How much of the variance in functional outcome related to intracerebral hemorrhage volume is already apparent in neurological status at admission?

BACKGROUND: Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model. METHODS: Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration. RESULTS: Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement. CONCLUSION: NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation.

Predictors of severe intracerebral hemorrhage expansion.

BACKGROUND: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE. METHODS: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression. RESULTS: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01-1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09-4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89-0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93-0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02-1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00-1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51). CONCLUSIONS: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH.

Functional outcome improvement from 3 to 12 months after intracerebral hemorrhage.

INTRODUCTION: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH. MATERIALS AND METHODS: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression. RESULTS: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96-1.00, p = 0.017 and OR 0.45, 95% CI 0.25-0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07-2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2-3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68-20.86, p < 0.001). DISCUSSION AND CONCLUSION: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.

Predictors and Prognostic Impact of Hematoma Expansion in Infratentorial Cerebral Hemorrhage.

BACKGROUND: Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH. METHODS: We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast computed tomography images were analyzed for the presence of hypodensities according to validated criteria, defined as any hypodense region strictly encapsulated within the hemorrhage with any shape, size, and density. Occurrence of HE (defined as > 33% and/or > 6-mL growth) and mortality at 90 days were the outcomes of interest. Their predictors were investigated using logistic regression with backward elimination at p < 0.1. Logistic regression models for HE were adjusted for baseline ICH volume, antiplatelet and anticoagulant treatment, onset to computed tomography time, and presence of hypodensities. The logistic regression model for mortality accounted for the ICH score and HE. RESULTS: A total of 175 patients were included (median age 75 years, 40.0% male), of whom 38 (21.7%) had HE and 43 (24.6%) died within 90 days. Study participants with HE had a higher frequency of hypodensities (44.7 vs. 24.1%, p = 0.013), presentation within 3 h from onset (39.5 vs. 24.8%, p = 0.029), and 90-day mortality (44.7 vs. 19.0%, p = 0.001). Hypodensities remained independently associated with HE after adjustment for confounders (odds ratio 2.44, 95% confidence interval 1.13-5.25, p = 0.023). The association between HE and mortality remained significant in logistic regression (odds ratio 3.68, 95% confidence interval 1.65-8.23, p = 0.001). CONCLUSION: Early presentation and presence of noncontrast computed tomography hypodensities were independent predictors of HE in infratentorial ICH, and the occurrence of HE had an independent prognostic impact in this population.

Association Between Hematoma Expansion Severity and Outcome and Its Interaction With Baseline Intracerebral Hemorrhage Volume.

BACKGROUND AND OBJECTIVES: Hematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE. METHODS: This was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States. All patients underwent baseline and follow-up imaging for HE assessment. Relative HE (rHE) was classified as follows: none (<0%), mild (0%-33%), moderate (33.1%-66%), and severe (>66%). Absolute HE (aHE) was classified as none (<0 mL), mild (0-6.0 mL), moderate (6.1-12.5 mL), and severe (>12.5 mL). Predictors of poor functional outcome (90 days modified Rankin Scale 4-6) were explored with logistic regression. RESULTS: We included 2,163 patients, of whom 1,211 (56.0%) had poor outcome. The occurrence of severe aHE or rHE was more common in patients with unfavorable outcome (13.9% vs 6.5%, p < 0.001 and 18.3% vs 7.2%, p < 0.001 respectively). This association was confirmed in logistic regression (rHE odds ratio [OR] 1.98, 95% CI 1.38-2.82, p < 0.001; aHE OR 1.73, 95% CI 1.23-2.45, p = 0.002) while there was no association between mild or moderate HE and poor outcome. The association between severe HE and poor outcome was significant only in patients with baseline ICH volume below 30 mL. DISCUSSION: The strongest association between HE and outcome was observed in patients with smaller initial volume experiencing severe HE. These findings may inform clinical trial design and guide clinicians in selecting patients for antiexpansion therapies.

External Validation and Retraining of DeepBleed: The First Open-Source 3D Deep Learning Network for the Segmentation of Spontaneous Intracerebral and Intraventricular Hemorrhage.

