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ZusammenfassungDie Durchführung einer oralen Antikoagulation ist bei Patienten mit einer zerebralen Amyloidangiopathie eine therapeutische Herausforderung. Die Assoziation der zerebralen Amyloidangiopathie mit Lobärblutungen, eine hohe Mortalität intrazerebraler Blutungen insbesondere unter oraler Antikoagulation sowie das hohe Rezidivrisiko solcher Blutungen erfordern eine strenge und interdisziplinäre Risiko-Nutzen-Abwägung. Vitamin-K-Antagonisten erhöhen das Risiko für die mit intrazerebralen Blutungen vergesellschaftete Mortalität um 60 % und sollten daher möglichst vermieden bzw. speziellen klinischen Situationen (z. B. mechanischer Aortenklappenersatz) vorbehalten sein. Auch der Einsatz von neuen oralen Antikoagulanzien und Thrombozytenaggregationshemmern bedarf einer strengen Risiko-Nutzen-Abwägung, da auch diese Substanzen das zerebrale Blutungsrisiko erhöhen. Insbesondere bei Patienten mit einer absoluten Arrhyhtmie bei Vorhofflimmern ist der interventionelle Vorhofohrverschluss eine therapeutische Alternative. Darüber hinaus sind weitere klinische Implikationen bei Patienten mit zerebraler Amyloidangiopathie Gegenstand dieser Literaturübersicht, beispielsweise Besonderheiten nach akutem ischämischem Schlaganfall und erforderlicher Sekundärprophylaxe, bei vorherigen intrazerebralen Blutungen und bei Patienten mit kognitiven Defiziten.

Background The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days.Results A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12).Conclusions Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)Endovascular Therapy for Basilar-Artery Stroke In a randomized trial involving 300 patients with basilar-artery stroke, endovascular thrombectomy was not significantly different from medical therapy with respect to a favorable functional outcome (modified Rankin scale score of 0 to 3) at 90 days, but a clinically significant benefit could not be excluded.

We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.ZIEL: Bestimmung der diagnostischen Übereinstimmung zwischen den multiparametrischen Ultraschallkriterien der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) und den Konsenskriterien der Society of Radiologists in Ultrasound (SRU) hinsichtlich der Graduierung von Karotisstenosen. Post-hoc-Analyse einer prospektiven multizentrischen Studie, welche die multiparametrischen DEGUM-Ultraschallkriterien mit der digitalen Subtraktionsangiografie validierte. Die Graduierung von Karotisstenosen in klinisch relevante NASCET-Kategorien (normal, leichtgradig (1–49 %), mittelgradig (50–69 %), hochgradig (70–99 %), Verschluss) erfolgte verblindet gemäß der DEGUM- und SRU-Ultraschallkriterien. Als Referenz wurde der nach NASCET bestimmte angiografische Stenosegrad verwendet. Wir analysierten 158 konsekutive Untersuchungen aus Ultraschall und Angiografie. Zwischen beiden sonografischen Graduierungsansätzen fand sich eine gute Übereinstimmung für hochgradige (κw 0,76; 95 %-KI 0,66–0,86) und eine mäßige Übereinstimmung für mittelgradige Stenosen (κw 0,38; 95 %-KI 0,19–0,58). Verglichen mit der Referenzangiografie fand sich kein Unterschied hinsichtlich Sensitivität für hochgradige Stenosen (79,7 % versus 79,7 %; p = 1,0), jedoch eine höhere Spezifität der DEGUM-Kriterien (70,2 % versus 56,4 %; p = 0,0002). In den sonstigen Stenosekategorien bestanden keine Unterschiede der Güteparameter (p 0,05). Verglichen mit den SRU-Kriterien weist die Graduierung nach DEGUM eine höhere Spezifität bei der Detektion hochgradiger Stenosen auf. Die Integration von mehr hämodynamischen Parametern scheint somit die Anzahl falsch positiver Diagnosen zu verringern.

Seit Veroffentlichung der grosen „Thrombektomiestudien“ ist die endovaskulare Therapie (EVT) bei Schlaganfallpatienten mit einem Gefasverschluss im vorderen zerebralen Kreislauf in die Standardtherapie ubergangen. Hinsichtlich der Behandlung akuter Gefasverschlusse im hinteren Stromgebiet und insbesondere der A. basilaris bestehen aufgrund der schlechteren Evidenzlage Unsicherheiten bez. der Indikation zur EVT. Der vorliegende Ubersichtsartikel geht auf die aktuelle Datenlage zur EVT im hinteren Stromgebiet und jungste Studienergebnisse ein. Daruber hinaus werden pathophysiologische Aspekte, Indikationen und Besonderheiten in der Behandlung dieser Patienten diskutiert. Trotz eingeschrankter Evidenz fur die EVT hat diese Behandlungsform einen hohen Stellenwert in der Schlaganfallbehandlung von Patienten mit Gefasverschluss im hinteren Stromgebiet erlangt. Aus technischer Sicht sind diese Gefasverschlusse einer EVT gut zuganglich, wobei sich die Atiologie und die erforderliche Technik im Vergleich zum vorderen Stromgebiet teilweise unterscheiden. Die EVT im hinteren Stromgebiet unterscheidet sich hinsichtlich aktueller Evidenz, Indikation und Technik von der EVT in der vorderen Zirkulation. Aufgrund der begrenzten wissenschaftlichen Evidenz mussen insbesondere fur Patienten im spaten Zeitfenster oder mit bereits deutlicher Infarktdemarkation individuelle Therapieentscheidungen basierend auf institutionellen Behandlungsprotokollen getroffen werden.

Buerger disease (thromboangiitis obliterans [TAO]) typically occurs in men younger than 40–45 years who have a history of heavy tobacco use.

