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The neural correlates of inner speech have been investigated previously using functional imaging. However, methodological and other limitations have so far precluded a clear description of the neural anatomy of inner speech and its relation to overt speech. Specifically, studies that examine only inner speech often fail to control for subjects' behaviour in the scanner and therefore cannot determine the relation between inner and overt speech. Functional imaging studies comparing inner and overt speech have not produced replicable results and some have similar methodological caveats as studies looking only at inner speech. Lesion analysis can avoid the methodological pitfalls associated with using inner and overt speech in functional imaging studies, while at the same time providing important data about the neural correlates essential for the specific function. Despite its advantages, a study of the neural correlates of inner speech using lesion analysis has not been carried out before. In this study, 17 patients with chronic post-stroke aphasia performed inner speech tasks (rhyme and homophone judgements), and overt speech tasks (reading aloud). The relationship between brain structure and language ability was studied using voxel-based lesion-symptom mapping. This showed that inner speech abilities were affected by lesions to the left pars opercularis in the inferior frontal gyrus and to the white matter adjacent to the left supramarginal gyrus, over and above overt speech production and working memory. These results suggest that inner speech cannot be assumed to be simply overt speech without a motor component. It also suggests that the use of overt speech to understand inner speech and vice versa might result in misleading conclusions, both in imaging studies and clinical practice. [ABSTRACT FROM AUTHOR]

There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established positive impact of penumbral salvage. In order to test this hypothesis, non-core-non-penumbral tissue was identified in two independent prospectively recruited cohorts, using computed tomography perfusion, and magnetic resonance perfusion- and diffusion-weighted imaging, respectively. Follow-up structural magnetic resonance imaging was obtained about 1 month later in all patients to map the final infarct. The volumes of both the acutely silent but eventually infarcted tissue, and the eventually non-infarcted penumbra, were determined by performing voxel-wise analysis of the acute and follow-up image sets, using previously validated perfusion thresholds. Early neurological course was expressed as change in National Institutes of Health Stroke Scale scores between the acute and 1-month assessments, relative to the acute score. The relationship between the acutely silent but eventually infarcted tissue volume and early neurological course was tested using a multivariate regression model that included the volume of non-infarcted penumbra. Thirty-four and 58 patients were recruited in the computed tomography perfusion and magnetic resonance perfusion cohorts, respectively (mean onset-to-imaging time: 136 and 156 min; 27 and 42 patients received intravenous thrombolysis, respectively). Infarction of acutely silent tissue was identified in most patients in both cohorts. Although its volume (median 0.2 and 2 ml, respectively) was much smaller than that of salvaged penumbra (59.3 and 93 ml, respectively), it was substantial in ∼10% of patients. As expected, salvaged penumbra strongly positively influenced early neurological course. Even after correcting for the latter effect in the multivariate model, infarction of acutely silent tissue independently negatively influenced early neurological course in both cohorts (P=0.018 and 0.031, respectively). This is the first systematic study to document infarction of acutely silent tissue after anterior circulation stroke, and to show that it affects a sizeable fraction of patients and has the predicted negative impact on clinical course. These findings were replicated in two independent cohorts, regardless of the perfusion imaging modality used. Preventing infarction of the tissue not initially at risk should have direct clinical benefit. [ABSTRACT FROM AUTHOR]

Background: Patients with aphasia often complain that there is a poor correlation between the words they think (inner speech) and the words they say (overt speech). Aims: This study tried to characterise the relation between inner speech and overt speech in post-stroke aphasia. Methods & Procedures: We tested language abilities, speech apraxia, and performance on inner speech tasks, including homophone and rhyme judgements, of 27 patients with chronic post-stroke aphasia. Outcomes & Results: The patients with aphasia were distributed across the entire spectrum of abilities related to both inner and overt speech. For most patients, performance levels of inner and overt speech were similar. However, some patients had relatively better-preserved inner speech with a marked deficit in overt speech, while in others the opposite pattern was observed. Conclusions: The results are discussed within the framework of current models of language, and their implications for language therapy and aphasia diagnosis are outlined. [ABSTRACT FROM AUTHOR]