BACKGROUND: The objective of this study was to assess the performance of the first publicly available automated 3D segmentation for spontaneous intracerebral hemorrhage (ICH) based on a 3D neural network before and after retraining. METHODS: We performed an independent validation of this model using a multicenter retrospective cohort. Performance metrics were evaluated using the dice score (DSC), sensitivity, and positive predictive values (PPV). We retrained the original model (OM) and assessed the performance via an external validation design. A multivariate linear regression model was used to identify independent variables associated with the model's performance. Agreements in volumetric measurements and segmentation were evaluated using Pearson's correlation coefficients (r) and intraclass correlation coefficients (ICC), respectively. With 1040 patients, the OM had a median DSC, sensitivity, and PPV of 0.84, 0.79, and 0.93, compared to thoseo f 0.83, 0.80, and 0.91 in the retrained model (RM). However, the median DSC for infratentorial ICH was relatively low and improved significantly after retraining, at p < 0.001. ICH volume and location were significantly associated with the DSC, at p < 0.05. The agreement between volumetric measurements (r > 0.90, p > 0.05) and segmentations (ICC ≥ 0.9, p < 0.001) was excellent. CONCLUSION: The model demonstrated good generalization in an external validation cohort. Location-specific variances improved significantly after retraining. External validation and retraining are important steps to consider before applying deep learning models in new clinical settings.

Non-contrast computed tomography features predict intraventricular hemorrhage growth.

OBJECTIVES: Non-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth. METHODS: Patients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models. RESULTS: A total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16-2.44]; p = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48-2.64]; p = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91-3.53]; p = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion. CONCLUSIONS: NCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies. CLINICAL RELEVANCE STATEMENT: Non-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies. KEY POINTS: • NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences. • The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion. • Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19 : Results of a retrospective multicenter neuroimaging-based study from three central European countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. MATERIALS AND METHODS: Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. RESULTS: 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. DISCUSSION: AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.

External validation of the diagnostic value of perihematomal edema characteristics in neoplastic and non-neoplastic intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Neoplastic intracerebral hemorrhage (ICH) may be incorrectly identified as non-neoplastic ICH on imaging. Relative perihematomal edema (relPHE) on computed tomography (CT) has been proposed as a marker to discriminate neoplastic from non-neoplastic ICH but has not been externally validated. The purpose of this study was to evaluate the discriminatory power of relPHE in an independent cohort. METHODS: A total of 291 patients with acute ICH on CT and follow-up magnetic resonance imaging (MRI) were included in this single-center retrospective study. ICH subjects were dichotomized into non-neoplastic or neoplastic ICH based on the diagnosis on the follow-up MRI. ICH and PHE volumes and density values were derived from semi-manually segmented CT scans. Calculated PHE characteristics for discriminating neoplastic ICH were evaluated using receiver-operating characteristic (ROC) curves. ROC curve-associated cut-offs were calculated and compared between the initial and the validation cohort. RESULTS: A total of 116 patients (39.86%) with neoplastic ICH and 175 (60.14%) with non-neoplastic ICH were included. Median PHE volumes, relPHE, and relPHE adjusted for hematoma density were significantly higher in subjects with neoplastic ICH (all p values <0.001). ROC curves for relPHE had an area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.66-0.78) and an AUC of 0.81 (95% CI 0.76-0.87) for adjusted relPHE. The cut-offs were identical in the two cohorts, with >0.70 for relPHE and >0.01 for adjusted relPHE. CONCLUSIONS: Relative perihematomal edema and adjusted relPHE accurately discriminated neoplastic from non-neoplastic ICH on CT imaging in an external patient cohort. These results confirmed the findings of the initial study and may improve clinical decision making.

Using Noncontrast Computed Tomography to Improve Prediction of Intracerebral Hemorrhage Expansion.