Concussion is a growing public health concern and generating concussion prevention programs depends on identifying high-risk sports and characteristics. Identifying the roles of sport, sex, and participation level (e.g., high school versus collegiate athletics) in concussion risk would facilitate more informed decision-making regarding sports participation and generate better targeted prevention strategies. The current study’s objectives were to: (1) determine the magnitude and hierarchy of sports-related concussion (SRC) risk across an array of events and (2) evaluate the modifying roles of sex, participation level, and session type on SRC rates. A literature search was conducted on PubMed, searching concussion studies published between 2001 and December 2019. Inclusion criteria for studies required: (1) concussion occurred during sport, (2) that the SRC was clinically diagnosed, and (3) athlete exposures and concussions could be extracted or estimated. A study was excluded if it: (1) was not an original research article, (2) was not written in English language, (3) was an animal study, (4) did not have enough data to calculate SRC rates, (5) included professional or youth sample, and/or (6) contained data collected prior to 2001. The meta-analysis and meta-regression analyses were fit using a random effects model. Search results returned 2695 unique research articles, with 83 studies included in analyses. Sport, sex, participation level, and session type all significantly influenced SRC rates. Overall, rugby had the highest concussion rate and was classified as the highest risk sport (28.25 concussions per 10,000 athlete exposures). Overall, females had a higher concussion rate than males. Only lacrosse demonstrated a higher concussion rate for males compared to females. Collegiate athletes had higher concussion rates than high school athletes. Games were associated with 2.01 more concussions per 10,000 AEs than practices. This meta-analysis demonstrated rugby has the highest concussion risk, followed by American Football, ice hockey, and wrestling. Concussion risk was influenced by sport, sex, participation, and session. Identifying the factors and environments that influence concussion risk can facilitate risk reduction and prevention strategies.

Social networks are commonly discussed in reference to processes of disaster recovery but rarely explicitly measured. We employ a mixed-methods approach drawing upon the personal-network data of 265 oysterworkers in the wake of the Deepwater Horizon oil spill and qualitative accounts of individual experiences during the recovery process. We find evidence of two potential mechanisms linking network structure with the receipt of formal support: a networks-as-pipes approach linking networks and access to relevant information in the wake of a disaster and a networks-as-prisms approach where networks signal their social identities, shaping post-disaster actions and behaviors.

Objective To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). Methods In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. Results Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52–2.81; p p p p Conclusion A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (−85%, −46%, −42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, −60%; thrombectomy, −61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

BackgroundTo assess whether thrombus surface morphology has an impact on first pass reperfusion in contact aspiration (CA) and stent retriever (SR) thrombectomy.MethodsFrom January 2016 to December 2018, consecutive stroke patients with an occlusion of the middle cerebral artery and thrombectomy (CA or SR) were examined in this retrospective study. We assessed patients’ characteristics, procedural data and clinical outcome. Thrombus surface on pretreatment digital subtraction angiography (DSA) was categorized into regular versus irregular phenotype by blinded three-reader-consensus. Primary outcome was successful reperfusion (modified treatment in cerebral ischemia (mTICI) 2b-3) after first pass. Data analysis was stratified according to thrombectomy technique and thrombus phenotype.ResultsAmong 203 patients (76 years (IQR 65.5–81.9), 47.3% male, National Institutes of Health Stroke Scale Score 16 (IQR 12–20)), 155 patients were treated primarily with CA and 48 with SR. 40% (n=62/155) CA and 41.7% (n=20/48) SR-treated patients had a regular thrombus phenotype. In the CA group, successful reperfusion after first pass was more frequently obtained in patients with regular compared with irregular phenotype (69.4% (n=43/62) vs 34.4% (n=32/93); PConclusionDirect CA is associated with higher rates of successful first pass reperfusion in patients with a regular thrombus phenotype in pretreatment DSA.

BACKGROUND: Recent studies show small-bore chest tubes, commonly 14 French pigtail catheters (PCs), are noninferior to large-bore chest tubes for treating various conditions, and they are associated with better patient comfort. The Medical College of Wisconsin implemented a bedside procedure service (BPS) that has been trained in the placement of PCs as an adjunct to its interventional radiology department. METHODS: The data regarding consults for PC placement was collected by the BPS over a 2-year period. Primary outcomes reviewed were insertion-related complications (IRCs), unsuccessful attempts (UAs), and adverse outcomes (AOs) because the authors believe these represent the safety and effectiveness of the group. It was determined which services consulted the BPS for PC placement, the indications for consults, and a brief review of declined PC consults. RESULTS: Of the 124 accepted consults, the service had 3 IRCs (2.4%), 2 UAs (1.6%), and 3 AOs (2.4%). A total of 18 consults were declined. The BPS was consulted by 12 services with 8 primary reasons for PC placement. CONCLUSIONS: At high-volume, tertiary care centers, and with the support of cardiothoracic surgical and interventional radiology services, procedure-focused hospitalists can safely serve as an adjunct service for PC placement in selected hospitalized patients.

Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared using the area under the receiver operating characteristic curve (AUC). Shapley values were used to determine marginal contributions of variables to outcome variance in the regression models. Results Among 1105 patients, functional independence was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95% CI, 0.71–0.77); this iteratively improved when treatment and posttreatment variables were added to the models (model 2: AUC, 0.77; 95% CI, 0.74–0.80; model 3: AUC, 0.80; 95% CI, 0.77–0.83; model 4: AUC, 0.82; 95% CI, 0.79–0.85). With baseline variables alone, 26% of patients who achieved functional independence were erroneously classified as not achieving functional independence. Even with the most comprehensive model, 19.8% of patients were misclassified as such. Patient age contributed most to outcome variance (Shapley value, 0.28), followed by severe adverse events including pneumonia (0.16) and intracranial hemorrhage at 24‐hours imaging (0.13). Conclusions A substantial contribution to outcomes after endovascular therapy comes from factors unrelated to currently collected baseline patient variables. One‐fifth of patients achieving functional independence were misclassified as not achieving independence, even with the most comprehensive model. Our findings suggest that the achievable accuracy of current outcome prediction models is limited, and caution should be used when applying them in clinical practice.

Key Points Question Why do some patients have poor outcomes despite small infarcts after endovascular therapy, while others with large infarcts fare better? Findings In this cohort study of 1091 patients who received endovascular therapy as part of a randomized clinical trial, discrepancies between infarct volume and functional outcome were associated with prespecified pretreatment factors, such as age, cancer, and vascular risk factors, as well as posttreatment factors, such as infarct in new territory, stroke progression, intracerebral hemorrhage, recurrent stroke, pneumonia, and heart failure. Models including these factors performed similar to those derived from stepwise regressions. Meaning In this study, discrepancies between outcome and infarct volume were associated with pretreatment and posttreatment factors, including complications related to index stroke evolution, secondary prevention, and quality of stroke unit care., This cohort study validates exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment, and posttreatment factors associated with discrepancies between follow-up infarct volume and 90-day functional outcome., Importance Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. Objective To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. Design, Setting, and Participants This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. Exposures Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases. Main Outcomes and Measures Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression–derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. Results Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92). Conclusions and Relevance In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.

