Thrombectomy in Patients With Ischemic Stroke Without Salvageable Tissue on CT Perfusion.

BACKGROUND: Computed tomography perfusion (CTP) imaging is regularly used to guide patient selection for mechanical thrombectomy (MT). However, the effect of MT in patients without salvageable tissue on CTP has not been investigated. The purpose of this study was to assess the effect of MT in patients with stroke without perfusion mismatch profiles. METHODS: This observational study analyzed patients with ischemic stroke consecutively treated between March 1, 2015, and January 31, 2022, triaged by multimodal-computed tomography undergoing MT. CTP lesion-core mismatch profiles were defined using a mismatch volume/ratio of ≥10 mL/1.2, respectively. The primary end point was the rate of functional independence at 90 days, defined as the modified Rankin Scale score of 0 to 2. Recanalization was evaluated with the modified Thrombolysis in Cerebral Infarction scale. The effect of baseline variables on functional outcome was assessed using multivariable logistic regression analysis. Outcomes of patients with and without CTP-mismatch profiles were compared using 1:1 propensity score matching. RESULTS: Of 724 patients who met the inclusion criteria of this retrospective observational study, 110 (15%) patients had no CTP mismatch and were analyzed. The median age was 74 (interquartile range, 62-80) years and 53% were women. Successful recanalization (modified Thrombolysis in Cerebral Infarction score, ≥2b) was achieved in 66% (73) and associated with functional independence at 90 days (adjusted odds ratio, 7.33 [95% CI, 1.22-43.70]; P=0.03). A significant interaction was observed between recanalization and age, as well as the extent of infarction, indicating MT to be most effective in patients <70 years and with a baseline Alberta Stroke Program Early Computed Tomography Score range between 3 and 7. These findings remained stable after propensity score matching, analyzing 152 matched pairs with similar rates of functional independence between patients with and without CTP-mismatch profiles (17% versus 23%; P=0.42). CONCLUSIONS: In patients without CTP-mismatch profiles defined according to the EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits) criteria, recanalization was associated with improved functional outcomes. This effect was associated with baseline Alberta Stroke Program Early Computed Tomography Score and age, but not with the time from onset to imaging.

Edema Reduction versus Penumbra Salvage: Investigating Treatment Effects of Mechanical Thrombectomy in Ischemic Stroke.

OBJECTIVE: Mechanical thrombectomy (MT) is of benefit to patients with ischemic stroke; however, the effect of recanalization on lesion pathophysiology is not yet well understood. The aim of this study was to quantitatively assess how the effect of vessel recanalization on clinical outcome is mediated by edema reduction versus penumbra salvage. METHODS: Consecutive analysis was made of anterior circulation ischemic stroke patients triaged by multimodal computed tomography (CT) undergoing MT. Edema reduction was defined using the difference of quantitative net water uptake (NWU) determined on baseline and follow-up CT (∆NWU). Penumbra salvage volume (PSV) was defined as the difference between admission penumbra and net infarct growth volumes to follow-up. Mediation analyses were performed with vessel recanalization as independent variable (modified Thrombolysis in Cerebral Infarction ≥ 2b) and ∆NWU/PSV as mediator variables. Modified Rankin Scale scores at 90 days served as endpoint. RESULTS: Of 422 included patients, 321 (76%) achieved successful recanalization. The median ∆NWU was 6.8% (interquartile range [IQR] = 3.9-10.4), and the median PSV was 66ml (IQR = 8-124). ∆NWU, PSV, and recanalization were significantly associated with functional outcome in logistic regression analysis. ∆NWU and PSV partially mediated the relationship between recanalization and outcome. Sixty-six percent of the relationship between recanalization and functional outcome could be explained by treatment-induced edema reduction, whereas 22% was mediated by PSV (p < 0.0001). INTERPRETATION: Compared to penumbra salvage, edema reduction was a stronger mediator of the effect of recanalization on functional outcome. Given the current trials on adjuvant neuroprotectants also targeting ischemic edema formation, combining reperfusion with antiedematous neuroprotectants may have synergistic effects resulting in better outcomes in patients with ischemic stroke. ANN NEUROL 2023.