BACKGROUND: Noncontrast computed tomography hypodensities are a validated predictor of hematoma expansion (HE) in intracerebral hemorrhage and a possible alternative to the computed tomography angiography (CTA) spot sign but their added value to available prediction models remains unclear. We investigated whether the inclusion of hypodensities improves prediction of HE and compared their added value over the spot sign. METHODS: Retrospective analysis of patients admitted for primary spontaneous intracerebral hemorrhage at the following 8 university hospitals in Boston, US (1994-2015, prospective), Hamilton, Canada (2010-2016, retrospective), Berlin, Germany (2014-2019, retrospective), Chongqing, China (2011-2015, retrospective), Pavia, Italy (2017-2019, prospective), Ferrara, Italy (2010-2019, retrospective), Brescia, Italy (2020-2021, retrospective), and Bologna, Italy (2015-2019, retrospective). Predictors of HE (hematoma growth >6 mL and/or >33% from baseline to follow-up imaging) were explored with logistic regression. We compared the discrimination of a simple prediction model for HE based on 4 predictors (antitplatelet and anticoagulant treatment, baseline intracerebral hemorrhage volume, and onset-to-imaging time) before and after the inclusion of noncontrast computed tomography hypodensities, using receiver operating characteristic curve and De Long test for area under the curve comparison. RESULTS: A total of 2465 subjects were included, of whom 664 (26.9%) had HE and 1085 (44.0%) had hypodensities. Hypodensities were independently associated with HE after adjustment for confounders in logistic regression (odds ratio, 3.11 [95% CI, 2.55-3.80]; P<0.001). The inclusion of noncontrast computed tomography hypodensities improved the discrimination of the 4 predictors model (area under the curve, 0.67 [95% CI, 0.64-0.69] versus 0.71 [95% CI, 0.69-0.74]; P=0.025). In the subgroup of patients with a CTA available (n=895, 36.3%), the added value of hypodensities remained statistically significant (area under the curve, 0.68 [95% CI, 0.64-0.73] versus 0.74 [95% CI, 0.70-0.78]; P=0.041) whereas the addition of the CTA spot sign did not provide significant discrimination improvement (area under the curve, 0.74 [95% CI, 0.70-0.78]). CONCLUSIONS: Noncontrast computed tomography hypodensities provided a significant added value in the prediction of HE and appear a valuable alternative to the CTA spot sign. Our findings might inform future studies and suggest the possibility to stratify the risk of HE with good discrimination without CTA.

Multilesion Segmentations in Patients with Intracerebral Hemorrhage: Reliability of ICH, IVH and PHE Masks.

Background and Purpose: Fully automated methods for segmentation and volume quantification of intraparenchymal hemorrhage (ICH), intraventricular hemorrhage extension (IVH), and perihematomal edema (PHE) are gaining increasing interest. Yet, reliabilities demonstrate considerable variances amongst each other. Our aim was therefore to evaluate both the intra- and interrater reliability of ICH, IVH and PHE on ground-truth segmentation masks. Methods: Patients with primary spontaneous ICH were retrospectively included from a German tertiary stroke center (Charité Berlin; January 2016−June 2020). Baseline and follow-up non-contrast Computed Tomography (NCCT) scans were analyzed for ICH, IVH, and PHE volume quantification by two radiology residents. Raters were blinded to all demographic and outcome data. Inter- and intrarater agreements were determined by calculating the Intraclass Correlation Coefficient (ICC) for a randomly selected set of patients with ICH, IVH, and PHE. Results: 100 out of 670 patients were included in the analysis. Interrater agreements ranged from an ICC of 0.998 for ICH (95% CI [0.993; 0.997]), to an ICC of 0.979 for IVH (95% CI [0.984; 0.993]), and an ICC of 0.886 for PHE (95% CI [0.760; 0.938]), all p-values < 0.001. Intrarater agreements ranged from an ICC of 0.997 for ICH (95% CI [0.996; 0.998]), to an ICC of 0.995 for IVH (95% CI [0.992; 0.996]), and an ICC of 0.980 for PHE (95% CI [0.971; 0.987]), all p-values < 0.001. Conclusion Manual segmentations of ICH, IVH, and PHE demonstrate good-to-excellent inter- and intrarater reliabilities, with the highest agreement for ICH and IVH and lowest for PHE. Therefore, the degree of variances reported in fully automated quantification methods might be related amongst others to variances in ground-truth masks.

Association Between Net Water Uptake and Functional Outcome in Patients With Low ASPECTS Brain Lesions: Results From the I-LAST Study.

