Exploring asymmetry induced entropy in tetraalkylammonium-urea DES systems: what can be learned from inelastic neutron scattering?

In this work, inelastic neutron scattering (INS) spectroscopy is used to investigate the impact of entropic factors on the behaviour of deep eutectic solvents (DES). Periodic density functional theory calculations (DFT) provide a reliable assignment of the vibrational modes of pure compounds. This assignment guides the analysis of INS spectra of binary mixtures - with particular attention to methyl torsional modes. Deviations from ideality in the mixtures of tetraalkylammonium salts with urea are readily determined through a simplified thermodynamic approach. This study reports and discusses the relationship between the cation's asymmetry, the INS spectra of the eutectic mixture and its deviation from ideality. Contrary to the majority of systems studied so far, the deep eutectic system comprised of [N2,2,2,1]Cl and urea appears to owe its deviation from ideality to entropic rather than enthalpic factors.

Cardiac thrombus dissolution in acute ischemic stroke: A substudy of Mind the Heart.

Background: Cardiac thrombi are an important cause of ischemic stroke but are infrequently detected on cardiac imaging. We hypothesized that this might be explained by early dissolution of these cardiac thrombi after stroke occurrence. Methods: We performed a single-center observational pilot study between November 2019 and November 2020, embedded in the larger "Mind-the-Heart" study. We included patients with AIS and a cardiac thrombus in the left atrium or ventricle (filling defect <100 Hounsfield Units) diagnosed on cardiac CT that was acquired during the initial stroke imaging protocol. We repeated cardiac CT within one week to determine if the thrombus had dissolved. Results: Five patients (four men, median age 52 years, three with atrial fibrillation and one with anticoagulation therapy at baseline) were included. Median time from symptom onset to first cardiac CT was 383 (range 42-852) minutes and median time from first to second cardiac CT was three days (range 1-7). Two patients received intravenous thrombolysis (IVT). In total, six thrombi were seen on initial CT imaging (one in the left ventricle, four in the left atrial appendage, one in the left atrium). The left atrium thrombus and one left atrial appendage thrombus had dissolved on follow-up cardiac CT, one of which was in a patient with IVT treatment. Conclusion: This pilot study illustrates that cardiac thrombi can dissolve within days of stroke occurrence both with and without IVT treatment.

Correlation between EEG spectral power and cerebral perfusion in patients with acute ischemic stroke.

Dry electrode electroencephalography (EEG) has the potential to diagnose ischemic stroke in the acute phase. In the current study we determined the correlation between EEG spectral power and ischemic stroke size and location as determined by computed tomography perfusion (CTP). Dry electrode EEG recordings were performed in patients with acute ischemic stroke in the emergency room. CTP preceded the EEG recordings as part of standard imaging protocol. Infarct core volume, total hypoperfused volume and local cerebral blood flow (CBF) were estimated with CTP. Additionally, global and local EEG spectral power were determined. We used Spearman's correlation coefficients to evaluate the correlation between variables. We included 27 patients (median age 72 [IQR:69-80] years, 15/27 [56%] men). Median CTP-to-EEG time was 32 (range:8-138) minutes. Hypoperfused volumes were estimated for 12/27 (44%) patients. Infarct core volume correlated best with global delta power (ρ = 0.76, p < 0.01), total hypoperfused volume with global alpha power (ρ = -0.58, p = 0.05), and local CBF with local alpha power (ρ = 0.43, p < 0.01). We conclude that dry electrode EEG signals slow down with increasing hypoperfused volume, which could potentially be used to discriminate between small and large ischemic strokes.

High performance clean versus artifact dry electrode EEG data classification using Convolutional Neural Network transfer learning.