Effect of short- versus long-term serum glucose levels on early ischemic water homeostasis and functional outcome in patients with large vessel occlusion stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, the impact of short- versus long-term blood glucose level (BGL) on early lesion pathophysiology and functional outcome has not been assessed. The purpose of this study was to directly compare the effect of long-term blood glucose (glycated hemoglobin [HbA1c]) versus serum BGL on early edema formation and functional outcome. METHODS: Anterior circulation ischemic stroke patients who underwent mechanical thrombectomy after multimodal computed tomography (CT) on admission were analyzed. Endpoints were early ischemic cerebral edema, measured by quantitative net water uptake (NWU) on initial CT and functional independence at Day 90. RESULTS: A total of 345 patients were included. Patients with functional independence had significantly lower baseline NWU (3.1% vs. 8.3%; p < 0.001) and lower BGL (113 vs. 123 mg/dL; p < 0.001) than those without functional independence, while HbA1c levels did not differ significantly (5.7% vs. 5.8%; p = 0.15). A significant association was found for NWU and BGL (ß = 0.02, 95% confidence interval [CI] 0.006-0.03; p = 0.002), but not for HbA1c and NWU (ß = -0.16, 95% CI -0.53-0.21; p = 0.39). Mediation analysis showed that 67% of the effect of BGL on functional outcome was mediated by early edema formation. CONCLUSION: Aggravated early edema and worse functional outcome was associated with elevated short-term serum BGL, but not with HbA1c levels. Hence, the link between short-term BGL and early edema development might be used as a target for adjuvant therapy in patients with ischemic stroke.

Benefit of Intravenous Alteplase before Thrombectomy Depends on ASPECTS.

PURPOSE: Baseline variables could be used to guide the administration of additional intravenous alteplase (IVT) before mechanical thrombectomy (MT). The aim of this study was to determine how baseline imaging and demographic parameters modify the effect of IVT on clinical outcomes in patients with ischemic stroke due to large vessel occlusion. METHODS: Multicenter retrospective cohort study of ischemic stroke patients triaged by multimodal-CT undergoing MT treatment after direct admission to an MT-eligible center. Inverse-probability weighting analysis (IPW) was used to assess the treatment effect of IVT adjusted for baseline variables. Multivariable logistic regression analysis with IPW-weighting and interaction terms for IVT was performed to predict functional independence (mRS 0-2 at 90-days). RESULTS: 720 patients were included, of which 366 (51%) received IVT. In IPW, the treatment effect of IVT on outcome (mRS 0-2) distinctively varied according to the ASPECTS subgroup (ASPECTS 9-10: +15%, ASPECTS 6-8: +7%, ASPECTS <6: -11%). In multivariable logistic regression analysis, IVT was independently associated with functional independence (aOR: 1.57, 95% CI: 1.16-2.14, p = 0.003) and the interaction term was significant for ASPECTS and IVT revealing that IVT was only significantly associated with better outcomes in patients with higher ASPECTS. No other significant baseline variable interaction terms were identified. INTERPRETATION: ASPECTS was the only baseline variable that showed a significant interaction with IVT for outcome prediction. Use of IVT prior to MT in patients with an ASPECTS of <6 was not associated with a treatment benefit and should be considered carefully. ANN NEUROL 2022;92:588-595.

Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia.