Background: In the chronic stage of stroke, previous work has shown that the worse the hand motor deficit, the greater the shift of primary motor cortex (M(1)) activation towards the contralesional hemisphere (ie, unphysiological) balance. Whether the same relationship applies at earlier stages of recovery in serially studied patients is not known.Methods: fMRI of fixed-rate auditory-cued affected index-thumb tapping was obtained at two time points (mean 36 and 147 days poststroke) in a cohort of nine patients with ischaemic stroke (age: 56+/-9 years; three women/six men; seven subcortical, one medullary and one cortical). On each fMRI day, the unaffected/affected ratio of maximal index tapping rate (IT-R) was obtained. To assess the M(1) hemispheric activation balance, the authors computed the classic Laterality Index (LI). The correlation between LI and IT-R was computed for each time point separately.Results: The expected correlation between LI-M(1) and IT-R, that is, motor performance worse with more unphysiological LI, prevailed at both time points (Kendall p=0.008 and 0.058, respectively), with no statistically significant difference between the two regressions. The same analysis for the dorsal premotor cortex and the supplementary motor area showed no significant correlation at either time-point.Conclusion: These results from a small cohort of longitudinally assessed patients suggest that the relationship between M(1) laterality index and hand motor performance appears independent of time since onset of stroke. This in turn may suggest that attempting to restore the hemispheric balance by enhancing ipsilesional M(1) and/or constraining contralesional M(1) activity may have consistent efficacy throughout recovery. [ABSTRACT FROM AUTHOR]

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of (18)F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 +/- 1.4% vs. 0.6 +/- 0.7%, P < 0.001) with a trend towards greater macrophage density in LCS compared to controls (P = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET (r = 0.95, P < 0.001) and well counting (r = 0.96, P < 0.001). Ex vivo FDG SUV was significantly different between the three groups (P < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant (r = 0.16, P = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls. [ABSTRACT FROM AUTHOR]

Current guidelines on thrombolysis post stroke with recombinant tissue plasminogen activator (rt-PA) exclude its use where time of onset is unknown, thus denying some patients potentially beneficial treatment. Contrast enhanced perfusion computed tomography (pCT) imaging can be used together with plain CT and information on clinical deficits to decide whether or not thrombolysis should be initiated even though the exact time of stroke onset is unknown. Based on the results of pCT and CT, rt-PA was administered to two patients with unknown time of stroke onset; one of the patients also underwent suction thrombectomy. Results in both cases were excellent. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy.Background: Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation.Methods: Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks.Results: Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks.Conclusions: Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589). [ABSTRACT FROM AUTHOR]

Background: Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood., Methods: We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18 F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBR max ). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events., Results: Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase)., Conclusions: Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Frailty-the loss of physiological reserve to withstand a stressor event-is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke., Methods: Total ischemic lesion volumes (comprising infarct core and penumbral volumes) were measured using computed tomography (CT) perfusion imaging to give the penumbral fraction within the ischemic lesion. Pre-stroke frailty was measured using a validated frailty index. The relationship between frailty and penumbral fraction was adjusted for age, onset-to-CT interval, collateral scores, small vessel disease burden and vascular comorbidities. Stroke severity was measured using the National Institutes of Health Stroke Scale at baseline and after 24 h., Results: In 55 individuals receiving thrombolysis for ischemic stroke, increasing frailty was associated with a reduction in penumbral fraction (rs = -0.36, P < 0.01). This remained significant after adjustment for age, onset-to-imaging time and collateral score (beta = -1.16, P < 0.001). Correspondingly, frailty was independently negatively associated with proportional improvement in stroke severity following treatment (beta = -2.00, P < 0.01). C-reactive protein (CRP) on presentation was associated with frailty index (rs = 0.38, P < 0.01) and penumbral fraction (rs = -0.30, P = 0.02)., Discussion: A reduction