Ability of Thromboelastography to Detect Hypercoagulability: A Systematic Review and Meta-Analysis.

OBJECTIVE: To review the current literature on the use of viscoelastic hemolytic assays, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), during the perioperative period of patients and determine the ability of TEG and ROTEM to detect hypercoagulability and identify increased risk of the development of venous thromboembolism (VTE). DATA SOURCES: PubMed, EMBASE, and Cochrane online databases were queried through February 11, 2018, by pairing the terms "thromboelastography," "viscoelastic hemostatic assays," and "rotational thromboelastometry" with "venous thromboembolism," "deep vein thrombosis," "pulmonary embolism," and "hypercoagulability." STUDY SELECTION: Inclusion and exclusion criteria were established to determine relevance and quality of data, of which 2.54% of initially identified studies met. DATA EXTRACTION AND SYNTHESIS: Articles and citations were reviewed for relevance by 2 independent individuals following PRISMA guidelines as well as a quality assessment of data as established by Zaza et al. In studies that separated patients postoperatively by VTE development or no VTE development, data were pooled utilizing a modified DerSimmion and Laird random effects model. RESULTS: One thousand eight hundred ninety-three articles were assessed for eligibility, yielding 370 abstracts. Of the 370 abstracts, 35 studies were included, and of these, only 5 were included in the meta-analysis. Studies included postsurgical patients in a variety of surgical fields, encompassing a total of 8939 patients, with 717 thrombotic events reported. Elevated maximum amplitude (MA) was a statistically significant indicator of hypercoagulability across at least 1 perioperative time point in 17 (50%) of the articles reviewed, consisting of 6348 (72%) patients. The pooled mean MA value for defining hypercoagulability was greater than 66.70 mm. Using a prepublished value for hypercoagulability of 65 mm, the combined effect of MA on the development of VTE in postsurgical patients was determined to be 1.31 (95% confidence, 0.74-2.34, P = 0.175) and was 46% sensitive and 62% specific in predicting a postoperative VTE. CONCLUSIONS: Only 1 parameter, MA, was consistently used to both define hypercoagulability and be predictive of VTE after traumatic injury and surgical intervention; however, there remains a broad variability in the definition of hypercoagulability as determined by MA and thus limits its predictive ability. In addition, when hypercoagulability was measured throughout the perioperative period, TEG consistently demonstrated hypercoagulability starting on post-op day 1 (POD1). LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Immobilization of Proteins with Controlled Load and Orientation.

Biomaterials based on immobilized proteins are key elements of many biomedical and industrial technologies. However, applications are limited by an inability to precisely construct materials of high homogeneity and defined content. We present here a general "protein-limited immobilization" strategy by combining the rapid, bioorthogonal, and biocompatible properties of a tetrazine-strained trans-cyclooctene reaction with genetic code expansion to site-specifically place the tetrazine into a protein. For the first time, we use this strategy to immobilize defined amounts of oriented proteins onto beads and flat surfaces in under 5 min at submicromolar concentrations without compromising activity. This approach opens the door to generating and studying diverse protein-based biomaterials that are much more precisely defined and characterized, providing a greater ability to engineer properties across a wide range of applications.

Improving identification of traumatic brain injury after nonmilitary bomb blasts.

OBJECTIVE: To improve identification of traumatic brain injury (TBI) in survivors of nonmilitary bomb blasts during the acute care phase. METHODS: The Centers for Disease Control and Prevention convened a meeting of experts in TBI, emergency medicine, and disaster response to review the recent literature and make recommendations. RESULTS: Seven key recommendations were proposed: (1) increase TBI awareness among medical professionals; (2) encourage use of standard definitions and consistent terminology; (3) improve screening methods for TBI in the acute care setting; (4) clarify the distinction between TBI and acute stress disorder; (5) encourage routine screening of hospitalized trauma patients for TBI; (6) improve identification of nonhospitalized TBI patients; and (7) integrate the appropriate level of TBI identification into all-hazards mass casualty preparedness. CONCLUSIONS: By adopting these recommendations, the United States could be better prepared to identify and respond to TBI following future bombing events.