BACKGROUND: In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood. OBJECTIVE: The objective of this study was to investigate the role of the cerebellum on sensorimotor associative plasticity in patients with CD. METHODS: Sixteen patients with CD and 13 healthy subjects received cerebellar transcranial direct current stimulation (ctDCS) followed by a paired associative stimulation (PAS) protocol based on transcranial magnetic stimulation that induces sensorimotor associative plasticity. Across three sessions the participants received excitatory anodal, inhibitory cathodal, and sham ctDCS in a double-blind crossover design. Before and after the intervention, motor cortical excitability and motor symptom severity were assessed. RESULTS: PAS induced an increase in motor cortical excitability in both healthy control subjects and patients with CD. In healthy subjects this effect was attenuated by both anodal and cathodal ctDCS with a stronger effect of cathodal stimulation. In patients with CD, anodal stimulation suppressed the PAS effect, whereas cathodal stimulation had no influence on PAS. Motor symptom severity was unchanged after the intervention. CONCLUSIONS: Cerebellar modulation with cathodal ctDCS had no effect on sensorimotor associative plasticity in patients with CD, in contrast with the net inhibitory effect in healthy subjects. This is further evidence that the cerebello-thalamo-cortical network plays a role in the pathophysiology of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cortical thickness of contralesional cortices positively relates to future outcome after severe stroke.

Imaging studies have evidenced that contralesional cortices are involved in recovery after motor stroke. Cortical thickness (CT) analysis has proven its potential to capture the changes of cortical anatomy, which have been related to recovery and treatment gains under therapy. An open question is whether CT obtained in the acute phase after stroke might inform correlational models to explain outcome variability. Data of 38 severely impaired (median NIH Stroke Scale 9, interquartile range: 6-13) acute stroke patients of 2 independent cohorts were reanalyzed. Structural imaging data were processed via the FreeSurfer pipeline to quantify regional CT of the contralesional hemisphere. Ordinal logistic regression models were fit to relate CT to modified Rankin Scale as an established measure of global disability after 3-6 months, adjusted for the initial deficit, lesion volume, and age. The data show that CT of contralesional cortices, such as the precentral gyrus, the superior frontal sulcus, and temporal and cingulate cortices, positively relates to the outcome after stroke. This work shows that the baseline cortical anatomy of selected contralesional cortices can explain the outcome variability after severe stroke, which further contributes to the concept of structural brain reserve with respect to contralesional cortices to promote recovery.

Post-traumatic stress disorder in refugee minors in an outpatient care center: prevalence and associated factors.

Due to their likelihood for experiencing a number of traumatic events, refugee minors have an increased risk of developing post-traumatic stress disorder (PTSD). However, the prevalence of PTSD in refugee children varies widely between studies, and it remains somewhat unclear what factors increase children's risk of PTSD. This study aimed to assess the prevalence of PTSD in a clinical outpatient sample of refugee minors, and to evaluate the association of different risk factors with a PTSD diagnosis. N = 417 refugee minors were recruited from an outpatient clinical center in Hamburg, Germany. The median age was 15.4 years and 74.6% of the minors were male. As part of the standard diagnostic process, their social history and a potential PTSD diagnosis using the Module K of the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) was assessed. The predictive value of age, gender, number of interpersonal traumatic events, un-/accompanied status, presence of family member in the host country, flight duration, residence status, and time since arrival in the host country were investigated using logistic regression analysis. The prevalence of PTSD among the young refugee patients was 61.6%. Significant predictors of a PTSD diagnosis were number of interpersonal traumatic life events, age, residence status, and time since arrival in the host country. The prediction model explained 33.8% of variance of the outcome with the number of interpersonal traumatic events having the largest contribution (20.8%). The high prevalence of PTSD among refugee minors in outpatient care emphasizes the need to establish appropriate care structures and train specialists in the treatment of PTSD.

Quantitative Lesion Water Uptake as Stroke Imaging Biomarker: A Tool for Treatment Selection in the Extended Time Window?

