Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Blood Pressure During Endovascular Treatment Under Conscious Sedation or Local Anesthesia

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Emergence of surfactant-​free micelles from ternary solutions

Curious effects ranging from enzyme activity to anomalies in evapn. rates that have been known for over fifty years suggest the existence and thermodn. stability of surfactant-free micelles. Only recently, joint X-ray, light and neutron scattering expts. have demonstrated that aggregates and bulk pseudo-phases coexist in presumably normal solns., in which a water insol. component is solubilized in a certain domain of concn. of a hydrotrope component like ethanol. Nevertheless, nothing is known about the mol.-level shape and structure of such aggregates. In this work we characterize mixts. of octanol, ethanol, and water by mol. dynamics simulations. For compns. in the "pre-ouzo" region (close to the single phase stability limit) we observe micelle-like aggregates that are clearly distinct from simple crit. d. fluctuations. We define an ethanol partition in the pseudo-phase from an integral of the van der Waals dispersion energy term. From this partition, octanol-rich aggregates swollen with ethanol appear with an emerging interface. Ethanol is present in the water pseudo-phase with an exponential decay similar to the one predicted by Marcelja and Radic forty years ago

Acute Endovascular Treatment of Patients With lschemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (raw mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Renal nerve stimulation: complete versus incomplete renal sympathetic denervation

Purpose Blood pressure (BP) reduction after renal sympathetic denervation (RDN) is highly variable. Renal nerve stimulation (RNS) can localize sympathetic nerves. The RNS trial aimed to investigate the medium-term BP-lowering effects of the use of RNS during RDN, and explore if RNS can check the completeness of the denervation. Material and methods Forty-four treatment-resistant hypertensive patients were included in the prospective, single-center RNS trial. The primary study endpoint was change in 24-h BP at 6- to 12-month follow-up after RDN. The secondary study endpoints were the acute procedural RNS-induced BP response before and after RDN; number of antihypertensive drugs at follow-up; and the correlation between the RNS-induced BP increase before versus after RDN (delta [Δ] RNS-induced BP). Results Before RDN, the RNS-induced systolic BP rise was 43(±21) mmHg, and decreased to 9(±12) mmHg after RDN (p 0 mmHg residual RNS-induced BP response (126 ± 4 mmHg versus 135 ± 10 mmHg, p = 0.04). 83% of the patients with ≤0 mmHg residual RNS-induced BP response had normal 24-h BP at follow-up, compared to 33% in the patients with >0 mmHg residual RNS-induced BP response (p = 0.023). Conclusion The use of RNS during RDN leads to clinically significant and sustained lowering of 24-h BP with fewer antihypertensive drugs at follow-up. RNS-induced BP changes were correlated with 24-h BP changes at follow-up. Moreover, patients with complete denervation had significant lower BP compared to the patients with incomplete denervation

Assessment of cervical spine CT scans by emergency physicians: A comparative diagnostic accuracy study in a non-clinical setting

Objectives: To determine and compare the diagnostic accuracy of assessing injuries on cervical spine computed tomography (CT) scans by trained emergency physicians and radiologists, both in a non-clinical setting. Methods: In this comparative diagnostic accuracy study, 411 cervical spine CT scans, of which 120 contained injuries (fractures and/or dislocations), were divided into 8 subsets. Eight emergency physicians received focused training and assessed 1 subset each before and after training. Four radiologists assessed 2 subsets each. Diagnostic accuracy between both groups was compared. The reference standard used was a multiverified data set, assessed by radiologists, neurosurgeons, and emergency physicians. The neurosurgeons also classified whether an "injury in need of stabilizing therapy" (IST) was present. Results: Posttraining, the emergency physicians demonstrated increased sensitivity and specificity for identifying cervical spine injuries compared to pretraining: sensitivity 88% (95% confidence interval [CI] 80% to 93%) versus 80% (95% CI 72% to 87%) and specificity 89% (95% CI 85% to 93%) versus 86% (95% CI 81% to 89%). When comparing the trained emergency physicians to the group of radiologists, no difference in sensitivity was found, 88% (95% CI 80% to 83%); however, the radiologists showed a significantly higher specificity (P < 0.01): 99% (95% CI 96% to 100%). In the 12% (15 scans) with missed injuries, emergency physicians missed more ISTs than radiologists, 6 versus 4 scans; however, this difference was not significant (P = 0.45). Conclusion: After focused training and in a non-clinical setting, no significant difference was found between emergency physicians and radiologists in ruling out cervical spine injuries; however, the radiologists achieved a significantly higher specificity

Renal nerve stimulation identifies aorticorenal innervation and prevents inadvertent ablation of vagal nerves during renal denervation

Purpose: Recently we reported the use of renal nerve stimulation (RNS) during renal denervation (RDN) procedures. RNS induced changes in blood pressure (BP) and heart rate are not fully delineated yet. We hypothesized that electrical stimulation of the sympathetic nerve tissue in the renal artery would lead to an increase in BP and vagal stimulation would cause a decrease in BP. We report the different patterns of BP and heart rate responses elicited by RNS prior to RDN. Methods: 35 patients with drug-resistant hypertension were included. RNS was performed under general anesthesia at four sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP and heart rate changes were monitored. Results: A total of 289 RNS sites in 35 patients were analyzed. An increase in systolic BP of >10 mmHg was regarded as a positive BP response to RNS. This pattern of response was observed in 180 sites (62%). 86 RNS sites (30%) showed an indifferent response with BP changes ≤10 mmHg. At 13 sites (4.5%) RNS elicited a decrease in BP up to −8 mmHg. However, 10 RNS sites (3.5%) showed a pronounced vagal response with hypotension and sinus cycle lengths ranging between 4224–10272 milliseconds. These sites were distributed among two patients. Conclusion: RNS identified sympathetic and parasympathetic nerve tissue in the renal arteries. RNS can be potentially used to map nerve bundles and guide selective ablation of sympathetic nerve fibers and prevent inadvertent ablation of parasympathetic nerve tissue during RDN