Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Cardiac ultrasound to identify sources of cardioembolism is part of the diagnostic workup of acute ischemic stroke. Recommendations on whether transesophageal echocardiography (TEE) should be performed in addition to transthoracic echocardiography (TTE) are controversial. We aimed to determine the incremental diagnostic yield of TEE in addition to TTE in patients with acute ischemic stroke with undetermined cause. METHODS: In a prospective, observational, pragmatic multicenter cohort study, patients with acute ischemic stroke or transient ischemic attack with undetermined cause before cardiac ultrasound were studied by TTE and TEE. The primary outcome was the rate of treatment-relevant findings in TTE and TEE as defined by a panel of experts based on current evidence. Further outcomes included the rate of changes in the assessment of stroke cause after TEE. RESULTS: Between July 1, 2017, and June 30, 2019, we enrolled 494 patients, of whom 492 (99.6%) received TTE and 454 (91.9%) received TEE. Mean age was 64.7 years, and 204 (41.3%) were women. TEE showed a higher rate of treatment-relevant findings than TTE (86 [18.9%] versus 64 [14.1%], P<0.001). TEE in addition to TTE resulted in 29 (6.4%) additional patients with treatment-relevant findings. Among 191 patients ≤60 years additional treatment-relevant findings by TEE were observed in 27 (14.1%) patients. Classification of stroke cause changed after TEE in 52 of 453 patients (11.5%), resulting in a significant difference in the distribution of stroke cause before and after TEE (P<0.001). CONCLUSIONS: In patients with undetermined cause of stroke, TEE yielded a higher number of treatment-relevant findings than TTE. TEE appears especially useful in younger patients with stroke, with treatment-relevant findings in one out of seven patients ≤60 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03411642.

Personalised haemodynamic management targeting baseline cardiac index in high-risk patients undergoing major abdominal surgery: a randomised single-centre clinical trial.

BACKGROUND: Despite several clinical trials on haemodynamic therapy, the optimal intraoperative haemodynamic management for high-risk patients undergoing major abdominal surgery remains unclear. We tested the hypothesis that personalised haemodynamic management targeting each individual's baseline cardiac index at rest reduces postoperative morbidity. METHODS: In this single-centre trial, 188 high-risk patients undergoing major abdominal surgery were randomised to either routine management or personalised haemodynamic management requiring clinicians to maintain personal baseline cardiac index (determined at rest preoperatively) using an algorithm that guided intraoperative i.v. fluid and/or dobutamine administration. The primary outcome was a composite of major complications (European Perioperative Clinical Outcome definitions) or death within 30 days of surgery. Secondary outcomes included postoperative morbidity (assessed by a postoperative morbidity survey), hospital length of stay, mortality within 90 days of surgery, and neurocognitive function assessed after postoperative Day 3. RESULTS: The primary outcome occurred in 29.8% (28/94) of patients in the personalised management group, compared with 55.3% (52/94) of patients in the routine management group (relative risk: 0.54, 95% confidence interval [CI]: 0.38 to 0.77; absolute risk reduction: -25.5%, 95% CI: -39.2% to -11.9%; P<0.001). One patient assigned to the personalised management group, compared with five assigned to the routine management group, died within 30 days after surgery (P=0.097). There were no clinically relevant differences between the two groups for secondary outcomes. CONCLUSIONS: In high-risk patients undergoing major abdominal surgery, personalised haemodynamic management reduces a composite outcome of major postoperative complications or death within 30 days after surgery compared with routine care. CLINICAL TRIAL REGISTRATION: NCT02834377.

Cortical thickness and cognitive performance in asymptomatic unilateral carotid artery stenosis.

BACKGROUND: We investigated changes of cortical thickness and its association with cognitive performance in patients with high-grade carotid artery stenosis without ischemic brain lesions. METHODS: We studied 25 patients with unilateral carotid artery stenosis ≥50% and 25 age-matched controls. All subjects underwent T1-weighted MRI, and cortical thickness was measured in 33 regions of interest in each hemisphere, as well as in brain regions belonging to the vascular territory of the middle cerebral artery (MCA). General linear mixed models were fitted to the dependent variable cortical thickness. Cognitive assessment comprised the Stroop Test and Trail Making Test B. RESULTS: In the linear mixed model, presence of carotid stenosis had no effect on cortical thickness. There was a significant interaction of stenosis and region with a trend towards lower cortical thickness in the MCA region on the side of carotid stenosis. Patients with carotid stenosis performed significantly worse on the Stroop test than controls, but there was no correlation with cortical thickness. CONCLUSION: In patients with carotid stenosis without ischemic brain lesions, neither a clear pattern of reduced cortical thickness nor an association of cortical thickness with cognitive function was observed. Our data do not support the hypothesized association of cortical thinning and cognitive impairment in carotid stenosis.