BACKGROUND AND PURPOSE: Patients presenting in the extended time window may benefit from mechanical thrombectomy. However, selection for mechanical thrombectomy in this patient group has only been performed using specialized image processing platforms, which are not widely available. We hypothesized that quantitative lesion water uptake calculated in acute stroke computed tomography (CT) may serve as imaging biomarker to estimate ischemic lesion progression and predict clinical outcome in patients undergoing mechanical thrombectomy in the extended time window. METHODS: All patients with ischemic anterior circulation stroke presenting within 4.5 to 24 hours after symptom onset who received initial multimodal CT between August 2014 and March 2020 and underwent mechanical thrombectomy were analyzed. Quantitative lesion net water uptake was calculated from the admission CT. Prediction of clinical outcome was assessed using univariable receiver operating characteristic curve analysis and logistic regression analyses. RESULTS: One hundred two patients met the inclusion criteria. In the multivariable logistic regression analysis, net water uptake (odds ratio, 0.78 [95% CI, 0.64-0.95], P=0.01), age (odds ratio, 0.94 [95% CI, 0.88-0.99]; P=0.02), and National Institutes of Health Stroke Scale (odds ratio, 0.88 [95% CI, 0.79-0.99], P=0.03) were significantly and independently associated with favorable outcome (modified Rankin Scale score ≤1), adjusted for degree of recanalization and Alberta Stroke Program Early CT Score. A multivariable predictive model including the above parameters yielded the highest diagnostic ability in the classification of functional outcome, with an area under the curve of 0.88 (sensitivity 92.3%, specificity 82.9%). CONCLUSIONS: The implementation of quantitative lesion water uptake as imaging biomarker in the diagnosis of patients with ischemic stroke presenting in the extended time window might improve clinical prognosis. Future studies could test this biomarker as complementary or even alternative tool to CT perfusion.

New imaging score for outcome prediction in basilar artery occlusion stroke.

OBJECTIVE: In ischemic posterior circulation stroke, the utilization of standardized image scores is not established in daily clinical practice. We aimed to test a novel imaging score that combines the collateral status with the rating of the posterior circulation Acute Stroke Prognosis Early CT score (pcASPECTS). We hypothesized that this score (pcASCO) predicts functional outcome and malignant cerebellar edema (MCE). METHODS: Ischemic stroke patients with acute BAO who received multimodal-CT and underwent thrombectomy on admission at two comprehensive stroke centers were analyzed. The posterior circulation collateral score by van der Hoeven et al was added to the pcASPECTS to define pcASCO as a 20-point score. Multivariable logistic regression analyses were performed to predict functional independence at day 90, assessed using modified Rankin Scale scores, and occurrence of MCE in follow-up CT using the established Jauss scale score as endpoints. RESULTS: A total of 118 patients were included, of which 84 (71%) underwent successful thrombectomy. Based on receiver operating characteristic curve analysis, pcASCO ≥ 14 classified functional independence with higher discriminative power (AUC: 0.83, 95%CI: 0.71-0.91) than pcASPECTS (AUC: 0.74). In multivariable logistic regression analysis, pcASCO was significantly and independently associated with functional independence (aOR: 1.91, 95%CI: 1.25-2.92, p = 0.003), and MCE (aOR: 0.71, 95%CI: 0.53-0.95, p = 0.02). CONCLUSION: The pcASCO could serve as a simple and feasible imaging tool to assess BAO stroke patients on admission and might be tested as a complementary tool to select patients for thrombectomy in uncertain situations, or to predict clinical outcome. KEY POINTS: • The neurological assessment of basilar artery occlusion stroke patients can be challenging and there are yet no validated imaging scores established in daily clinical practice. • The pcASCO combines the rating of early ischemic changes with the status of the intracranial posterior circulation collaterals. • The pcASCO showed high diagnostic accuracy to predict functional outcome and malignant cerebellar edema and could serve as a simple and feasible imaging tool to support treatment selection in uncertain situations, or to predict clinical outcome.

Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy-related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT.

