Mobile stroke units: taking stroke care to the patient.

PURPOSE OF REVIEW: Since the development of intravenous tissue plasminogen activator (tPA) for acute ischemic stroke (AIS), functional outcome has improved when treatment occurs within 4.5 h of stroke onset and treatment benefits are greater with earlier treatment. Endovascular revascularization also is better the sooner it is delivered. RECENT FINDINGS: The Get with the Guidelines Stroke registry found that less than one-third of treatment-eligible AIS patients receive intravenous tPA within 60 min of hospital arrival. Initiatives have tried to improve public education and awareness of stroke symptoms to decrease time to presentation. The mobile stroke unit (MSU) facilitates earlier computed tomography scans, delivery of tPA, proper triage and on-scene goal-directed care. MSUs reduce time from stroke alarm to treatment by 25-40 min and increase the rate of intravenous tPA use without an increase in hemorrhage risk. In addition, three-month favorable outcome is increased. SUMMARY: MSUs likely will evolve further and be used for other acute neurologic disorders, help triage patients for endovascular therapy, and be incorporated into systems of care in remote areas. Further studies are awaited to fully understand the overall medical and health-economic benefit of MSUs.

Minimally invasive surgery for intracerebral hemorrhage.

PURPOSE OF REVIEW: Spontaneous intracerebral hemorrhage (ICH) is common, associated with a high degree of mortality and long-term functional impairment, and remains without effective proven treatments. Surgical hematoma evacuation can reduce mass effect and decrease cytotoxic effects from blood product breakdown. However, results from large clinical trials that have examined the role of open craniotomy have not demonstrated a significant outcome benefit over medical management. We review the data on minimally invasive surgery (MIS) that is emerging as a treatment modality for spontaneous ICH. RECENT FINDINGS: The use of MIS for supratentorial ICH has increased significantly in recent years and appears to be associated with decreased mortality and improved functional outcome compared with medical management. The role of MIS for posterior fossa ICH is ill-defined. Currently available MIS devices allow for stereotactic aspiration and thrombolysis, endoport-mediated evacuation, and endoscopic aspiration. Clinical series demonstrate that MIS can facilitate significant hematoma volume reduction and may be associated with less morbidity than conventional open surgical approaches. SUMMARY: MIS is an appealing treatment modality for supratentorial ICH and with careful patient selection and technologic advances has the potential to improve neurologic outcomes and reduce mortality. Early and extensive hematoma evacuation are important therapeutic targets and current studies are underway that have the potential to change the management for ICH patients.

The Effect of Goal-Directed Therapy on Patient Morbidity and Mortality After Traumatic Brain Injury: Results From the Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial.

OBJECTIVES: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial. DESIGN: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial. SETTING: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network. PATIENTS: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4-12. MEASUREMENTS AND MAIN RESULTS: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a "transgression." Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either: 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model. RESULTS: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002). CONCLUSIONS: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.

Neuroprotection in acute brain injury: an up-to-date review.

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

Data collection and interpretation.

Patient monitoring is routinely performed in all patients who receive neurocritical care. The combined use of monitors, including the neurologic examination, laboratory analysis, imaging studies, and physiological parameters, is common in a platform called multi-modality monitoring (MMM). However, the full potential of MMM is only beginning to be realized since for the most part, decision making historically has focused on individual aspects of physiology in a largely threshold-based manner. The use of MMM now is being facilitated by the evolution of bio-informatics in critical care including developing techniques to acquire, store, retrieve, and display integrated data and new analytic techniques for optimal clinical decision making. In this review, we will discuss the crucial initial steps toward data and information management, which in this emerging era of data-intensive science is already shifting concepts of care for acute brain injury and has the potential to both reshape how we do research and enhance cost-effective clinical care.

A global analysis of bidirectional interactions in alpine plant communities shows facilitators experiencing strong reciprocal fitness costs.

Facilitative interactions are defined as positive effects of one species on another, but bidirectional feedbacks may be positive, neutral, or negative. Understanding the bidirectional nature of these interactions is a fundamental prerequisite for the assessment of the potential evolutionary consequences of facilitation. In a global study combining observational and experimental approaches, we quantified the impact of the cover and richness of species associated with alpine cushion plants on reproductive traits of the benefactor cushions. We found a decline in cushion seed production with increasing cover of cushion-associated species, indicating that being a benefactor came at an overall cost. The effect of cushion-associated species was negative for flower density and seed set of cushions, but not for fruit set and seed quality. Richness of cushion-associated species had positive effects on seed density and modulated the effects of their abundance on flower density and fruit set, indicating that the costs and benefits of harboring associated species depend on the composition of the plant assemblage. Our study demonstrates 'parasitic' interactions among plants over a wide range of species and environments in alpine systems, and we consider their implications for the possible selective effects of interactions between benefactor and beneficiary species.