Objective: Convolutional Neural Networks (CNNs) are promising for artifact detection in electroencephalography (EEG) data, but require large amounts of data. Despite increasing use of dry electrodes for EEG data acquisition, dry electrode EEG datasets are sparse. We aim to develop an algorithm for clean versus artifact dry electrode EEG data classification using transfer learning. Methods: Dry electrode EEG data were acquired in 13 subjects while physiological and technical artifacts were induced. Data were per 2-second segment labeled as clean or artifact and split in an 80% train and 20% test set. With the train set, we fine-tuned a pre-trained CNN for clean versus artifact wet electrode EEG data classification using 3-fold cross validation. The three fine-tuned CNNs were combined in one final clean versus artifact classification algorithm, in which the majority vote was used for classification. We calculated accuracy, F1-score, precision, and recall of the pre-trained CNN and fine-tuned algorithm when applied to unseen test data. Results: The algorithm was trained on 0.40 million and tested on 0.17 million overlapping EEG segments. The pre-trained CNN had a test accuracy of 65.6%. The fine-tuned clean versus artifact classification algorithm had an improved test accuracy of 90.7%, F1-score of 90.2%, precision of 89.1% and recall of 91.2%. Conclusions: Despite a relatively small dry electrode EEG dataset, transfer learning enabled development of a high performing CNN-based algorithm for clean versus artifact classification. Significance: Development of CNNs for classification of dry electrode EEG data is challenging as dry electrode EEG datasets are sparse. Here, we show that transfer learning can be used to overcome this problem.

Detection of patent foramen ovale in patients with ischemic stroke on prospective ECG-gated cardiac CT compared to transthoracic echocardiography.

BACKGROUND: Cardiac CT acquired during the acute stroke imaging protocol is an emerging alternative to transthoracic echocardiography (TTE) to screen for sources of cardioembolism. Currently, its diagnostic accuracy to detect patent foramen ovale (PFO) is unclear. METHODS: This was a substudy of Mind the Heart, a prospective cohort in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent TTE. We included patients < 60 years who underwent TTE with agitated saline contrast (cTTE) and assessed sensitivity, specificity, negative and positive predictive value of cardiac CT for the detection of PFO using cTTE as the reference standard. RESULTS: Of 452 patients in Mind the Heart, 92 were younger than 60 years. Of these, 59 (64%) patients underwent both cardiac CT and cTTE and were included. Median age was 54 (IQR 49-57) years and 41/59 (70%) were male. Cardiac CT detected a PFO in 5/59 (8%) patients, 3 of which were confirmed on cTTE. cTTE detected a PFO in 12/59 (20%) patients. Sensitivity and specificity of cardiac CT were 25% (95% CI 5-57%) and 96% (95% CI 85-99%), respectively. Positive and negative predictive values were 59% (95% CI 14-95) and 84% (95% CI 71-92). CONCLUSION: Prospective ECG-gated cardiac CT acquired during the acute stroke imaging protocol does not appear to be a suitable screening method for PFO due to its low sensitivity. Our data suggest that if cardiac CT is used as a first-line screening method for cardioembolism, additional echocardiography remains indicated in young patients with cryptogenic stroke, in whom PFO detection would have therapeutic consequences. These results need to be confirmed in larger cohorts.

Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone.

BACKGROUND AND PURPOSE: Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone. MATERIALS AND METHODS: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10 mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression. RESULTS: From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4-35) mL versus 11 (interquartile range = 6-24) mL. The median follow-up infarct volume was 13 (interquartile range, 4-48) mL versus 17 (interquartile range = 4-50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment. CONCLUSIONS: No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5 hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.

Endovascular treatment for isolated posterior cerebral artery occlusion stroke in the MR CLEAN registry.

BACKGROUND: Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) occlusions are limited, although PCA occlusions can cause severe neurological deficit. OBJECTIVE: To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions. METHODS: We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (ΔNIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications. RESULTS: Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median ΔNIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred. CONCLUSIONS: EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study.

Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV.