OBJECTIVES: Cancer therapy-related cardiac dysfunction (CTRCD) is a relevant clinical problem and needs early prediction. This study aimed to analyze myocardial injury using serial laboratory and cardiac magnetic resonance imaging (CMR) parameters after epirubicin-based chemotherapy compared with left-sided radiotherapy and to study their value for early prediction of CTRCD. METHODS: Sixty-six consecutive women (53 ± 13 years) including n = 39 with epirubicin-based chemotherapy and n = 27 with left-sided radiotherapy were prospectively studied by 3 T CMR including left ventricular (LV) mass and volumes for ejection fraction (LVEF), as well as feature-tracking with global longitudinal strain (GLS) and T1/T2 mapping. CMR was performed at baseline, at therapy completion (follow-up 1, FU1), and after 13 ± 2 months (FU2). CTRCD was defined as LVEF decline of at least 10% to < 55% or a > 15% GLS change at FU2. RESULTS: T1 and T2 increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. CTRCD occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. T1 at FU1 was the best single parameter to predict CTRCD with an area under the curve (AUC) of 0.712 (CI 0.587-0.816, p = 0.005) with excellent sensitivity (100%, 66-100%), but low specificity (44%, 31-58%). Combined use of increased T1 and LVEF ≤ 60% at FU1 improved AUC to 0.810 (0.695-0.896) resulting in good sensitivity (78%, 44-95%) and specificity (84%, 72-92%). CONCLUSION: Only epirubicin-based chemotherapy, but not left-sided radiotherapy, resulted in increased T1/T2 myocardial relaxation times as a marker of myocardial injury. Combined use of CMR parameters may allow an early prediction of subsequent CTCRD. KEY POINTS: • Myocardial T1 and T2 relaxation times increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. • Cancer therapy-related cardiac dysfunction (CTRCD) occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. • Combined use of increased T1 and reduced LVEF had an AUC of 0.810 (0.695-0.896) to predict CTRCD with good sensitivity (78%, 44-95%) and specificity (84%, 72-92%).

Impact of relative cerebral blood volume reduction on early neurological improvement in extensive ischemic stroke.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for patients with low Alberta Stroke Program early computed tomography score (ASPECTS) is still ambiguous and is currently being investigated in randomized trials. Computed tomography (CT) perfusion, used to estimate infarct extent and progression, might predict early neurological improvement (ENI) after EVT. We hypothesized that the degree of relative cerebral blood volume (rCBV) reduction is directly associated with ENI in low ASPECTS patients undergoing EVT. METHODS: Ischemic stroke patients with ASPECTS ≤ 5 who received multimodal CT and underwent thrombectomy were analyzed. rCBV reduction was defined as the ratio of cerebral blood volume (CBV), measured in the ischemic lesion to contralateral CBV. Complete reperfusion was defined as an expanded Thrombolysis in Cerebral Infarction score 2c-3. The clinical endpoint was ENI at 24 h, defined continuously (National Institutes of Health Stroke Scale [NIHSS] score change from baseline to 24 h) and binarized (NIHSS score at 24 h ≤ 8). RESULTS: A total of 102 patients were included. Lower rCBV reduction and complete EVT were independently associated with ENI (-11.4 NIHSS points, p = 0.04; -7.3 points, p < 0.0001, respectively). The effect of complete EVT on ENI was directly linked to the degree of rCBV reduction: the probability for binary ENI was +34.6% (p = 0.004) in patients with low rCBV reduction versus +8.2% (p = 0.28) in patients with high rCBV reduction). CONCLUSION: In patients with ischemic stroke with low ASPECTS, ENI was directly linked to the degree of rCBV reduction, a potential indicator of ischemia depth in extensive baseline infarction. Lower rCBV reduction was associated with higher probability of ENI after complete reperfusion, suggesting less pronounced lesion progression despite its large extent and hence, a higher susceptibility to EVT.

The moderating effects of social support and depressive symptoms on pain among elderly multimorbid patients-data from the multicentre, prospective, observational cohort study MultiCare.

