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This study aimed to assess the prognostic significance of total leukocyte count (TLC) and hemoglobin (Hb) levels upon admission for patients with acute pulmonary embolism (PE), considering the European Society of Cardiology (ESC) model for mortality risk. 1622 patients from a regional PE registry were included. Decision tree statistics were employed to evaluate the prognostic value of TLC and Hb, both independently and in conjunction with the ESC model. The results indicated all-cause and PE-related in-hospital mortality rates of 10.7% and 6.5%, respectively. Subgrouping patients based on TLC cut-off values (≤11.2, 11.2–16.84, >16.84 × 109/L) revealed increasing all-cause mortality risks (7.0%, 11.8%, 30.2%). Incorporating Hb levels (≤126 g/L or above) further stratified the lowest risk group into two strata with all-cause mortality rates of 10.1% and 4.7%. Similar trends were observed for PE-related mortality. Notably, TLC improved risk assessment for intermediate–high-risk patients within the ESC model, while Hb levels enhanced mortality risk stratification for lower-risk PE patients in the ESC model for all-cause mortality. In conclusion, TLC and Hb levels upon admission can refine the ESC model's mortality risk classification for patients with acute PE, providing valuable insights for improved patient management. [ABSTRACT FROM AUTHOR]

• S wave resolution in aVL predicts lower mortality in PE patients. • Its prognostic value sustains across age, gender, or thrombolysis use. • This ECG sign may serve as a marker for successful thrombolytic reperfusion in PE. • It may provide valuable insights for clinical decision-making in acute PE. [ABSTRACT FROM AUTHOR]

Estimation of bleeding risk is an unmet need for individualized therapy in acute pulmonary embolism (PE) patients with increased mortality risk. We analyzed the association between various patients' characteristics and occurrence of major bleeding (MB) according to the modified International Society of Thrombosis and Hemostasis (ISTH) criteria ("overt" bleeding is the only modification from the original criteria) at 7 days from admission to the hospital and thrombolytic therapy with a tissue-plasminogen activator (tPA). Pulmonary embolism bleeding score index (PEBSI) was created using multivariate regression analyses, and finely, dichotomous index was used for the discrimination of patients with low risk for MB from those with high risk. During the 6-year period (2015–2021) 367 PE patients were treated with tPA and included in the Regional PE registry. Among them, 29 (7.9%) fulfilled the criteria for MB. Five factors were identified as significantly associated with MB and were used to build the PEBSI score: previous bleeding, recent surgery, diabetes, the use of drugs that could be associated with bleeding, and anemia. PEBSI score showed c-index for 7-day MB 0.794 (95CI% 0.698–0.889). Patients with PEBSI scores of 0 or 1 had a low risk for MB (2.8%) and those with scores>1 had a high risk for MB (18.6%) (p < 0.001). Internal validation of PEBSI score using a randomly, equally split method confirmed the discriminative value of the PEBSI score. Novel PEBSI score has significant power to discriminate patients with low risk for MB on thrombolytic therapy from those with high risk. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate whether the high sensitive C-reactive protein (hsCRP) is associated with an ejection fraction of left ventricle (EFLV) in the early phase of ST-elevation myocardial infarction (STEMI), treated with the primary percutaneous intervention (pPCI), and to establish whether there exists a relationship between its values and the presence of major adverse cardiovascular events (MACE) within six months of pPCI. Materials and Methods: In this prospective study, 357 patients who were diagnosed with STEMI and who underwent pPCI within 24 hours of pain onset were included. The following were monitored and recorded: 1) hsCRP values, which were measured between 24 and 48 hours of pPCI, 2) EFLV values, which were measured five days after the pPCI, and 3) MACE, which was established within six months of pPCI. Results: The EFLV values measured five days after the pPCI were significantly lower with increasing hsCRP values (rho=- 0.384, p<0.0001). There was a significant difference in hsCRP values between patients who had MACE and those without it (38.35 [98.10] vs. 12.97 [23.80], p=0.0001). In addition, hsCRP values were significantly increased in patients who died during the first six months after the pPCI compared with patients who survived (115.00 [202.80] vs. 15.84 [31.5], p=0.001). Conclusion: The hsCRP values in patients with STEMI who were treated with the pPCI are related to systolic function in the early phase of STEMI, as well as MACE during the first six months of follow-up. [ABSTRACT FROM AUTHOR]