Background: In 2007, the American Board of Internal Medicine eliminated numeric procedure requirements for licensing. The level of exposure to procedures during residency, and subsequent competence of graduating residents, is variable. In 2015, our institution developed a bedside procedure service (BPS) with the intent to teach ultrasound guidance and procedural training to internal medicine residents with direct supervision of technique by Hospital Medicine faculty to optimize learning, increase confidence, and improve patient safety. Objective: In this study, we review the number and complication rates of resident procedures on a dedicated internal medicine bedside procedure service (BPS) as a resident elective.Methods: In this retrospective, observational, single-center study, we reviewed internally collected data from BPS procedures performed from 2015-2019. The BPS offers a variety of procedures done with ultrasound guidance at an adult tertiary care referral center. BPS services are available to all inpatient hospital services. A rotation with the BPS was offered as a stand-alone resident elective for the first time in 2015. Results: 69 residents performed a total of 2700 ultrasound-guided/assisted procedures and 146 diagnostic ultrasound scans from 2015-2019. Residents performed an average of 40 procedures during their elective month. There were 5 resident performed procedural complications with an overall complication rate of 0.19%.Conclusions: Our BPS increased procedural opportunities for residents and allowed for real-time feedback by an experienced faculty member in a one-on-one setting. A dedicated rotation allows the time to focus on becoming proficient in invasive procedures with expert supervision.

Background: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2–97.7%, specificity 31.6%, 95% CI 12.6–56.6% vs. sensitivity 72.7%, 95% CI 39.0–94.0%, specificity 36.8%, 95% CI 16.3–61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4–100%, specificity 66.7%, 95% CI 41–86.7%). Conclusions: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.

Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83–0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41–77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background Several studies have reported that haemophilia carriers have a bleeding tendency independent of factor activity. However, investigations have been fraught with methodological concerns. The ATHNdataset houses the largest data set of haemophilia carriers in the world. We undertook an analysis of haemophilia carriers in this data set using methodologies that characterize bleeding symptoms in carriers. Aim Determine the proportion of haemophilia carriers who have a normal bleeding score (BLS) and factors that affect the BLS. Methods The ATHNdataset was queried for haemophilia carriers with a documented BLS. Collected data included demographics, ISTH-BAT score, factor activity level, type of haemophilia (A or B), genotype and geographic residence. Results Nine hundred twenty-two haemophilia carriers in the ATHNdataset reported a BLS. When adjusted for age, 74% reported a normal score. Logistic regression identified age, factor activity level, ethnicity and region of residence as risk factors for an abnormal score. Conclusions The majority of haemophilia carriers (74%) in the ATHNdataset had a normal BLS, including the majority (59%) with factor activity levels > 40 IU/dl reported an abnormal BLS. These results are consistent with previous studies of haemophilia carriers. Additional investigation is needed to determine why a majority of haemophilia carriers with low factor activity levels report normal BLSs while a significant minority of haemophilia carriers with normal activity levels report abnormal BLSs.

We aimed to assess how evidence-based stroke care changed over the two waves of the COVID-19 pandemic. We analyzed acute stroke patients admitted to a tertiary care hospital in Germany during the first (2 March 2020–9 June 2020) and second (23 September 2020–31 December 2020, 100 days each) infection waves. Stroke care performance indicators were compared among waves. A 25.2% decline of acute stroke admissions was noted during the second (n = 249) compared with the first (n = 333) wave of the pandemic. Patients were more frequently tested SARS-CoV-2 positive during the second than the first wave (11 (4.4%) vs. 0; p < 0.001). There were no differences in rates of reperfusion therapies (37% vs. 36.5%; p = 1.0) or treatment process times (p > 0.05). However, stroke unit access was more frequently delayed (17 (6.8%) vs. 5 (1.5%); p = 0.001), and hospitalization until inpatient rehabilitation was longer (20 (1, 27) vs. 12 (8, 17) days; p < 0.0001) during the second compared with the first pandemic wave. Clinical severity, stroke etiology, appropriate secondary prevention medication, and discharge disposition were comparable among both waves. Infection control measures may adversely affect access to stroke unit care and extend hospitalization, while performance indicators of hyperacute stroke care seem to be untainted.

Introduction: Endovascular therapy (EVT) is established as first-line treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. For basilar artery occlusion, recent randomized clinical trials demonstrated not only equipoise but also advantages for EVT under particular circumstances. It remains unclear whether EVT offers an advantage over best medical management (BMM) including thrombolysis (IVT) in isolated occlusion of the proximal posterior cerebral artery (PCAO).Methods: Patients with AIS due to PCAO proven by CT or MR angiography were retrospectively identified from local databases at four comprehensive stroke centers in Germany, USA, and Taiwan between 2012 and 2020. Demographic and clinical data were collected, and imaging characteristics including pretherapeutic, interventional, and follow-up imaging were reviewed locally at each center. Patients were grouped according to therapy, i.e., BMM including IVT alone vs. BMM and EVT. Efficacy endpoints were early neurological improvement (ENI) after 24 h or at discharge, good outcome (modified Rankin scale 0–2) after 3 months, as well as hemorrhagic complications and in-house deaths as safety endpoints.Results: We included 130 patients of whom 23 (17.7%) received EVT. EVT patients had more proximal occlusions (69.9 vs. 43%, p = 0.023) and had a better premorbid function [premorbid mRS, 0 (0–4) vs. 1 (0–3), p < 0.01] when compared to BMM patients. IVT showed a trend toward being less performed in the EVT group (21.7 vs. 41.1%, p = 0.1), while other baseline parameters were balanced. Successful reperfusion was achieved in 52% of EVT patients. ENI was more frequent in the EVT group (61 vs. 35.5%, p = 0.034). Good outcome at 90 days and safety endpoints did not differ. In a bivariate analysis, ENI was independently predicted by the use of EVT (OR, 2.76; CI, 1.055–7.04) and the baseline National Institutes of Health Stroke Scale (NIHSS) (OR, 1.082; CI, 1.027–1.141 per point increase).Discussion: EVT in isolated PCAO appears safe and feasible. Positive effects on clinical outcome are primarily on ENI but also depend on the initial stroke severity. Further prospective or randomized studies are needed to better describe the potential long-term clinical benefits of EVT for PCAO as compared with best medical management.

