Search

Posté sur bioRxiv le 22 juin 2021.; International audience; Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but was not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.

Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Author(s): Vitt, Jeffrey R; Sun, Chung-Huan; Le Roux, Peter D; Hemphill, J Claude | Abstract: Purpose of reviewSpontaneous 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 findingsThe 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.SummaryMIS 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.

International audience; Thermocline thermal energy storage is one of the most promising solutions for recovering waste heat in industrial plants. This paper aims to optimise the shape of a thermal energy storage to minimise its environmental impacts and maximise its exergy efficiency. The reference storage is an existing industrial high-temperature air/ceramic packed-bed heat storage called EcoStock®. The physical model used to determine the performances of the tank is a one dimensional model with two equations: one for the heat transfer fluid and one for the filler material. The environmental impacts are analysed using a life cycle assessment through four selected indicators: cumulative energy demand, global warming potential, abiotic depletion potential and particulate matter. To solve this multi-criteria problem, a particle swarm optimisation algorithm was applied with several exergy and environmental weighting factors. A Pareto set is obtained, bounded by the single exergy or environmental optimisations. Favouring exergy efficiency reduces the volume of the tank. However, environmental footprint of the tank is increased: the indicators of cumulative energy demand and abiotic depletion potential are considerably higher. The shape of the tank evolves with the exergy weight, from a square shape (environmental optimisation) to a tapered shape (exergy optimisation).

A non-linear first principle model of an industrial methane rich gas (MRG) network for a large petrochemical plant is developed in this paper. The model is validated against industrial plant data. The non-linearity of gas compressibility, which is sensitive to changes in pressure, composition and temperature, is a challenge for the control of such a network. This model addresses these non-linearities, and is validated with industrial plant data. Each subsystem in the network is modelled separately, and includes models for the pipe segments, gas compressibility, pipe friction factor and gas viscosity. A first principle non-linear model of the system will assist the design of supervisory and optimisation controllers which remain relevant over a large operating region.

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.

Bariatric surgery is currently the most effective therapeutic modality through which sustained beneficial effects on weight loss and metabolic improvement are achieved. During recent years, indications for bariatric surgery have been expanded to include cases of poorly controlled type 2 (T2DM) diabetes mellitus in lesser extremes of body weight. A spectrum of the beneficial effects of surgery is attributed to robust changes of postprandial gut peptide responses that are observed post operatively. Consolidated knowledge regarding gut peptide physiology as well as emerging new evidence shedding light on the mode of action of previously overlooked gut hormones provide appealing potential obesity and T2DM therapeutic perspectives. The accumulation of evidence from the effect of exogenous administration of native gut peptides alone or in combinations to humans as well as the development of mimetic agents exerting agonistic effects on combinations of gut hormone receptors pave the way for future integrated gut peptide-based treatments, which may mimic the effects of bariatric surgery. © 2019 Elsevier Inc.

The states and unknown parameters of a non-linear model of a grinding mill circuit are shown to be identifiable from manipulated, controlled and measurable variables. All the states in the mill and sump, the breakage rates in the mill, the mill and cyclone parameters and the mill power draw parameters can be algebraically expressed in terms of known variables. Theoretically, the tiered approach to estimate all states and parameters enables model-fitting without the need for unnecessary assumptions regarding model parameters. The analysis shows the necessity of accurate density and flow-rate measurements across the circuit, and especially the cyclone, to estimate all states and parameters. The aim is to enable non-linear model-based control through model characterisation using available real-time plant measurements.

A dynamic non-linear model was fitted to the grind curve data of an industrial semi-autogenous grinding (SAG) mill by means of a step-wise procedure. Grind curves give the steady-state values of the performance variables throughput, power draw, and grind in terms of the mill filling and critical mill speed. The grind curves indicate the operable region of the grinding mill. An analysis and dynamic simulation of the model show that the model captures the main dynamics of the grinding mill. Further simulations demonstrate that the model represents the full range of steady-state conditions defined by the grind curves. In other words, the dynamic model is quantitatively accurate as it settles at the correct steady-state for the operable region of the grinding mill. Therefore, the model is suitable as a simulator to test and develop optimizing control strategies for global operating conditions rather than only for local operating conditions.