in salvageable penumbra in frailty may explain the treatment-attenuating effects of frailty on reperfusion therapies. The association with CRP motivates further research into a possible inflammatory component of this relationship., Conclusion: Frailty is independently associated with reduced penumbra and poorer neurological recovery in acute stroke. These findings may explain the attenuated response to stroke reperfusion therapies seen in frailer individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Introduction: 18 F-sodium fluoride (NaF) positron-emission tomography (PET) is increasingly being used to measure microcalcification in atherosclerotic disease in vivo. Correlations have been drawn between sodium fluoride uptake and the presence of high-risk plaque features, as well as its association with clinical atherosclerotic sequelae. The aim of this study was to perform a meta-analysis of NaF uptake on PET imaging and its relation to symptomatic and asymptomatic disease., Methods: A systematic review was performed according to PRISMA guidelines, via searching the Ovid MEDLINE, Ovid Embase, Cochrane Library, PubMed, Scopus, and Web of Science Core Collection databases up to May 2024. The search strategy included the terms 'NaF', 'PET', and 'plaque', and all studies with data regarding the degree of microcalcification, as measured by 18 F-NaF uptake in symptomatic and asymptomatic atherosclerotic plaques, were included. Analysis involved calculating mean differences between uptake values and comparison using a random-effects model., Results: A total of 16 articles, involving 423 participants, were included in the meta-analysis (10 carotid artery studies, five coronary artery studies, and one in peripheral vascular disease). Comparing 18 F-NaF uptake in symptomatic versus asymptomatic atherosclerotic plaques, a mean difference of 0.43 (95% CI 0.29 to 0.57; p < 0.0001, I 2 = 65%) was noted in studies comparing symptomatic and asymptomatic plaques in the same participant, with a significant difference in effect based on arterial territory studied (χ 2 = 12.68, p = 0.0018). In studies of participants with and without symptomatic disease, there was no significant difference between symptomatic and asymptomatic plaques (mean difference 0.27, 95% CI -0.26 to 0.80, p = 0.28, I 2 = 85%)., Conclusions: PET imaging using 18 F-NaF can detect differences in microcalcification between symptomatic and asymptomatic atherosclerotic plaques within, but not between, individuals, and thus, is a marker of symptomatic disease. The standardization of 18 F-NaF PET imaging protocols, and its future use as a risk stratification tool or outcome measure, requires further study. (PROSPERO Registration ID: CRD42023451363)., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To assess radiomics and deep learning (DL) methods in identifying symptomatic Carotid Artery Disease (CAD) from carotid CT angiography (CTA) images. We further compare the performance of these novel methods to the conventional calcium score., Methods: Carotid CT angiography (CTA) images from symptomatic patients (ischaemic stroke/transient ischaemic attack within the last 3 months) and asymptomatic patients were analysed. Carotid arteries were classified into culprit, non-culprit and asymptomatic. The calcium score was assessed using the Agatston method. 93 radiomic features were extracted from regions-of-interest drawn on 14 consecutive CTA slices. For DL, convolutional neural networks (CNNs) with and without transfer learning were trained directly on CTA slices. Predictive performance was assessed over 5-fold cross validated AUC scores. SHAP and GRAD-CAM algorithms were used for explainability., Results: 132 carotid arteries were analysed (41 culprit, 41 non-culprit, and 50 asymptomatic). For asymptomatic vs symptomatic arteries, radiomics attained a mean AUC of 0.96(± 0.02), followed by DL 0.86(± 0.06) and then calcium 0.79(± 0.08). For culprit vs non-culprit arteries, radiomics achieved a mean AUC of 0.75(± 0.09), followed by DL 0.67(± 0.10) and then calcium 0.60(± 0.02). For multi-class classification, the mean AUCs were 0.95(± 0.07), 0.79(± 0.05), and 0.71(± 0.07) for radiomics, DL and calcium, respectively. Explainability revealed consistent patterns in the most important radiomic features., Conclusions: Our study highlights the potential of novel image analysis techniques in extracting quantitative information beyond calcification in the identification of CAD. Though further work is required, the transition of these novel techniques into clinical practice may eventually facilitate better stroke risk stratification., Competing Interests: The authors declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Introduction: Atrial fibrillation (AF) detected after stroke (AFDAS) may represent a distinct clinical entity to that of known AF (KAF). However, there is limited long-term outcome data available for patients with AFDAS. More information regarding prognosis in AFDAS is required to inform future trial design in these patients., Patients and Methods: We used data (2015-2019) from a national prospective stroke registry of consecutive patients with acute