350 research outputs found

    Development and first results of a dedicated chronic total occlusion programme

    Get PDF
    Objective To describe the development and first results of a dedicated chronic total occlusion (CTO) programme in a tertiary medical centre. Background Because of the complexity and the increased risk of complications during percutaneous coronary intervention (PCI) for CTO, it is essential that less experienced and evolving CTO centres perform regular quality analyses. Methods We therefore performed analyses to describe the results during the first 3 years of a dedicated CTO programme at a high-volume PCI centre. In addition, we discuss the strategies employed to develop such a programme. Results A total of 179 consecutive patients undergoing 187 CTO procedures were included in the study. The complexity of the CTO lesions increased from a mean J-CTO (Japanese Multicentre CTO Registry) score of 1.3 in 2015 to 2.1 in 2017. In the majority of cases, the antegrade wire escalation technique was performed. Final technical success rate was 78.5% in 175 patients with a single CTO and 80.2% of all 187 CTO procedures. No peri-procedural or in-hospital deaths occurred. One peri-procedural myocardial infarction occurred. Cardiac tamponade occurred in 2 cases, both managed by pericardiocentesis. No urgent cardiac surgery was necessary. Survival and revascularisation rates at 30 days and 1 year were excellent. Conclusion Following initiation of a dedicated CTO programme, using up-to-date techniques and strategies, procedural and clinical outcome were comparable with current standards in established centres

    Transfusion practice in the bleeding critically ill:An international online survey-The TRACE-2 survey

    Get PDF
    Background: Transfusion is very common in the intensive care unit (ICU), but practice is highly variable, as has recently been shown in non-bleeding critically ill patients practices survey. Bleeding patients in ICU require different blood products across a range of specific patient categories. We hypothesize that a large variety in transfusion practice exists in bleeding patients. Study design and methods: An international online survey was performed among physicians working in the ICU. Transfusion practice in massively and non-massively bleeding patients was examined, including transfusion ratios, thresholds, and the presence of transfusion guidelines. Results: Six hundred eleven respondents filled in the survey of which 401 could be analyzed, representing 64 countries. Among the respondents, 52% had a massive transfusion protocol (MTP) available at their ICU. In massively bleeding patients, 46% of the respondents used fixed transfusion component ratios. Of those who used fixed blood ratios, the 1:1:1 ratio (red blood cell [RBC] concentrates: plasma: platelet concentrates) was most commonly used (33%). The presence of an MTP was associated with a more frequent use of fixed ratios (p <.001). For RBC transfusion in the general non-massively bleeding ICU population, a hemoglobin (Hb) threshold of 7.0[7.0–7.3] g/dl was reported. In the general ICU population, a platelet count threshold of 50[26–50] × 109/L was applied. Discussion: Half of the centers had no massive transfusion protocol available. Transfusion practice in massively bleeding critically ill patients is highly variable and driven by the presence of an MTP. In the general non-massively bleeding ICU population restrictive transfusion triggers were chosen

    Monitoring, management, and outcome of hypotension in Intensive Care Unit patients, an international survey of the European Society of Intensive Care Medicine

    Get PDF
    INTRODUCTION: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines. METHODS: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension. RESULTS: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%). CONCLUSIONS: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol

    Definition and incidence of hypotension in intensive care unit patients, an international survey of the European Society of Intensive Care Medicine

    Get PDF
    Introduction: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists. Methods: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension. Results: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p &lt; 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p &lt; 0.001). Conclusions: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians.</p

    Lentiviral gene therapy with IGF2-tagged GAA normalizes the skeletal muscle proteome in murine Pompe disease

