Amnesia after Repeated Head Impact Is Caused by Impaired Synaptic Plasticity in the Memory Engram.

Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

The weekend effect in aneurysmal subarachnoid haemorrhage: a single centre experience and review.

Clinical outcomes for patients admitted to hospital during weekend hours have been reported to be poorer than for those admitted during the week. Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of haemorrhagic stroke, with a mortality rate greater than 30%. A number of studies have reported higher mortality for patients with aSAH who are admitted during weekend hours. This study evaluates the effect of weekend admission on patients in our unit with aSAH in terms of time to treatment, treatment type, rebleeding rates, functional outcome, and mortality. We analysed a retrospective database of all patients admitted to our tertiary referral centre with aneurysmal subarachnoid haemorrhage between February 2016 and February 2020. Chi-square tests and t-tests were used to compare weekday and weekend demographic and clinical variables. Univariate and multivariate logistic regression analyses were performed to assess for any association between admission during weekend hours and increased neurological morbidity (assessed via Glasgow Outcome Scale at 3 months) and mortality. Of the 571 patients included in this study, 191 were admitted during on-call weekend hours. There were no significant differences found in time to treatment, type of treatment, rebleeding rates, neurological morbidity, or mortality rates between patients admitted during the week and those admitted during weekend hours. Weekend admission was not associated with worsened functional outcome or increased mortality in this cohort. These results suggest that provision of 7-day cover by vascular neurosurgeons and interventional neuroradiologists in high-volume centres could mitigate the weekend effect sometimes reported in the aSAH cohort.

Outcomes following poor-grade aneurysmal subarachnoid haemorrhage: a prospective observational study.

BACKGROUND: Up to 35% of aneurysmal subarachnoid haemorrhage (aSAH) cases may present as poor grade, defined as World Federation of Neurosurgical Societies (WFNS) grades IV and V. In this study, we evaluate functional outcomes and prognostic factors. METHODS: This prospective study included all patients referred to a national, centralized neurosurgical service with a diagnosis of poor-grade aSAH between 01/01/2016 and 31/12/2019. Multivariable logistic regression models were used to estimate probability of poor functional outcomes, defined as a Glasgow Outcome Scale (GOS) of 1-3 at 3 months. RESULTS: Two hundred fifty-seven patients were referred, of whom 116/257 (45.1%) underwent treatment of an aneurysm, with 97/116 (84%) treated within 48 h of referral. Median age was 62 years (IQR 51-69) with a female predominance (167/257, 65%). Untreated patients tended to be older; 123/141 (87%) had WFNS V, 60/141 (45%) unreactive pupils and 21/141 (16%) circulatory arrest. Of all referred patients, poor outcome occurred in 169/230 (73.5%). Unreactive pupils or circulatory arrest conferred a universally poor prognosis, with mortality in 55/56 (98%) and 19/19 (100%), respectively. The risk of a poor outcome was 14.1% (95% CI 4.5-23.6) higher in WFNS V compared with WFNS IV. Age was important in patients without circulatory arrest or unreactive pupils, with risk of a poor outcome increasing by 1.8% per year (95% CI 1-2.7). In patients undergoing aneurysm securement, 48/101 (47.5%) had a poor outcome, with age, rebleeding, vasospasm and cerebrospinal fluid (CSF) diversion being important prognosticators. The addition of serum markers did not add significant discrimination beyond the clinical presentation. CONCLUSIONS: The overall outcomes of WFNS IV and V aSAH remain poor, mainly due to the devastating effects of the original haemorrhage. However, in patients selected for aneurysm securement, good outcomes can be achieved in more than half of patients. Age, pre-intervention rebleeding, vasospasm, and CSF diversion are important prognostic factors.

k-Fold Cross-Validation Can Significantly Over-Estimate True Classification Accuracy in Common EEG-Based Passive BCI Experimental Designs: An Empirical Investigation.