BACKGROUND: We assessed whether the treatment effect of intravenous alteplase (IVT) prior to endovascular treatment (EVT) on functional outcome is modified by time metrics. METHODS: We used data from all patients included in MR CLEAN-NO IV, a randomized trial of IVT followed by EVT versus EVT alone in patients who presented directly to EVT-capable hospitals. The primary outcome was the modified Rankin Scale score at 90 days. We used ordinal regression with a multiplicative interaction term to assess if the effect of IVT is modified by onset-to-randomization (OTR), onset-to-IV-needle (OTN), door-to-groin (DTG) or needle-to-groin (NTG) times. Secondary outcomes included successful reperfusion (extended Thrombolysis In Cerebral Infarction Scale 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: In 539 included patients (266 allocated to IVT+EVT and 273 to EVT alone), median workflow times were OTR: 93 (IQR 71-145) min; OTN: 98 (IQR 75-156) min; DTG: 64 (IQR 51-78) min; and NTG: 28 (IQR 20-41) min. There was a significant association between worse outcomes and longer time intervals for all metrics except NTG. We found no interaction between any of the time metrics and IVT for the effect on functional outcome (p values for interaction: OTR=0.40, OTN=0.39, DTG=0.61, NTG=0.56). We also did not observe any significant interaction for successful reperfusion or sICH. CONCLUSION: In MR CLEAN-NO IV, the effect of IVT prior to EVT was not modified by OTR, OTN, DTG or NTG times. Our results do not support the use of these metrics to guide IVT treatment decisions prior to EVT in comprehensive stroke centres. TRIAL REGISTRATION NUMBER: ISRCTN80619088.

Association between Dural AVFs and Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Recent reports suggest an association between dural AVFs and cerebral venous thrombosis. We aimed to investigate the specific temporal and anatomic association between the 2 conditions. MATERIALS AND METHODS: A consecutive cohort of adult patients with dural AVFs was seen at Amsterdam University Medical Centers (2007-2020). An experienced neuroradiologist re-evaluated the presence and imaging characteristics of dural AVFs and cerebral venous thrombosis on all available imaging. The temporal (previous/concurrent/subsequent) and anatomic (same/adjacent/unrelated venous sinus or vein) association between dural AVFs and cerebral venous thrombosis was determined. RESULTS: Among 178 patients with dural AVFs, the mean age was 58.3 (SD, 13.2) years and 85 (48%) were women. Of 55 patients (31%) with cerebral venous thrombosis, 34 (62%) were women. Four patients (7%) had cerebral venous thrombosis before the development of a dural AVF, 33 (60%) had cerebral venous thrombosis at the time of dural AVF diagnosis (concurrent), and 18 (33%) developed cerebral venous thrombosis during follow-up after conservative treatment. The incidence rate of cerebral venous thrombosis after a dural AVF was 79 per 1000 person-years (95% CI, 50-124). In 45 (82%) patients with dural AVFs and cerebral venous thrombosis, the thrombosis was located in the same venous sinus as the dural AVF, whereas in 8 (15%) patients, thrombosis occurred in a venous sinus adjacent to the dural AVF. CONCLUSIONS: One-third of patients with a dural AVF in this study were diagnosed with cerebral venous thrombosis. In almost two-thirds of patients, cerebral venous thrombosis was diagnosed prior to or concurrent with the dural AVF. In 97% of patients, there was an anatomic association between the dural AVF and cerebral venous thrombosis. These data support the hypothesis of a bidirectional association between the 2 diseases.

Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum.

The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3-4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 µg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.

Endovascular treatment for cerebral venous thrombosis: current status, challenges, and opportunities.

Cerebral venous thrombosis (CVT) mostly affects young people. So far, endovascular treatment (EVT) has not been shown to be beneficial in CVT, partially because venous EVT tools are not yet fully optimized, and therefore EVT is only used as a rescue treatment in rare cases. Identifying a subgroup of CVT patients that could benefit from EVT is challenging, given the milder course of disease compared with acute ischemic stroke, the paucity of data on prognostic factors (both in the clinical and imaging domain), and the lack of consensus on what constitutes 'technical success' in CVT EVT. In this review, we discuss the major obstacles that are encountered when trying to identify CVT patients that may benefit from EVT, and propose a roadmap that could help to overcome these challenges in the near future.

Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review.

With the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms "ischemic stroke brain" in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action: systemic haemodynamics, excitotoxicity, neuro-inflammation, blood-brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.

Impact of the COVID-19 outbreak on acute stroke care.

BACKGROUND AND PURPOSE: There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands. METHODS: We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th-May 3th 2020) and one prior to the outbreak (October 21st-December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications. RESULTS: During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65-0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%, p < 0.001). There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%, p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19. CONCLUSION: We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.

Presentation outside office hours does not negatively influence treatment times for reperfusion therapy for acute ischemic stroke.

BACKGROUND: Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this "off-hours effect" also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands. METHODS: Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT: 2009-2015, EVT: 2014-2017). Office hours were defined as presentation during weekdays between 8 AM and 5 PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle [DNT] for IVT, door-to-groin [DGT] for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90 days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values. RESULTS: In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30 min, p = 0.024, adjusted difference 2.5 min, 95% CI 0.7-4.2). Presentation outside office hours was not associated with a longer DGT (median 130 min for both groups, adjusted difference 7.0 min, 95% CI - 4.2 to 18.1). Clinical outcome and sICH rate also did not differ. CONCLUSION: Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.

Microalgal solutions in the cultivation of rotifers and artemia: scope for the modulation of the fatty acid profile.

The microalgae Aurantiochytrium sp. (AUR), Isochrysis sp. (ISO), and Nannochloropsis sp (NAN) were studied as possible alternative feeds to well established commercial compound feeds for both rotifers (Brachionus plicatilis) and Artemia franciscana. Fatty acid (FA) composition -relative (in % of total FAs) and absolute (in mg/g dw)-was determined in order to assess their potential for providing essential FAs. The FA profiles showed relevant differences between the four feeds (compound feed and the three microalgal species), but less stark than in the feeds themselves. Whereas Isochrysis sp. was relatively rich in DHA and poor in EPA, 18.6 ± 1.7% vs 0.6 ± 0.0%, respectively, Nannochloropsis sp. had the opposite pattern, 0.2 ± 0.3% vs 28.3 ± 0.7%. Aurantiochytrium sp. was rich in DHA (19.1 ± 0.2% corresponding to 89.8 ± 0.2 mg/g dw), but posed difficulties as a feed for both rotifers and artemia, given its low lipid incorporation and, in particular, poor DHA deposition. Rotifers fed the compound feed had the best combination of n3 PUFA levels (22.1 ± 0.1 mg/g dw), DHA contents (13.6 ± 0.4 mg/g dw), and DHA/EPA ratios (~3), being rotifers fed AUR and ISO feeds second best. Hence, these microalgae may deserve to be further explored as potential sources of specific FAs in rotifers and artemia.

The development of a novel functional food: bioactive lipids in yogurts enriched with Aurantiochytrium sp. biomass.

Western diets are poor in healthy n3 polyunsaturated fatty acids, such as docosahexaenoic acid. Since microalga Aurantiochytrium sp. is rich in docosahexaenoic acid, a functional food based on lean yogurt and this microalga was tested. This study entailed characterizing the lipid fraction and determining the fatty acid bioaccessibility. The tested yogurts (control and 2% w/w, Aurantiochytrium sp.) had differences. Docosahexaenoic acid was not detected in the control product, but it was the second most important fatty acid in Aurantiochytrium sp. and Aurantiochytrium yogurt, 29.7 ± 0.4% and 18.7 ± 2.0%, respectively. Based on the fatty acid profile only, an amount of 158.7 g of Aurantiochytrium yogurt in wet weight terms would be required to ensure an appropriate intake of healthy fatty acids. Generally, the fatty acid bioaccessibility was not high, remaining below 60-70% in almost all cases. Considering the docosahexaenoic acid bioaccessibility (44 ± 3%), an amount of 360.7 g of Aurantiochytrium yogurt would be advisable. A reasonable dietary prescription would be a daily consumption of 125 ml of Aurantiochytrium yogurt.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