Pediatric cirrhotic cardiomyopathy: Impact on liver transplant outcomes.

In adults, cirrhotic cardiomyopathy (CCM) has a significant incidence and impact on liver transplantation. For pediatric liver transplantation (pLT), data on liver-induced cardiac changes are scarce, and in particular, the comparison between cirrhotic and noncirrhotic liver disease has not been investigated. We retrospectively evaluated cardiac changes associated with CCM by echocardiography and 12-lead electrocardiogram in 198 pLT-candidates (median age 4.1 years) 4.2 before and 12 months after pLT. Results were correlated with the stage of liver fibrosis and cholestasis before transplantation. The left ventricular end-diastolic diameter (LVIDd) z score, left ventricular mass z score, and left ventricular mass index were significantly higher in cirrhotic patients (-0.10 versus 0.98, P < 0.001; -1.55 versus -0.42, P = 0.001; 78.99 versus 125.64 g/m2 , P = 0.001, respectively) compared with children with noncirrhotic liver disease. Pathological z scores (>2SDS) for the LVIDd occurred more frequently in cirrhotic patients compared with patients with noncirrhotic liver disease (31/169 versus 1/29; P = 0.03) and were significantly associated with cholestasis. All observed cardiac changes were reversible 1 year after pLT. Pathological LVIDd z scores correlated highly with intensive care unit (ICU) stay (9.6 days versus 17.1 days, respectively, P = 0.002) but not with patient survival pre-LT or post-LT. In contrast to other studies, prolonged QTc time was not associated with liver cirrhosis in our patients. In conclusion, CCM-associated cardiac changes in pLT candidates with cirrhotic liver disease are frequent, mild, and associated with cholestasis and reversible after pLT. They may impact peritransplant care and posttransplant hospitalization time. Further prospective evaluation is warranted. In particular, for QTc time prolongation etiological factors, possible protective effects of ursodeoxycholic acid treatment and the use as a screening parameter for CCM should be verified. Liver Transplantation 24 820-830 2018 AASLD.

Validity of acute stroke lesion volume estimation by diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomographic Score depends on lesion location in 496 patients with middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL. METHODS: We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume. RESULTS: A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (r=-0.78; P<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (r=-0.19; P=0.038) when compared with superficial (r=-0.72; P<0.001) or combined superficial and deep MCA lesions (r=-0.72; P<0.001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume; however, positive predictive value was low (0.35). CONCLUSIONS: ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.

Intrinsic functional brain connectivity is resilient to chronic hypoperfusion caused by unilateral carotid artery stenosis.

INTRODUCTION: Chronic cerebral hypoperfusion caused by asymptomatic high-grade stenosis of the internal carotid artery (ICA) has been associated with impaired cognitive function. Only few studies exist on underlying changes of functional connectivity (FC). METHODS: 20 patients with unilateral high-grade ICA stenosis without MRI lesions and 25 aged-match controls underwent resting-state functional MRI (rsfMRI) and neuropsychological assessment. Patients were examined within ten days before and 6-10 weeks after surgical or interventional revascularization of carotid stenosis. We examined mean resting-state FC ipsi- and contralateral to stenosis and network topology using graph-theoretical measures. RESULTS: At baseline, intrahemispheric FC was similar for patients and healthy controls. After revascularization mean FC increased moderately without an effect on network topology. Patients performed worse in TMT B and Stroop test, while performance in global screening tests for dementia (Mini Mental Status Examination, DemTect) were comparable. Test results did not improve after revascularization. CONCLUSION: In our study population, we find no effect of chronic hypoperfusion on FC and global cognitive function, although we observe minor impairments in processing speed and mental flexibility. The subtle increase of FC after revascularization could indicate excessive upregulation after restoration of perfusion. However, it might as well be a coincidental finding due to the limited sample size.