Background. Experimental and first clinical studies suggest that the transplanlation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial Infarction. Aim. This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. Methods and results. Four male patients (age range 47-68 years) with the first extensive anterior, ST elevation, acute myocardial infarction (AMI), were treated by primary angioptasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centri-fuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamin stress echocardiography testing and single-photon emission computed tomography (SPECT) 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Hotter ECG showed only isolated ventricular ectopic heats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction). Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction.... [ABSTRACT FROM AUTHOR]

Background: Periventricular/intraventricular hemorrhage (PVH/IVH) has a major impact on neurodevelopment due to its complications and sequelae. Objectives: This study aimed to determine the frequency of neurosonographic examination and the length of the monitoring period in children diagnosed with PVH/IVH. Methods: This clinical observational analytical retrospective cohort study was performed on 102 children diagnosed with PVH/IVH. The examinations were done on the third, seventh, fourteenth, and twenty-first days after birth and then in the fourth and sixth weeks and the third and sixth months afterbirth. The results of the examinations performed overtime were subjected to the kappa measure of agreement test, with a significance threshold of 0.05, to determine the period when the most significant changes occur in the patient's condition, as well as to determine the optimum frequency of the examination. Results: There was statistically significant agreement between the results of all the examinations performed in the observed moments (P< 0.0005). However, it is indicative that the agreement was excellent for the fourth week (kappa agreement was more than 0.85), followed by the sixth week that was very good (kappa agreement was 0.79); however, the agreement for the sixth week and the third month was very small (kappa agreement was less than 0.1). Also, there were no major changes (kappa agreement between results from the third and sixth months was 0.88). Conclusions: The first neurosonographic examination should be conducted in the first 7 days after birth, and the control examination should be conducted at the age of 4 - 6 weeks. If a pathological finding is observed, the examination is repeated after the specified period until a stationary finding is observed. After the third month, no new changes in the finding are observed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this study was to investigate whether there are differences between brain natriuretic peptide (BNP) levels and computed tomography pulmonary angiography (CTPA) parameters, in patients with acute PE, with respect of sex. BACKGROUND: Acute pulmonary embolism (PE) may provoke sudden right ventricle overload and stretching of their thin walls, causing significant raise of BNP blood levels, which correlates to acute PE severity. The properties of RV are different between sexes. METHODS: This retrospective analysis was gained from the data of 1612 PE patients from the regional PE register. The patients have had CTPA verification of PE, with described localization of thrombus masses, as well as the ratio between RV and left ventricle (RV/LV), and BNP as biomarker, measured during the first 24 hours upon admission. RESULTS: Out of 96 male patients with detected central thrombus, 75.0% patients had an increase in BNP level compared to 25.0% patients with normal BNP value (p<0.001). Of the 94 female patients with central thrombus, 85.1% patients had an elevated BNP level, compared to 14.9% patients, with BNP normal values (p<0.001). Of the 135 male patients with RV/LV>1, 79.3% of them, had elevated BNP, compared to 20.7% patients whose BNP level was normal (p<0.001). Out of 123 female patients with RV/LV>1, 91.1% patients had elevated BNP compared to 8.9%, whose BNP was normal (p<0.001). CONCLUSION: Elevated BNP blood level correlates with CTPA parameters, such as the presence of central thrombus and the ratio between right and left ventricles greater than 1, in patients with acute PE, regardless of sex [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is a complex disorder of unclear etiology that develops in the elderly population. It is a debilitating, progressive neurodegeneration for which disease-modifying therapies do not exist. Previous studies have suggested that, for a subset of patients, dysregulation in hemostasis might be one of the molecular mechanisms that ultimately leads to the development of neurodegeneration resulting in cognitive decline that represents the most prominent symptomatic characteristic of Alzheimer's disease.Objective: To examine a relationship between factors that are part of coagulation and anticoagulation pathways with cognitive decline that develops during Alzheimer's disease.Methods: SOMAscan assay was used to measure levels of coagulation/anticoagulation factors V, VII, IX, X, Xa, XI, antithrombin III, protein S, protein C, and activated protein C in plasma samples obtained from three groups of subjects: 1) subjects with stable cognitively healthy function, 2) subjects with stable mild cognitive impairment, and 3) subjects diagnosed with probable Alzheimer's disease.Results: Our results show that protein levels of coagulation factor XI are significantly increased in patients who are diagnosed with probable Alzheimer's disease compared with cognitively healthy subjects or patients diagnosed with mild cognitive impairment. Furthermore, our results demonstrate that significant predictors of Alzheimer's-type diagnosis are factors IX and XI-an increase in both factors is associated with a reduction in cognitive function.Conclusion: Our study justifies further investigations of biological pathways involving coagulation/anticoagulation factors in relation to dementia, including dementia resulting from Alzheimer's-type neurodegeneration. [ABSTRACT FROM AUTHOR]