In passive BCI studies, a common approach is to collect data from mental states of interest during relatively long trials and divide these trials into shorter "epochs" to serve as individual samples in classification. While it is known that using k-fold cross-validation (CV) in this scenario can result in unreliable estimates of mental state separability (due to autocorrelation in the samples derived from the same trial), k-fold CV is still commonly used and reported in passive BCI studies. What is not known is the extent to which k-fold CV misrepresents true mental state separability. This makes it difficult to interpret the results of studies that use it. Furthermore, if the seriousness of the problem were clearly known, perhaps more researchers would be aware that they should avoid it. In this work, a novel experiment explored how the degree of correlation among samples within a class affects EEG-based mental state classification accuracy estimated by k-fold CV. Results were compared to a ground-truth (GT) accuracy and to "block-wise" CV, an alternative to k-fold which is purported to alleviate the autocorrelation issues. Factors such as the degree of true class separability and the feature set and classifier used were also explored. The results show that, under some conditions, k-fold CV inflated the GT classification accuracy by up to 25%, but block-wise CV underestimated the GT accuracy by as much as 11%. It is our recommendation that the number of samples derived from the same trial should be reduced whenever possible in single-subject analysis, and that both the k-fold and block-wise CV results are reported.

Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke.

BACKGROUND AND PURPOSE: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. METHODS: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b-3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. RESULTS: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P=0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P=0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality (Pinteraction=0.003) and symptomatic intracranial hemorrhage (Pinteraction=0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. CONCLUSIONS: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Prefrontal cortical activation associated with prospective memory while walking around a real-world street environment.

Rostral PFC (area 10) activation is common during prospective memory (PM) tasks. But it is not clear what mental processes these activations index. Three candidate explanations from cognitive neuroscience theory are: (i) monitoring of the environment; (ii) spontaneous intention retrieval; (iii) a combination of the two. These explanations make different predictions about the temporal and spatial patterns of activation that would be seen in rostral PFC in naturalistic settings. Accordingly, we plotted functional events in PFC using portable fNIRS while people were carrying out a PM task outside the lab and responding to cues when they were encountered, to decide between these explanations. Nineteen people were asked to walk around a street in London, U.K. and perform various tasks while also remembering to respond to prospective memory (PM) cues when they detected them. The prospective memory cues could be either social (involving greeting a person) or non-social (interacting with a parking meter) in nature. There were also a number of contrast conditions which allowed us to determine activation specifically related to the prospective memory components of the tasks. We found that maintaining both social and non-social intentions was associated with widespread activation within medial and right hemisphere rostral prefrontal cortex (BA 10), in agreement with numerous previous lab-based fMRI studies of prospective memory. In addition, increased activation was found within lateral prefrontal cortex (BA 45 and 46) when people were maintaining a social intention compared to a non-social one. The data were then subjected to a GLM-based method for automatic identification of functional events (AIDE), and the position of the participants at the time of the activation events were located on a map of the physical space. The results showed that the spatial and temporal distribution of these events was not random, but aggregated around areas in which the participants appeared to retrieve their future intentions (i.e., where they saw intentional cues), as well as where they executed them. Functional events were detected most frequently in BA 10 during the PM conditions compared to other regions and tasks. Mobile fNIRS can be used to measure higher cognitive functions of the prefrontal cortex in "real world" situations outside the laboratory in freely ambulant individuals. The addition of a "brain-first" approach to the data permits the experimenter to determine not only when haemodynamic changes occur, but also where the participant was when it happened. This can be extremely valuable when trying to link brain and cognition.

Stroke imaging prior to thrombectomy in the late window: results from a pooled multicentre analysis.