Supplemental Digital Content is available in the text., Background and Purpose— Computed tomography (CT) perfusion (CTP) provides potentially valuable information to guide treatment decisions in acute stroke. Assessment of interobserver reliability of CTP has, however, been limited to small, mostly single center studies. We performed a large, internet-based study to assess observer reliability of CTP interpretation in acute stroke. Methods— We selected 24 cases from the IST-3 (Third International Stroke Trial), ATTEST (Alteplase Versus Tenecteplase for Thrombolysis After Ischaemic Stroke), and POSH (Post Stroke Hyperglycaemia) studies to illustrate various perfusion abnormalities. For each case, observers were presented with noncontrast CT, maps of cerebral blood volume, cerebral blood flow, mean transit time, delay time, and thresholded penumbra maps (dichotomized into penumbra and core), together with a short clinical vignette. Observers used a structured questionnaire to record presence of perfusion deficit, its extent compared with ischemic changes on noncontrast CT, and an Alberta Stroke Program Early CT Score for noncontrast CT and CTP. All images were viewed, and responses were collected online. We assessed observer agreement with Krippendorff-α. Intraobserver agreement was assessed by inviting observers who reviewed all scans for a repeat review of 6 scans. Results— Fifty seven observers contributed to the study, with 27 observers reviewing all 24 scans and 17 observers contributing repeat readings. Interobserver agreement was good to excellent for all CTP. Agreement was higher for perfusion maps compared with noncontrast CT and was higher for mean transit time, delay time, and penumbra map (Krippendorff-α =0.77, 0.79, and 0.81, respectively) compared with cerebral blood volume and cerebral blood flow (Krippendorff-α =0.69 and 0.62, respectively). Intraobserver agreement was fair to substantial in the majority of readers (Krippendorff-α ranged from 0.29 to 0.80). Conclusions— There are high levels of interobserver and intraobserver agreement for the interpretation of CTP in acute stroke, particularly of mean transit time, delay time, and penumbra maps.

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8+ tumours formed multiple liver and spleen metastases, while Tspan8− tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8+ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. We observed increased protein levels of E‐cadherin and p120‐catenin in these EVs; furthermore, Tspan8 and p120‐catenin were co‐immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Endovascular therapy (EVT) trials enrolled ischemic stroke patients with good pre-stroke functional status. However, this information needed for rapid decision-making is commonly lacking in clinical practice. We hypothesized that initial misjudgment of pre-stroke functional status attenuates clinical outcomes of EVT. Data were derived from our prospective registry of ischemic stroke patients undergoing EVT for anterior circulation large vessel occlusion (01/2016–12/2017). Considering all information accumulated during hospital course, pre-stroke modified Rankin scale (mRS) was independently re-assessed and compared with pre-EVT assessments. Misjudgment was defined as any difference in mRS categories between first- and second-look assessments. Multivariable model was built to adjust for confounding variables of unfavorable outcome (mRS 3–6) and death at 90 days. Overall, we studied 217 patients: median age 75 years (IQR 64–81), 54% women, median NIHSS 17 (12–20) points. Second-look assessment of pre-stroke mRS revealed 73 (34%) cases initially being misjudged by ≥ 1 category and 17 (8%) by ≥ 2 categories. None of the second-look mRS assessments resulted in a lower mRS category than initially rated. Patients whose pre-stroke mRS score was misjudged prior to EVT showed more frequently unfavorable outcome (62/73 [84.9%] vs. 94/144 [65.3%], p = 0.002) or were deceased (30/73 [41.1%] vs. 25/144 [17.4%], p

Immediate freezing is perhaps the most preferred method used for preserving gut microbial samples, but research on sample preservation has been principally based around samples from mammalian species, and little is known about the advantages or disadvantages relating to different storage methods for fish guts. Fish gut samples may pose additional challenges due to the different chemical and enzymatic profile, as well as the higher water content, which might affect the yield and purity of DNA recovered. To explore this, we took gut content and mucosal scrape samples from 10 rainbow trout (Oncorhynchus mykiss), and tested whether different preservation methods have any effect on the ability to construct high quality genomic libraries for shotgun and 16S rRNA gene sequencing. Four different storage methods were compared for the gut content samples (immediate freezing on dry ice, 96% ethanol, RNAlater and DNA/RNA shield), while two different methods were compared for mucosal scrape samples (96% ethanol and RNAlater). The samples were thereafter stored at −80 °C. Our findings concluded that 96% ethanol outperforms the other storage methods when considering DNA quantity, quality, cost and labor. Ethanol works consistently well for both gut content and mucosal scrape samples, and enables construction of DNA sequencing libraries of sufficient quantity and with a fragment length distribution suitable for shotgun sequencing. Two main conclusions from our study are i) sample storage optimisation is an important part of establishing a microbiome research program in a new species or sample type system, and ii) 96% ethanol is the preferred method for storing rainbow trout gut content and mucosal scrape samples.

Aims Neoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation. Methods and results This study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1-10% VTC = 27%, 10-50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four-tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re-evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter-rater agreement, with kappa value 0.891. Conclusion Compared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.

BACKGROUND AND PURPOSE Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome. METHODS We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (

BackgroundIn the 2ndyear of the Covid-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021.MethodsThe KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4,433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys®Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N=2768) as well as leisure time activities (N=1263) were collected in summer 2020.ResultsWeighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2021 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences.ConclusionThe number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2ndwave of the pandemic. Antibodies remained present in the majority of baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Introduction: To explore kidney safety profile of osmotic diuretic mannitol in patients with malignant middle cerebral artery (MCA) infarction. Methods: We analyzed data from consecutive patients with malignant MCA infarction (01/2008-12/2017). Malignant MCA infarction was defined according to clinical and radiographic DESTINY criteria. Clinical and laboratory variables were collected for all patients. We compared clinical endpoints including acute kidney failure (AKF; according to Kidney Disease: Improving Global Outcomes [KDIGO] definition) and hemodialysis between patients who received mannitol and those who did not. Multivariable model was built to explore predictor variables of AKF, in-hospital death and functional outcome at discharge. Results: Overall, 228 patients with malignant MCA infarction were analyzed: median age 67 years (IQR, 56-76), 58% men, median NIHSS 23 (17-32) points. Decompressive craniectomy was performed in 103/228 (45.2%) patients. Mannitol was administered in 100/228 (43.9%) patients over an average of 85 (30.3-139.3) hours. Average dosage was 700 (250-1050) g. Patients treated with mannitol more frequently suffered from AKF (40% vs. 7.9%; p0.05). Conclusions: Acute kidney failure appears to be a frequent complication of osmotic diuretic mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its use should be carefully considered.

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.