Anaemia at admission is associated with poor clinical outcome in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Anaemia is associated with poor clinical outcome after ischaemic and haemorrhagic stroke. The association between anaemia and outcome in patients with cerebral venous thrombosis (CVT) was examined. METHODS: Consecutive adult patients with CVT were included from seven centres. Anaemia at admission was scored according to World Health Organization definitions. Poor clinical outcome was defined as a modified Rankin Scale score 3-6 at last follow-up. A multiple imputation procedure was applied for handling missing data in the multivariable analysis. Using binary logistic regression analysis, adjustments were made for age, sex, cancer and centre of recruitment (model 1). In a secondary analysis, adjustments were additionally made for coma, intracerebral haemorrhage, non-haemorrhagic lesion and deep venous system thrombosis (model 2). In a sensitivity analysis, patients with cancer were excluded. RESULTS: Data for 952 patients with CVT were included, 22% of whom had anaemia at admission. Patients with anaemia more often had a history of cancer (17% vs. 7%, P < 0.001) than patients without anaemia. Poor clinical outcome (21% vs. 11%, P < 0.001) and mortality (11% vs. 6%, P = 0.07) were more common amongst patients with anaemia. After adjustment, anaemia at admission increased the risk of poor outcome [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.7, model 1]. Model 2 revealed comparable results (aOR 1.9, 95% CI 1.2-3.2), as did the sensitivity analysis excluding patients with cancer (aOR 2.3, 95% CI 1.3-3.8, model 1). CONCLUSION: The risk of poor clinical outcome is doubled in CVT patients presenting with anaemia at admission.

What Is the Role of the New Index Relative Fat Mass (RFM) in the Assessment of Nonalcoholic Fatty Liver Disease (NAFLD)?

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of adiposopathy. Recently, a new score was developed to estimate body fat percentage (relative fat mass, RFM). We aimed to evaluate the value of RFM in predicting the presence and severity of NAFLD, compared with other anthropometric measurements. METHODS: RFM, body mass index (BMI), and other anthropometric measurements were evaluated in two cohorts of subjects: a cohort from a Portuguese prospective epidemiological study (e_Cor) and morbidly obese patients with biopsy-proven NAFLD. We evaluated if RFM and BMI were related with the presence and severity of liver disease, which was assessed by noninvasive tools in the first cohort and by liver histology in the morbidly obese cohort. The independence of relations found in univariate analysis was assessed with multivariable logistic regression analysis. RESULTS: In the general population cohort, 744 subjects (48% male) were enrolled. BMI-defined obesity was present in 23% and RFM-defined obesity in 86%. Insulin resistance (IR) related with BMI-defined obesity (OR 4.37 [2.16-8.84]) and weight (OR 1.05 [1.02-1.08]) in men, and waist circumference (WC) (OR 1.07 [1.03-1.11]) in women. Dyslipidemia and hypertension related with RFM-defined obesity in men (OR 2.96 [1.36-6.47] and OR 5.37 [1.31-22.06], respectively). Ultrasound-diagnosed NAFLD in 33% related with weight in men (OR 1.03 [1.003-1.06] and WC in women (OR 1.06 [1.02-1.10]). In men, ALT elevation related with weight (OR 1.04 [1.02-1.07]). In women, advanced fibrosis (estimated by NAFLD Fibrosis Score) associated with BMI-defined obesity (OR 42.43 [3.61-498.13]). In the morbidly obese cohort, 152 subjects were enrolled, of whom 84% were female, 37% had steatohepatitis, and 9.4% had advanced fibrosis. Adiponectin associated inversely and leptin positively with RFM in men. The severity of steatosis increased linearly with BMI and WC in women. Higher BMI associated with steatohepatitis in women and advanced fibrosis in men. CONCLUSION: RFM-defined obesity better predicted dyslipidemia and hypertension (though not IR) and adipokine imbalance; however, it did not add value to BMI-defined obesity in predicting NAFLD or liver injury.