with HDLc levels. Dominance of BAT or BeAT markers was not assessed in PPGL. In SAT of PPGL, we found higher expression of ADRB3, CIDEA (both p < 0.05), and PPARGC1A (p = 0.001), but not UCP1. Conclusion: We demonstrate signs of UCP1-dependent norepinephrine-induced thermogenesis connected with higher expression of DIO2, PPARGC1A, CEBPB and PRDM16 in retroperitoneal VAT of PPGL and its relations to circulating HDLc and triglycerides levels. However, no direct relationship with increased basal energy metabolism measured by calorimetry was found.

Hypermetabolism and Substrate Utilization Rates in Pheochromocytoma and Functional Paraganglioma.

The overproduction of catecholamines in pheochromocytoma/paraganglioma (PPGL) induces a hypermetabolic state. The aim of this study was to evaluate the incidence of a hypermetabolic state and differences in substrate metabolism in consecutive PPGL patients divided by catecholamine phenotype. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in 108 consecutive PPGL patients and 70 controls by indirect calorimetry. Hypermetabolic state was defined according to the Mifflin St. Jeor Equation as a ratio above 110%. Hypermetabolic state was confirmed in 70% of PPGL patients, regardless of phenotype. Older age, prevalence of diabetes mellitus and arterial hypertension were correlated with hypermetabolic PPGL as compared to normometabolic form. Analysis according to overproduced catecholamine showed differences in VCO2 (p < 0.05) and RQ (p < 0.01) and thus different substate metabolism between phenotypes in hypermetabolic form of PPGL. Lipid utilization was higher in the adrenergic phenotype (p = 0.001) and positively associated with the percentage of REE ratio (R = 0.48, p < 0.001), whereas the noradrenergic phenotype preferentially oxidizes carbohydrates (P = 0.001) and is correlated with the percentage of REE ratio (R = 0.60, p < 0.001). Hypermetabolic state in PPGL is a common finding in both catecholamine phenotypes. Hypermetabolic PPGL patients are older and suffer more from diabetes mellitus and arterial hypertension. Under basal conditions, the noradrenergic type preferentially metabolizes carbohydrates, whereas the adrenergic phenotype preferentially metabolizes lipids.

Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study.

Background: Idiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features. Methods: Thirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications. Results: Compared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure. Conclusions: No significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM.

Effect of adrenalectomy on remission of subclinical left ventricular dysfunction in patients with pheochromocytoma: a speckle-tracking echocardiography study.

BACKGROUND: Pheochromocytomas (PHEO) are tumours with the ability to produce, metabolize and secrete catecholamines. Catecholamines overproduction leads to the decrease of longitudinal function of the left ventricle (LV) measured by speckle-tracking echocardiography. Patients with PHEO have a lower magnitude of global longitudinal strain (GLS) than patients with essential hypertension. GLS normalization is expected after resolution of catecholamine overproduction. METHODS: Twenty-four patients (14 females and 10 males) with a recent diagnosis of PHEO have been examined before and 1 year after adrenalectomy. An echocardiographic examination including speckle-tracking analysis with the evaluation of GLS and regional longitudinal strain (LS) in defined groups of LV segments (basal, mid-ventricular and apical) was performed. RESULTS: One year after adrenalectomy, the magnitude of GLS increased (-14.3 ± 1.8 to -17.7 ± 1.6%; P < 0.001). When evaluating the regional LS, the most significant increase in the differences was evident in the apical segment compared to mid-ventricular and basal segments of LV (-5.4 ± 5.0 vs -1.9 ± 2.7 vs -1.6 ± 3.8; P < 0.01). CONCLUSIONS: In patients with PHEO, adrenalectomy leads to an improvement of subclinical LV dysfunction represented by the increasing magnitude of GLS, which is the most noticeable in apical segments of LV.

Two novel fibrinogen variants in the C-terminus of the Bß-chain: fibrinogen Rokycany and fibrinogen Znojmo.

Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bß Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bß Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bß Asn351Lys (fibrinogen Rokycany) and Bß Arg237Ser (fibrinogen Znojmo), respectively.

An embolus in the right atrium caught in the Chiari network and resistant to thrombolysis.

Case report is presented, which describes a patient with thromboemboli trapped in the Chiari network within the right heart and resistant to thrombolysis. The right atrial masses were completely removed under cardiopulmonary bypass. Histological evaluation confirmed a mixed thromboemboli, with thrombus structures showing signs of organization and surrounded by a fibrous capsule. A heterozygous methylenetetrahydrofolate reductase gene polymorphism was found, and the plasma level of the plasminogen activator inhibitor type-1 (PAI-1) was 50% higher than the normal upper limit. In this presented case, the Chiari network displayed a protective function, but the expansion and organization of the thromboembolus caught there made it resistant to lytic therapy. Another important factor which could have influenced the resistance to thrombolysis was the high level of PAI-1. PAI-1 is the primary physiologic inhibitor of plasminogen activation in blood. Elevated pre-treatment levels of PAI-1 may reduce the efficacy of thrombolytic therapy by preventing or retarding clot dissolution. The patient's DNA was tested for a common single-base-pair polymorphism (four or five guanine bases) in the promoter region of the gene (4G/5G), but the presence of this variant allele was not confirmed: the patient was homozygous for the 5G allele (5G/5G genotype).

[Hereditary thrombophilias--recommendations for genetic testing in the clinical praxis]. / Dedicné trombofilie--doporucení k provádení genetických testu v klinické praxi.

Venous thromboembolism is a common serious clinical condition, in which genetic factors play an important role, too. The objective of this review is to summarize current knowledge regarding the hereditary thrombophilias and submit their simple classification. Recommended Consensus of the Czech Societies on Thrombosis and Haemostasis, Haematology and Medical Genetics for genetic testing in specific patients' groups at venous thromboembolism high-risk situation is also presented.

Clopidogrel resistance "Live" - the risk of stent thrombosis should be evaluated before procedures.

Every year, millions of people undergo percutaneous coronary intervention (PCI) with intracoronary stent implantation. A patient from the PRAGUE-8 trial (Optimal pre-PCI clopidogrel loading: 600 mg before every coronary angiography vs. 600 mg in the cath-lab only for PCI patients) is described who suffered from acute stent thrombosis. This patient did not have any relevant inhibition of platelet activation even after the 600 mg dose of clopidogrel. Dose uptitration would have been ineffective. New P2Y12 receptor inhibitors are desperately needed. In the light of recently published data, the use of prasugrel may be considered as an alternative.

Catecholamines Induce Left Ventricular Subclinical Systolic Dysfunction: A Speckle-Tracking Echocardiography Study.

Background: Pheochromocytomas (PHEO) are tumors arising from chromaffin cells from the adrenal medulla, having the ability to produce, metabolize and secrete catecholamines. The overproduction of catecholamines leads by many mechanisms to the impairment in the left ventricle (LV) function, however, endocardial measurement of systolic function did not find any differences between patients with PHEO and essential hypertension (EH). The aim of the study was to investigate whether global longitudinal strain (GLS) derived from speckle-tracking echocardiography can detect catecholamine-induced subclinical impairments in systolic function. Methods: We analyzed 17 patients (10 females and seven males) with PHEO and 18 patients (nine females and nine males) with EH. The groups did not differ in age or in 24-h blood pressure values. Results: The patients with PHEO did not differ in echocardiographic parameters including LV ejection fraction compared to the EH patients (0.69 ± 0.04 vs. 0.71 ± 0.05; NS), nevertheless, in spackle-tracking analysis, the patients with PHEO displayed significantly lower GLS than the EH patients (-14.8 ± 1.5 vs. -17.8 ± 1.7; p < 0.001). Conclusions: Patients with PHEO have a lower magnitude of GLS than the patients with EH, suggesting that catecholamines induce a subclinical decline in LV systolic function.