Background and ObjectivesTo test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset.MethodsWe therefore performed the Retrospective Multicenter Hypoperfusion-Hypodensity Mismatch for The identification of Patients With Stroke Within 4.5 Hours study of patients with acute ischemic stroke and known time of symptom onset. The predictive values of hypoperfusion-hypodensity mismatch for the identification of patients with symptom onset within 4.5 hours were the main outcome measure.ResultsOf 666 patients, 548 (82.3%) had multimodal CT within 4.5 hours and 118 (17.7%) beyond 4.5 hours. Hypoperfusion-hypodensity mismatch was visible in 516 (94.2%) patients with symptom onset within and in 30 (25.4%) patients beyond 4.5 hours. CT hypoperfusion-hypodensity mismatch identified patients within 4.5 hours of stroke onset with 94.2% (95% confidence interval [CI] 91.9%–95.8%) sensitivity, 74.6% (95% CI 66.0%–81.6%) specificity, 94.5% (95% CI 92.3%–96.1%) positive predictive value, and 73.3% (95% CI 64.8%–80.4%) negative predictive value. Interobserver agreement for hypoperfusion-hypodensity mismatch was substantial (κ = 0.61, 95% CI 0.53–0.69).DiscussionPatients with acute ischemic stroke with absence of a hypodensity on native CT (NCCT) within the hypoperfused core lesion on perfusion CT (hypoperfusion-hypodensity mismatch) are likely to be within the time window of thrombolysis. Applying this method may guide the decision to use thrombolysis in patients with unknown time of stroke onset.Trial Registration InformationClinicalTrials.gov Identifier: NCT04277728.Classification of EvidenceThis study provides Class III evidence that CT hypoperfusion-hypodensity mismatch identifies patients with stroke within 4.5 hours of onset.

ObjectiveTo investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO).MethodsTo determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated.ResultsWe included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7–32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3–12; p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40–71] minutes) vs alteplase-treated patients (110 [IQR 51–185] minutes; p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; p = 0.9).ConclusionsTNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted.Clinicaltrials.gov IdentifiersNCT02388061 and NCT03340493.Classification of EvidenceThis study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.

Background: Population-based studies investigating the dynamics of the SARS-CoV-2 pandemic are needed. Here, we report on baseline findings from April through June 2020 of a prospective cohort study in Munich, Germany. Methods: We drew a representative sample of 2994 private households. The 5313 participating household members 14 years and older completed questionnaires and provided blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0·4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Findings: Seropositivity for SARS-CoV-2 specific antibodies was 1·82% (95% confidence interval (CI) 1·28-2·37%) as compared to 0·46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47·4; 95% CI 7·2-307·0) and infections clustered within households. Participants suffering from respiratory allergies (OR 2·7; 95% CI 0·9-8·6) and working in high-risk jobs (OR 2·0; 95% CI 0·5-6·7) showed non-significantly increased odds for SARS-CoV-2 seropositivity. Interpretation: Applying a validated assay, we demonstrate a low SARS-CoV-2 seroprevalence in the Munich population 14 years and older towards the end of the first pandemic wave. However, we noted official sub-registration at this early stage of the pandemic. Funding: Bavarian State Ministry of Science and the Arts, University Hospital of LMU Munich, Helmholtz Centre Munich, University of Bonn, and University of Bielefeld. Declaration of Interests: FF, TF, DM, LO, and VT report grants from the Bavarian State Ministry of Science and the Arts during the conduct oft he study. TF reports grants from the University Hospital of LMU Munich, Helmholtz Center Munich, University of Bonn, University of Bielefeld, and German Ministry for Education and Research during the conduct of the study. JH reports grants from the German Federal Ministry of Education and Research during the conduct of the study. MH and AW report personal fees and non-financial support, LO and MP report non-financial support from Roche Diagnostics. MH, LO, MP, and AW report non-financial support from Euroimmun, Viramed, and Mikrogen. MH, MP, and AW report grants, non-financial support, and other from German Center for Infection Research (DZIF). FF, MH, LO, MP, VT, and AW report grants and non-financial support from the Government of Bavaria. MH, LO, MP, and AW report non-financial support from BMW, Mercedes Benz, Munich Police, and Accenture. MH and AW report personal fees and non-financial support from Dr. Box Betrobox during the conduct of the study. LO and MP report non-financial support from Dr. Box Betrobox. MH and AW have a patent Sample System for Sputum Diagnostics of SARS-CoV-2 pending. DM reports to be a a sub-investigator on a Phase I SARS-CoV-2 vaccine trial and on a Phase I rabies vaccine trial, both sponsored by CureVac AG. MP and AW report non-financial support from Dr. Becker MVZ. VT reports support from CureVac AG outside the submitted work. AW reports personal fees and other from Haeraeus Sensors. AW reports non-financial support from Bruker Daltronics outside the submitted work. AW is involved in other different patents and companies not in relation with the serology of SARS-CoV-2. All other authors report nothing to disclose. Ethics Approval Statement: Prior to study initiation, this study had been approved by the respective Institutional Review Board.

BackgroundSerosurveys are essential to understand SARS-CoV-2 exposure and enable population-level surveillance, but currently available tests need further in-depth evaluation. We aimed to identify testing-strategies by comparing seven seroassays in a population-based cohort.MethodsWe analysed 6,658 samples consisting of true-positives (n=193), true-negatives (n=1,091), and specimens of unknown status (n=5,374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2; and virus-neutralisation, GeneScript®cPass™, VIRAMED-SARS-CoV-2-ViraChip®, and Mikrogen-recomLine-SARS-CoV-2-IgG, including common-cold CoVs, for confirmatory testing. Statistical modelling generated optimised assay cut-off-thresholds.FindingsSensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3%; for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer’s/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median titres remained stable for at least 90-120 days after RT-PCR-positivity. Of true-positives with positive RT-PCR (recomLine-RBD) were >94.9% sensitive, >98.1% specific. Seasonality had limited effects; cross-reactivity with common-cold CoVs 229E and NL63 in SARS-CoV-2 true-positives was significant.ConclusionOptimised cut-offs improved test performances of several tests. Non-reactive serology in true-positives was uncommon. For epidemiological purposes, confirmatory testing with virus-neutralisation may be replaced with GeneScript®cPass™ or recomLine-RBD. Head-to-head comparisons given here aim to contribute to the refinement of testing-strategies for individual and public health use.

To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction.We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death.Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p 0.001).Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered.

Background and purpose Basilar artery occlusion (BAO) leads to high rates of morbidity and mortality, despite successful recanalization. The discordance between flow restoration and long-term functional status clouds clinical decision-making regarding further aggressive care. We sought to develop and validate a practical, prognostic tool for the prediction of 3-month favorable outcome after acute reperfusion therapy for BAO. Methods This retrospective, multicenter, observational study was conducted at four high-volume stroke centers in the USA and Europe. Multivariate regression analysis was performed to identify predictors of favorable outcome (90-day modified Rankin scale scores 0-2) and derive a clinically applicable prognostic model (the Pittsburgh Outcomes after Stroke Thrombectomy-Vertebrobasilar (POST-VB) score). The POST-VB score was evaluated and internally validated with regard to calibration and discriminatory ability. External validity was assessed in patient cohorts at three separate centers. Results In the derivation cohort of 59 patients, independent predictors of favorable outcome included smaller brainstem infarct volume on post-procedure magnetic resonance imaging (P = 125. Conclusions The POST-VB score effectively predicts 3-month functional outcome following acute reperfusion therapy for BAO and may aid in guiding post-procedural care.