BACKGROUND AND PURPOSE: Collateral assessment using CT angiography is a promising modality for selecting patients for endovascular thrombectomy (EVT) in the late window (6-24 hours). The outcome of these patients compared with those selected using perfusion imaging is not clear. METHODS: We pooled data from seven trials and registries of EVT-treated patients in the late-time window. Patients were classified according to the baseline imaging into collateral imaging alone (collateral cohort) and perfusion plus collateral imaging (perfusion cohort). The primary outcome was the proportion of patients achieving independent 90-day functional outcome (modified Rankin Scale 'mRS' 0-2). We used the propensity score-weighting method to balance important predictors between the cohorts. RESULTS: In 608 patients, the median onset/last-known-well to emergency arrival time was 8.8 hours and 53.2% had wake-up strokes. Both cohorts had collateral imaging and 379 (62.3%) had perfusion imaging. Independent functional outcome was achieved in 43.1% overall: 168/379 patients (45.5%) in the perfusion cohort versus 94/214 (43.9%) in the collateral cohort (p=0.71). A logistic regression model adjusting for inverse-probability-weighting showed no difference in 90-day mRS score of 0-2 among the perfusion versus collateral cohorts (adjusted OR 1.05, 95% CI 0.69 to 1.59, p=0.83) or in a favourable shift in 90-day mRS (common adjusted OR 1.01, 95% CI 0.69 to 1.47, p=0.97). CONCLUSION: This pooled analysis of late window EVT showed comparable functional outcomes in patients selected for EVT using collateral imaging alone compared with patients selected using perfusion and collateral imaging. PROSPERO REGISTRATION NUMBER: CRD42020222003.

Simultaneous Classification of Both Mental Workload and Stress Level Suitable for an Online Passive Brain-Computer Interface.

Research studies on EEG-based mental workload detection for a passive BCI generally focus on classifying cognitive states associated with the performance of tasks at different levels of difficulty, with no other aspects of the user's mental state considered. However, in real-life situations, different aspects of the user's state such as their cognitive (e.g., level of mental workload) and affective (e.g., level of stress/anxiety) states will often change simultaneously, and performance of a BCI system designed considering just one state may be unreliable. Moreover, multiple mental states may be relevant to the purposes of the BCI-for example both mental workload and stress level might be related to an aircraft pilot's risk of error-and the simultaneous prediction of states may be critical in maximizing the practical effectiveness of real-life online BCI systems. In this study we investigated the feasibility of performing simultaneous classification of mental workload and stress level in an online passive BCI. We investigated both subject-specific and cross-subject classification approaches, the latter with and without the application of a transfer learning technique to align the distributions of data from the training and test subjects. Using cross-subject classification with transfer learning in a simulated online analysis, we obtained accuracies of 77.5 ± 6.9% and 84.1 ± 5.9%, across 18 participants for mental workload and stress level detection, respectively.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.

Role of routine post-operative CT brain following evacuation of extradural haematoma in children: a single-centre experience.

PURPOSE: Extradural haematoma (EDH) is a serious neurosurgical emergency in children, which confers significant morbidity and mortality rates. The objective of this study was to retrospectively evaluate the role of post-operative imaging in children with EDH who were managed surgically in a national paediatric neurosurgical unit over a 9-year period (January 2008 to December 2016). METHODS: A retrospective case review of paediatric patients who underwent surgical evacuation of extradural haematoma between January 2008 and December 2016 was performed. This included demographic and clinical details, indications for post-operative imaging and outcomes. RESULTS: Seventy patients underwent surgical management of EDH during this time period, with a male preponderance (69%) and a mean age of 8 years. The commonest location of haematoma in this cohort was in the parietal region (n = 24), with a mean maximum thickness of 25.9 mm and mean volume of 57 ml. Post-operative imaging was performed in 84% of patients. However, only one patient had a change in the course of their post-operative management as a result of post-operative imaging findings. CONCLUSIONS: Post-operative imaging in asymptomatic paediatric patients after evacuation of EDH could therefore be avoided as a routine investigation.

