Chronic subdural haematoma: the role of peri-operative medicine in a common form of reversible brain injury.

Epidemiological studies project a significant rise in cases of chronic subdural haematoma over the next 20 years. Patients with this condition are frequently older and medically complex, with baseline characteristics that may increase peri-operative risk. The intra-operative period is only a small portion of a patient's total hospital stay, with a majority of patients in the United Kingdom transferred between institutions for their surgical and rehabilitative care. Definitive management remains surgical, but peri-operative challenges exist which resonate with other surgical cohorts where multidisciplinary working has become the gold standard. These include shared decision-making, medical optimisation, the management of peri-operative anticoagulation and the identification of key points of equipoise for examination in the future trials. In this narrative review, we use a stereotyped patient journey to provide context to the recent literature, highlighting where multidisciplinary expertise may be required to optimise patient care and maximise the benefits of surgical management. We discuss the triage, pre-operative optimisation, intra-operative management and immediate postoperative care of patients undergoing surgery for a chronic subdural haematoma. We also discuss where adjunctive medical management may be indicated. In so doing, we present the current and emerging evidence base for the role of an integrated peri-operative medicine team in the care of patients with a chronic subdural haematoma.

Study on airway assessment practices for elective procedures during pre-anesthetic evaluation in COVID-19 pandemic- A national online survey (SAFE PAC Survey).

Background and Aims: A pilot study among anesthesiologists, revealed a wide variation among individual practices including skipping pre-anesthetic airway assessment during COVID-19 pandemic because of the fear of getting infected. Risk of infection during pre-anesthetic airway assessment has not been studied. The primary objective of the survey was to evaluate the practices of airway examination by anesthesiologists during this pandemic period. Secondary objectives were to study the effects of institutional factors and other individual practices on risk modification and the incidence of COVID-19 infection among anesthesiologists. Material and Methods: A survey was conducted using a pre-validated questionnaire comprising of 35 questions. The questionnaire was circulated among 4676 members of the Indian Society of Anaesthesiologists (ISA) through Google Forms by email. Results: Of the 4676 members contacted via email, 470 were returned undelivered. From the remaining 4206 questionnaire recipients, 456 completed responses were obtained giving a response rate of 10.8%. Percentage, mean and standard deviation were calculated using EZR software. The conduct of pre-anesthetic airway assessment has decreased by 31.7% during the pandemic, leading to 5.2% of participants encountering unanticipated difficult airway. Among the respondents, eight percent were infected. Conclusion: Avoidance of preoperative airway assessment by anesthesiologists during the COVID-19 pandemic has led to rising unanticipated difficult airway undermining the patient safety. Adherence to recommended practices ensures safety from risk of COVID-19 infection.

Neuropathological findings in two patients with fatal COVID-19.

AIMS: To describe the neuropathological findings in two cases of fatal Coronavirus Disease 2019 (COVID-19) with neurological decline. METHODS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection was confirmed in both patients by reverse transcription polymerase chain reaction (RT-PCR) from nasopharyngeal swabs antemortem. Coronial autopsies were performed on both patients and histological sampling of the brain was undertaken with a variety of histochemical and immunohistochemical stains. RNAscope® in situ hybridization (ISH) using the V-nCoV2019-S probe and RT-PCR SARS-CoV-2 ribonucleic acid (RNA) was performed in paraffin-embedded brain tissue sampled from areas of pathology. RESULTS: Case 1 demonstrated severe multifocal cortical infarction with extensive perivascular calcification and numerous megakaryocytes, consistent with a severe multi-territorial cerebral vascular injury. There was associated cerebral thrombotic microangiopathy. Case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. In both cases, ISH and RT-PCR for SARS-CoV-2 RNA were negative in tissue sampled from the area of pathology. CONCLUSIONS: Our case series adds calcifying cerebral cortical infarction with associated megakaryocytes and brainstem encephalitis to the spectrum of neuropathological findings that may contribute to the neurological decompensation seen in some COVID-19 patients. Viral RNA was not detected in post-mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para-infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered.

An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

INTRODUCTION: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy. METHODS: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used. RESULTS: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021. CONCLUSION: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.

Comparison of the single simple question and the patient acceptable symptom state in myasthenia gravis.