BACKGROUND AND OBJECTIVES: The effect of mechanical thrombectomy (MT) on functional outcome in patients with ischemic stroke with low ASPECTS is still uncertain. ASPECTS rating is based on the presence of ischemic hypoattenuation relative to normal; however, the degree of hypoattenuation, which directly reflects net uptake of water, is currently not considered an imaging biomarker in stroke triage. We hypothesized that the effect of thrombectomy on functional outcome in low ASPECTS patients depends on early lesion water uptake. METHODS: For this multicenter observational study, patients with anterior circulation stroke with ASPECTS ≤5 were consecutively analyzed. Net water uptake (NWU) was assessed as a quantitative imaging biomarker in admission CT. The primary end point was the rate of favorable functional outcome defined as modified Rankin Scale score 0-3 at day 90. The effect of recanalization on functional outcome was analyzed according to the degree of NWU within the early infarct lesion. RESULTS: A total of 254 patients were included, of which 148 (58%) underwent MT. The median ASPECTS was 4 (interquartile range [IQR] 3-5), and the median NWU was 11.4% (IQR 8.9%-15.1%). The rate of favorable outcome was 27.6% in patients with low NWU (<11.4%) vs 6.3% in patients with high NWU (≥11.4%; p < 0.0001). In multivariable logistic regression analysis, NWU was an independent predictor of outcome, whereas vessel recanalization (modified thrombolysis in cerebral infarction ≥2b) was only significantly associated with better outcomes if NWU was lower than 12.6%. In inverse-probability weighting analysis, recanalization was associated with 20.7% (p = 0.01) increase in favorable outcome in patients with low NWU compared with 9.1% (p = 0.06) in patients with high NWU. DISCUSSION: Early NWU was independently associated with clinical outcome and might serve as an indicator of futile MT in low ASPECTS patients. NWU could be tested as a tool to select low ASPECTS patients for MT. TRIAL REGISTRATION INFORMATION: The study is registered within the ClinicalTrials.gov Protocol Registration and Results System (NCT04862507).

Non-contrast CT markers of intracerebral hemorrhage expansion: The influence of onset-to-CT time.

BACKGROUND: Hematoma expansion (HE) is an appealing therapeutic target in intracerebral hemorrhage (ICH) and non-contrast computed tomography (NCCT) features are promising predictors of HE. AIMS: We investigated whether onset-to-CT time influences the diagnostic performance of NCCT markers for HE. METHODS: Retrospective multicentre analysis of patients with primary ICH. The following NCCT markers were analyzed: hypodensities, heterogeneous density, blend sign, and irregular shape. HE was defined as growth ⩾6 mL and/or ⩾33%. We calculated the sensitivity, specificity, positive, and negative predictive values (PPVs and NPVs) of NCCT markers for HE, stratified by onset-to-CT time (<2 h, 2-4 h, 4-6 h, >6 h). RESULTS: We included 1135 patients (median age 69, 53% males), of whom 307 (27%) experienced HE.Overall hypodensities had the highest sensitivity (0.68) and blend sign the highest specificity (0.87) for HE. Hypodensities were more common and had higher sensitivity (0.80) in patients with imaging within 2 h. The same result was observed for heterogeneous density, whereas irregular shape had a similar prevalence across time strata and higher sensitivity (0.79) beyond 6 h from onset. The frequency of blend sign increased with longer onset-to-CT time, whereas its specificity declined after 6 h from onset. CONCLUSION: The diagnostic performance of NCCT markers is influenced by imaging time. Hypodensities identified four out of five patients with HE within 2 h from onset, whereas irregular shape performed better in late presenters. Our findings may improve the use of NCCT markers in future studies and trials targeting HE.

Commercial volumetric MRI reporting tools in multiple sclerosis: a systematic review of the evidence.