Per-Pass Analysis of Thrombus Composition in Patients With Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

Background and Purpose- Mechanical thrombectomy may involve multiple attempts to retrieve the occluding thrombus. This study examined the composition of thrombus fragments retrieved with each pass of a device during the thrombectomy procedure. Second, the per-pass composition was compared with procedural and clinical data including angiographic outcome and stroke etiology. Methods- Thrombi were retrieved from 60 patients with acute ischemic stroke, where thrombus fragments retrieved in each pass were segregated as individual samples and maintained throughout the histological analysis as independent samples. All samples were stained with hematoxylin and eosin and Martius Scarlet Blue. The relative composition of red blood cells, fibrin, and white blood cells in thrombus fragments from each pass was quantified. Results- Over the 60 cases, thrombus material was retrieved in 106 of 138 passes. The number of passes required to complete the cases ranged from 1 to 6 passes. The analysis of thrombus fragments retrieved in each pass provided a greater insight into the thrombectomy procedure progression than the overall thrombus composition; the red blood cell content of thrombus fragments retrieved in passes 1 and 2 was significantly higher than that retrieved in passes 3 to 6. The removal of thrombus material in a total of 1, 2, or 3 passes was associated with the highest percentage of final modified Thrombolysis in Cerebral Infarction score of 2c-3. There was no association between modified Thrombolysis in Cerebral Infarction score and per-pass thrombus composition. Conclusions- The differentiation achieved through the per-pass analysis of acute ischemic stroke thrombi provides a greater insight into the thrombectomy procedure progression than the combined per-case thrombus analysis. Insights gained may be a useful consideration in determining the treatment strategy as a case evolves and may be useful for the development of new devices to increase rates of 1-pass recanalization.

A novel GLM-based method for the Automatic IDentification of functional Events (AIDE) in fNIRS data recorded in naturalistic environments.

Recent technological advances have allowed the development of portable functional Near-Infrared Spectroscopy (fNIRS) devices that can be used to perform neuroimaging in the real-world. However, as real-world experiments are designed to mimic everyday life situations, the identification of event onsets can be extremely challenging and time-consuming. Here, we present a novel analysis method based on the general linear model (GLM) least square fit analysis for the Automatic IDentification of functional Events (or AIDE) directly from real-world fNIRS neuroimaging data. In order to investigate the accuracy and feasibility of this method, as a proof-of-principle we applied the algorithm to (i) synthetic fNIRS data simulating both block-, event-related and mixed-design experiments and (ii) experimental fNIRS data recorded during a conventional lab-based task (involving maths). AIDE was able to recover functional events from simulated fNIRS data with an accuracy of 89%, 97% and 91% for the simulated block-, event-related and mixed-design experiments respectively. For the lab-based experiment, AIDE recovered more than the 66.7% of the functional events from the fNIRS experimental measured data. To illustrate the strength of this method, we then applied AIDE to fNIRS data recorded by a wearable system on one participant during a complex real-world prospective memory experiment conducted outside the lab. As part of the experiment, there were four and six events (actions where participants had to interact with a target) for the two different conditions respectively (condition 1: social-interact with a person; condition 2: non-social-interact with an object). AIDE managed to recover 3/4 events and 3/6 events for conditions 1 and 2 respectively. The identified functional events were then corresponded to behavioural data from the video recordings of the movements and actions of the participant. Our results suggest that "brain-first" rather than "behaviour-first" analysis is possible and that the present method can provide a novel solution to analyse real-world fNIRS data, filling the gap between real-life testing and functional neuroimaging.

Characteristics and Outcome of Cancer Patients Admitted to the ICU in England, Wales, and Northern Ireland and National Trends Between 1997 and 2013.

OBJECTIVE: To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. DESIGN: Retrospective analysis. SETTING: Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. PATIENTS: Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for gastrointestinal (odds ratio, 1.12), respiratory (odds ratio, 1.48) or neurological (odds ratio, 1.65) reasons, and previous ICU admission (odds ratio, 1.18). In patients with a hematological malignancy admitted between 2009 and 2013, hospital mortality was 53.6%. Independent risk factors for hospital mortality were age (odds ratio, 1.02), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.90), Intensive Care National Audit & Research Centre Physiology Score (odds ratio, 1.12), admission for hematological (odds ratio, 1.48) or respiratory (odds ratio, 1.56) reasons, bone marrow transplant (odds ratio, 1.53), previous ICU admission (odds ratio, 1.43), and mechanical ventilation within 24 hours of admission (odds ratio, 1.33). Trend analysis showed a significant decrease in ICU and hospital mortality and length of stay between 1997 and 2013 despite little change in severity of illness during this time. CONCLUSIONS: Between 1997 and 2013, the outcome of cancer patients with an unplanned admission to ICU improved significantly. Among those admitted between 2009 and 2013, independent risk factors for hospital mortality were age, severity of illness, previous cardiopulmonary resuscitation, previous ICU admission, metastatic disease, and admission for respiratory reasons.