Intracranial pressure after the BEST TRIP trial: a call for more monitoring.

PURPOSE OF REVIEW: Increased intracranial pressure (ICP) is associated with worse outcome after traumatic brain injury (TBI), but whether its management improves the outcome is unclear. In this review, we will examine the implications of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) trial, evidence for an influence of ICP care on outcome, and a need for greater understanding of the pathophysiology than just ICP through multimodal monitoring (MMM) to enhance the outcome. RECENT FINDINGS: The primary impact of the BEST TRIP trial, a randomized clinical trial that examined two TBI management strategies, one that used an ICP monitor, is in research and should not alter clinical practice. Analyses of large databases suggest TBI care based on the Brain Trauma Foundation guidelines and management of intracranial hypertension can improve patient outcome. However, accumulating evidence demonstrates there are several mechanisms of secondary brain injury (SBI), for example, microvascular dysfunction or alterations in glucose utilization that cannot be detected using an ICP monitor. In these patients, growing clinical evidence suggests that MMM can help manage SBI and improve TBI outcome. SUMMARY: ICP-based monitoring and treatment alone may not be enough to enhance TBI outcome, but ICP and cerebral perfusion pressure therapy remain important in TBI care. Although high-quality evidence for MMM is limited, it should be more widely adapted to better understand the complex pathophysiology after TBI, better target care, and identify new therapeutic opportunities.

Intracranial pressure monitoring: fundamental considerations and rationale for monitoring.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.

The International Multi-disciplinary Consensus Conference on Multimodality Monitoring: future directions and emerging technologies.

Neuromonitoring has evolved rapidly in recent years and there now are many new monitors that have revealed a great deal about the ongoing pathophysiology of brain injury and coma. Further evolution will include the consolidation of multi-modality monitoring (MMM), the development of next-generation informatics tools to identify complex physiologic events and decision support tools to permit targeted individualized care. In this review, we examine future directions and emerging technologies in neuromonitoring including: (1) device development, (2) what is the current limitation(s) of MMM in its present format(s), (3) what would improve the ability of MMM to enhance neurocritical care, and (4) how do we develop evidence for use of MMM?

Intracranial pressure and cerebral perfusion pressure monitoring in non-TBI patients: special considerations.

The effect of intracranial pressure (ICP) and the role of ICP monitoring are best studied in traumatic brain injury (TBI). However, a variety of acute neurologic illnesses e.g., subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, meningitis/encephalitis, and select metabolic disorders, e.g., liver failure and malignant, brain tumors can affect ICP. The purpose of this paper is to review the literature about ICP monitoring in conditions other than TBI and to provide recommendations how the technique may be used in patient management. A PubMed search between 1980 and September 2013 identified 989 articles; 225 of which were reviewed in detail. The technique used to monitor ICP in non-TBI conditions is similar to that used in TBI; however, indications for ICP monitoring often are intertwined with the presence of obstructive hydrocephalus and hence the use of ventricular catheters is more frequent. Increased ICP can adversely affect outcome, particularly when it fails to respond to treatment. However, patients with elevated ICP can still have favorable outcomes. Although the influence of ICP-based care on outcome in non-TBI conditions appears less robust than in TBI, monitoring ICP and cerebral perfusion pressure can play a role in guiding therapy in select patients.

The Subarachnoid Hemorrhage International Trialists (SAHIT) Repository: advancing clinical research in subarachnoid hemorrhage.

Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15 years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuroimaging, and laboratory results and various outcome measures. We have compiled the largest known dataset of patients with SAH. The SAHIT repository may be an important resource for advancing clinical research in SAH and will benefit from contributions of additional datasets.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: evidentiary tables: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a list of recommendations and additional conclusions: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

TerrANTALife 1.0 Biodiversity data checklist of known Antarctic terrestrial and freshwater life forms.

Background: Incomplete species inventories for Antarctica represent a key challenge for comprehensive ecological research and conservation in the region. Additionally, data required to understand population dynamics, rates of evolution, spatial ranges, functional traits, physiological tolerances and species interactions, all of which are fundamental to disentangle the different functional elements of Antarctic biodiversity, are mostly missing. However, much of the fauna, flora and microbiota in the emerged ice-free land of the continent have an uncertain presence and/or unresolved status, with entire biodiversity compendia of prokaryotic groups (e.g. bacteria) being missing. All the available biodiversity information requires consolidation, cross-validation, re-assessment and steady systematic inclusion in order to create a robust catalogue of biodiversity for the continent. New information: We compiled, completed and revised eukaryotic species inventories present in terrestrial and freshwater ecosystems in Antarctica in a new living database: terrANTALife (version 1.0). The database includes the first integration in a compendium for many groups of eukaryotic microorganisms. We also introduce a first catalogue of amplicon sequence variants (ASVs) of prokaryotic biodiversity. Available compendia and literature to date were searched for Antarctic terrestrial and freshwater species, integrated, taxonomically harmonised and curated by experts to create comprehensive checklists of Antarctic organisms. The final inventories comprises 470 animal species (including vertebrates, free-living invertebrates and parasites), 306 plants (including all Viridiplantae: embryophytes and green algae), 997 fungal species and 434 protists (sensu lato). We also provide a first account for many groups of microorganisms, including non-lichenised fungi and multiple groups of eukaryotic unicellular species (Stramenophila, Alveolata and Rhizaria (SAR), Chromists and Amoeba), jointly referred to as "protists". In addition, we identify 1753 bacterial (obtained from 348117 ASVs) and 34 archaeal genera (from 1848 ASVs), as well as, at least, 14 virus families. We formulate a basic tree of life in Antarctica with the main lineages listed in the region and their "known-accepted-species" numbers.