Traumatic brain injuries after mass-casualty incidents: lessons from the 11 September 2001 World Trade Center attacks.

INTRODUCTION: The 11 September 2001 terrorist attacks on the World Trade Center (WTC) resulted in thousands of deaths and injuries. Research on previous bombings and explosions has shown that head injuries, including traumatic brain injuries (TBIs), are among the most common injuries. OBJECTIVE: The objective of this study was to identify diagnosed and undiagnosed (undetected) TBIs among persons hospitalized in New York City following the 11 September 2001 WTC attacks. METHODS: The medical records of persons admitted to 36 hospitals in New York City with injuries or illnesses related to the WTC attacks were abstracted for signs and symptoms of TBIs. Diagnosed TBIs were identified using the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Undiagnosed TBIs were identified by an adjudication team of TBI experts that reviewed the abstracted medical record information. Persons with an undiagnosed TBI were contacted and informed of the diagnosis of potential undetected injury. RESULTS: A total of 282 records were abstracted. Fourteen cases of diagnosed TBIs and 21 cases of undiagnosed TBIs were identified for a total of 35 TBI cases (12% of all of the abstracted records). The leading cause of TBI was being hit by falling debris (22 cases). One-third of the TBIs (13 cases) occurred among rescue workers. More than three years after the event, four out of six persons (66.67%) with an undiagnosed TBI who were contacted reported they currently were experiencing symptoms consistent with a TBI. CONCLUSIONS: Not all of the TBIs among hospitalized survivors of the WTC attacks were diagnosed at the time of acute injury care. Some persons with undiagnosed TBIs reported problems that may have resulted from these TBIs three years after the event. For hospitalized survivors of mass-casualty incidents, additional in-hospital, clinical surveys could help improve pre-discharge TBI diagnosis and provide the opportunity to link patients to appropriate outpatient services. The use and adequacy of head protection for rescue workers deserves re-evaluation.

Using a cost-benefit analysis to estimate outcomes of a clinical treatment guideline: testing theBrain Trauma Foundation guidelines for the treatment of severe traumatic brain injury.

BACKGROUND: A decade after promulgation of treatment guidelines by the Brain Trauma Foundation (BTF), few studies exist that examine the application of these guidelines for severe traumatic brain injury (TBI) patients. These studies have reported both cost savings and reduced mortality. MATERIALS: We projected the results of previous studies of BTF guideline adoption to estimate the impact of widespread adoption across the United States. We used surveillance systems and national surveys to estimate the number of severely injured TBI patients and compared the lifetime costs of BTF adoption to the current state of treatment. RESULTS: After examining the health outcomes and costs, we estimated that a substantial savings in annual medical costs ($262 million), annual rehabilitation costs ($43 million) and lifetime societal costs ($3.84 billion) would be achieved if treatment guidelines were used more routinely. Implementation costs were estimated to be $61 million. The net savings were primarily because of better health outcomes and a decreased burden on lifetime social support systems. We also estimate that mortality would be reduced by 3,607 lives if the guidelines were followed. CONCLUSIONS: Widespread adoption of the BTF guidelines for the treatment of severe TBI would result in substantial savings in costs and lives. The majority of cost savings are societal costs. Further validation work to identify the most effective aspects of the BTF guidelines is warranted.

Incidence of traumatic brain injury in the United States, 2003.

Traumatic brain injury (TBI) is an important public health problem in the United States. In 2003, there were an estimated 1,565,000 TBIs in the United States: 1,224,000 emergency department visits, 290,000 hospitalizations, and 51,000 deaths. Findings were similar to those from previous years in which rates of TBI were highest for young children (aged 0-4) and men, and the leading causes of TBI were falls and motor vehicle traffic.

The epidemiology and impact of traumatic brain injury: a brief overview.

Traumatic brain injury (TBI) is an important public health problem in the United States and worldwide. The estimated 5.3 million Americans living with TBI-related disability face numerous challenges in their efforts to return to a full and productive life. This article presents an overview of the epidemiology and impact of TBI.