BACKGROUND AND PURPOSE: The single simple question (SSQ) is a simple and validated question asking what percentage of normal a patient feels with respect to their myasthenia gravis (MG), with 100% being normal. Patient acceptable symptom states (PASS) are based on a dichotomous 'Yes' or 'No' response, asking whether a patient is satisfied overall with their current status and thus measures holistic satisfaction with their MG state. Both are patient-reported self-assessments but assess different dimensions of MG. The objective was to determine thresholds for the SSQ when patients with MG achieve an acceptable PASS status. METHODS: A retrospective chart review was performed of consecutive MG patients attending a neuromuscular clinic, and SSQ and PASS responses, demographic, clinical and serological characteristics and disease severity by the MG impairment index were extracted. RESULTS: One hundred and fifty-seven consecutive patients were identified: 43 (27.4%) patients responded 'No' to the PASS question. Between the PASS 'Yes'/'No' groups, only SSQ (87.5 ± 13.4 vs. 52.3 ± 23.3; P < 0.001) and MG impairment index scores (9.2 ± 10.3 vs. 29.6 ± 16; P < 0.001) were significantly different. The receiver operating characteristic curve for PASS and SSQ had an area under the curve of 0.92 ± 0.024 (confidence interval 0.872-0.965, P < 0.001). An SSQ score ≥72.5% had 84.2% sensitivity and 86% specificity to classify patients as PASS positive. CONCLUSION: The PASS and SSQ patient-reported outcomes are closely associated and a SSQ threshold ≥72.5% predicts an acceptable MG state. Other demographic and disease-related factors did not influence the PASS response in this study.

Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study.

Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.

Brain network disintegration during sedation is mediated by the complexity of sparsely connected regions.

The precise mechanism of anaesthetic action on a neural level remains unclear. Recent approaches suggest that anaesthetics attenuate the complexity of interactions (connectivity) however evidence remains insufficient. We used tools from network and information theory to show that, during propofol-induced sedation, a collection of brain regions displayed decreased complexity in their connectivity patterns, especially so if they were sparsely connected. Strikingly, we found that, despite their low connectivity strengths, these regions exhibited an inordinate role in network integration. Their location and connectivity complexity delineated a specific pattern of sparse interactions mainly involving default mode regions while their connectivity complexity during the awake state also correlated with reaction times during sedation signifying its importance as a reliable indicator of the effects of sedation on individuals. Contrary to established views suggesting sedation affects only richly connected brain regions, we propose that suppressed complexity of sparsely connected regions should be considered a critical feature of any candidate mechanistic description for loss of consciousness.

Predictive genetic markers in neoadjuvant chemoradiotherapy for locally advanced esophageal cancer: a long way to go. Review of the literature.

The role of genetic molecular markers in neoadjuvant treatment for locally advanced esophageal cancer has been reviewed, focusing strictly on concurrent chemoradiation protocols followed by surgery. Eleven studies evaluated the role of mRNA expression profile; the end point was overall survival (OS) in two studies and different definitions of histological response in nine. Genes reported as significant were involved in cell cycle control (30), apoptosis (7), structural molecules (9), cell metabolism (6) and DNA repair (1). Seven studies reported about 15 microRNA (miRNA) molecules associated with OS (2) or histological response (13), however, defined with different classifications. Their target genes were prevalently involved in cell cycle control (4), apoptosis (1), cell adhesion (1), migration (1) and angiogenesis (1). Gene polymorphisms (single-nucleotide polymorphisms (SNPs)) have been evaluated in 8 studies reporting 10 variants associated with survival or pathological response. OS was the end point in six of these studies. SNPs reported as significant were involved in DNA repair system (4), detoxification (2), folate metabolism (6), drug efflux (2) and others (2). In a study, a panel including histology, pathological response and five SNPs discriminated two subsets of patients with 5-year survival rates of 79.3% and 26.3% (hazard ratio 6.25, P<0.0001). In another study, combination of stage, grade and 4 miRNAs improved prediction of pathological response (P=10-30). At present, given the great inconsistency of the data and the variability of the end points, definite conclusions are extremely difficult, if not impossible. More consistent data can derive only from analyses obtained from patients included in prospective randomized trials while panels combining genetic and clinical factors may improve prediction.

Moving to human trials for argon neuroprotection in neurological injury: a narrative review.

Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term cognitive outcome. Ventilation could be an easily modifiable variable in resuscitation; gases are relatively simple to administer. Xenon is the prototypic agent of a new generation of experimental treatments which show promise. However, use is hindered by its prohibitive cost and anaesthetic properties. Argon is an attractive option, being cheaper, easy to transport, non-sedating, and mechanistically distinct from xenon. In vitro and in vivo models provide evidence of argon reducing brain injury, with improvements in neurocognitive, histological, and biomarker metrics, as well as improved survival. Current data suggest that the effect of argon is mediated via the toll-like receptors 2 and 4, the extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3 kinase (PI-3K)-AKT pathways. Ventilation with argon appears to be safe in pigs and preliminary human trials. Given recent evidence that arterial hyperoxia may be harmful, the supplementation of high-concentration argon may not necessitate changes to clinical practice. Given the logistic benefits, and the evidence for argon neuroprotection summarized in this manuscript, we believe that the time has come to consider developing Phase II clinical trials to assess its benefit in acute neurological injury.

