Changes in Coagulation following Brain Injury.

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.

Diagnosis and Treatment of Trauma-Induced Coagulopathy by Viscoelastography.

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.

Whole Blood for Civilian Urban Trauma Resuscitation: Historical, Present, and Future Considerations.

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

Viscoelastic testing in benign hematologic disorders: Clinical perspectives and future implications of point-of-care testing to assess hemostatic competence.

Viscoelastic tests (VETs) have been used routinely for liver transplantation, cardiac surgery, and trauma, but only recently have found clinical utility in benign hematologic disorders. Therefore, guidelines for diagnosis and treatment of these disorders based on viscoelastic variables have been adapted from the existing transplant, cardiothoracic surgery, and trauma resuscitation literature. As a result, diagnostic and therapeutic strategies for benign hematologic disorders utilizing VETs are not uniform. Accordingly, even though there has been a recent increase in the utilization of VET for the diagnosis and treatment of such disorders, the literature is still in its early stages. Analysis of point-of-care viscoelastic tracings from benign hematologic disorders has the potential to allow prompt recognition of disease and to guide patient-specific intervention. Here we present a review describing the application of VETs to benign hematologic disorders.

Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.

Small herbaria contribute unique biogeographic records to county, locality, and temporal scales.

PREMISE: With digitization and data sharing initiatives underway over the last 15 years, an important need has been prioritizing specimens to digitize. Because duplicate specimens are shared among herbaria in exchange and gift programs, we investigated the extent to which unique biogeographic data are held in small herbaria vs. these data being redundant with those held by larger institutions. We evaluated the unique specimen contributions that small herbaria make to biogeographic understanding at county, locality, and temporal scales. METHODS: We sampled herbarium specimens of 40 plant taxa from each of eight states of the United States of America in four broad status categories: extremely rare, very rare, common native, and introduced. We gathered geographic information from specimens held by large (≥100,000 specimens) and small (<100,000 specimens) herbaria. We built generalized linear mixed models to assess which features of the collections may best predict unique contributions of herbaria and used an Akaike information criterion-based information-theoretic approach for our model selection to choose the best model for each scale. RESULTS: Small herbaria contributed unique specimens at all scales in proportion with their contribution of specimens to our data set. The best models for all scales were the full models that included the factors of species status and herbarium size when accounting for state as a random variable. CONCLUSIONS: We demonstrated that small herbaria contribute unique information for research. It is clear that unique contributions cannot be predicted based on herbarium size alone. We must prioritize digitization and data sharing from herbaria of all sizes.

Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review.

The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin-thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.

Assessing ex situ genetic and ecogeographic conservation in a threatened but widespread oak after range-wide collecting effort.

Although the genetic diversity and structure of in situ populations has been investigated in thousands of studies, the genetic composition of ex situ plant populations has rarely been studied. A better understanding of how much genetic diversity is conserved ex situ, how it is distributed among locations (e.g., botanic gardens), and what minimum sample sizes are needed is necessary to improve conservation outcomes. Here we address these issues in a threatened desert oak species, Quercus havardii Rydb. We assess the genetic, geographic, and ecological representation of 290 plants from eight ex situ locations, relative to 667 wild individuals from 35 in situ locations. We also leverage a recent dataset of >3000 samples from 11 other threatened plants to directly compare the degree of genetic conservation for species that differ in geographic range size. We found that a majority of Q. havardii genetic diversity is conserved; one of its geographic regions is significantly better conserved than the other; genetic diversity conservation of this widespread species is lower than documented for the 11 rarer taxa; genetic diversity within each garden is strongly correlated to the number of plants and number of source populations; and measures of geographic and ecological conservation (i.e., percent area and percent of ecoregions represented) were typically lower than the direct assessment of genetic diversity (i.e., percent alleles). This information will inform future seed sampling expeditions to ensure that the intraspecific diversity of threatened plants can be effectively conserved.

The genomic basis of the plant island syndrome in Darwin's giant daisies.

The repeated, rapid and often pronounced patterns of evolutionary divergence observed in insular plants, or the 'plant island syndrome', include changes in leaf phenotypes, growth, as well as the acquisition of a perennial lifestyle. Here, we sequence and describe the genome of the critically endangered, Galápagos-endemic species Scalesia atractyloides Arnot., obtaining a chromosome-resolved, 3.2-Gbp assembly containing 43,093 candidate gene models. Using a combination of fossil transposable elements, k-mer spectra analyses and orthologue assignment, we identify the two ancestral genomes, and date their divergence and the polyploidization event, concluding that the ancestor of all extant Scalesia species was an allotetraploid. There are a comparable number of genes and transposable elements across the two subgenomes, and while their synteny has been mostly conserved, we find multiple inversions that may have facilitated adaptation. We identify clear signatures of selection across genes associated with vascular development, growth, adaptation to salinity and flowering time, thus finding compelling evidence for a genomic basis of the island syndrome in one of Darwin's giant daisies.

Blunt Thoracic Trauma-Induced Mitral Papillary Muscle Avulsion with Pericardial Rupture and Cardiac Herniation: Difficult and Delayed Diagnoses.

