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Trauma patients present to the emergency department with a spectrum of fibrinolytic activity. This wide variance in fibrinolysis activity is a complex multifactorial process impacted by the degree of hemorrhagic shock and the amount of tissue injury the individual sustains. The fibrinolytic activity of the trauma patient at presentation to the hospital has prognostic and therapeutic implications. Those patients with high fibrinolytic activity (hyperfibrinolysis) are at risk of mortality from hemorrhage, whereas those patients with low fibrinolytic activity (shutdown or hypofibrinolysis) are at an increased risk of delayed mortality from traumatic brain injury or organ failure. These phenotypes of fibrinolysis acutely following injury change with resuscitation, and the majority of trauma patients will transition to a fibrinolytic resistant state several hours after injury. The mechanism for this near-global transition to this acquired fibrinolysis appears to be related to the generation of plasminogen activator inhibitor-1 in the liver. Those patients who do not recover from this fibrinolytic state 24 hours after injury have a poor prognosis. The purpose of this article is to review the different states of fibrinolytic activity following injury and how they change over time following resuscitation and in the intensive care unit. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Plasmin generation in trauma patients has wide-ranging effects, from breakdown of clots to remodeling the extracellular matrix. An evolving recognition of plasmin as a critical effector molecule in various inflammatory signals and pathways has rendered the study of plasmin(ogen) and its regulation by upstream activators and downstream targets and inhibitors key to understanding the inflammatory responses to trauma. Tranexamic acid, a widely available lysine analogue medication on the World Health Organization's list of essential medicines, has rapidly become one of the most commonly implemented adjunct treatments for bleeding after traumatic injury in clinical practice. In this article, we review the effects, both anti- and proinflammatory, of tranexamic acid, with a focus on the injured trauma patient. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Traumatic brain injury (TBI) is a worldwide public health concern due to increasing mortality, affecting around 10 million patients per year. A wide variety of clinical presentations are a function of the magnitude of injury and the anatomical perturbation of the brain parenchyma, supporting structures, and cerebral vasculature, with subsequent alteration of the blood-brain barrier. These disturbances correspond with the evolution of intracerebral hemorrhage and clinical outcomes. The associated hemostatic alterations associated with TBI are caused by the disruption of the delicate balance between bleeding and thrombosis formation, which can exacerbate initial injury. TBI-associated coagulopathy is a function of a cross-talk between coagulation and inflammation, with varying influences on the immunomodulation and regulation of coagulation that occur on platelets and the endothelium of injured TBI patients. In addition to the severity of initial injury, the following factors modulate the hemocoagulative response to TBI time from the onset of injury to treatment, age, gender, catecholamine secretion, platelet dysfunction, endotheliopathy, premorbid anticoagulation, fibrinolysis, tissue factor, and activated protein C contribution. All these entities are intertwined and influence the pathologic evolution of TBI. These factors have implications for therapeutic options such as the choice of blood components for transfusion and hemostatic agents such as tranexamic acid. Monitoring hemostatic changes of TBI patients requires an understanding of these interactions between immunology and coagulation, which can be discerned by point-of-care viscoelastic testing with specific limitations. This review considers the implications of these interrelated influences on the evaluation of coagulopathy in TBI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Trauma-induced coagulopathy (TIC) is well documented in injured children. However, many important features of pediatric hemostasis are still in development in early childhood and may impact TIC. Certain pediatric subgroups are at a higher risk. Traumatic brain injury, which occurs with a higher rate in children, and physical child abuse are known risk factors for TIC that deserve special consideration. Resuscitation of a pediatric trauma patient follows many of the same goals as in the injured adult trauma, although some key aspects of pediatric resuscitation require ongoing investigation. Venous thromboembolism occurs with higher rates in certain high-risk groups of pediatric trauma patients, although overall it is considerably less frequent in children as compared with adults. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.This article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohemostatic agents, and improved clinical outcomes such as the mortality of critically bleeding patients. We describe different VETs and provide guidance for blood component therapy and prohemostatic therapy based on specific VET parameters. Because the two most commonly used VET systems, rotational thromboelastometry and thromboelastography, use different activators and have different terminologies, this practical narrative review will directly compare and contrast these two VETs to help the clinician easily interpret either and use the interpretation to determine hemostatic integrity in the bleeding trauma patient. Finally, we anticipate the future of new viscoelastic technologies that can be used in this setting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Trauma induces a change in nearly every observable aspect of hemostasis, generally tipping the balance toward trauma-induced coagulopathy (TIC) and bleeding in the critical early stages. Two particularly important aspects of TIC are platelets and fibrinogen, which are the primary determinants of clot formation and hemostasis. [https://www.selleckchem.com/products/mcc950-sodium-salt.html CP-456773 molecular weight] Their loss and dysfunction represent important transition points between coagulopathy phenotypes, highlighting their mechanistic roles in TIC as well as unveiling new potential avenues toward important diagnostic and therapeutic interventions. This review synthesizes current knowledge of platelets and fibrinogen during TIC, with a focus on emerging concepts related to their dysfunction and development of new therapeutic approaches. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Herr Professor Dr. med. Ludwig Gortner, geboren 1950 in Pirmasens, hat sein berufliches Leben 40 Jahre lang in den Dienst an kranken Früh- und Neugeborenen, Kindern und Jugendlichen gestellt. © Georg Thieme Verlag KG Stuttgart · New York.Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. link2 Severe renal impairment influences the allocation of chemotherapy, its tolerability, and affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. link3 We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with mean eGFR of 13±11 mL/min/1.73m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), cortical and medullary inflammation (95 and 75%). Medullary inflammation, giant cell reaction and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43±30 mL/min/1.73m2. Age, β2-microglobulin, best hematologic response, number of cortical casts/mm2 and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response which, in turn, is associated with overall survival. Copyright © 2020 American Society of Hematology.PURPOSE Rapid, intra-operative identification of tumor tissue in the margins of excised specimens has become an important focus in the pursuit of reducing re-excision rates, especially for breast conserving surgery. Dual-probe difference specimen imaging (DDSI) is an emerging approach that uses the difference in uptake/clearance kinetics between a pair of fluorescently-labeled stains, one targeted to a biomarker-of-interest and the other an untargeted isotype, to reveal receptor-specific images of the specimen. Previous studies using antibodies labeled with either enhanced Raman particles or organic fluorophores have shown promising tumor vs. normal diagnostic performance. Yet, the unique properties of quantum dot-labeled antibody complexes (QDACs), which provide spectrally-distinct fluorescence emission from a common excitation source, make them ideal candidates for this application. Herein, we evaluate the diagnostic performance of QDAC-based DDSI in excised xenografts. PROCEDURES Excised fresh specimens oferspectral imaging. Our results show promising diagnostic performance under certain conditions, and compel further optimization and evaluation of this intra-operative margin assessment technique.OBJECTIVE To identify food choices allowing the fulfillment of nutritionally adequate diets resembling actual food patterns at the lowest cost achievable for the Brazilian population, stratified by income level. METHODS Food consumption and prices were obtained from the Household Budget Survey (n = 55,970 households) and National Dietary Survey (n = 32,749 individuals). The sample was stratified into capitals of the states and further by income levels according to the official minimum wage (totaling 108 geographic-economic strata, or GES). Linear programming models were performed for each GES in order to find the lowest cost of diets that meet a set of nutritional constraints. In order to find realistic diets, constraints referring to preferences were introduced in the models allowing optimized food quantities to depart progressively from the current intake for each food and food group. The impact of meeting each target nutrient was assessed by performing models removing each nutrient at the time. RESULTS The observed and optimized diet costs were US$2.