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Background: Early mortality assessment in acute pulmonary embolism (PE) is crucial for treatment decisions. The role of natriuretic peptides in this context is debated. This study explores elevated B-type natriuretic peptide (BNP) levels, relative to the upper normal limit (UNL), predicting mortality in PE, comparing with troponin (Tn)., Methodology: A multicenter PE registry analyzed predictive values for early mortality risk using BNP and Tn, based on proportional elevation to the UNL. Patients followed current PE guidelines., Results: Among 1677 PE patients, BNP's AUC exceeded Tn for all-cause (0.727 vs. 0.614) and PE-related mortality (0.785 vs. 0.644), though nonsignificant. BNP's cutoff was 3.5 times UNL for both all-cause and PE-related mortalities; Tn cutoffs were 1.38 and 1.23 times UNL, respectively., Conclusion: Elevated BNP relative to UNL significantly predicts all-cause and PE-related mortality. While akin to Tn, BNP merits consideration in assessing acute PE risk, especially in intermediate-high-risk cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The management of patients with acute pulmonary embolism (aPE) depends on the severity of aPE. The timing of death in various aPE risk subgroups is only partially known., Methods: 1618 patients with an objectively established aPE diagnosis with computed tomography pulmonary angiography enrolled in the regional PE registry were included in the study. According to ESC criteria, patients were stratified at admission to the hospital in four risk strata. The timing of PE-related and non-PE-related deaths was analyzed regarding mortality risk., Results: PE-related, and non-PE-related hospital death rates were 1.1 % and 1.5 % in low, 1.1 % and 4.8 % in intermediate-low, 8.1 % and 5.9 % in intermediate-high, and 27.7 % and 6.9 % in high-risk groups, respectively. The median time of PE-related and non-PE-related death across the PE mortality risk were: 4 (1.7-7.5) and 7.0 (4-14.7) days in low, 1.5 (1.0-9.5) and 11.5 (2.0-21.0) days in intermediate-low, 4.0 (2.0-9.0) and 9.0 (5.7-18.2) days in intermediate-high, 2.0 (1.0-4.75) and 7.0 (3.0-21.2) days in high-risk subgroups. 48.2 % and 17.1 % of patients who died in the high and intermediate-high risks died during the first hospital day. After the 6th hospitalization day, PE-related deaths were recorded in 43.9 % of deaths from intermediate-high and 17.9 % from high-risk subgroups., Conclusion: PE-related mortality is prominent on the first hospitalization day in high and intermediate-high-risk PE. A substantial proportion of intermediate-high and high-risk patient's PE deaths occurred after the first 6 days of hospitalization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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 × 10 9 /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.

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.