Blunt thoracic trauma (BTT) and the resultant isolated mitral papillary muscle avulsion, pericardial rupture, and cardiac herniation injuries are each rarely diagnosed clinical entities. We describe the first case of combined pericardial tear with cardiac herniation and ruptured mitral papillary muscles following BTT. Preoperative transesophageal echocardiography (TEE) diagnosed the delayed mitral papillary muscle rupture while all previous diagnostic modalities failed to delineate the pericardial rupture and cardiac herniation. Particular emphasis is placed on the clinical and radiologic aspects of the case that would heighten clinical suspicion in the emergency setting where blunt cardiac injury sequelae are suspected and frequently missed.

The Radiation of Darwin's Giant Daisies in the Galápagos Islands.

Evolutionary radiations on oceanic islands have fascinated biologists since Darwin's exploration of the Galápagos archipelago [1, 2]. Island radiations can provide key insights for understanding rapid speciation, including evolutionary patterns and the processes behind them. However, lack of resolution of species relationships has historically hindered their investigation, particularly in the plant kingdom [3-5]. Here, we report a time-calibrated phylogenomic analysis based on genotyping-by-sequencing data [6] of the 15 species of Scalesia (Darwin's giant daisies), an iconic and understudied plant radiation endemic to the Galápagos Islands and considered the plant counterpart to Darwin's finches [1, 7-9]. Results support a Pliocene to early Pleistocene divergence between Scalesia and the closest South American relatives, and rapid diversification of extant Scalesia species from a common ancestor dated to the Middle Pleistocene. Major evolutionary patterns in Scalesia include the following: (1) lack of compliance with the "progression rule" hypothesis, in which earlier diverging lineages are expected to occupy older islands; (2) a predominance of within-island speciation over between-island speciation; and (3) repeated convergent evolution of potentially adaptive traits and habitat preferences on different islands during the course of diversification. Massive sequencing provided the essential framework for investigating evolutionary and ecological processes in the complex natural laboratory of the Galápagos, thereby advancing our understanding of island plant radiations.

Emergency Department and Radiological Cost of Delayed Diagnosis of Cannabinoid Hyperemesis.

Background. Chronic cannabis use has become prevalent with decriminalization, medical prescription, and recreational legalization in numerous US states. With this increasing incidence of chronic cannabis use a new clinical syndrome has become apparent in emergency departments and hospitals across the country, termed Cannabinoid Hyperemesis (CH). CH has been described as cyclical vomiting and abdominal pain in the setting of chronic cannabis use, which is often temporarily relieved by hot showers. CH presents a diagnostic challenge to clinicians who do not have a high clinical suspicion for the syndrome and can result in high costs and resource utilization for hospitals and patients. This study investigates the expenditures associated with delayed CH evaluation and delayed diagnosis. Methods. This is a retrospective observational study of 17 patients diagnosed with CH at three medical centers in the United States from 2010 to 2015, consisting of two academic centers and a community hospital. Emergency department (ED) costs were calculated and analyzed for patients eventually diagnosed with CH. Results. For the 17 patients treated, the total cost for combined ED visits and radiologic evaluations was an average of $76,920.92 per patient. On average these patients had 17.9 ED visits before the diagnosis of CH was made. Conclusion. CH provides a diagnostic challenge to clinicians without a high suspicion of the syndrome and may become increasingly prevalent with current trends toward cannabis legalization. The diagnosis of CH can be made primarily through a thorough history and physical examination. Awareness of this syndrome can save institutions money, prevent inappropriate utilization of healthcare resources, and save patients from unnecessary diagnostic tests.

Isolation, characterization and cross-amplification of polymorphic microsatellite loci in Laelia speciosa (Orchidaceae).

Laelia speciosa is an endangered epiphytic orchid endemic to central Mexico. Here, we report on the development of 14 perfect and imperfect microsatellite repeat loci for this species. Numbers of alleles ranged from two to 16 and levels of observed heterozygosities among the 14 loci ranged from 0.28 to 1.00 across two widely divergent populations. All loci were also tested for cross-amplification in four other Laelia species and other selected genera of the subtribe Laeliinae.

Isolation, characterization, and cross-amplification of polymorphic microsatellite loci in Guaiacum coulteri (Zygophyllaceae).

Guaiacum coulteri is a dry forest hardwood species of conservation concern endemic to the Pacific coast of Mexico. Fifteen microsatellite markers were developed which show high levels of polymorphism across two populations with the number of alleles ranging from four to 21. Most loci additionally exhibited consistent multiple banding patterns, indicating the likely polyploidy of this species. All loci were tested for cross-amplification with most found to amplify well across the genus Guaiacum, although amplification in other related genera of the Zygophyllaceae was limited.

Isolation and characterization of microsatellite loci in Coccoloba cereifera (Polygonaceae), an endangered species endemic to the Serra do Cipó, Brazil.

Microsatellite primers were isolated from the microendemic and threatened species Coccoloba cereifera, a shrub known only from a small region in the Serra do Cipó, Brazil. Thirteen primer pairs amplifying perfect and imperfect microsatellite regions were tested in 40 individuals from the one known occurrence of the species. Number of alleles ranged from two to six and levels of observed heterozygosities ranged from 0.21 to 0.95. These markers will be useful for the analysis of questions concerning population genetic structure and will assist in providing information for future conservation management programmes.