Management of perceived devastating brain injury after hospital admission: a consensus statement from stakeholder professional organizations.

Patients with severe grades of life-threatening brain injury are commonly characterized as having devastating brain injury (DBI), which we have defined as: 'any neurological condition that is assessed at the time of hospital admission as an immediate threat to life or incompatible with good functional recovery AND where early limitation or withdrawal of therapy is being considered'. The outcome in patients with DBI is often death or severe disability, and as a consequence rapid withdrawal of life sustaining therapies is commonly contemplated or undertaken. However, accurate prognostication in life-threatening brain injury is difficult, particularly at an early stage. Evidence from controlled studies to guide decision-making is limited, and there is a risk of a 'self-fulfilling prophecy', with early prognostication leading to early withdrawal of life sustaining therapies and death. The Joint Professional Standards committee of the Faculty of Intensive Care Medicine and the Intensive Care Society convened a consensus group with representation from stakeholder professional organizations to develop clear professional guidance in this area. It recognized that the weak evidence base makes GRADE guidelines difficult to justify. We have made 12 practical, pragmatic recommendations to help clinicians deliver safe, effective, equitable, and justifiable care within resource constrained healthcare systems. In the situation where patient-centred outcomes are recognized to be unacceptable, regardless of the extent of neurological improvement, then early transition to palliative care is appropriate. These recommendations are intended to apply where the primary pathology is DBI, rather than where DBI has compounded a progressive and irreversible deterioration in other life-threatening comorbidities.

Pressure Reactivity-Based Optimal Cerebral Perfusion Pressure in a Traumatic Brain Injury Cohort.

OBJECTIVES: Retrospective data from patients with severe traumatic brain injury (TBI) indicate that deviation from the continuously calculated pressure reactivity-based "optimal" cerebral perfusion pressure (CPPopt) is associated with worse patient outcome. The objective of this study was to assess the relationship between prospectively collected CPPopt data and patient outcome after TBI. METHODS: We prospectively collected intracranial pressure (ICP) monitoring data from 231 patients with severe TBI at Addenbrooke's Hospital, UK. Uncleaned arterial blood pressure and ICP signals were recording using ICM+® software on dedicated bedside computers. CPPopt was determined using an automatic curve fitting procedure of the relationship between pressure reactivity index (PRx) and CPP using a 4-h window, as previously described. The difference between an instantaneous CPP value and its corresponding CPPopt value was denoted every minute as ΔCPPopt. A negative ΔCPPopt that was associated with impaired PRx (>+0.15) was denoted as being below the lower limit of reactivity (LLR). Glasgow Outcome Scale (GOS) score was assessed at 6 months post-ictus. RESULTS: When ΔCPPopt was plotted against PRx and stratified by GOS groupings, data belonging to patients with a more unfavourable outcome had a U-shaped curve that shifted upwards. More time spent with a ΔCPPopt value below the LLR was positively associated with mortality (area under the receiver operating characteristic curve = 0.76 [0.68-0.84]). CONCLUSIONS: In a recent cohort of patients with severe TBI, the time spent with a CPP below the CPPopt-derived LLR is related to mortality. Despite aggressive CPP- and ICP-oriented therapies, TBI patients with a fatal outcome spend a significant amount of time with a CPP below their individualised CPPopt, indicating a possible therapeutic target.

ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity.

BACKGROUND: To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately. METHODS: Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP), PAx-correlation between pulse amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow velocity (FVm) and CPP, Mx_a-correlation between FVm and MAP, Sx-correlation between systolic flow velocity (FVs) and CPP, Sx_a-correlation between FVs and MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx_a-correlation between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a-correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA). RESULTS: LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin. CONCLUSIONS: Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

Angular default mode network connectivity across working memory load.

Initially identified during no-task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large-scale brain networks. Nevertheless, its contribution to whole-brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI-based n-back paradigm with parametric increases in difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n-back task load. Subsequent seed-based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large-scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n-back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41-52, 2017. © 2016 Wiley Periodicals, Inc.

Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer.

Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.

Impact of obstructive sleep apnea on neurological recovery after ischemic stroke: A prospective study.