OBJECTIVES: Depressive symptoms and chronic pain are common among patients with multimorbidity creating a complex medical condition for both the patient and the general practitioner. Perceived social support may function as a protective measure.To examine the impact of perceived social support as a potential moderator between depressive symptoms and pain intensity and pain disability in daily activities in multimorbid patients aged 75+. METHOD: Data from 3,189 patients of the German longitudinal cohort study MultiCare were obtained at baseline and follow-ups during 5 years. Multilevel linear mixed-effects analyses were conducted for pain intensity (model 1) and pain disability in daily activities (model 2). The interaction term social support by depression score was included to test for moderation. RESULTS: The interaction between social support and depressive symptoms was significantly associated with the pain intensity score 0.41 (SE=.17; 95-CI[.08;.74]) but not with the pain disability score 0.35 (SE=.19; 95-CI[-.01;.72]). Additionally, men and individuals with medium or higher educational level showed reduced pain intensity and disability scores. Pain disability scores increased with age and depressive symptoms. Increased pain scores were also found for body mass index and burden of multimorbidity. CONCLUSION: Perceived social support amplified the association of depressive symptoms on pain intensity and did not show a protective function. The high scores of perceived social support among the participants may point to the practice of secondary gain due to the patients immense health burden.

Predictors of change in depressive symptoms in older and multimorbid patients: a longitudinal analysis of the multicare cohort.

BACKGROUND: Depression in older adults is becoming an increasing concern. As depressive symptoms change over time, it is important to understand the determinants of change in depressive symptoms. The aim of our study is to use a longitudinal study design to explore the predictors of change, remission and incident depression in older patients with multimorbidity. METHODS: Data from the MultiCare cohort study were used. The cohort studied 3,189 multimorbid general practice patients aged 65-85. Data were collected during personal interviews. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Predictors of change in depressive symptoms were determined using multivariate linear regression, while multivariate logistic regression was used to analyze predictors of remission and incident depression. Models included depressive symptoms at baseline and follow-up, socio-demographics and data on health status and social support. RESULTS: Overall, 2,746 participants with complete follow-up data were analyzed. Mean age was 74.2 years, 59.2% were female, and 11.3% were classified as depressed at baseline. Burden of multimorbidity and social support were statistically significant predictors in all regression analyses. Further predictors of change in depressive symptoms were: income, pain, nursing grade, self-rated health and self-efficacy. LIMITATIONS: The sample size for prediction of remission limited statistical certainty. Assessment of depressive symptoms using GDS-15 differs from routine clinical diagnoses of depression. CONCLUSIONS: Predictors of change in depressive symptoms in older multimorbid patients are similar to those predicting remission and incident depression, and do not seem to differ significantly from other older patient populations with depressive symptoms.

Management of intra-thoracic anastomotic leakages after esophagectomy: updated systematic review and meta-analysis of endoscopic vacuum therapy versus stenting.

Despite a significant decrease of surgery-related mortality and morbidity, anastomotic leakage still occurs in a significant number of patients after esophagectomy. The two main endoscopic treatments in case of anastomotic leakage are self-expanding metal stents (SEMS) and the endoscopic vacuum therapy (EVT). It is still under debate, if one method is superior to the other. Therefore, we performed a systematic review and meta-analysis of the existing literature to compare the effectiveness and the related morbidity of SEMS and EVT in the treatment of esophageal leakage. We systematically searched for studies comparing SEMS and EVT to treat anastomotic leak after esophageal surgery. Predefined endpoints including outcome, treatment success, endoscopy, treatment duration, re-operation rate, intensive care and hospitalization time, stricture rate, morbidity and mortality were assessed and included in the meta-analysis. Seven retrospective studies including 338 patients matched the inclusion criteria. Compared to stenting, EVT was significantly associated with higher healing (OR 2.47, 95% CI [1.30 to 4.73]), higher number of endoscopic changes (pooled median difference of 3.57 (95% CI [2.24 to 4.90]), shorter duration of treatment (pooled median difference - 11.57 days; 95% CI [- 17.45 to - 5.69]), and stricture rate (OR 0.22, 95% CI [0.08 to 0.62]). Hospitalization and intensive care unit duration, in-hospital mortality rate, rate of major and treatment related complications, of surgical revisions and of esophago-tracheal fistula failed to show significant differences between the two groups. Our analysis indicates a high potential for EVT, but because of the retrospective design of the included studies with potential biases, these results must be interpreted with caution. More robust prospective randomized trials should further investigate the potential of the two procedures.