The incidence of traumatic brain injury among children in the United States: differences by race.

OBJECTIVE: This report summarizes the epidemiology of traumatic brain injury (TBI) deaths, hospitalizations, and emergency department (ED) visits by race among children aged 0-14 years in the United States. Few other studies have reported the incidence of TBI in this population by race. METHODS: Data from 3 nationally representative sources maintained by the National Center for Health Statistics were used to report the annual numbers and rates of TBI-related deaths, hospitalizations, and ED visits during 1995-2001 by race, age, and external cause of injury. RESULTS: An estimated 475,000 TBIs occurred among children aged 0-14 each year. Rates were highest among children aged 0-4. For children aged 0-9 years, both death and hospitalization rates were significantly higher for blacks than whites for motor vehicle-traffic-related TBIs. CONCLUSION: With nearly half a million children affected each year, TBI is a serious public health problem. Variation in rates by race suggest the need to more closely examine the factors that contribute to these differences, such as the external causes of the injury and associated modifiable factors (e.g., the use of seatbelts and child safety seats).

Traumatic brain injury hospitalizations among American Indians/Alaska Natives.

OBJECTIVES: To compare the incidence of nonfatal traumatic brain injury (TBI) hospitalization among American Indians/Alaska Natives (AI/AN) with that of other race groups and to assess alcohol and protective equipment (PE) use among those who sustained TBI related to a motor vehicle (MV) incident. METHODS: Data were obtained from 13 states funded by the Centers for Disease Control and Prevention to conduct TBI surveillance from 1997 to 1999. Rates by race and by cause were calculated for the 13 states combined. Blood alcohol concentration (BAC) levels and PE use were compared between AI/AN and "other" races in a subgroup of these states. RESULTS: Although not significantly different, AI/AN had the highest overall age-adjusted TBI hospitalization rate (71.5 per 100,000). Rates were significantly higher among AI/AN than among whites for ages 20 to 44 years (78.5 per 100,000 vs 54.7 per 100,000, P < .0001). MV incidents were the leading cause of TBI (40.1% of cases) among AI/AN, and AI/AN injured in MV incidents had higher BAC levels (65.7% > or = 0.08 g/dL vs 31.6% > or = 0.08 g/dL, P < .0001) and lower PE use (22.0% vs 40.4%, P < .0001) than the "other" race group. CONCLUSION: AI/AN have high rates of TBI hospitalization compared with other races. High BAC levels and low use of PE in MV incidents appear to be associated with the higher rates in this population.

Using body diagrams and disease protocols as part of an integrated approach to the medical consultation in Nepal.

Neither medical assistants nor doctors in Nepal receive adequate training in medical consultation techniques. Patients often leave the consultation with poor understanding of their disease. Moreover, disease management counselling and preventative health counselling are rarely done. In order to address these issues, simple body diagrams and disease protocols were developed and tested in a random cohort survey of 300 outpatients. While 72% of patients who were shown a body diagram achieved basic understanding of their disease, only 38% of patients who were not shown a body diagram understood their disease. This improvement was significant and independent of other factors. Satisfactory disease management counselling was given in 38% of cases, and preventative health counselling in 36%. There was correlation between use of body diagrams and provision of disease management counselling and preventative health counselling. These findings emphasize the need for simple consultation tools such as body diagrams and disease management protocols in developing countries.

Phylogenetic position of the Pentastomida and (pan)crustacean relationships.

Pentastomids are a small group of vermiform animals with unique morphology and parasitic lifestyle. They are generally recognized as being related to the Arthropoda; however, the nature of this relationship is controversial. We have determined the complete sequence of the mitochondrial DNA (mtDNA) of the pentastomid Armillifer armillatus and complete or nearly complete mtDNA sequences from representatives of four previously unsampled groups of Crustacea: Remipedia (Speleonectes tulumensis), Cephalocarida (Hutchinsoniella macracantha), Cirripedia (Pollicipes polymerus) and Branchiura (Argulus americanus). Analyses of the mtDNA gene arrangements and sequences determined in this study indicate unambiguously that pentastomids are a group of modified crustaceans probably related to branchiurans. In addition, gene arrangement comparisons strongly support an unforeseen assemblage of pentastomids with maxillopod and cephalocarid crustaceans, to the exclusion of remipedes, branchiopods, malacostracans and hexapods.

Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: duplication and nonrandom loss.

We determined the complete mitochondrial DNA (mtDNA) sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified, in both genomes, all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from others found in arthropod mtDNAs in the location of at least four genes or gene blocks. This novel gene arrangement is unusual for animal mtDNA in that genes with identical transcriptional polarities are clustered in the genome, and the two clusters are separated by two noncoding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

EVOLUTIONARY HISTORY OF NORTHERN HEMISPHERE NUCELLA (GASTROPODA, MURICIDAE): MOLECULAR, MORPHOLOGICAL, ECOLOGICAL, AND PALEONTOLOGICAL EVIDENCE.

By combining data from a variety of sources we explore patterns of evolution and speciation in Nucella, a widely studied genus of shallow-water marine neogastropods. We present a hypothesis of phylogenetic relationships for all of the currently recognized species of northern hemisphere Nucella, based on an analysis of 718 base pairs of nucleotide sequence from the mitochondrial cytochrome b gene. The order of appearance of species in the fossil record is congruent with this hypothesis. The topology of the inferred phylogeny of Nucella, coupled with ecological, morphological, and fossil evidence, was used to address three main questions: (1) At what time and by which route was the North Atlantic invaded from the North Pacific compared to prior studies of the trans-Arctic interchange? (2) Do patterns of molecular variation within species corroborate the importance of climatic cycles in driving speciation in north temperate marine animals? (3) Was radiation in the direction of increased or decreased ecological specialization, body size, or vulnerability to predation? Molecular evidence confirmed that the sole North Atlantic species, N. lapillus, arose from a North Pacific ancestor. Biogeographic and paleontological evidence supported the dispersal of Nucella, and perhaps other interchange species, via the Eurasian Arctic. Rather intriguingly, the linkage of N. lapillus to a western as opposed to eastern Pacific clade, and the biogeographic origins of the eastern Pacific species, parallel closely similar patterns observed in another genus of rocky-shore gastropods, Littorina. This congruence, in conjunction with information on the climatic and geographic histories of the region, as well as the geographic arrangement of mtDNA haplotypes within Nucella species, supports a model of speciation in Nucella driven by cycles of climatic amelioration and deterioration that began during the Miocene. Calibrations from the fossil record of Nucella suggest that third position transitions and transversions accrue at a rate of 3-4% and 0.5% respectively per million yr. This supports an early participation by Nucella in the trans-Arctic interchange, as suggested by paleobiogeographic studies. Consistent with the unstable taxonomic history of species of Nucella, we found few nonmolecular traits to be phylogenetically informative. Among North Pacific species, more recently derived species (N. canaliculata and the N. emarginata clade) were more ecologically specialized (narrower diet and habitat range). Consistent with extensive intraspecific variation, shell traits were quite labile evolutionarily: neither overall size nor development of antipredatory traits exhibited consistent evolutionary trends over the history of the genus. Nurse eggs (unfertilized eggs consumed by developing embryos) were an ancestral trait that was lost evolutionarily in the two clades that also exhibited increased body size, suggesting that these two life-history traits may be coupled. The reduced number of chromosomes in N. lapillus is clearly a derived state and is consistent with White's (1978) observations on chromosome evolution in other clades.

INTRASPECIFIC MOLECULAR PHYLOGENY IN THE YELLOW WARBLER (DENDROICA PETECHIA), AND IMPLICATIONS FOR AVIAN BIOGEOGRAPHY IN THE WEST INDIES.