In patients with pulmonary embolism (PE), the D-dimer assay is commonly utilized as part of the diagnostic workup, but data on D-dimer for early risk stratification and short-term mortality prediction are limited. The purpose of this study was to determine D-dimer levels as a predictive biomarker of PE outcomes in younger (<50 years of age) compared to older patients. We conducted retrospective analysis for 930 patients diagnosed with PE between 2015 and 2019 as part of the Serbian University Multicenter Pulmonary Embolism Registry (SUPER).All patients had D-dimer levels measured within 24 hours of hospital admission. The primary outcome was mortality at 30 days or during hospitalization. Patients were categorized into two groups based on age (≤ 50 and >50 years of age). Younger patients constituted 20.5% of the study cohort. Regarding all-cause mortality, 5.2% (10/191)of patients died in group under the 50 years of age; the short-term all-causemortality was 12.4% (92/739) in older group.We have found that there was significant difference in plasma D-dimer level between patients ≤ 50 years of age and older group (>50), p= 0.006.D-dimer plasma level had good predictive value for the primary outcome in younger patients (c-statistics 0.710; 95% CI, 0.640-0.773; p<0.031). The optimal cutoff level for D-dimer to predict PE-cause death in patients aged > 50 years was found to be 8.8 mg/l FEU(c-statistics 0,580; 95% CI 0.544-0.616; p=0.049). In younger PE patients, D-dimer levels have good prognostic performance for 30-day all-cause mortalityand concentrations above 6.3 mg/l FEU are associated with increased risk of death. D-dimer in patients aged over 50 years does not have predictive ability for all-caused short-term mortality. The relationship between D-dimer and age in patients with PE may need further evaluation. [ABSTRACT FROM AUTHOR]

Background: Patients with acute pulmonary embolism (PE) may have various types of atrial fibrillation (AF). The role of AF in hemodynamic states and outcomes may differ between men and women. Methods: In total, 1600 patients (743 males and 857 females) with acute PE were enrolled in this study. The severity of PE was assessed using the European Society of Cardiology (ESC) mortality risk model. Patients were allocated into three groups according to their electrocardiography recordings taken during hospitalization: sinus rhythm, new-onset paroxysmal AF, and persistent/permanent AF. The association between the types of AF and all-cause hospital mortality was tested using regression models and net reclassification index (NRI) and integrated discrimination index (IDI) statistics with respect to sex. Results: There were no differences between the frequencies of the types of AF between men and women: 8.1% vs. 9.1% and 7.5% vs. 7.5% (p = 0.766) for paroxysmal and persistent/permanent AF, respectively. We found that the rates of paroxysmal AF significantly increased across the mortality risk strata in both sexes. Among the types of AF, the presence of paroxysmal AF had a predictive value for all-cause hospital mortality independent of mortality risk and age in women only (adjusted HR, 2.072; 95% CI, 1.274–3.371; p = 0.003). Adding paroxysmal AF to the ESC risk model did not improve the reclassification of patient risk for the prediction of all-cause mortality, but instead enhanced the discriminative power of the existing model in women only (NRI, not significant; IDI, 0.022 (95% CI, 0.004–0.063); p = 0.013). Conclusion: The occurrence of paroxysmal AF in female patients with acute PE has predictive value for all-cause hospital mortality independent of age and mortality risk. [ABSTRACT FROM AUTHOR]