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.

In this chapter we will review anemia in traumatic brain injury (TBI), the pathophysiology of anemia, the effects of anemia on outcome, the physiology of transfusion, and the relationship between red blood cell transfusion (RBCT) and outcome. The role of hematopoiesis-stimulating agents and hemoglobin-based blood substitutes will be briefly considered, and the chapter will conclude with a suggested approach to anemia management in TBI. Coagulation, coagulopathy, and the administration of other blood products (e.g., platelets or coagulation factors) are beyond the scope of this chapter.

A commonly used continuous grinding mill circuit model is expanded to a hybrid model which contains both continuous and discrete dynamics. The discrete dynamics in the grinding mill circuit are as a result of switching individual cyclones in a cluster of cyclones. With the additional discrete dynamics an investigation was conducted to establish whether the switching of cyclones can be used as an additional manipulated variable. A nonlinear model predictive controller was implemented using the hybrid grinding mill model. Through simulations it is shown that the switching of cyclones can be used to extend the range of control for the product particle size. When applying a substantial disturbance it was found that certain setpoints could not be reached by the NMPC controller, however by switching in an additional cyclone the particle size setpoint could be reached. Simulation results are given to show that the discrete switching of hydrocyclones can be considered as a manipulated variable for hybrid model based controllers to achieve additional controller benefits.

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.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Secondary cerebral insults can adversely affect patients with traumatic brain injury. By contrast, the incidence of secondary cerebral insults after aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have been less well studied.Four hundred and twenty-one patients with SAH who underwent surgical occlusion of their ruptured aneurysm and who received intensive care unit care for ≥48 hours were retrospectively identified from a prospective observational database. Patients were managed according to standard recommendations for SAH. Three secondary cerebral insults were examined: hypotension (90 mmHg systolic), hypoxia (PaoA secondary cerebral insult was observed in 309 (73.4%) patients including 135 (32.1%) who had multiple insults. There was an association between worse clinical grade and development of secondary insults (P = 0.0002), particularly multiple insults (P0.0001). When stratified by clinical grade, single (adjusted odds ratio [OR], 2.23; 95% confidence interval [CI], 1.10-4.51; P = 0.026) and multiple (adjusted OR, 4.37; 95% CI, 2.14-8.93; P0.0001) secondary cerebral insults were associated with worse outcome. In multivariate analysis and controlling for age, admission clinical grade, severity of SAH on computed tomography, intracerebral hematoma, increased intracranial pressure (20 mm Hg), rebleed, intraoperative rupture, and hydrocephalus, secondary cerebral insults were independently associated with poor outcome (adjusted OR, 2.45; 95% CI, 1.20-5.02; P = 0.014).Secondary cerebral insults (hypoxia, hypotension, and hyperglycemia) are common after SAH, including among patients with a good clinical grade. These insults after SAH are associated with worse outcome. These data suggest that prevention of secondary cerebral insults may provide an opportunity to improve patient outcome after SAH.

We investigate experimentally the time evolution of the wetted surface during the lifting of a body initially floating at the water surface. This phenomenon is referred to as the water exit problem. The water exit experiments were conducted with transparent (PMMA) mock-ups of two different shapes: a circular disc and a square flat plate. Two different lighting systems were used to diffuse light in the mock-up material: a central high-power LED light normal to the surface and an edge-lighting system featuring an array of LED lights. These setups make it possible to illuminate the contact line, which delimits the surface of contact between the mock-up and the water. The characteristic size of the mock-ups is about 20 cm and the acceleration of the mock-up oscillates between 0 and 25 m/ $$\mathrm{s}^2$$ . We show that the central light setup gives satisfactory results for the circular disc and that the edge lighting technique makes it possible to follow a contact line with a time-evolving complex shape (strong changes of convexity) up to 1000 fps. The observations presented in the paper support the possibility of extending this promising technique to more general three-dimensional bodies with arbitrary motion (e.g., including pitch motion).