A phylogenetic analysis of mitochondrial DNA (mtDNA) restriction sites was used to examine the evolutionary history of populations of yellow warbler (Dendroica petechia) sampled from North America, Central America, South America, and the West Indies. Thirty-seven haplotypes were identified, and only one was found in more than one of these regions. Estimated sequence divergence among haplotypes ranged from 0.14 to 3.17%, and mtDNAs from North American migratory populations clearly were differentiated from those of most tropical sedentary populations. Parsimony analysis of haplotypes suggested multiple colonizations of the West Indies archipelago and of individual Caribbean islands. The inference of multiple colonizations has important implications for studies of avian ecology and evolution in this region.

THE EVOLUTIONARY HISTORY OF PARTHENOGENETIC CNEMIDOPHORUS LEMNISCATUS (SAURIA, TEIIDAE). I. EVIDENCE FOR A HYBRID ORIGIN.

Chromosomes and allozymes were studied from chromosomally distinct unisexual (races B and C) and bisexual (races D and E) populations of the teiid lizard Cnemidophorus lemniscatus, and from selected outgroup taxa (C. murinus, C. nigricolor, Ameiva ameiva, and A. auberi). Karyotyping confirmed the racial identity of individuals and showed that the chromosomal composition of populations at specific localities has remained the same for 20 years. All individuals of both unisexual populations were heterozygous for a pericentric inversion that distinguishes D and E bisexuals. Also, the unisexuals were all heterozygous for 8 of 11 protein loci for which D and E were fixed or nearly fixed for different alleles. Most of these alleles represent derived states relative to the other Cnemidophorus and Ameiva analyzed, and the fixed heterozygote condition at these nine markers provides unequivocal support for the hypothesis that the unisexual C. lemniscatus arose by hybridization between ancestors genetically similar to extant D and E populations. At the remaining three loci for which D and E show fixed differences, the unisexuals were homozygous rather than heterozygous. This suggests that either (1) allozymes have been lost by mutations to null, silent, or convergent mobility states, (2) ancestral genotypes were similar to but not identical with the extant D and E races, and/or (3) limited recombination may occur between unisexual genomes. Allozyme-based genetic distances between D and E were large, suggesting that bisexual races D and E are genetically isolated; each race should be accorded full species status. This conclusion is supported by the absence of any clear biochemical evidence for their monophyly with respect to the other Cnemidophorus examined. Cladistic analyses of 17 phylogenetically informative loci revealed two equally parsimonious shortest trees, one supporting monophyly and the other paraphyly of the C. lemniscatus complex. Further testing of the monophyly of C. lemniscatus requires additional data. With the present study, the evidence that all parthenogenetic Cnemidophorus are of hybrid origin is complete.

MITOCHONDRIAL-DNA ANALYSES AND THE ORIGIN AND RELATIVE AGE OF PARTHENOGENETIC LIZARDS (GENUS CNEMIDOPHORUS). II. C. NEOMEXICANUS AND THE C. TESSELATUS COMPLEX.

Restriction-endonuclease analyses of mitochondrial DNAs from all six color-pattern classes (A-F) of the parthenogenetic lizard Cnemidophorus tesselatus yield estimates of nucleotide divergence that are extremely low (π = 0.06%). In digests of 75 C. tesselatus mtDNAs with 20 different restriction enzymes, only four cleavage-site differences were noted, three of which were found only in pattern class F. The near-identity of these mitochondrial DNAs with those from C. tigris marmoratus shows unequivocally that C. t. marmoratus was the species to which the maternal parent(s) of all C. tesselatus belonged. Mitochondrial-DNA analyses of another unisexual species, C. neomexicanus, led to the same conclusion. Mitochondrial DNAs from 96 individuals of these three species were extensively analyzed for cleavage-site differences; only 13 were found. The low interspecific sequence diversity found within C. neomexicanus and the C. tesselatus complex suggests a recent origin for both. Based on diversity data for mitochondrial DNA and allozymes, we estimate that a minimum of two hybridizations were required to produce all diploid C. tesselatus (C-F), followed by at least two more to generate the triploids (A and B). These data and those presented in the two accompanying papers indicate that events leading to parthenogenesis in Cnemidophorus are rare and strengthen the hypothesis that interspecific hybridization is a necessary, causal event in its establishment.