Publications by authors named "Vera Ignjatovic"

Objectives: To determine if a priori standardization of outcome hemostatic definitions alone was adequate to enable useful comparison between two cohorts of pediatric extracorporeal membrane oxygenation (ECMO) patients, managed according to local practice and protocol.

Design: Comparison of two separate prospective cohort studies performed at different centers with standardized outcome definitions agreed upon a priori.

Setting: General and cardiac PICUs at the Royal Children's Hospital (RCH) in Melbourne, Australia, and the Sophia Children's Hospital (SCH) in Rotterdam, The Netherlands.

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Article Synopsis
  • Congenital heart disease (CHD) significantly increases the risk of thromboembolism (TE) in children, with a study finding that 33% of affected patients experienced recurrent TE within a year.
  • Among the risk factors identified, immobility and the presence of central venous catheters (CVC) were strongly associated with a higher likelihood of recurrence, demonstrating the need for careful monitoring and management in this population.
  • The study calls for larger multicenter research to further validate these findings and improve understanding of TE recurrence in pediatric patients with CHD.
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Introduction: Thromboembolism is a complication in paediatric patients with CHD requiring cardiac surgery. Previous research has focused on post-operative thromboembolism. This study aimed to describe thromboembolism frequency before or after cardiac surgery in children with CHD.

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Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023.

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Article Synopsis
  • Direct oral anticoagulants (DOACs) are the preferred choice for preventing venous thromboembolism (VTE) in most patients, but their effectiveness and safety in those with severe inherited thrombophilias are not well understood.
  • Current research primarily comes from small studies, and there's insufficient data on how well patients stick to their treatment plans.
  • Although DOACs and vitamin K antagonists show similar effectiveness and bleeding risks for preventing VTE in these patients, caution is advised with low-dose DOACs, and more extensive studies are needed for a definitive treatment strategy.
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Objective: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children.

Design: Single-center observational prospective study, April to November 2021.

Setting: PICU, Royal Children's Hospital, Melbourne, Australia.

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Objective: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion.

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Introduction: Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the "modified mini-euglobulin clot lysis assay [ECLA]"), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts.

Methods: The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate.

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The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients.

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Article Synopsis
  • The study aimed to understand different recovery patterns in neurocognitive function after pediatric concussions over three months and identify factors that influence recovery trajectories.
  • Researchers analyzed data from 74 kids aged 8-17 and found three distinct recovery groups: two groups showed improvement in information processing, while one group had minimal change and lower scores on cognitive tests.
  • The findings highlighted that a previous history of headaches was linked to the group with the least improvement, suggesting that pre-existing conditions could help identify children who may need more support after a concussion.
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Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV).

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In response to growing recognition that nonadherence prevents children, adolescents, and young adults from achieving the therapeutic benefits of anticoagulant medication, the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis convened a working party on medication adherence. The primary aim of this article was to synthesize recommendations from the larger adherence science literature to provide guidance regarding the classification, collection, and interpretation of anticoagulation adherence data. The secondary aim of this article was to evaluate the degree to which trials published from 2013 to 2023 adhered to these guidance recommendations.

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Of the four million children who experience a concussion each year, 30-50% of children will experience delayed recovery, where they will continue to experience symptoms more than two weeks after their injury. Delayed recovery from concussion encompasses emotional, behavioral, physical, and cognitive symptoms, and as such, there is an increased focus on developing an objective tool to determine risk of delayed recovery. This study aimed to identify a blood protein signature predictive of delayed recovery from concussion in children.

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Objective: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury.

Methods: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion.

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Changes in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed.

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Clinical proteomics studies aiming to develop markers of clinical outcome or disease typically involve distinct discovery and validation stages, neither of which focus on the clinical applicability of the candidate markers studied. Our clinically useful selection of proteins (CUSP) protocol proposes a rational approach, with statistical and non-statistical components, to identify proteins for the validation phase of studies that could be most effective markers of disease or clinical outcome. Additionally, this protocol considers commercially available analysis methods for each selected protein to ensure that use of this prospective marker is easily translated into clinical practice.

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Background: Extracorporeal membrane oxygenation (ECMO) is used in children with cardiopulmonary failure. While the majority of ECMO centers use unfractionated heparin, other anticoagulants, including factor XI and factor XII inhibitors are emerging, which may prove suitable for ECMO patients. However, before these anticoagulants can be applied in these patients, baseline data of FXI and FXII changes need to be acquired.

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Article Synopsis
  • - ECMO support for neonates and pediatric patients has progressed significantly due to advances in technology and increasing interest in anticoagulation methods.
  • - The review highlights the importance of selecting appropriate anticoagulation agents and laboratory monitoring strategies for children undergoing ECMO.
  • - Clinicians can find valuable evidence-based guidance in the review to improve the management of anticoagulation for pediatric ECMO patients.
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Post-traumatic headache (PTH) represents the most common acute and persistent symptom following concussion in children, yet the underlying pathophysiology remains unclear. This systematic review sought to: (i) rigorously examine the current evidence of PTH pathophysiology in paediatric concussion (0-18 years), (ii) assess the quality of evidence, and (iii) provide directions for future research in accordance with PRISMA guidelines. Eligible studies (n = 19) totalling 1214 concussion participants investigated cerebrovascular function (n = 6), white matter integrity (n = 3), functional connectivity (n = 3), electrophysiology (n = 1), neurometabolics (n = 2), biological fluid markers (n = 4), vestibular and oculomotor function (n = 4); two studies used a multi-modal approach.

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Objectives: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.

Design: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.

Setting: PICUs within U.

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Objective: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion.

Methods: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.

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Background: Invasive mechanical ventilation (IMV) has been independently associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children, including extremity deep venous thrombosis and pulmonary embolism.

Objectives: We aimed to characterize the frequency and timing of HA-VTE following IMV exposure.

Methods: This was a single-center, retrospective cohort study including children aged <18 years, hospitalized in a pediatric intensive care unit, undergoing mechanical ventilation for >24 hours from October 2020 through April 2022.

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Blood clot formation represents a key component of the coagulation process for preventing excessive hemorrhage. The structural characteristics of blood clots are associated with their strength and susceptibility to fibrinolysis. Scanning electron microscopy is a technique that allows for state-of-the-art image capture of blood clots, providing visualization of topography, fibrin thickness, fibrin network density, and blood cell involvement and morphology.

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Objective: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion.

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Synopsis of recent research by authors named "Vera Ignjatovic"

  • - Vera Ignjatovic's recent research primarily focuses on thrombosis and hemostatic disorders, particularly in pediatric populations undergoing complex medical treatments such as cardiac surgery and ECMO, illustrating the prevalence and implications of thromboembolism in these settings
  • - The studies encompass systematic reviews on treatment options like direct thrombin inhibitors and the safety and efficacy of direct oral anticoagulants in patients with severe thrombophilia, aiming to bridge the knowledge gap in managing anticoagulation therapy in children
  • - Additional investigations delve into neurocognitive outcomes following pediatric concussions, employing advanced imaging techniques to assess white matter changes, highlighting the need for better diagnostic markers in postconcussive symptoms and recovery trajectories