Background Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on admission is unclear in the literature. The goal of this study is to identify predictors of clinical DCI in this group of patients. Methods An exploratory subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage International Trialists) data repository to identify predictors of clinical DCI in patients with good-grade aSAH (World Federation of Neurological Surgeons grade I and II) with angiographic vasospasm on admission. Predictors considered include age, sex, systolic blood pressure at presentation, World Federation of Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment modality, hydrocephalus requiring external ventricular drain insertion, and severity of vasospasm. The predictors were ranked based on dominance analysis with R2 as fit statistics and assessed in a set of logistic regression analysis models. Results Four data sets out of 16 studies in the SAHIT database were analyzed, with a total of 4125 patients. One hundred and ninety-one patients (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78 patients (40.8%) developed clinical DCI. Univariate analysis showed significant associations between severe vasospasm on admission and development of clinical DCI (odds ratio, 9.5, 95% confidence interval, 2.07–43.50; P = 0.004). None of the studied predictors was associated with the development of clinical DCI on multivariate analysis. Conclusions Asymptomatic angiographic vasospasm in patients with good-grade aSAH on admission is uncommon. Further studies are needed to identify high-risk patients for the development of DCI in the context of asymptomatic early vasospasm.

This paper presents the design and application of fractional single-input–single-output (SISO) controllers to a grinding mill circuit, which is a multiple-input–multiple-output (MIMO) process. Two kinds of controllers are presented: fractional order proportional-integral (FOPI) controllers, and a combination of FOPI and fractional order model reference adaptive controllers (FOMRAC). The parameters of the controller are tuned using off-line particle swarm optimization. In the presence of disturbances and process noise, the SISO fractional controllers achieve similar or better performance compared to linear model predictive control (LMPC).

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.

Study design Retrospective medical record review and literature review. Objective To identify cases where a cerebrospinal fluid (CSF) leak occurred during an anterior cervical discectomy and fusion (ACDF) and to create a management algorithm based on the findings. Summary of background data ACDF is a commonly performed spinal operation. It is effective with very low complication rates. One rare complication of ACDF is a CSF leak. There is limited information on the management of CSF leaks after ACDF and management is on a surgeon-by-surgeon basis. Methods We reviewed 3 surgeons' case logs and identified cases where a CSF leak was encountered during ACDF and reviewed the patients' medical records, operative reports and imaging to determine how these leaks were managed. We also performed a PubMed search for articles about the presentation and management of CSF leaks after ACDF. Results Thirteen CSF leaks were identified in 1223 ACDFs, corresponding to a CSF leak rate of 1%. Of these, 9 were successfully treated with intraoperative repair. Postoperative lumbar drainage was used in the remaining 4 patients and was successful in 1 patient. Three patients underwent neck re-exploration and attempted delayed repair. Three patients, including one who was found to have hydrocephalus, ultimately required continuous CSF diversion via shunting. We identified 7 case reports of CSF leak in ADCF in the literature and 1 article that reviewed the prevalence and management of this complication. Conclusion CSF leak after ACDF is an uncommon complication that can usually be repaired. We provide a stepwise management strategy for CSF leaks in ACDF.

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.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.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.

A novel suboptimal control technique for output tracking was developed using model predictive static programming (MPSP). The control technique was applied to a nonlinear model of a single-stage closed grinding mill circuit in simulation. The control technique could determine a suboptimal input trajectory to maintain the output variables at their desired values within 7 iterations. The input trajectory determined after only 2 iterations was already close to the final solution. This technique shows promise to significantly reduce computational time to find a suboptimal input trajectory for output tracking in large industrial processes.

Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last decades. Yet, case fatality remains nearly 40% and survivors often have permanent neurological, cognitive and/or behavioural sequelae. Other than nimodipine drug or clinical trials have not consistently improved outcome. We formed a collaboration of SAH investigators to create a resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase 3 trials in aneurysmal SAH. We identified investigators with data from randomized, clinical trials of patients with aneurysmal SAH or prospectively collected single- or multicentre databases of aneurysmal SAH patients. Data are being collected and proposals to use the data and to design future phase 3 clinical trials are being discussed. This paper reviews some issues discussed at the first meeting of the SAH international trialists (SAHIT) repository meeting. Investigators contributed or have agreed to contribute data from several phase 3 trials including the tirilazad trials, intraoperative hypothermia for aneurysmal SAH trial, nicardipine clinical trials, international subarachnoid aneurysm trial, intravenous magnesium sulphate for aneurysmal SAH, magnesium for aneurysmal SAH and from prospectively-collected data from four institutions. The number of patients should reach 15,000. Some industry investigators refused to provide data and others reported that their institutional research ethics boards would not permit even deidentified or anonymized data to be included. Others reported conflict of interest that prevented them from submitting data. The problems with merging data were related to lack of common definitions and coding of variables, differences in outcome scales used, and times of assessment. Some questions for investigation that arose are discussed. SAHIT demonstrates the possibility of SAH investigators to contribute data for collaborative research. The problems are similar to those already documented in other similar collaborative efforts such as in head injury research. We encourage clinical trial and registry investigators to contact us and participate in SAHIT. Key issues moving forward will be to use common definitions (common data elements), outcomes analysis, and to prioritize research questions, among others.

Background The optimal red blood cell transfusion (RBCT) trigger for patients with aneurysmal subarachnoid hemorrhage (SAH) is unknown. In patients with cerebral vasospasm, anemia may increase susceptibility to ischemic injury; conversely, RBCT may worsen outcome given known deleterious effects. Objective To examine the association between RBCT, delayed cerebral ischemia (DCI), vasospasm, and outcome after SAH. Methods A total of 421 consecutive patients with SAH, admitted to a neurocritical care unit at a university-affiliated hospital and who underwent surgical occlusion of their ruptured aneurysm were retrospectively identified from a prospective observational database. Propensity score methods were used to reduce the bias associated with treatment selection. Results Two hundred and sixty-one patients (62.0%) received an RBCT. Angiographic vasospasm (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.1–2.3; P = 0.025) but not severe angiographic spasm, DCI, or delayed infarction was associated with RBCT. A total of 283 patients (67.2%) experienced a favorable outcome, defined as good or moderately disabled on the Glasgow Outcome Scale; 47 (11.2%) were severely disabled or vegetative and 91 patients (21.6%) were dead at 6-month follow-up. Among patients who survived ≥2 days, RBCT was associated with unfavorable outcome (OR, 2.6; 95% CI, 1.6–4.1). Transfusion of ≥3 units of blood was associated with an increased incidence of unfavorable outcome. Propensity analysis to control for the probability of exposure to RBCT conditional on observed covariates measured before RBCT indicates that RBCT is associated with unfavorable outcome in the absence of DCI (OR, 2.17; 95% CI, 1.56–3.01; P P = 0.65). Conclusions Blood transfusions are associated with unfavorable outcome after SAH particularly when DCI is absent. Propensity analysis suggests that RBCT may be associated with poor outcome rather than being a marker of disease severity. However, when DCI is present, RBCT may help improve outcome.

To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome.This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11;11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2)20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3).We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p0.001). Anemia with simultaneous PbtO(2)20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score.In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