Comprehensive Evaluation of Cerebral Hemodynamics and Oxygen Metabolism in Revascularization of Asymptomatic High-Grade Carotid Stenosis.

INTRODUCTION: Revascularization procedures in carotid artery stenosis have shown a positive effect in the restoration of cerebral oxygen metabolism as assessed by T2' (T2 prime) imaging as well as capillary homeostasis by measurement of capillary transit time heterogeneity (CTH); however, data in patients with asymptomatic carotid stenosis without manifest brain lesions are scarce. PATIENTS AND METHODS: The effect of revascularization on the hemodynamic profile and capillary homeostasis was evaluated in 13 patients with asymptomatic high-grade carotid stenosis without ischemic brain lesions using dynamic susceptibility contrast perfusion imaging and oxygenation-sensitive T2' mapping before and 6-8 weeks after revascularization by endarterectomy or stenting. The cognitive performance at both timepoints was further assessed. RESULTS: Perfusion impairment at baseline was accompanied by an increased CTH (p = 0.008) in areas with a time to peak delay ≥ 2 s in the affected hemisphere compared to contralateral regions. Carotid intervention improved the overall moderate hemodynamic impairment at baseline by leading to an increase in normalized cerebral blood flow (p = 0.017) and a decrease in mean transit time (p = 0.027), oxygen extraction capacity (OEC) (p = 0.033) and CTH (p = 0.048). The T2' values remained unchanged. CONCLUSION: This study presents novel evidence of a state of altered microvascular function in patients with high-grade carotid artery stenosis in the absence of ischemic brain lesions, which shows sustained normalization after revascularization procedures.

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity.

Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis.

Internal carotid artery stenosis is a risk factor for ischemic stroke. Even in the absence of visible structural brain changes, patients with asymptomatic stenosis are prone to cognitive impairment. On a neuronal level, it was suggested that stenosis may lead to disturbed functional brain connectivity. If so, carotid revascularization should have an effect on hypothesized brain network disturbances. We studied functional connectivity in a motor network by resting-state electroencephalography in 12 patients with high grade asymptomatic carotid stenosis before and after interventional or surgical revascularization as compared to 23 controls. In patients with stenosis, functional connectivity of neural oscillations was significantly decreased prior and improved returning to normal connectivity after revascularization. In a subgroup of patients, also studied by contrast perfusion magnetic resonance imaging, reduced connectivity was associated with decreased regional brain perfusion reflected by increased mean transit time in the middle cerebral artery borderzone. Cognitive testing revealed only minor differences between patients and controls. In summary, we identified oscillatory connectivity changes in patients with asymptomatic carotid stenosis correlating with regional hypoperfusion, which both normalized after revascularization. Hence, electrophysiological changes might be a reversible precursor preceding macroscopic structural brain damage and behavioral impairment in patients with asymptomatic carotid stenosis.

Dynamics of brain perfusion and cognitive performance in revascularization of carotid artery stenosis.

INTRODUCTION: There is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy. METHODS: 17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6-8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated. RESULTS: Multivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization. CONCLUSION: We found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance.

Conjunctival provocation tests: prediction of seasonal allergy.

PURPOSE OF REVIEW: The conjunctival provocation test (CPT) is often used to clearly identify the specific allergen causing the symptoms of allergic rhinoconjunctivitis but also to assess the clinical efficacy of an allergen immunotherapy (AIT). As there is no consensus about its predictive value, the aim of this publication is to evaluate under which conditions the CPT can predict the symptom severity during the allergy season after previous AIT. RECENT FINDINGS: Three out of four randomized controlled trials (RCTs) showed a correlation between CPT reactivity and symptoms occurring under natural allergen exposure after previous AIT. Furthermore, one RCT found that performing the CPT 4 weeks after initiating AIT can identify early responders who also show a benefit during the season. Another RCT suggested that conducting the CPT prior to starting AIT can be used to identify patients who may benefit more from treatment than others. SUMMARY: The assessment of the reviewed literature led us to the conclusion that the CPT has a predictive value and can consequently be used to assess the efficacy of an administered AIT if performed according to a standardized challenge protocol with high-quality allergen extracts.