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI-FLAIR Mismatch.

PURPOSE: In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset. METHODS: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke. RESULTS: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%). CONCLUSION: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis. ANN NEUROL 2020;88:1144-1152.

Impact of intravenous alteplase on sub-angiographic emboli in high-resolution diffusion-weighted imaging following successful thrombectomy.

OBJECTIVE: Thrombus microfragmentation causing peripheral emboli (PE) during mechanical thrombectomy (MT) may modulate treatment effects, even in cases with successful reperfusion. This study aims to investigate whether intravenous alteplase is of potential benefit in reducing PE after successful MT. METHODS: Patients from a prospective study treated at a tertiary care stroke center between 08/2017 and 12/2019 were analyzed. The main inclusion criterion was successful reperfusion after MT (defined as expanded thrombolysis in cerebral infarction (eTICI) scale ≥ 2b50) of large vessel occlusion anterior circulation stroke. All patients received a high-resolution diffusion-weighted imaging (DWI) follow-up 24 h after MT for PE detection. Patients were grouped as "direct MT" (no alteplase) or as MT plus additional intravenous alteplase. The number and volume of ischemic core lesions and PE were then quantified and analyzed. RESULTS: Fifty-six patients were prospectively enrolled. Additional intravenous alteplase was administered in 46.3% (26/56). There were no statistically significant differences of PE compared by groups of direct MT and additional intravenous alteplase administration regarding mean numbers (12.1, 95% CI 8.6-15.5 vs. 11.1, 95% CI 7.0-15.1; p = 0.701), and median volume (0.70 mL, IQR 0.21-1.55 vs. 0.39 mL, IQR 0.10-1.62; p = 0.554). In uni- and multivariable linear regression analysis, higher eTICI scores were significantly associated with reduced PE, while the administration of alteplase was neither associated with numbers nor volume of peripheral emboli. Additional alteplase did not alter reperfusion success. CONCLUSIONS: Intravenous alteplase neither affects the number nor volume of sub-angiographic DWI-PE after successful endovascular reperfusion. In the light of currently running randomized trials, further studies are warranted to validate these findings. KEY POINTS: • Thrombus microfragmentation during endovascular stroke treatment may cause peripheral emboli that are only detectable on diffusion-weighted imaging and may directly compromise treatment effects. • In this prospective study, the application of intravenous alteplase did not influence the occurrence of peripheral emboli detected on high-resolution diffusion-weighted imaging. • A higher degree of recanalization was associated with a reduced number and volume of peripheral emboli and better functional outcome, while contrariwise, peripheral emboli did not modify the effect of recanalization on modified Rankin Scale scores at day 90.

Agreement between continuous and intermittent pulmonary artery thermodilution for cardiac output measurement in perioperative and intensive care medicine: a systematic review and meta-analysis.

BACKGROUND: Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution are used in clinical practice it is important to know whether cardiac output measurements by the two methods are clinically interchangeable. METHODS: We performed a systematic review and meta-analysis of clinical studies comparing cardiac output measurements assessed using continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients. 54 studies with 1522 patients were included in the analysis. RESULTS: The heterogeneity across the studies was high. The overall random effects model-derived pooled estimate of the mean of the differences was 0.08 (95%-confidence interval 0.01 to 0.16) L/min with pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7 (95%-confidence interval 20.5 to 38.9)%. CONCLUSION: The heterogeneity across clinical studies comparing continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients is high. The overall trueness/accuracy of continuous pulmonary artery thermodilution in comparison with intermittent pulmonary artery thermodilution is good (indicated by a pooled mean of the differences < 0.1 L/min). Pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7% suggest that continuous pulmonary artery thermodilution barely passes interchangeability criteria with intermittent pulmonary artery thermodilution. PROSPERO registration number CRD42020159730.

Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.

BACKGROUND AND PURPOSE: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine. METHODS: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively. RESULTS: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC)NIHSS 24 hours area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROCNIHSS 24 hours AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC% change AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROCΔ change AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROCAdm AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days. CONCLUSION: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value.