PURPOSE: MRI is integral to the diagnosis of multiple sclerosis (MS) and is important for clinical prognostication. Quantitative volumetric reporting tools (QReports) can improve the accuracy and objectivity of MRI-based assessments. Several QReports are commercially available; however, validation can be difficult to establish and does not currently follow a common pathway. To aid evidence-based clinical decision-making, we performed a systematic review of commercial QReports for use in MS including technical details and published reports of validation and in-use evaluation. METHODS: We categorized studies into three types of testing: technical validation, for example, comparison to manual segmentation, clinical validation by clinicians or interpretation of results alongside clinician-rated variables, and in-use evaluation, such as health economic assessment. RESULTS: We identified 10 companies, which provide MS lesion and brain segmentation and volume quantification, and 38 relevant publications. Tools received regulatory approval between 2006 and 2020, contextualize results to normative reference populations, ranging from 620 to 8000 subjects, and require T1- and T2-FLAIR-weighted input sequences for longitudinal assessment of whole-brain volume and lesions. In MS, six QReports provided evidence of technical validation, four companies have conducted clinical validation by correlating results with clinical variables, only one has tested their QReport by clinician end-users, and one has performed a simulated in-use socioeconomic evaluation. CONCLUSION: We conclude that there is limited evidence in the literature regarding clinical validation and in-use evaluation of commercial MS QReports with a particular lack of clinician end-user testing. Our systematic review provides clinicians and institutions with the available evidence when considering adopting a quantitative reporting tool for MS.

Foreign Healthcare Professionals in Germany: A Questionnaire Survey Evaluating Discrimination Experiences and Equal Treatment at Two Large University Hospitals.

OBJECTIVE: To identify facilitators and barriers and derive concrete measures towards better workplace integration of migrants working in the German healthcare sector. DESIGN: Two-centre cross-sectional quantitative online survey of experiences of discrimination among healthcare professionals with a migration history in two large German university hospitals. PARTICIPANTS: 251 participants fully completed the questionnaires. MAIN OUTCOME MEASURES: Experiences of discrimination and perception of inequality. RESULTS: Fifty-five percent of migrant health workers had had at least some command of German before arriving in Germany. Members of all professional groups surveyed expressed experiences of discrimination related to language, nationality, race/ethnicity, and sex/gender. The proportions of staff with experiences of discrimination by peers differed significantly among occupational roles, with nurses and technologists having the most experiences of discrimination. The perception of inequality was reported more frequently than experiences of discrimination and had a negative impact on workplace satisfaction. Specifically, the compulsion to compete was a frequent feeling stated by participants. CONCLUSION: The mechanisms of discrimination and structural inequality revealed by our survey could inform specific measures, for example at the management level, to increase workplace satisfaction and attract migrant health workers in the long term.

Diagnostic Accuracy and Reliability of Noncontrast Computed Tomography Markers for Acute Hematoma Expansion among Radiologists.

BACKGROUND: Noncontrast Computed Tomography (NCCT) features are promising markers for acute hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH). It remains unclear whether accurate identification of these markers is also reliable in raters with different levels of experience. METHODS: Patients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. In total, nine NCCT markers were rated by one radiology resident, one radiology fellow, and one neuroradiology fellow with different levels experience in ICH imaging. Interrater reliabilities of the resident and radiology fellow were evaluated by calculated Cohen's kappa (κ) statistics in reference to the neuroradiology fellow who was referred as the gold standard. Gold-standard ratings were evaluated by calculated interrater κ statistics. Global interrater reliabilities were evaluated by calculated Fleiss kappa statistics across all three readers. A comparison of receiver operating characteristics (ROCs) was used to evaluate differences in the diagnostic accuracy for predicting acute hematoma expansion (HE) among the raters. RESULTS: Substantial-to-almost-perfect interrater concordance was found for the resident with interrater Cohen's kappa from 0.70 (95% CI 0.65-0.81) to 0.96 (95% CI 0.94-0.98). The interrater Cohen's kappa for the radiology fellow was moderate to almost perfect and ranged from 0.58 (95% CI 0.52-0.65) to 94 (95% CI 92-0.97). The intrarater gold-standard Cohen's kappa was almost perfect and ranged from 0.79 (95% CI 0.78-0.90) to 0.98 (95% CI 0.78-0.90). The global interrater Fleiss kappa ranged from 0.62 (95%CI 0.57-0.66) to 0.93 (95%CI 0.89-0.97). The diagnostic accuracy for the prediction of acute hematoma expansion (HE) was different for the island sign and fluid sign, with p-values < 0.05. CONCLUSION: The NCCT markers had a substantial-to-almost-perfect interrater agreement among raters with different levels of experience. Differences in the diagnostic accuracy for the prediction of acute HE were found in two out of nine NCCT markers. The study highlights the promising utility of NCCT markers for acute HE prediction.

