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INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.
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Eletrocardiografia , Embolia Pulmonar , Angiografia por Tomografia Computadorizada , Ventrículos do Coração , Humanos , Artéria Pulmonar , Embolia Pulmonar/diagnósticoRESUMO
In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.
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BACKGROUND: Bridging anticoagulation is used in vitamin-K antagonist (VKA) patients undergoing invasive procedures and involves complex risk assessment in order to prevent thromboembolic and bleeding outcomes. OBJECTIVES: Our aim was to assess guideline compliance and identify factors associated with bridging and especially, non-compliant bridging. METHODS: A retrospective review of 256 patient records in 13 Dutch hospitals was performed. Demographic, clinical, surgical and care delivery characteristics were collected. Compliance to the American College of Chest Physicians ninth edition guideline (AT9) was assessed. Multilevel regression models were built to explain bridging use and predict non-compliance. RESULTS: Bridging use varied from 15.0 to 83.3% (mean = 41.8%) of patients per hospital, whereas guideline compliance varied from 20.0 to 88.2% (mean = 68.5%) per hospital. Both established thromboembolic risk factors and characteristics outside thromboembolic risk assessment were associated with bridging use. Predictors for overuse were gastrointestinal surgery (OR 14.85, 95% CI 2.69-81.99), vascular surgery (OR 13.01, 95% CI 1.83-92.30), non-elective surgery (OR 8.67, 95% CI 1.67-45.14), lowest 25th percentile socioeconomic status (OR 0.33, 95% CI 0.11-1.02) and use of VKA reversal agents (OR 0.22, 95% CI 0.04-1.16). CONCLUSION: Bridging anticoagulation practice was not compliant with the AT9 in 31.5% of patients. The aggregated AT9 thromboembolic risk was inferior to individual thromboembolic risk factors and other characteristics in explaining bridging use. Therefor the AT9 risk seems less important for the decision making in everyday practice. Additionally, a heterogeneous implementation of the guideline between hospitals was found. Further research and interventions are needed to improve bridging anticoagulation practice in VKA patients.
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Due to the nonspecific symptoms of the condition, a diagnosis of acute pulmonary embolism (PE) is frequently considered. However, PE will only be confirmed in 10-20% of patients. Because the imaging test of choice, computed tomography pulmonary angiography (CTPA), is costly and associated with radiation exposure and other complications, a validated diagnostic algorithm consisting of a clinical decision rule and D-dimer test should be used to safely exclude PE in 20-30% of patients without the need for CTPA. Recently, the age-adjusted D-dimer threshold has been validated, and this has increased the proportion of patients at older age in whom PE can be excluded without CTPA. Initial therapeutic management of PE depends on the risk of short-term PE-related mortality. Haemodynamically unstable patients should be closely monitored and receive thrombolytic therapy unless contraindicated because of an unacceptably high bleeding risk, whereas patients with low-risk PE may be safely discharged early from hospital or receive only outpatient treatment. The PESI score and Hestia decision rule are available to select patients in whom early discharge or outpatient treatment will be safe, although the safety of these strategies should be confirmed in additional studies. Standard PE therapy consists of low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs). Recently, several nonvitamin K-dependent oral anticoagulants have been shown to be as effective as LMWH/VKAs, and maybe safer. Determining the optimal duration of treatment for a first unprovoked PE remains a challenge, although clinical prediction rules for estimating the risk of recurrence of venous thromboembolism and anticoagulation-associated haemorrhage are under investigation. Using these prediction rules may lead to both more standardized and more individualized long-term treatment of PE.
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Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Diagnóstico por Imagem , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina de Baixo Peso Molecular , Humanos , Terapia Trombolítica , Vitamina K/antagonistas & inibidoresRESUMO
Straightforward, accurate diagnostic management in patients presenting with clinically suspected pulmonary embolism (PE) is essential, since starting anticoagulant treatment may give important adverse effects of bleeding, while false exclusion of the disease may lead to recurrent VTE, with associated morbidity and mortality. In the past three decades, considerable improvement in the diagnostic management of PE has been made. Computed tomography pulmonary angiography (CTPA) has largely replaced conventional pulmonary angiography and ventilation-perfusion lung scanning as the imaging methods of choice. Several diagnostic algorithms, all able to minimize the need for radiological imaging have been developed and validated. Lastly, within the diagnostic algorithms, varying D-dimer cut-off levels have successfully been introduced to further downsize the need for radiological imaging.