    Get PDF
    Pompe disease is a lysosomal storage disorder caused by deficiency of acid alpha-glucosidase (GAA), resulting in glycogen accumulation with profound pathology in skeletal muscle. We recently developed an optimized form of lentiviral gene therapy for Pompe disease in which a codon-optimized version of the GAA transgene (LV-GAAco) was fused to an insulin-like growth factor 2 (IGF2) peptide (LV-IGF2.GAAco), to promote cellular uptake via the cation-independent mannose-6-phosphate/IGF2 receptor. Lentiviral gene therapy with LV-IGF2.GAAco showed superior efficacy in heart, skeletal muscle, and brain of Gaa−/− mice compared to gene therapy with untagged LV-GAAco. Here, we used quantitative mass spectrometry using TMT labeling to analyze the muscle proteome and the response to gene therapy in Gaa−/− mice. We found that muscle of Gaa−/− mice displayed altered levels of proteins including those with functions in the CLEAR signaling pathway, autophagy, cytoplasmic glycogen metabolism, calcium homeostasis, redox signaling, mitochondrial function, fatty acid transport, muscle contraction, cytoskeletal organization, phagosome maturation, and inflammation. Gene therapy with LV-GAAco resulted in partial correction of the muscle proteome, while gene therapy with LV-IGF2.GAAco resulted in a near-complete restoration to wild type levels without inducing extra proteomic changes, supporting clinical development of lentiviral gene therapy for Pompe disease. Significance: Lysosomal glycogen accumulation is the primary cause of Pompe disease, and leads to a cascade of pathological events in cardiac and skeletal muscle and in the central nervous system. In this study, we identified the proteomic changes that are caused by Pompe disease in skeletal muscle of a mouse model. We showed that lentiviral gene therapy with LV-IGF2.GAAco nearly completely corrects disease-associated proteomic changes. This study supports the future clinical development of lentiviral gene therapy with LV-IGF2.GAAco as a new treatment option for Pompe disease.</p

    Mechanical Ventilation and the Titer of Antibodies as Risk Factors for the Development of Transfusion-Related Lung Injury

    Get PDF
    Purpose. Onset of transfusion-related acute lung injury (TRALI) is suggested to be a threshold-event. Data is lacking on the relation between titer of antibodies infused and onset of TRALI. We determined whether onset of TRALI is dependent on the titer of MHC-I antibodies infused in a combined model of ventilator-induced lung injury and antibody-induced TRALl. Methods. BALB/c mice were ventilated for five hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume. After three hours of MV, TRALI was induced by infusion of 0.5 mg/kg, 2.0 mg/kg or 4.5 mg/kg MHC-I antibodies. Control animals received vehicle. After five hours of MV, animals were sacrificed. Results. MV with high tidal volumes resulted in increased levels of all markers of lung injury compared to animals ventilated with low tidal MV. In ventilator-induced lung injury, infusion of 4.5 mg/kg of antibodies further increased pulmonary wet-to-dry ratio, pulmonary neutrophil influx and pulmonary KC levels, whereas infusion of lower dose of antibodies did not augment lung injury. In contrast, mice ventilated with low tidal volumes did not develop lung injury, irrespective of the dose of antibody used. Conclusions. In the presence of injurious MV, onset of TRALI depends on the titer of antibodies infused

    Transfusion practice in the non-bleeding critically ill:an international online survey-the TRACE survey

    Get PDF
    Background Over the last decade, multiple large randomized controlled trials have studied alternative transfusion strategies in critically ill patients, demonstrating the safety of restrictive transfusion strategies. Due to the lack of international guidelines specific for the intensive care unit (ICU), we hypothesized that a large heterogeneity in transfusion practice in this patient population exists. The aims of this study were to describe the current transfusion practices and identify the knowledge gaps. Methods An online, anonymous, worldwide survey among ICU physicians was performed evaluating red blood cell, platelet and plasma transfusion practices. Furthermore, the presence of a hospital- or ICU-specific transfusion guideline was asked. Only completed surveys were analysed. Results Nine hundred forty-seven respondents filled in the survey of which 725 could be analysed. Hospital transfusion protocol available in their ICU was reported by 53% of the respondents. Only 29% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin (Hb) threshold for the general ICU population was 7 g/dL (7-7). The highest reported variation in transfusion threshold was in patients on extracorporeal membrane oxygenation or with brain injury (8 g/dL (7.0-9.0)). Platelets were transfused at a median count of 20 x 10(9) cells/L IQR (10-25) in asymptomatic patients, but at a higher count prior to invasive procedures (p &lt;0.001). In patients with an international normalized ratio (INR) &gt; 3, 43% and 57% of the respondents would consider plasma transfusion without any upcoming procedures or prior to a planned invasive procedure, respectively. Finally, doctors with base specialty in anaesthesiology transfused critically ill patients more liberally compared to internal medicine physicians. Conclusion Red blood cell transfusion practice for the general ICU population is restrictive, while for different subpopulations, higher Hb thresholds are applied. Furthermore, practice in plasma and platelet transfusion is heterogeneous, and local transfusion guidelines are lacking in the majority of the ICUs.</p

    2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups

    Get PDF
    Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.</p

    A guide to immunotherapy for COVID-19

    Get PDF
    Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections
    corecore