Background: The incidence of the signs and symptoms of acute pulmonary embolism (PE) according to mortality risk, age and sex has been partly explored., Patients and Methods: A total of 1242 patients diagnosed with acute PE and included in the Regional Pulmonary Embolism Registry were enrolled in the study. Patients were classified as low risk, intermediate risk or high risk according to the European Society of Cardiology mortality risk model. The incidence of the signs and symptoms of acute PE at presentation with respect to sex, age, and PE severity was investigated., Results: The incidence of haemoptysis was higher in younger men with intermediate-risk (11.7% vs 7.5% vs 5.9% vs 2.3%; p=0.01) and high-risk PE (13.8% vs 2.5% vs 0.0% vs 3.1%; p=0.031) than in older men and women. The frequency of symptomatic deep vein thrombosis was not significantly different between subgroups. Older women with low-risk PE presented with chest pain less commonly (35.8% vs 55.8% vs 48.8% vs 51.9%, respectively; p=0.023) than men and younger women. However, younger women had a higher incidence of chest pain in the lower-risk PE group than in the intermediate-risk and high-risk PE subgroups (51.9%, 31.4% and 27.8%, respectively; p=0.001). The incidence of dyspnoea (except in older men), syncope and tachycardia increased with the risk of PE in all subgroups (p<0.01). In the low-risk PE group, syncope was present more often in older men and women than in younger patients (15.5% vs 11.3% vs 4.5% vs 4.5%; p=0.009). The incidence of pneumonia was higher in younger men with low-risk PE (31.8% vs<16% in the other subgroups, p<0.001)., Conclusion: Haemoptysis and pneumonia are prominent features of acute PE in younger men, whereas older patients more frequently have syncope with low-risk PE. Dyspnoea, syncope and tachycardia are symptoms of high-risk PE irrespective of sex and age., Competing Interests: Competing interests: The interpretation of the data and presentation of this investigation were not influenced by personal or financial relationships with other people or organisations., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deep vein thrombosis (DVT) can be symptomatic or asymptomatic in patients with acute pulmonary embolism (PE). The prognostic value of the symptomatic DVT at the presentation regarding the prognosis of PE is unknown., Methods: Data were extracted from the REgional Pulmonary Embolism Registry (REPER) which enrolled 1604 hospitalized patients after multidetector computed tomography (MDCT) diagnosed symptomatic acute PE. According to the ESC risk model, patients were classified into four subgroups. Patients who had leg edema with or without pain, and patients with leg pain and DVT confirmed by compression ultrasound were considered to have symptomatic DVT. This study aimed to compare all-cause hospital mortality between patients with symptomatic DVT and patients without symptoms or signs of DVT across the PE risk stratums., Results: All-cause mortality in patients with symptomatic DVT compared to those who had no symptoms or signs of DVT were 2/196 (1.0%) vs. 11/316 (3.5%), P=0.145, 4/129 (3.1%) vs. 17/228 (7.5%), P=0.106, 14/196 (7.1%) vs. 54/290 (18.6%), P<0.001 and 16/55 (29.1%) vs. 51/139 (36.7%), P=0.402 in patients with low, intermediate-low, intermediate-high and high-risk PE, respectively. In multivariate analysis symptomatic DVT was associated with decreased in-hospital mortality only in patients with intermediate-high PE (OR 0.320, 95%CI 0.164-0.627; P=0.001). Intermediate-high risk PE patients with symptomatic DVT who were treated with thrombolysis had significantly lower hospital mortality than patients without symptoms or signs of DVT (2.2% vs. 11.4%, P=0.003)., Conclusions: Intermediate-high risk PE patients with symptomatic DVT at presentation may benefit from thrombolysis and have lower hospital all-cause mortality in such circumstances.

Background: Estimation of bleeding risk is an unmet need for individualized therapy in acute pulmonary embolism (PE) patients with increased mortality risk., Methods: 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., Results: 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., Conclusion: Novel PEBSI score has significant power to discriminate patients with low risk for MB on thrombolytic therapy from those with high risk., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The Republic of Macedonia (RoM) has experienced a rapid rise in the prevalence of type 2 diabetes (T2D) over the past 2 decades, a period characterized by significant social, political, and economic change. RoM now has one of the highest rates of diabetes in Europe., Objectives: To explore the modifiable conditions that may underlie and exacerbate the T2D epidemic; describe the state of diabetes care; and consider improved mechanisms for prevention and treatment, including research priorities, in RoM., Methods: Methods included data mining from reliable sources and collaboration of authors to consider and describe applications of research from outside RoM and to identify evidence-based strategies to reduce the burden of T2D in RoM., Findings: In 2014, the national prevalence of diabetes was 11.44% of the population (20-79 years) of RoM. Per capita caloric intake has increased significantly over the past 2 decades, with the majority of these calories coming from sugar, pork, chicken, beef, and sunflower oil. Excess calories, in the form of nutrient-deficient foods, animal products, and added oils promote insulin resistance and T2D. Tobacco use and lack of physical activity also contribute to the diabetes epidemic. Insulin, especially insulin analogues, are widely available and used to manage diabetes, often over other interventions that are more appropriate for patients with T2D, and more frequently than in other more developed countries, resulting in higher and unsustainable related costs., Conclusions: A new National eHealth System allows for better identification and monitoring of citizens with diabetes. However, the rapidly growing expense of insulin in the past has been unsustainable. The potential exists for a stronger role for lifestyle interventions in prevention and treatment of T2D. Significant changes in dietary patterns parallel the rise in diabetes prevalence and are likely a leading cause of diabetes and its complications. Research in RoM is needed to determine the impact and acceptability of dietary interventions for prevention and treatment of T2D, as a first step toward reduction of diabetes prevalence and its complications and controlling spiraling health care costs., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

This article gives contemporary review on the forearm approach for percutaneous diagnostic and interventional coronary procedures. Advantages and disadvantages as well as practical issues and current controversies regarding both radial and ulnar artery approach are discussed throughout the paper. Having in mind advantages of forearm approach in terms of safety and comfort over the traditional femoral approach, as well as the rapid development of invasive technology in the past years, it will probably become the default vascular approach for all percutaneous coronary procedures in the near future.