Posttraumatic stress disorder (PTSD) during pregnancy is a significant global mental health concern that affects up to 1 in 5 trauma-exposed pregnant women and is associated with an increased risk of adverse maternal and infant complications and health outcomes. This systematic literature review, conducted in accordance with PRISMA guidelines, examined findings from studies of psychological interventions and treatments for prenatal PTSD to inform recommendations for future research. Relevant evidence was identified from reference reviews and electronic databases (i.e., PubMed, Google Scholar, PsychInfo, and Scopus). Included studies reported on the effect of nonpharmacological intervention or treatment of PTSD symptomatology delivered during pregnancy, with at least one postintervention follow-up collected during pregnancy to assess prenatal treatment outcomes. The systematic review was augmented with a discussion of lower-level evidence. Of the 954 articles screened, six peer-reviewed, quantitative reports met the inclusion criteria and featured three empirically based interventions, including two randomized controlled trials: Two psychoeducation interventions for PTSD and one treatment study of interpersonal psychotherapy in trauma-exposed pregnant women. Effect sizes for PTSD symptom change ranged from small to large, Cohen's d/ηp2 = 0.16-0.78. No studies examined evidence-based PTSD treatments (e.g., exposure therapy, cognitive processing therapy). A risk of bias assessment indicated variability in study quality. This review demonstrates that research on prenatal PTSD symptoms, diagnosis, and treatment is extremely limited despite a clear link between prenatal PTSD and perinatal complications. Early evidence supports further scientific inquiry into psychoeducation, psychotherapy treatments (e.g., exposure therapy), integrated prenatal care approaches, and community-based approaches.

Key Points Question What is the effect of electroacupuncture vs sham treatment on pain severity in adults with chronic low back pain? Findings In this randomized clinical trial including 121 adults with chronic low back pain, there was no significant difference between real and sham electroacupuncture conditions in reduction in pain scores 2 weeks after treatment; however, real electroacupuncture resulted in statistically and clinically greater reduction in back pain–specific disability compared with the sham control. Having coping strategies and not being White race were associated with treatment response to real electroacupuncture. Meaning This randomized clinical trial found no difference in pain reduction between real and sham electroacupuncture, but there was greater reduction in back pain–specific disability compared with sham control., This randomized clinical trial examines real vs sham electropuncture in treating chronic low back pain in adults., Importance Chronic low back pain has high societal and personal impact but remains challenging to treat. Electroacupuncture has demonstrated superior analgesia compared with placebo in animal studies but has not been extensively studied in human chronic pain conditions. Objective To evaluate the treatment effect of real electroacupuncture vs placebo in pain and disability among adults with chronic low back pain and to explore psychophysical, affective, and demographic factors associated with response to electroacupuncture vs placebo in treating chronic low back pain. Design, Setting, and Participants This double-blind randomized clinical trial was conducted between August 2, 2016, and December 18, 2018, at a single center in Stanford, California. Primary outcomes were collected at approximately 2 weeks before and after intervention. Participants included English-speaking adults with at least 6 months of chronic low back pain, pain intensity of at least 4 on a scale of 0 to 10, and no radiculopathy. Data analyses for this intent-to-treat study were conducted from June 2019 to June 2020. Interventions Twelve sessions of real or placebo (sham) electroacupuncture administered twice a week over 6 weeks. Main Outcomes and Measures The main outcome was change in pain severity from baseline to 2 weeks after completion of treatment, measured by the National Institutes of Health PROMIS pain intensity scale. A secondary outcome was change in the Roland Morris Disability Questionnaire (RMDQ). Baseline factors potentially associated with these outcomes included psychophysical testing (ie, thermal temporal summation, conditioned pain modulation, pressure pain threshold), participant’s self-report (ie, widespread pain, coping strategies, expectations, self-efficacy, and pain catastrophizing), and demographic characteristics (eg, age, sex, and race). Results A total of 121 adults were recruited to the study, among whom 59 participants (mean [SD] age, 46.8 [11.9] years; 36 [61.0%] women) were randomized to real electroacupuncture and 62 participants (mean [SD] age, 45.6 [12.8] years; 33 [53.2%] women) were randomized to sham electroacupuncture. At baseline, the mean (SD) PROMIS T-score was 50.49 (3.36) in the real electroacupuncture group and 51.71 (4.70) in the sham acupuncture group, and the mean (SD) RMDQ score was 10.16 (4.76) in the real electroacupuncture group and 10.03 (5.45) in the sham acupuncture group. After adjusting for baseline pain scores, there was no statistically significant difference between groups in change in T-scores 2 weeks after completion of treatment (real electroacupuncture: −4.33; 95% CI, −6.36 to −2.30; sham acupuncture: −2.90; 95% CI, −4.85 to −0.95; difference: −2.09; 95% CI, −4.27 to 0.09; P = .06). After adjusting for baseline RMDQ, there was a significantly greater reduction in RMDQ in the real electroacupuncture group (−2.77; 95% CI, −4.11 to −1.43) compared with the sham electroacupuncture group (−0.67; 95% CI, −1.88 to 0.55; difference: −2.11; 95% CI, −3.75 to −0.47; P = .01). Within the real electroacupuncture group, effective coping at baseline was associated with greater RMDQ reduction (r = −0.32; 95% CI, −0.54 to −0.05; P = .02), and White race was associated with worse outcomes in PROMIS score (β = 3.791; 95% CI, 0.616 to 6.965; P = .02) and RMDQ (β = 2.878; 95% CI, 0.506 to 5.250; P = .02). Conclusions and Relevance This randomized clinical trial found no statistically significant difference in change in PROMIS pain score in real electroacupuncture vs sham electroacupuncture. There was a statistically significant treatment effect for the secondary outcome of RMDQ compared with sham electroacupuncture. Effective coping skills and non-White race were associated with response to electroacupuncture. Trial Registration ClinicalTrials.gov Identifier: NCT02890810