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The first-choice imaging test for visualization of thromboemboli in the pulmonary vasculature in patients with suspected acute pulmonary embolism (PE) is multidetector computed tomography pulmonary angiography (CTPA) - a readily available and widely used imaging technique. Through technological advancements over the past years, alternative imaging techniques for the diagnosis of PE have become available, whilst others are still under investigation. In particular, the evolution of artificial intelligence (AI) is expected to enable further innovation in diagnostic management of PE. In this narrative review, current CTPA techniques and the emerging technology photon-counting CT (PCCT), as well as other modern imaging techniques of acute PE are discussed, including CTPA with iodine maps based on subtraction or dual-energy acquisition, single-photon emission CT (SPECT), magnetic resonance angiography (MRA), and magnetic resonance direct thrombus imaging (MRDTI). Furthermore, potential applications of AI are discussed.
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Embolia Pulmonar , Embolia Pulmonar/diagnóstico por imagem , Humanos , Doença Aguda , Angiografia por Tomografia Computadorizada/métodosRESUMO
Background: Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern. Objectives: We evaluated current risk scores' predictive accuracy for MB in LVAD recipients. Methods: We conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS). Results: One hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk. Conclusion: Current bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.
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BACKGROUND: It is unclear how often cancer patients with acute pulmonary embolism (PE) are discharged from the emergency department (ED) or outpatient clinic and whether direct discharge is safe. We assessed treatment setting and early safety outcomes in cancer patients with acute symptomatic and incidental PE. METHODS: Cancer patients diagnosed with PE at the ED or outpatient clinic between August 2017 and May 2021 were included in Four Cities VTE Cancer, a Dutch multicenter retrospective cohort study. The main outcome was direct discharge versus hospitalization. Safety outcomes were cumulative 14-day mortality and PE-related readmission incidences. RESULTS: We included 602 patients (median age 71 years; 49.5 % female) of whom 285 (47.3 %) were discharged directly and 317 (52.7 %) were hospitalized. The cumulative 14-day mortality incidence was 0.7 % (95 % CI, 0.1-2.4 %) in patients discharged directly and 9.0 % (95 % CI, 6.2-12.5 %) in those hospitalized. The cumulative 14-day PE-related readmission incidence was 1.8 % (95 % CI, 0.7-3.9 %) and 1.4 % (95 % CI, 0.5-3.3 %) in directly discharged and hospitalized patients, respectively. Of the 220 patients with incidental PE, 180 (81.8 %) were discharged directly compared to 105 of 382 (27.5 %) patients with symptomatic PE (P < 0.001). Mortality and readmission incidences in symptomatic and incidental PE were consistent with the main analysis. CONCLUSIONS: About 28 % and 82 % of cancer patients with symptomatic or incidental PE, respectively, were discharged directly, with low 14-day mortality and PE-related readmission incidences. These data underline the need for PE risk stratification in oncological populations and suggest that clinicians successfully identify a proportion of patients in whom direct discharge is safe.
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Neoplasias , Embolia Pulmonar , Humanos , Feminino , Idoso , Masculino , Alta do Paciente , Estudos Retrospectivos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Instituições de Assistência Ambulatorial , Neoplasias/complicações , Serviço Hospitalar de EmergênciaRESUMO
OBJECTIVE: AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant dose. This post hoc study aimed to externally validate these findings in the ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor Xa next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48) trial. METHODS: The ENGAGE AF-TIMI 48 trial randomized AF patients to higher-dose edoxaban regimen (HDER 60/30 mg) versus lower-dose edoxaban regimen (LDER 30/15 mg), with prespecified dose reduction criteria. AF-BLEED was calculated in the modified intention-to-treat cohort (n = 21,026 patients) used for primary outcome analysis. Annualized event rates and hazard ratios (HRs) were obtained for the primary composite outcome (PCO) and its single components (MB, ischemic stroke/systemic embolism and death) to compare LDER 30 mg with HDER 60 mg in both AF-BLEED classes. RESULTS: AF-BLEED classified 2882 patients (13.7 %) as high-risk, characterized by a two- to three-fold higher MB risk than AF-BLEED classified low-risk patients. AF-BLEED classified high-risk patients randomized to LDER 30 mg demonstrated a 3.3 % reduction in MB at the cost of a 0.5 % increase in ischemic stroke/systemic embolism. LDER 30 mg resulted in a 3.1 % reduction of PCO compared to HDER 60 mg (HR of 0.81; 95%CI 0.65-1.01). Additional to existing dose reduction criteria, another 6 % of patients could potentially benefit of this dose adjustment strategy. CONCLUSION: AF-BLEED could identify AF patients to be at high risk of major bleeding. Our findings support the hypothesis that LDER 30 mg might provide a reasonable option in AF patients with legitimate bleeding concerns.