Introduction: Activation of haemostasis during physical stress or during myocardial ischemia could be an important mechanism to trigger coronary and stent thrombosis. We examined changes in haemostatic parameters and its association with myocardial ischemia during adenosine-exercise-SPECT (adeno-EX) stress test in coronary patients at least 4 months after coronary stenting., Objective: The aim of this study was to examine relationship between changes in haemostatic parameters and stress induced myocardial ischemia quantified by perfusion scintigraphy in stented coronary patients., Methods: Thirty-seven patients on dual antiplatelet therapy (26 on clopidogrel plus aspirin and 11 on aspirin only) 4-8 months after successful intracoronary stent implantation were enrolled in the study. We determined the levels of platelet aggregability (PA) on ADP (PA-ADP) and epinephrine (PA-EPI), beta-thromboglobulin, platelet factor-4, protein C (PC) and antithrombin (AT) before and 15 minutes after intravenous injection of 150 micro/kg adenosine for4 minutes concomitant with supine ergo-bicycle exercise test for 50 W. The size of stress perfusion defect was measured 15 minutes after stress and in rest 4 hours later by 99mTc-tetrofosmin single photon emission computed tomography (SPECT) within 17 myocardial segments., Results: There were no differences between haemostatic parameters before and after stress. A significant myocardial ischemia after exercise was registered in 12 patients on combined antiaggregation therapy and in 5 patients on aspirin. In this preliminary report, because of a small number of patients in the aspirin group we did not analyse difference in the levels of haemostatic markers and their correlations with the size of perfusion defect. The only significant difference between measured haemostatic parameters in the patients with stress induced ischemia compared to the patients without it, was a lower level of AT activity after stress (81.0% vs. 87.5%; p = 0.027). Antithrombin activity before stress had significant negative correlation with the size of perfusion defect in rest (R2 = 0.219; p = 0.016) and PC activity before stress had significant linear correlation with stress perfusion defect (R2 = 0.248; p = 0.010)., Conclusion: Baseline activities of natural anticoagulant proteins AT and PC are associated with the size of myocardial perfusion defect during adeno-EX-SPECT test. Patients with significant stress-induced ischemia had lower levels of AT activity after stress.

High aggregatory responses despite antiplatelet treatment is associated with an increased risk of thrombotic complications following percutaneous coronary intervention (PCI). In the present study, we investigated the relationship between platelet aggregatory responses to ADP and the release of CD40L (sCD40L): an immunomodulatory compound involved in atherothrombosis - in patients undergoing PCI. ADP-induced platelet aggregation, sCD40L and soluble P-selectin (sP-selectin) were determined before and 24 h after PCI, in samples from 52 patients receiving aspirin and thienopyridines. Platelet aggregation to ADP above the median was defined as 'high aggregation', and aggregation below the median as 'low aggregation'. Data below are medians and interquartile ranges. Patients with 'high platelet aggregability' had a significantly higher increase in both sCD40L (Delta-values: 0.78 (-0.19-3.18) vs. -0.65 (-2.10-0.00) ng/ml, P = 0.002) and sP-selectin (Delta-values: 8.0 (-2.00-16.00) vs. 4.50 (-13.00-0.50) ng/ml, P = 0.001) compared with patients with 'low platelet aggregability'. In a multivariate linear regression analysis adjusted for clinical characteristics and type of preintervention therapy, the only independent predictors of sCD40L and sP-selectin were platelet aggregation to ADP before PCI (P < 0.001) and the combination of platelet aggregation to ADP before PCI and urgency of PCI (P < 0.001). Circulating CD40L is more markedly increased after PCI in patients with high ADP-induced platelet aggregation.