Allergic-like Reactions to the MR Imaging Contrast Agent Gadobutrol: A Prospective Study of 32 991 Consecutive Injections.

Purpose To determine the frequency and severity of allergic-like reactions to gadobutrol. Materials and Methods Data collection during the study period was part of a hospital quality assurance initiative to confirm the safety of gadobutrol after its introduction at this institute from 2010 to 2013. The study also included an electronic health records review approved by the institutional review board of the University Health Network, Toronto. The institutional review board waived the requirement for informed consent. At the time of each reaction to contrast material, the patient's age and sex, whether premedication was given, the contrast agent used, the volume injected, the patient's symptoms, and the treatment administered were recorded. Allergic-like reactions from physiologic reactions were differentiated and the frequency and severity of allergic-like reactions, the prevalence of risk factors for reactions, the frequency of reactions despite the use of premedication (a "breakthrough reaction"), and the frequency of delayed reactions were calculated. A χ(2) test to determine whether there was a difference in reaction rates during the 4 years of the study was performed. Results The frequency of allergic-like reactions to gadobutrol was 0.32% (96 reactions among 30 373 gadobutrol-enhanced magnetic resonance [MR] imaging examinations) during the study period. These 96 reactions occurred in 82 patients. There was only one severe reaction. There were identifiable risk factors in 40 of the 82 patients (48.8%). Of the 82 patients with an allergic-like reaction, 28 (34.1%) received a gadolinium-based contrast agent before and had no reaction. A total of 12 of 33 (36.4%) breakthrough reactions occurred, and there were 15 of 96 (15.6%) reactions with a delayed onset. Conclusion The frequency of allergic-like reactions to gadobutrol is very low, accounting for 96 reactions among 30 373 gadobutrol-enhanced MR imaging examinations (0.32%), and severe reactions are rare. In patients who experience a reaction, breakthrough reactions and delayed reactions are relatively common. (©) RSNA, 2016.

Natural history and management of basilar trunk artery aneurysms.

BACKGROUND AND PURPOSE: Basilar trunk aneurysms (BTAs), defined as aneurysms distal to the basilar origin and proximal to the origin of the superior cerebellar artery, are rare and challenging to manage. We describe the natural history and management in a consecutive series of BTAs. METHODS: Between 2000 and 2013, 2522 patients with 3238 aneurysms were referred to our institution for aneurysm management. A retrospective review of this database was conducted to identify all patients with BTAs. RESULTS: In total, 52 patients had a BTA. Mean age was 56 (SD±18) years. Median clinical follow-up was 33 (interquartile range, 8-86) months, and imaging follow-up was 26 (interquartile range, 2-80.5) months. BTAs were classified into 4 causal subtypes: acute dissecting aneurysms, segmental fusiform ectasia, mural bleeding ectasia, and saccular aneurysms. Multiple aneurysms were more frequently noticed among the 13 saccular aneurysms when compared with overall population (P=0.021). There was preponderance of segmental ectasia or mural bleeding ectasia (P=0.045) in patients presenting with transit ischemic attack/stroke or mass effect. Six patients with segmental and 4 with mural bleeding ectasia demonstrated increasing size of their aneurysm, with 2 having subarachnoid hemorrhage caused by aneurysm rupture. None of the fusiform aneurysms that remained stable bled. CONCLUSIONS: BTAs natural histories may differ depending on subtype of aneurysm. Saccular aneurysms likely represent an underlying predisposition to aneurysm development because more than half of these cases were associated with multiple intracranial aneurysms. Intervention should be considered in segmental ectasia and chronic dissecting aneurysms, which demonstrate increase in size over time as there is an increased risk of subarachnoid hemorrhage.