Ontogenetic shifts in plant interactions vary with environmental severity and affect population structure.

Environmental conditions and plant size may both alter the outcome of inter-specific plant-plant interactions, with seedlings generally facilitated more strongly than larger individuals in stressful habitats. However, the combined impact of plant size and environmental severity on interactions is poorly understood. Here, we tested explicitly for the first time the hypothesis that ontogenetic shifts in interactions are delayed under increasingly severe conditions by examining the interaction between a grass, Agrostis magellanica, and a cushion plant, Azorella selago, along two severity gradients. The impact of A. selago on A. magellanica abundance, but not reproductive effort, was related to A. magellanica size, with a trend for delayed shifts towards more negative interactions under greater environmental severity. Intermediate-sized individuals were most strongly facilitated, leading to differences in the size-class distribution of A. magellanica on the soil and on A. selago. The A. magellanica size-class distribution was more strongly affected by A. selago than by environmental severity, demonstrating that the plant-plant interaction impacts A. magellanica population structure more strongly than habitat conditions. As ontogenetic shifts in plant-plant interactions cannot be assumed to be constant across severity gradients and may impact species population structure, studies examining the outcome of interactions need to consider the potential for size- or age-related variation in competition and facilitation.

Horizontal, but not vertical, biotic interactions affect fine-scale plant distribution patterns in a low-energy system.

Studies of species range determinants have traditionally focused on abiotic variables (typically climatic conditions), and therefore the recent explicit consideration of biotic interactions represents an important advance in the field. While these studies clearly support the role of biotic interactions in shaping species distributions, most examine only the influence of a single species and/or a single interaction, failing to account for species being subject to multiple concurrent interactions. By fitting species distribution models (SDMs), we examine the influence of multiple vertical (i.e., grazing, trampling, and manuring by mammalian herbivores) and horizontal (i.e., competition and facilitation; estimated from the cover of dominant plant species) interspecific interactions on the occurrence and cover of 41 alpine tundra plant species. Adding plant-plant interactions to baseline SDMs (using five field-quantified abiotic variables) significantly improved models' predictive power for independent data, while herbivore-related variables had only a weak influence. Overall, abiotic variables had the strongest individual contributions to the distribution of alpine tundra plants, with the importance of horizontal interaction variables exceeding that of vertical interaction variables. These results were consistent across three modeling techniques, for both species occurrence and cover, demonstrating the pattern to be robust. Thus, the explicit consideration of multiple biotic interactions reveals that plant-plant interactions exert control over the fine-scale distribution of vascular species that is comparable to abiotic drivers and considerably stronger than herbivores in this low-energy system.

Soil moisture's underestimated role in climate change impact modelling in low-energy systems.

Shifts in precipitation regimes are an inherent component of climate change, but in low-energy systems are often assumed to be less important than changes in temperature. Because soil moisture is the hydrological variable most proximally linked to plant performance during the growing season in arctic-alpine habitats, it may offer the most useful perspective on the influence of changes in precipitation on vegetation. Here we quantify the influence of soil moisture for multiple vegetation properties at fine spatial scales, to determine the potential importance of soil moisture under changing climatic conditions. A fine-scale data set, comprising vascular species cover and field-quantified ecologically relevant environmental parameters, was analysed to determine the influence of soil moisture relative to other key abiotic predictors. Soil moisture was strongly related to community composition, species richness and the occurrence patterns of individual species, having a similar or greater influence than soil temperature, pH and solar radiation. Soil moisture varied considerably over short distances, and this fine-scale heterogeneity may contribute to offsetting the ecological impacts of changes in precipitation for species not limited to extreme soil moisture conditions. In conclusion, soil moisture is a key driver of vegetation properties, both at the species and community level, even in this low-energy system. Soil moisture conditions represent an important mechanism through which changing climatic conditions impact vegetation, and advancing our predictive capability will therefore require a better understanding of how soil moisture mediates the effects of climate change on biota.