Impact of Lesion Load Thresholds on Alberta Stroke Program Early Computed Tomographic Score in Diffusion-Weighted Imaging.

BACKGROUND AND AIMS: Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating. MATERIALS AND METHODS: We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist. RESULTS: By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κw = 0.020 1%: κw = 0.151; 10%: κw = 0.386; 20% κw = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695). CONCLUSION: Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.

A Critical Review of Alberta Stroke Program Early CT Score for Evaluation of Acute Stroke Imaging.

Assessment of ischemic stroke lesions on computed tomography (CT) or MRI using the Alberta Stroke Program Early CT Score (ASPECTS) is widely used to guide acute stroke treatment. We aimed to review the current evidence on ASPECTS. Originally, the score was developed for standardized lesion assessment on non-contrast CT (NCCT). Early studies described ASPECTS as a predictor of functional outcome and symptomatic intracranial hemorrhage after iv-thrombolysis with a threshold of ≤7 suggested to identify patients at high risk. Following studies rather pointed toward a linear relationship between ASPECTS and functional outcome. ASPECTS has also been applied to assess perfusion CT and diffusion-weighted MRI (DWI). Cerebral blood volume ASPECTS proved to be the best predictor of outcome, outperforming NCCT-ASPECTS in some studies. For DWI-ASPECTS varying thresholds to identify patients at risk for poor outcome were reported. ASPECTS has been used for patient selection in three of the five groundbreaking trials proving efficacy of mechanical thrombectomy published in 2015. ASPECTS values predict functional outcome after thrombectomy. Moreover, treatment effect of thrombectomy appears to depend on ASPECTS values being smaller or not present in low ASPECTS, while patients with ASPECTS 5-10 do clearly benefit from mechanical thrombectomy. However, as patients with low ASPECTS values were excluded from recent trials data on this subgroup is limited. There are several limitations to ASPECTS addressed in a growing number of studies. The score is limited to the anterior circulation, the template is unequally weighed and correlation with lesion volume depends on lesion location. Overall ASPECTS is a useful and easily applicable tool for assessment of prognosis in acute stroke treatment and to help guide acute treatment decisions regardless whether MRI or CT is used. Patients with low ASPECTS values are unlikely to achieve good outcome. However, methodological constraints of ASPECTS have to be considered, and based on present data, a clear cutoff value to define "low ASPECTS values" cannot be given.

A Virtual Reality System for PTCD Simulation Using Direct Visuo-Haptic Rendering of Partially Segmented Image Data.

This study presents a new visuo-haptic virtual reality (VR) training and planning system for percutaneous transhepatic cholangio-drainage (PTCD) based on partially segmented virtual patient models. We only use partially segmented image data instead of a full segmentation and circumvent the necessity of surface or volume mesh models. Haptic interaction with the virtual patient during virtual palpation, ultrasound probing and needle insertion is provided. Furthermore, the VR simulator includes X-ray and ultrasound simulation for image-guided training. The visualization techniques are GPU-accelerated by implementation in Cuda and include real-time volume deformations computed on the grid of the image data. Computation on the image grid enables straightforward integration of the deformed image data into the visualization components. To provide shorter rendering times, the performance of the volume deformation algorithm is improved by a multigrid approach. To evaluate the VR training system, a user evaluation has been performed and deformation algorithms are analyzed in terms of convergence speed with respect to a fully converged solution. The user evaluation shows positive results with increased user confidence after a training session. It is shown that using partially segmented patient data and direct volume rendering is suitable for the simulation of needle insertion procedures such as PTCD.

Real-Time Ultrasound Simulation for Training of US-Guided Needle Insertion in Breathing Virtual Patients.

One draw-back of most existing VR ultrasound training simulators is the use of static 3D patient models neglecting physiological changes induced e.g. by respiration or heart motion. In this paper to the aim of more realistic Ultrasound simulation, breathing motion extracted from 4D CT image data is integrated into our visuo-haptic simulation framework. The simulated ultrasound images are used for the training of US-guided needle insertion procedures in liver surgery. The methodology developed enables US simulation, 3D visualization and haptic steering of the ultrasound probe and the needle in real-time in breathing virtual bodies.