Endoscopic vacuum therapy versus stenting for postoperative esophago-enteric anastomotic leakage: systematic review and meta-analysis.

BACKGROUND: Esophageal anastomotic leakage still represents a challenging complication after esophageal surgery. Endoscopically placed self-expandable metal stents (SEMS) are the treatment of choice, but since the introduction of endoscopic vacuum therapy (EVT) for esophageal leakage 10 years ago, increasing evidence has demonstrated that EVT might be a superior alternative. Therefore, we performed a systematic review and meta-analysis to compare the effectiveness and related morbidity of SEMS and EVT in the treatment of esophageal leak. METHODS: We systematically searched for studies comparing SEMS and EVT to treat anastomotic leakage after esophageal surgery. Predefined end points including outcome, treatment success, endoscopy, treatment duration, hospitalization time, morbidity, and mortality were assessed and included in the meta-analysis. RESULTS: Five retrospective studies including 274 patients matched the inclusion criteria. Compared with stenting, EVT was significantly associated with a higher rate of leak closure (odds ratio [OR] 3.14, 95 % confidence interval [CI] 1.23 to 7.98), more endoscopic device changes (pooled median difference of 3.09; 95 %CI 1.54 to 4.64]), a shorter duration of treatment (pooled median difference -11.90 days; 95 %CI -18.59 to -5.21 days), and a lower mortality rate (OR 0.39, 95 %CI 0.18 to 0.83). There were no significant differences in short-term and major complications. CONCLUSIONS: Owing to the retrospective quality of the studies with potential biases, the results of the meta-analysis must be interpreted with caution. However, the analysis indicates the potential benefit of EVT, which should be further investigated with standardized and prospectively collected data.

Clinical benefit of thrombectomy in stroke patients with low ASPECTS is mediated by oedema reduction.

The impact of endovascular vessel recanalization on patients with a low initial Alberta Stroke Program Early Computer Tomography Score (ASPECTS) is still uncertain. We hypothesized that vessel recanalization leads to an improvement in mortality and degree of disability by reducing brain oedema and malignant mass effect. In this multicentre observational study, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and an ASPECTS of ≤ 5 were analysed. Patients were assembled into two groups: successful vessel recanalization (thrombolysis in cerebral infarctions, TICI scale 2b/3) or persistent vessel occlusion (no endovascular procedure or TICI scale 0-2a). Observers were blinded to clinical data. Net water uptake within brain infarct, a quantitative biomarker based on CT densitometry, was used to quantify oedema in admission and follow-up CT and Δ-water uptake was calculated as difference between water uptake at both time points. Occurrence of malignant infarctions and secondary parenchymal haemorrhage was documented. Furthermore, modified Rankin scale score at 90 days was used for functional outcome. We included 117 patients admitted between March 2015 and August 2017 in three German stroke centres: 71 with persistent vessel occlusion and 46 with successful recanalization. The mean water uptake in the admission imaging was not different between both groups: 10.0% (±4.8) in patients with persistent vessel occlusion and 9.0% (±4.8) in patients with vessel recanalization (P = 0.4). After follow-up CT, the mean Δ-water uptake was 16.0% (±7.5) in patients with persistent vessel occlusion and 8.0% (±5.7) in patients with vessel recanalization (P < 0.001). Successful reperfusion was independently associated with a lowered Δ-water uptake of 8.0% (95% confidence interval, CI: -10.5 to -5.3%; P < 0.001) and lowered modifed Rankin scale score after 90 days of 1.5 (95% CI: -2.2 to -0.8; P < 0.001). The prevalence of malignant infarctions was 44.3% in patients with persistent vessel occlusion and 26.1% in patients with vessel recanalization. There was no significant difference for secondary haemorrhage in both groups (P = 0.7). In conclusion, successful recanalization in patients with low initial ASPECTS resulted in a significant reduction of oedema formation and was associated with a decreased prevalence of malignant infarctions and an improvement of clinical outcome.