BACKGROUND Prediction of clinical course and outcome after severe traumatic brain injury (TBI) is important. OBJECTIVE To examine whether clinical scales (Glasgow Coma Scale [GCS], Injury Severity Score [ISS], and Acute Physiology and Chronic Health Evaluation II [APACHE II]) or radiographic scales based on admission computed tomography (Marshall and Rotterdam) were associated with intensive care unit (ICU) physiology (intracranial pressure [ICP], brain tissue oxygen tension [PbtO2]), and clinical outcome after severe TBI. METHODS One hundred one patients (median age, 41.0 years; interquartile range [26-55]) with severe TBI who had ICP and PbtO2 monitoring were identified. The relationship between admission GCS, ISS, APACHE II, Marshall and Rotterdam scores and ICP, PbtO2, and outcome was examined by using mixed-effects models and logistic regression. RESULTS Median (25%-75% interquartile range) admission GCS and APACHE II without GCS scores were 3.0 (3-7) and 11.0 (8-13), respectively. Marshall and Rotterdam scores were 3.0 (3-5) and 4.0 (4-5). Mean ICP and PbtO2 during the patients' ICU course were 15.5 ± 10.7 mm Hg and 29.9 ± 10.8 mm Hg, respectively. Three-month mortality was 37.6%. Admission GCS was not associated with mortality. APACHE II (P = .003), APACHE-non-GCS (P = .004), Marshall (P < .001), and Rotterdam scores (P < .001) were associated with mortality. No relationship between GCS, ISS, Marshall, or Rotterdam scores and subsequent ICP or PbtO2 was observed. The APACHE II score was inversely associated with median PbtO2 (P = .03) and minimum PbtO2 (P = .008) and had a stronger correlation with amount of time of reduced PbtO2. CONCLUSION Following severe TBI, factors associated with outcome may not always predict a patient's ICU course and, in particular, intracranial physiology.

OPINION STATEMENT: Anemia develops in about 50% of patients hospitalized with traumatic brain injury (TBI) and is recognized as a cause of secondary brain injury. This review examines the effects of anemia and transfusion on TBI patients through a literature search to identify original research on anemia and transfusion in TBI, the effects of transfusion on brain physiology, and the role of erythropoietin or hemoglobin-based blood substitutes (HBBSs). However, the amount of high-quality, prospective data available to help make decisions about when TBI patients should be transfused is very small. Randomized transfusion trials have involved far too few TBI patients to reach definitive conclusions. Thus, it is hardly surprising that there is widespread practice variation. In our opinion, a hemoglobin transfusion threshold of 7 g/dL cannot yet be considered safe for TBI patients admitted to hospital, and in particular to the ICU, as it is for other critically ill patients. Red blood cell transfusions often have immediate, seemingly beneficial effects on cerebral physiology, but the magnitude of this effect may depend in part upon how long the cells have been stored before administration. In light of existing physiological data, we generally aim to keep hemoglobin concentrations greater than 9 g/dL during the first several days after TBI. In part, the decision is based on the patient's risk of or development of secondary ischemia or brain injury. An increasing number of centers use multimodal neurologic monitoring, which may help to individualize transfusion goals based on the degree of cerebral hypoxia or metabolic distress. When available, brain tissue oxygen tension values less than 15-20 mm Hg or a lactate:pyruvate ratio greater than 30-40 would influence us to use more aggressive hemoglobin correction (e.g., a transfusion threshold of 10 g/dL). Clinicians can attempt to reduce transfusion requirements by limiting phlebotomy, minimizing hemodilution, and providing appropriate prophylaxis against gastrointestinal hemorrhage. Administration of exogenous erythropoietin may have a small impact in further reducing the need for transfusion, but it also may increase complications, most notably deep venous thrombosis. Erythropoietin is currently of great interest as a potential neuroprotective agent, but until it is adequately evaluated in randomized controlled trials, it should not be used routinely for this purpose. HBBSs are also of interest, but existing preparations have not been shown to be beneficial-or even safe-in the context of TBI.

Observational clinical studies demonstrate that brain hypoxia is associated with poor outcome after severe traumatic brain injury (TBI). In this study, available medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)-based therapy is associated with improved patient outcome after severe TBI. Clinical studies published between 1993 and 2010 that compared PbtO2-based therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)-based therapy to ICP/CPP-based therapy alone were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. For analysis, each selected paper had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs) of outcome described by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2- to ICP/CPP-based therapy were identified. There were no randomized studies and no comparison studies in children. Four studies, published in 2003, 2009, and 2010 that included 491 evaluable patients were used in the final analysis. Among patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191 (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome. Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI 1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy is associated with better outcome after severe TBI than ICP/CPP-based therapy alone. Cross-organizational practice variances cannot be controlled for in this type of review and so we cannot answer whether PbtO2-based therapy improves outcome. However, the potentially large incremental value of PbtO2-based therapy provides justification for a randomized clinical trial.