ischaemic stroke and AF. AFDAS was defined as a new diagnosis of AF after stroke detected on electrocardiograph or cardiac monitoring. The co-primary endpoints were: (1) all-cause mortality; (2) recurrent major adverse cardiovascular events (MACE) at 3 years. Secondary endpoints were: (1) recurrent stroke; (2) functional outcome at discharge; (3) presence of co-existing stroke mechanisms., Results: 583 patients were included. After a median follow-up of 2.65 years (cumulative 1064 person-years) 309 patients died and 23 had recurrent MACE. Compared with AFDAS, KAF was associated with a higher risk of all-cause mortality (adjusted Hazard Ratio (aHR) 1.56, 95% CI 1.12-2.18), a higher prevalence of co-existing stroke mechanisms (adjusted odds ratio (aOR) 2.28, 95% CI 1.14-4.59), but not poor functional outcome (aOR 1.61, 95% CI 0.98-2.64). A trend towards a higher risk of MACE was observed in patients with KAF, but this was limited by statistical power (aHR 2.90, 95% CI 0.67-12.51). All 14 recurrent strokes occurred in the KAF group (Log-rank p  = 0.03)., Discussion and Conclusion: These data provide further evidence that AFDAS differs to KAF with respect to risk of recurrent stroke, MACE, and all-cause mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. II is now employed by Boehringer Ingelheim but was working full-time as a Clinical Lecturer at the University of Cambridge during the time this work was carried out and Boehringer Ingelheim have had no input into this work.

Background: Frailty is common in stroke, where it exerts disease- and treatment-modifying effects. However, there has been little work evaluating how frailty influences outcomes after percutaneous endoscopic gastrostomy (PEG) tube insertion. This study investigates the relationship between pre-stroke frailty and one-year mortality following PEG insertion., Methods: A pre-stroke frailty index (FI) was calculated for individuals with post-stroke dysphagia who underwent PEG insertion between March 2019 and February 2021. Mortality was recorded at one year, as well as instances of post-PEG pneumonia and discharge destination., Results: Twenty-nine individuals underwent PEG insertion, eleven (37.9%) of whom died in the subsequent year. The mean (SD) FI for those who survived was 0.10 (0.09), compared to 0.27 (0.19) for those who died ( p = 0.02). This remained significant after adjustment for age and sex, with each 0.1 increase in the FI independently associated with an increased odds of one-year mortality (aOR 1.39, 95% CI 1.17-1.67). There was no association between frailty and post-PEG pneumonia (0.12 (0.21) in those who aspirated versus 0.11 (0.18) in those who did not, p = 0.75)., Conclusions: Pre-stroke frailty is associated with increased one-year mortality after PEG, a finding that may help inform shared clinical decision-making in complex decisions regarding PEG feeding.

Background: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke (IS) and transient ischaemic attack (TIA). The timely detection of first-diagnosed or "new" AF (nAF) would prompt a switch from antiplatelets to anticoagulation to reduce the risk of stroke recurrence; however, the optimal timing and duration of rhythm monitoring to detect nAF remains unclear., Aims: We searched MEDLINE, PubMed, Cochrane database, and Google Scholar to undertake a systematic review and meta-analysis of randomized controlled trials (RCT) between 2012 and 2023 investigating nAF detection after IS and TIA. Outcome measures were overall detection of nAF (control; (usual care) compared to intervention; (continuous cardiac monitoring >72 h)) and the time period in which nAF detection is highest (0-14 days, 15-90 days, 91-180 days, or 181-365 days). A random-effects model with generic inverse variance weights was used to pool the most adjusted effect measure from each trial., Summary of Review: A total of eight RCTs investigated rhythm monitoring after IS, totaling 5820 patients. The meta-analysis of the studies suggested that continuous cardiac monitoring was associated with a pooled odds ratio of 3.81 (95% CI 2.14 to 6.77), compared to usual care (control), for nAF detection. In the time period analysis, the odds ratio for nAF detection at 0-14 days, 15-90 days, 91-180 days, 181-365 days were 1.79 (1.24-2.58); 2.01 (0.63-6.37); 0.98 (0.16-5.90); and 2.92 (1.30-6.56), respectively., Conclusion: There is an almost fourfold increase in nAF detection with continuous cardiac monitoring, compared to usual care. The results also demonstrate two statistically significant time periods in nAF detection; at 0-14 days and 6-12 months following monitoring commencement. These data support the utilization of different monitoring methods to cover both time periods and a minimum of 1 year of monitoring to maximize nAF detection in patients after IS and TIA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases., Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma., Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation., Setting: Neurosurgical units in the UK., Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging., Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care., Main Outcome Measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year., Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19., Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group., Future Work and Limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study., Trial Registration: This trial is registered as ISRCTN80782810., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Aims: Atrial fibrillation (AF) is detected in over 30% of patients following an embolic stroke of undetermined source (ESUS) when monitored with an implantable loop recorder (ILR). Identifying AF in ESUS survivors has significant therapeutic implications, and AF risk is essential to guide screening with long-term monitoring. The present study aimed to establish the role of left atrial (LA) function in subsequent AF identification and develop a risk model for AF in ESUS., Methods and Results: We conducted a single-centre retrospective case-control study including all patients with ESUS referred to our institution for ILR implantation from December 2009 to September 2019. We recorded clinical variables at baseline and analysed transthoracic echocardiograms in sinus rhythm. Univariate and multivariable analyses were performed to inform variables associated with AF. Lasso regression analysis was used to develop a risk prediction model for AF. The risk model was internally validated using bootstrapping. Three hundred and twenty-three patients with ESUS underwent ILR implantation. In the ESUS population, 293 had a stroke, whereas 30 had suffered a transient ischaemic attack as adjudicated by a senior stroke physician. Atrial fibrillation of any duration was detected in 47.1%. The mean follow-up was 710 days. Following lasso regression with backwards elimination, we combined increasing lateral PA (the time interval from the beginning of the P wave on the surface electrocardiogram to the beginning of the A' wave on pulsed wave tissue Doppler of the lateral mitral annulus) [odds ratio (OR) 1.011], increasing Age (OR 1.035), higher Diastolic blood pressure (OR 1.027), and abnormal LA reservoir Strain (OR 0.973) into a new PADS score. The probability of identifying AF can be estimated using the formula. Model discrimination was good [area under the curve (AUC) 0.72]. The PADS score was internally validated using bootstrapping with 1000 samples of 150 patients showing consistent results with an AUC of 0.73., Conclusion: The novel PADS score can identify the risk of AF on prolonged monitoring with ILR following ESUS and should be considered a dedicated risk stratification tool for decision-making regarding the screening strategy for AF in stroke., Competing Interests: Conflict of interest: V.S.V. reports lecturer fees from Daiichi Sankyo and Novartis. V.S.V. and P.J.P. receive investigator-initiated research funding from Medtronic unrelated to this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction  Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke. Methods  A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n  = 30). Results  Patients with AF have similar total GPVI surface expression ( p  = 0.58) and P-selectin exposure ( p  = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression ( p  = 0.02 ). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide ( p  < 0.0001 ) and high sensitivity C-reactive protein ( p  < 0.0001 ) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population ( p  = 0.02 ) . Conclusion  GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported., Competing Interests: Conflict of interests None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Sepsis can lead to cardiac arrhythmias, of which the most common is atrial fibrillation (AF). Sepsis is associated with up to a six-fold higher risk of developing AF, where it occurs most commonly in the first 3 days of hospital admission. In many patients, AF detected during sepsis is the first documented episode of AF, either as an unmasking of sub-clinical AF or as a newly developed arrhythmia. In the short term, sepsis that is complicated by AF leads to longer hospital stays and an increased risk of inpatient mortality. Sepsis-driven AF can also increase an individual's risk of inpatient stroke by nearly 3-fold, compared to sepsis patients without AF. In the long-term, it is estimated that up to 50% of patients have recurrent episodes of AF within 1-year of their episode of sepsis. The common perception that once the precipitating illness is treated or sinus rhythm is restored the risk of stroke is removed is incorrect. For clinicians, there is a paucity of evidence on how to reduce an individual's risk of stroke after developing AF during sepsis, including whether to start anticoagulation. This is pertinent when considering that more patients are surviving episodes of sepsis and are left with post-sepsis sequalae such as AF. This review provides a summary on the literature available surrounding sepsis-driven AF, focusing on AF recurrence and ischaemic stroke risk. Using this, pragmatic advice to clinicians on how to better detect and reduce an individual's stroke risk after developing AF during sepsis is discussed., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)