OBJECTIVES: The presence of obstructive sleep apnea (OSA) has been found to adversely affect the neurological recovery after acute ischemic stroke (AIS) in previous observational studies. However, in most of these studies, diagnosis of OSA was based on oximetry data alone, raising concern in the accuracy of diagnosis as well as estimation of severity. Purpose of our study was to determine the prevalence and severity of OSA (based on polysomnography and American Association of Sleep Medicine [AASM] criteria) in patients with AIS and to compare the post-stroke neurological and functional outcome, in those with and without OSA. MATERIALS AND METHODS: A prospective single-centre study was conducted over a period of eighteen months from January 2013. The demographic and clinical data were collected, and the etiology of stroke was classified according to TOAST classification. Subsequently, all selected patients (N=99) underwent premorbid sleep status assessment by Epworth Sleepiness Scale followed by polysomnography using Resmed ApneaLink polysomnograph. Data were analyzed to find out the prevalence and severity of OSA as well as its impact on neurological recovery as assessed by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at different time points, starting from admission. RESULTS: There was a high prevalence of OSA (~60%) with a quarter of them having severe OSA. The OSA group had a significantly higher mean NIHSS score at discharge (P=.002) and significantly higher mRS score (irrespective of severity of OSA) at all points of evaluation. CONCLUSION: Ischemic stroke patients with OSA tend to have poor neurological and functional recovery, across all segments of stroke and OSA severity.

Predictive markers in elderly patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors: an array-based pharmacogenetic study.

So far, no reliable predictive clinicopathological markers of response to aromatase inhibitors (AIs) have been identified, and little is known regarding the role played by host genetics. To identify constitutive predictive markers, an array-based association study was performed in a cohort of 55 elderly hormone-dependent breast cancer (BC) patients treated with third-generation AIs. The array used in this study interrogates variants in 225 drug metabolism and disposition genes with documented functional significance. Six variants emerged as associated with response to AIs: three located in ABCG1, UGT2A1, SLCO3A1 with a good response, two in SLCO3A1 and one in ABCC4 with a poor response. Variants in the AI target CYP19A1 resulted associated with a favourable response only as haplotype; haplotypes with increased response association were also detected for ABCG1 and SLCO3A1. These results highlight the relevance of host genetics in the response to AIs and represent a first step toward precision medicine for elderly BC patients.

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective.

TBI-the most complex disease in the most complex organ: the CENTER-TBI trial-a commentary.

Each year, approximately 2.5 million people experience some form of traumatic brain injury (TBI) in Europe. One million of these are admitted to hospital and 75 000 will die. TBI represents a major cause of death and disability, particularly among those of working age. Substantial investments have been made in an effort to improve diagnosis, management and survival in TBI, but with little success. The Collaborative European Neuro-Trauma Effectiveness Research in TBI (CENTER-TBI) study promises to use the natural variability seen in the management of TBI across Europe with the application of Comparative Effectiveness Research (CER). It will generate repositories of baseline and comprehensive TBI patient data, neuroimaging, neurogenetics and biomarkers, which aim to improve the diagnosis, stratification, management and prognostication of patients with TBI.

Default mode network connectivity during task execution.

Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrates their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing.

Predictors and outcome impact of perioperative serum sodium changes in a high-risk population.

BACKGROUND: The perioperative period may be associated with a marked neurohumoral stress response, significant fluid losses, and varied fluid replacement regimes. Acute changes in serum sodium concentration are therefore common, but predictors and outcomes of these changes have not been investigated in a large surgical population. METHODS: We carried out a retrospective cohort analysis of 27 068 in-patient non-cardiac surgical procedures in a tertiary teaching hospital setting. Data on preoperative conditions, perioperative events, hospital length of stay, and mortality were collected, along with preoperative and postoperative serum sodium measurements up to 7 days after surgery. Logistic regression was used to investigate the association between sodium changes and mortality, and to identify clinical characteristics associated with a deviation from baseline sodium >5 mmol litre(-1). RESULTS: Changes in sodium concentration >5 mmol litre(-1) were associated with increased mortality risk (adjusted odds ratio 1.49 for a decrease, 3.02 for an increase). Factors independently associated with a perioperative decrease in serum sodium concentration >5 mmol litre(-1) included age >60, diabetes mellitus, and the use of patient-controlled opioid analgesia. Factors associated with a similar increase were preoperative oxygen dependency, mechanical ventilation, central nervous system depression, non-elective surgery, and major operative haemorrhage. CONCLUSIONS: Maximum deviation from preoperative serum sodium value is associated with increased hospital mortality in patients undergoing in-patient non-cardiac surgery. Specific preoperative and perioperative factors are associated with significant serum sodium changes.