Intravenous tPA (Tissue-Type Plasminogen Activator) Correlates With Favorable Venous Outflow Profiles in Acute Ischemic Stroke.

BACKGROUND: Intravenous tPA (tissue-type plasminogen activator) is often administered before endovascular thrombectomy (EVT). Recent studies have questioned whether tPA is necessary given the high rates of arterial recanalization achieved by EVT, but whether tPA impacts venous outflow (VO) is unknown. We investigated whether tPA improves VO profiles on baseline computed tomography (CT) angiography (CTA) images before EVT. METHODS: Retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion undergoing EVT triage. Included patients underwent CT, CTA, and CT perfusion before EVT. VO profiles were determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on CTA as 0, not visible; 1, moderate opacification; and 2, full. Pial arterial collaterals were graded on CTA, and tissue-level collaterals were assessed on CT perfusion using the hypoperfusion intensity ratio. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analysis, we determined the correlation between tPA administration and favorable VO profiles. RESULTS: Seven hundred seventeen patients met inclusion criteria. Three hundred sixty-five patients received tPA (tPA+), while 352 patients were not treated with tPA (tPA-). Fewer tPA+ patients had atrial fibrillation (n=128 [35%] versus n=156 [44%]; P=0.012) and anticoagulants/antiplatelet treatment before acute ischemic stroke due to large vessel occlusion onset (n=130 [36%] versus n=178 [52%]; P<0.001) compared with tPA- patients. One hundred eighty-five patients (51%) in the tPA+ and 100 patients (28%) in the tPA- group exhibited favorable VO (P<0.001). Multivariable regression analysis showed that tPA administration was a strong independent predictor of favorable VO profiles (OR, 2.6 [95% CI, 1.7-4.0]; P<0.001) after control for favorable pial arterial CTA collaterals, favorable tissue-level collaterals on CT perfusion, age, presentation National Institutes of Health Stroke Scale, antiplatelet/anticoagulant treatment, history of atrial fibrillation and time from symptom onset to imaging. CONCLUSIONS: In patients with acute ischemic stroke due to large vessel occlusion undergoing thrombectomy triage, tPA administration was strongly associated with the presence of favorable VO profiles.

Cerebrovascular Events in Suspected Sepsis: Retrospective Prevalence Study in Critically Ill Patients Undergoing Full-Body Computed Tomography.

Purpose: This study aimed at retrospectively evaluating full-body computed tomography (CT) examinations for the prevalence of cerebrovascular events in patients with suspected sepsis treated in the intensive care unit (ICU). Methods: All full-body CT examinations, i.e., both cranial CT (cCT) and body CT including chest, abdomen and pelvis, for focus search in septic patients over a 12-months period were identified from three ICUs, using full-text search. From this retrospective cohort, we fully analyzed 278 cCT examinations for the occurrence of acute cerebral findings. All acute cerebrovascular events were independently reviewed by two blinded readers. Clinical and laboratory findings were extracted. The data were statistically analyzed using contingency tests. Results: In our population of patients with suspected sepsis, 10.8% (n = 30/278) were identified to have major cerebral events, including 7.2% (n = 20/278) major cerebrovascular events and 4.3% (n = 12/278) generalized parenchymal damage. 13.4% (n = 22/163) of patients with a severe coma as compared with non-severe coma, 4.4% (n = 3/68), showed a major cerebral event (p = 0.04). Patients referred from the cardiology/nephrology ICU ward showed major cerebral events in 16.3% (n = 22/135), as compared with 4.9% (n = 3/61) in patients from pulmonary ICU and 6.1% (n = 5/82) major cerebral events with surgical referral (p = 0.02). Conclusion: Our study provides further evidence that septic patients may suffer from cerebral events with relevance to their prognosis. Severe coma and the referring ward were associated with acute cerebral conditions. Full-body CT has the advantage of both detecting of septic foci and possibly identifying ischemic or hemorrhagic stroke in this vulnerable patient population.