Highlights • Despite rigorous universal testing in a protected code stroke protocol, none of the consecutive 116 stroke patients tested were positive for SARS-CoV-2. • Universal testing did not adversely affect hyperacute stroke care. • Information on SARS-CoV-2 status can be used to guide protective measures in patients with acute stroke., Objective Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. Methods Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. Results During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). Conclusions Universal laboratory testing for SARS-CoV-2 provided useful information on patients’ infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Assessing the status and distribution of fish populations in rivers is essential for management and conservation efforts in these dynamic habitats. Currently, methods detecting environmental DNA (eDNA) are being established as an alternative and/or complementary approach to the traditional monitoring of fish species. In lotic systems, a sound understanding of hydrological conditions and their influence on the local target detection probability and DNA quantity is key for the interpretation of eDNA-based results. However, the effect of seasonal and diurnal changes in discharge and the comparability of semi-quantitative results between species remain hardly addressed. We conducted a cage experiment with four fish species (three salmonid and one cyprinid species) in a glacier-fed, fish-free river in Tyrol (Austria) during summer, fall, and winter discharge situations (i.e. 25-fold increase from winter to summer). Each season, water samples were obtained on three consecutive days at 13 locations downstream of the cages including lateral sampling every 1-2 m across the wetted width. Fish eDNA was quantified by species-specific endpoint PCR followed by capillary electrophoresis. Close to the cages, lateral eDNA distribution was heterogenous and mirrored cage placement within the stream. In addition to the diluting effect of increased discharge, longitudinal signal changes within the first 20 m were weakest at high discharge. For downstream locations with laterally homogenous eDNA distribution, the signals decreased significantly with increasing distance and discharge. Generally, the eDNA of the larger-bodied salmonid species was less frequently detected, and signal strengths were lower compared to the cyprinid species. This study exemplifies the importance of hydrological conditions for the interpretation of eDNA-based data across seasons. To control for heterogenous eDNA distribution and enable comparisons over time, sampling schemes in lotic habitats need to incorporate hydrological conditions and species traits.

Background: Tenecteplase (TNK) is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase. The recent Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial demonstrated that increased reperfusion with TNK compared to alteplase prior to endovascular thrombectomy (EVT) in large vessel occlusion ischaemic strokes. However, only 6 patients with basilar artery occlusion (BAO) were included. We aimed to investigate the efficacy of TNK versus alteplase before EVT in patients with basilar artery occlusion (BAO). Methods: Clinical and procedural data of consecutive BAO diagnosed on CT Angiography or MR Angiography from the multisite international Basilar Artery Treatment and MANagement (BATMAN) collaboration were retrospectively analysed. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or absence of retrievable thrombus at the time of the initial angiographic assessment. Results: We included 119 BAO patients treated with intravenous thrombolysis prior to EVT; mean age 68 (SD 14), median NIHSS 16 (IQR 7-32). Eleven patients were treated with TNK (0.25mg/kg or 0.4mg/kg) and 108 with alteplase (0.9mg/kg). Overall, 113 patients had catheter angiography or early repeat imaging after thrombolysis. Reperfusion of greater than 50% of the ischemic territory or absence of retrievable thrombus occurred in 4/11 (36%) of patients treated with TNK vs 8/102 (8%) treated with alteplase (p=0.02). Onset-to-needle time did not differ between the two groups (p=0.4). Needle-to-groin-puncture time was 61 (IQR 33-100) mins in patients reperfused with TNK vs 111 (IQR 86-198) mins in patients reperfused with alteplase (p=0.048). Overall, the rate of symptomatic haemorrhage was 3/119 (2.5%). No differences were found in the rate of symptomatic intracranial haemorrhage (p=0.3) between the two thrombolytic agents. Conclusions: Despite shorter needle-to-groin-puncture times, tenecteplase was associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare tenecteplase with alteplase in BAO patients before endovascular thrombectomy are warranted.

Introduction: Hypothermia may be neuroprotective in acute ischemic stroke. Stroke patients with anterior circulation large vessel occlusion (acLVO) who receive endovascular therapy (EVT) are frequently hypothermic after the procedure. We sought to analyze whether this unintended hypothermia was associated with improved functional outcome. Methods: We extracted data of consecutive patients (01/2016-04/2019) from our prospective EVT database that includes all patients screened for EVT at our center. We included patients with acLVO who received EVT and analyzed recanalization (mTICI 2b-3) and complications (i.e., pneumonia, bradyarrhythmia, venous thromboembolism) during the hospital course. We assessed functional outcome at 3 months and analyzed risk ratios (RR) for good outcome (mRS scores 0-2) and mortality of patients who were hypothermic (> 36°C) after EVT. We compared the frequency of complications and calculated RRs for good outcome and mortality in the subgroup with recanalization. Results: Among 674 patients with anterior circulation ischemic stroke, 372 patients received EVT for acLVO (178 [47%] male, age 77 years [65-82], NIHSS score 16 [12 - 20]). Of these, 186 patients (50%) were hypothermic (median [IQR] temperature 35.2°C [34.7-35.6]) and 186 patients were normothermic (media temperature 36.4 [36.2-36.8]) after EVT. At 3 months, 54 of 186 (29.0%) hypothermic patients compared with 65 of 186 (35.0%) normothermic patients had a good outcome (RR, 0.83; 95%CI 0.62-1.12) and 52 of 186 (27.9%) hypothermic patients compared with 46 of 186 (24.7%) normothermic patients had died (RR, 1.13; 95%CI 0.8-1.59). This relation was consistent in 307 patients (82.5% of all EVTs) with successful recanalization (good outcome: RR, 0.85; 95%CI 0.63-1.14.; mortality: RR, 1.05; 95%CI 0.7-1.57). More hypothermic patients suffered pneumonia (37.8% vs. 24.7%; p=0.003) or bradyarrhythmia (55.6% vs. 18.3%; p Conclusion: Unintended hypothermia following EVT for acLVO was not associated with improved functional outcome or reduced mortality but an increased complication rate in patients with acute ischemic stroke.

Introduction: In patients with acute ischaemic stroke (AIS) dysregulation of cardiac function with decreased heart rate variability (HRV) due to impaired integrity of the autonomic nervous system is a frequent complication which is associated with increased mortality and worsening of clinical outcome. HRV biofeedback has previously been suggested to improve cardiac autonomic function by increasing parasympathetic tone. Hypothesis: We hypothesized that HRV biofeedback can be used to complement stroke unit care and alleviate autonomic cardiac dysfunction following AIS. Methods: We randomly allocated patients with AIS to either receive 9 sessions of HRV (n=24) or sham (n=24) biofeedback in addition to standard stroke unit care. These patients underwent detailed assessment of autonomic cardiac function including analysis of HRV via standard deviation of NN intervals (SDNN) and spectral analysis. Furthermore, we assessed vasomotor and sudomotor autonomic function, severity of autonomic symptoms and neurological and functional outcomes. Results: We included 48 patients (19 females, ages 65±14 years, baseline NIHSS 2.2 ± 2.2, mean ± standard deviation). Patients who had undergone HRV biofeedback displayed improved cardiac function compared to baseline (SDNN 72.6 ± 52.4 ms vs. 45.5 ± 34.7 ms, p Discussion: HRV biofeedback can modulate autonomic cardiac function post AIS to increase HRV and alleviate autonomic symptoms which might be beneficial in facilitating recovery from functional impairment. This seems to be mediated by a predominantly parasympathetic mechanism of action.