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BACKGROUND: Pulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown. AIM: To evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes. METHODS: We studied a convenience cohort with computed tomography pulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis. RESULTS: At re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1-3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2-6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1-2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01-9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results. CONCLUSIONS: PE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling.
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Embolia Pulmonar , Infarto Pulmonar , Humanos , Infarto Pulmonar/complicações , Angiografia por Tomografia Computadorizada/métodos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Artéria Pulmonar , DispneiaRESUMO
Direct oral anticoagulants (DOACs) have become the cornerstone for prevention of thromboembolic events in patients with atrial fibrillation and patients with a history of venous thromboembolism. However, studies show that DOAC prescriptions are commonly inconsistent with guideline recommendations. DOAC dosing in the acutely ill patient could impose an even greater challenge. In this review, we describe the prevalence of inappropriate inpatient prescribing of DOACs and the associated rationales, predictors and clinical consequences. With the aim of promoting appropriate prescriptions of DOACs to hospitalized patients, we further outline DOAC dose reduction criteria justified by various guidelines, illustrating the complexities of appropriate dosing, especially in acutely ill patients. Moreover, we will discuss the impact of anticoagulant stewardship programs and the vital role that pharmacists may play in optimizing inpatient DOAC treatment.
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Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Rivaroxabana/uso terapêutico , Prescrição Inadequada , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/complicações , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Administração Oral , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice. AIMS: This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab. METHODS: A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation. RESULTS: Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %-69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %-37.2 %), to enable thrombolysis (range: 2.0 %-27.3 %), dabigatran intoxication without bleeding (range: 3.6 %-7.0 %) or unspecified reasons (range: 0.4 %-18.8 %). Overall, 2.8 % (95%CI 0.5 %-6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %-87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %-100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %-17.9 %) and 2.0 % (95%CI 0.8 %-3.4 %), respectively. CONCLUSION: Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.
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Hemostáticos , Tromboembolia , Humanos , Dabigatrana/efeitos adversos , Antitrombinas/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológicoRESUMO
BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.
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Fibrinolíticos , Neoplasias , Humanos , Fibrinolíticos/uso terapêutico , Qualidade de Vida , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Morte , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. METHODS AND RESULTS: Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. CONCLUSIONS: Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury.
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Antígenos CD34/metabolismo , Plaquetas/citologia , Plaquetas/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Comunicação Celular/fisiologia , Diabetes Mellitus Tipo 2/sangue , Endossomos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Multipotentes/efeitos dos fármacos , Selectina-P/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Receptores CXCR4/metabolismoRESUMO
BACKGROUND: Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. RESULTS: The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment. CONCLUSIONS: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.
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Síndrome de Cushing , Doenças do Sistema Endócrino , Endometriose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Síndrome de Cushing/complicações , Síndrome de Cushing/tratamento farmacológico , Feminino , Humanos , Doenças Raras/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controleRESUMO
Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73â m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73â m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.
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AIM: To evaluate recovery of cardiac function after acute pulmonary embolism (PE). MATERIALS AND METHODS: Routine breath-held computed tomography (CT)-pulmonary angiography was performed in patients with suspected PE to confirm or exclude the diagnosis of PE at initial presentation. Electrocardiogram (ECG)-triggered cardiac CT was performed to assess biventricular function. After 6 months, cardiac magnetic resonance imaging (MRI) was performed. In total, 15 consecutive patients with PE and 10 without were studied. A significant change in ventricular volume was defined as a >15% change in end-diastolic or -systolic volumes (EDV, ESV), and significant ventricular function improvement as a >5% increase in ejection fraction (EF) as based on reported cut-off values. RESULTS: Right and left ventricular (RV and LV) EDV and ESV changed non-significantly (<1.3%) in the patients without PE, indicating good comparability of those values measured by CT and MRI. PE patients with baseline normal RV function (RVEF ≥ 47%) revealed a >5% improvement in the RVEF (+5.4 ± 3.1%) due to a decrease in the RVESV. Patients with baseline abnormal RV function showed a >5% improvement in the RVEF (+14 ± 15%) due to decreases in both the RVESV and RVEDV. Furthermore, the LVEDV increased in this latter patient group. CONCLUSIONS: The present study demonstrated an improvement in RV function in the majority of patients with PE, independent of baseline RV function. The degree of RV and LV recovery was dependent on the severity of baseline RV dysfunction.