Abstract: Background: The occurrence of a floating thrombus in the right heart, although rare, is a life-threatening condition requiring a specific approach. In most cases, these thrombi are a result of embolization from deep venous thrombosis, and have lodged temporarily in the right heart. The management of this condition is variable, depending on whether or not there is a thrombus entrapped within a foramen ovale (FO). Objectives: To present the management of 2 patients with a free-floating thrombus in the right heart, and a third patient with an entrapped thrombus in the FO. Case Reports: Two patients with a free-floating thrombus in the right atrium who were treated with thrombolytic therapy had an immediate excellent outcome. The patient with a thrombus entrapped within the FO was scheduled for surgical removal of the thrombus due to an unacceptable risk of systemic embolization if treated with thrombolytic and anticoagulant therapy. Unfortunately, he developed an ischemic stroke on the fifth day of presentation, just a few hours before the scheduled surgery, despite meticulous monitoring of continuous heparin infusion with activated partial thromboplastin time. Conclusion: Thrombolytic therapy is recommended in patients with a free-floating thrombus in the right heart. However, in patients with a thrombus entrapped within an FO, delaying surgical removal of the thrombus may be deleterious due to unpredictable systemic embolization. [Copyright &y& Elsevier]

Unicuspid aortic valve (UAV) is a rare congenital anomaly of aorta associated with a faster progress of valvular dysfunction, aortic dilatation and with necessity for more frequent controls and precise evaluation Asymptomatic 35 year old man had abnormal systolic diastolic murmur on aortic valve during routine examination. Initial diagnostic with transthoracic echocardiography (TTE) supposed bicuspid aortic valve, while three-dimensional transesophageal echocardiography (3D TEE) and multidetector computed tomography defined unicuspid, unicomissural aortic valve with moderate aortic stenosis and regurgitation. This case report confirmed that 3D TEE gives us opportunity for early, improved and precise diagnosis of UAV. [ABSTRACT FROM AUTHOR]

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5–10.0 mmol/L; III: 10.0–15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5–6.3 mmol/L; III: 6.3–7.9 mmol/L; IV: > 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality. [ABSTRACT FROM AUTHOR]

Background. Predilection site for the acute myocardial infarction of the right ventricle, (AMI-RV) is the upper third of the right coronary artery and for this reason such an infarction is followed by numerous complications, primarily by conduction disorders and very often by sudden and rapid cardiogenic shock development. Methods. Primary percutaneous transluminal coronary angioplasty (PPTCA) was performed on three patients, in whom the acute infarction of the right ventricular was diagnosed and who had been hospitalized six hours after the beginning of chest pain. In all three patients intracoronary stent was implanted. On the admission patients had been in the threatening cardiogenic shock, with the prominent chest pain and with the elevation of ST-segment in V4R>2 mV. In the course of intervention patients were administered low-molecular intracoronary heparin, with direct platelet glycoprotein IIb/IIIa inhibitors (abciximab), according to the established procedure applied in such cases. Results. The complete dilatation of the infarcted artery was established with the signs of reperfusion and the further clinical course was completely normal, there was no heart failure and patients had no subjective difficulties. Conclusion. Invasive approach in the treatment of AMI-RV is justifiable, and possibly the therapy of choice of these patients, providing well trained and equipped team is available. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies report that syncope is not a significant predictor of 30‐day mortality in pulmonary embolism (PE) patients, yet some data suggest sex‐related differences may be relevant. Objectives: To evaluate sex‐specific prediction significance of syncope for 30‐day mortality in PE patients. Methods: A multicentric, retrospective, observational, registry‐based study on consecutive PE patients was undertaken. Patients were allocated into either a men or a women group before comparisons were made between patients with syncope and those without syncope. A sex‐related prediction of the significance of syncope for 30‐day mortality was evaluated. Results: Overall 588 patients [294 (50%) men and 294 (50%) women] were included within the study. Among men, patients with syncope were older and had significantly higher parameters of increased 30‐day mortality then patients without syncope. Within the same group, however, difference in the 30‐day mortality rate was not significant (log rank P =.942). In contrast to the men, fewer differences in admission characteristics were noticed among women, but those with syncope had significantly increased signs of the right ventricular dysfunction and increased 30‐day mortality rate, as compared with those without syncope (log rank P =.025). After adjustment for age in a Cox regression analysis, syncope was a significant predictor of 30‐day mortality in women (HR = 2.01, 95%CI 1.02‐3.95). Conclusion: Although syncope is associated with other predictors of higher early mortality in both male and female PE patients, only in women it is a significant predictor of 30‐day mortality. [ABSTRACT FROM AUTHOR]

Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients. The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events. Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30–60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243–11.911, p < 0.001; HR 2.554, 95% CI 1.598–4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups. Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality. • Glomerular filtration rate has a predictive role in pulmonary embolism. • Patients with pulmonary embolism and renal dysfunction have poor prognosis. • Renal dysfunction is associated with higher bleeding rates in pulmonary embolism. [ABSTRACT FROM AUTHOR]

Abstract Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882–1.000, p =.001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745–0.902, p <.001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group. Highlights • BNP has the strongest predictive value for spontaneous and provoked PE. • CRP and cTnI have very predictive value for spontaneous PE. • D-dimer had very weak predictive value in provoked PE. [ABSTRACT FROM AUTHOR]

Summary: What is known and Objective: Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients. Methods: After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D‐dimer and fibrinogen, were measured, and the values were compared between the groups. Results and Discussion: One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0‐4.0) vs 2.1 (1.5‐2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D‐dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups. What is new and Conclusion: Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption. This cross‐sectional study followed‐up patients who continued the treatment with one of the DOACs (rivaroxaban, apixaban or dabigatran) after the initial treatment of acute pulmonary embolism. After one month on stable therapy, the activity of certain coagulation‐cascade factors such as II, VII, VIII, protein C, antithrombin as well as the serum concentration of fibrinogen and D‐dimer were measured. The main finding was that patients on apixaban had a significantly higher activity of factor II then patients on rivaroxaban and dabigatran whereas no difference in the concentrations of fibrinogen and D‐dimer existed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate the effect of two of the most important functional CYP1A2 variations −3860G > A and −163C > A on carbamazepine pharmacokinetics in Serbian pediatric epileptic patients. Methods: The study involved 40 Serbian pediatric epileptic patients on steady-state carbamazepine treatment. Genotyping for −3860G > A and −163C > A was carried out using PCR-RFLP method, and carbamazepine plasma concentrations were determined by high pressure liquid chromatography (HPLC) method. For pharmacokinetic analysis, NONMEM software with implementation of ADVAN 1 subroutine was used. Results: CYP1A2 polymorphism −163C > A was found at the frequency of 65.0 %, while −3860G > A was not detected. The correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in carriers of −163C/C and C/A genotypes ( r = 0.68, p = 0.0004). The equation that described population clearance (CL) was CL (l/h) = 0.176 + 0.0484 * SEX + 0.019 * CYP1A2 + 0.000156 * DD, where SEX has a value of 1 if male and 0 if female, CYP1A2 has a value of 1 if −163A/A and 0 if −163C/C or C/A, and DD is the total carbamazepine daily dose (mg/day). Conclusions: CYP1A2 −163A/A genotype influence carbamazepine pharmacokinetics. In addition to sex and total carbamazepine daily dose, −163C > A CYP1A2 polymorphism should be considered as a predictor of carbamazepine clearance. [ABSTRACT FROM AUTHOR]

This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 ( ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide ( TRAP values) and arachidonic acid ( ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel ( ADPHS10). There was a significant difference between TRAP values divided into quartiles according to ADPHS10, 10, 45 and 90 days after stopping clopidogrel ( P < 0.001, all), and ASPI values across the same quartiles 10 and 45 days after the cessation of clopidogrel ( P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets. [ABSTRACT FROM AUTHOR]

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed. [ABSTRACT FROM AUTHOR]

There is a long latent period in the clinical course of aortic valve stenosis in adults. Symptoms ussually occur in the case of critical stenosis, when aortic orifice area is under 0.7cm² (0.4 cm²/m²). In this study 78 patients with critical aortic valve stenosis were investigated. The first manifestation of the disease was dyspnea (78.2%), angina (52.5%), less often a syncope (34.6%), while 17.9% of patients were asymptomatic. Left ventricular systolic function was preserved in 77% of patients, while left ventricular dyastolic dysfunction occured in almost all the patients. In 42 patients (53.4%) aortic valve replacement was performed. Left ventricular systolic function improved in 88.1% of patients postoperativelly, as well as in patients with preoperativelly preserved or poor systolic function. Recovery was fast particularly during the first 6 postoperative months. After the surgery the improvement of the left ventricular dyastolic function was slower then systolic, particularly in patients with extreme hypertrophy of myocardium in whom the process of recovery might last several years. [ABSTRACT FROM AUTHOR]