Impedance-based monitoring of cell-based assays has evolved to a multi-functional tool in fundamental and applied biomedical research. The majority of studies rely on gold-films as the electrode material which serves as growth surface and electrode at a time. Besides all its favorable properties like inertness, biocompatibility and superior electrochemical characteristics, gold-film electrodes in contact to cell culture medium show a capacitance of the electrode/electrolyte interface that may become limiting for the sensitivity of the readout. This study describes the use of laser-scribed graphene (LSG) as an alternative electrode material in impedance-based cell monitoring. LSG electrodes are prepared from commercial polyimide foils by simple CO2-laser-induced carbonization. The resulting electrodes show a 25times larger interface capacitance than standard gold-film electrodes due to their foam-like surface topography. Furthermore, LSG-electrodes are (i) highly compatible with cell attachment, (ii) easy to prepare in customized geometries from μm to cm with tunable surface topography and (iii) accessible by roll-to-roll production lines. We conclude from time- and frequency dependent impedance measurements of cell-covered LSG electrodes in direct comparison to the reference material gold that LSG provides an enormous potential to improve the sensitivity of impedance-based monitoring and electric-field mediated manipulation of adherent cells.

Background and purpose Safety and efficacy of intravenous (IV) thrombolysis and endovascular therapy in children with acute ischemic stroke (AIS) are unknown to date. We aimed to review and synthesize currently available evidence on these acute recanalization therapies in pediatric stroke patients. Methods We performed a systematic review and meta-analysis of all available data on safety and efficacy of acute treatment including thrombolysis and endovascular therapy in pediatric AIS patients aged Results We identified 222 records, of which 3 studies with a total of 16,987 pediatric stroke patients met our eligibility criteria of whom 181 received IV thrombolysis. No data exists from randomized trials and no data is available on endovascular thrombectomy. Risk of any ICH was increased in children receiving thrombolysis (risk ratio = 3.48, 95%CI: 1.66–7.29; p = 0.001) compared with controls, with no evidence of heterogeneity (I2 = 0%). None of the included studies reported complete data on symptomatic ICH. In-hospital mortality was similar between pediatric stroke patients treated with thrombolysis and controls (risk ratio = 1.44, 95%CI: 0.39–5.40; p = 0.586), with evidence of heterogeneity (I2 = 62%). Efficacy of revascularization therapies could not be analyzed due to lack of outcome data. Conclusions Our analyses demonstrate a substantial lack of data on efficacy and safety of acute recanalization therapies in children with AIS. PROSPERO Registration Information URL: http://www.crd.york.ac.uk/PROSPERO . Unique identifier: CRD42016047140.

The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS-angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.ZIEL: Die multiparametrischen Ultraschallkriterien zur Graduierung von Karotisstenosen der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) wurden revidiert, bislang aber nicht mit dem Goldstandard Angiografie validiert. Ziel dieser prospektiven multizentrischen Validierungsstudie war es, die diagnostische Güte der DEGUM Ultraschallkriterien zu bestimmen. An vier Zentren wurden konsekutive Patienten eingeschlossen, bei denen routinemäßig eine digitale Subtraktionsangiografie (DSA) der extrakraniellen Arteria carotis interna (ACI) durchgeführt wurde. Die Graduierung des Stenosegrades der ACI erfolgte verblindet gemäß der multiparametrischen DEGUM Ultraschallkriterien. Angiografisch erfolgte die verblindete Stenosegraduierung entsprechend der NASCET Definition. Endpunkte umfassten die Gesamttrefferquote zur Vorhersage von Stenosen in vorgegebenen DEGUM Stenoseintervallen, Vorhersage von klinisch relevanten Stenosekategorien und diagnostische Übereinstimmung beider Methoden im kontinuierlichen Stenosebereich. Von insgesamt 121 rekrutierten Patienten (mittleres Alter, 69 [IQR, 16] Jahre, 74 % Männer, mediane Zeit zwischen Duplexsonografie und DSA, 1 Tag [IQR, 2]) ergaben sich 163 Duplex-DSA Gefäßpaare für die Validierung. Die Gesamttrefferquote der DEGUM-Ultraschallkriterien zur Vorhersage des Stenosegrades innerhalb von 10 % -Schritten im Vergleich zur DSA betrug 34,9 % (95 % CI, 28,0 – 42,6). Die Sensitivität der Ultraschallkriterien für den Nachweis von mittelgradigen (50 – 69 %) und hochgradigen (70 – 99 %) Stenosen betrug 35 % und 81 % mit einer Gesamtgenauigkeit von 73 % und 74 %. Die Spezifität betrug 89 % und 69 %. Der Bland-Altman-Übereinstimmungsbereich zwischen beiden Methoden betrug 51 %. In der Identifikation von klinisch relevanten Stenosekategorien der ACI beseitigen die multiparametrischen DEGUM Ultraschallkriterien nicht die Notwendigkeit eines vaskulären Bestätigungstestes.

BACKGROUND AND PURPOSE The aim was to determine the predictors of focal hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute posterior circulation stroke and its association with long-term outcome. METHODS Patients with posterior circulation stroke were selected from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as an area of visually well demarcated mean transit time prolongation corresponding to an arterial territory on standard reconstruction CTP imaging maps. Areas of hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis Early CT Score. Clinical and imaging associations with focal hypoperfusion were identified using multiple imputation analyses, and the adjusted functional outcome measured by the modified Rankin Scale at 3 and 12 months was determined. RESULTS Of the 3595 consecutive patients from the ASTRAL registry between 2003 and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic changes and 37.4% had focal hypoperfusion. In multiple imputation analysis, visual field deficits, reduced level of consciousness, cardiac and multiple stroke mechanisms, significant vessel pathology and ischaemic changes visible on plain CT were associated with focal hypoperfusion. Focal hypoperfusion was independently associated with outcome at 12 months (odds ratio 2.04, 95% confidence interval 1.22-3.42, P