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Objective: Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke. HT can be the result of stroke progression or a complication of reperfusion treatment for stroke. The aim of this study is to apply a previously proposed HT mathematical model within a computational whole brain model to determine the factors that affect the severity of HT. In addition, these simulations are directly compared with neuroimaging data. Approach: The MR CLEAN–NO IV trial assessed the effect of endovascular therapy (EVT) alone compared with intravenous alteplase treatment (IVT) followed by EVT for patients with acute ischaemic stroke due to anterior circulation large vessel occlusion. We included imaging data of 15 HT patients from the MR CLEAN–NO IV trial, 5 patients suffered from haemorrhagic infarction type 1, 5 from haemorrhagic infarction type 2 and 5 had parenchymal haematoma type 1. The comparison of simulations with patient image data is carried out by comparing the haematoma locations and haematoma volume. The parameters of the model are then optimised to improve agreement with clinical data. Finally, the model is used to investigate the factors that affect the severity of HT. Main results: Based on the computational whole brain model, we found that perfusion reduced by 5–16% after HT onset. The results are in good agreement with the clinical data. We then showed that 1% increase of blood viscosity reduces perfusion by 0.04% and increases haematoma volume by 10.35% from baseline, and 1% increase of blood pressure reduces perfusion by 0.80% and increases haematoma volume by 4.73% from baseline. These results indicate that increased blood glucose and hypertension (among other factors) both appear to lead to a higher severity of HT. Significance: This model, by enabling us to bridge the gap between the mathematical HT model and clinical imaging data, provides the first whole brain prediction model for HT severity assessment.

Purpose The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin.

BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Background: This study aimed to assess the feasibility of postmortem ultra-high-field magnetic resonance imaging (UHF-MRI) to study fetal musculoskeletal anatomy and explore the contribution of variation in iodine and formaldehyde (paraformaldehyde, PFA) treatment of tissue. Methods: Seven upper extremities from human fetuses with gestational ages of 19 to 24 weeks were included in this experimental study, approved by the Medical Research Ethics Committee. The specimens were treated with various storage (0.2–4% PFA) and staining (Lugol’s solution) protocols and the wrist joint was subsequently imaged with 7.0 T UHF-MRI. Soft-tissue contrast was quantified by determining regions of interest within a chondrified carpal bone (CCB) from the proximal row, the triangular fibrocartilage (TFC), and the pronator quadratus muscle (PQM) and calculating the contrast ratios (CRs) between mean signal intensities of CCB to TFC and CCB to PQM. Results: UHF-MRI showed excellent soft-tissue contrast in different musculoskeletal tissues. Increasing storage time in 4% PFA, CRs decreased, resulting in a shift from relatively hyperintense to hypointense identification of the CCB. Storage in 0.2% PFA barely influenced the CRs over time. Lugol’s solution caused an increase in CRs and might have even contributed to the inversion of the CRs. Conclusions: UHF-MRI is a feasible technique to image musculoskeletal structures in fetal upper extremities and most successful after short storage in 4% PFA or prolonged storage in 0.2% PFA. The use of Lugol’s solution is not detrimental on soft-tissue MRI contrast and therefore enables effectively combining UHF-MRI with contrast-enhanced micro-computed tomography using a single preparation of the specimen. Relevance statement: UHF-MRI can be performed after CE-micro-CT to take advantage of both techniques. Key points: • UHF-MRI is feasible to study human fetal cartilaginous and ligamentous anatomy. • Storage in low PFA concentrations (i.e., 0.2%) improves soft-tissue contrast in UHF-MRI. • Limited preservation time in high concentrations of PFA improves soft-tissue contrast in UHF-MRI. • Prior staining with Lugol’s solution does not reduce soft-tissue contrast in UHF-MRI. Graphical Abstract: [Figure not available: see fulltext.].

BACKGROUND AND AIMS: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.METHODS: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions.RESULTS: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77).DISCUSSION: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.

Background: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE. Methods: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models. Results: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8–42.3] mm versus 24.4 [interquartile range, 17.1–32.4] mm; P P for interaction=0.04. Conclusions: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

IntroductionThe efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics.MethodsIn this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014–November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed.ResultsOf the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750–2 50 000)) or alteplase (median dose, 20 mg (IQR, 12–20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt.ConclusionLocal IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.

Purpose To relate [18F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. Methods Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [18F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. Results In the spine, 69 lesions with enhanced [18F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. Conclusion [18F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [18F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. Clinical trial registration NL43223.029.13 registered at 02-05-2013. https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A

Executive functioning (EF) is a higher order cognitive process that is thought to depend on a network organization facilitating integration across subnetworks, in the context of which the central role of the fronto-parietal network (FPN) has been described across imaging and neurophysiological modalities. However, the potentially complementary unimodal information on the relevance of the FPN for EF has not yet been integrated. We employ a multilayer framework to allow for integration of different modalities into one ‘network of networks.’ We used diffusion MRI, resting-state functional MRI, MEG, and neuropsychological data obtained from 33 healthy adults to construct modality-specific single-layer networks as well as a single multilayer network per participant. We computed single-layer and multilayer eigenvector centrality of the FPN as a measure of integration in this network and examined their associations with EF. We found that higher multilayer FPN centrality, but not single-layer FPN centrality, was related to better EF. We did not find a statistically significant change in explained variance in EF when using the multilayer approach as compared to the single-layer measures. Overall, our results show the importance of FPN integration for EF and underline the promise of the multilayer framework toward better understanding cognitive functioning.

Physical exercise training has been positioned as a behavioral strategy to prevent or alleviate obesity via promotion of energy expenditure as well as modulation of energy intake resulting from changes in dietary preference. Brain adaptations underlying the latter process are incompletely understood. Voluntary wheel running (VWR) is a self-reinforcing rodent paradigm that mimics aspects of human physical exercise training. Behavioral and mechanistic insight from such fundamental studies can help optimize therapies that improve body weight and metabolic health based on physical exercise training in humans. To assess the effects of VWR on dietary self-selection, male Wistar rats were given access to a two-component "no-choice" control diet (CD; consisting of prefabricated nutritionally complete pellets and a bottle with tap water) or a four-component free-choice high-fat high-sucrose diet (fc-HFHSD; consisting of a container with prefabricated nutritionally complete pellets, a dish with beef tallow, a bottle with tap water, and a bottle with 30% sucrose solution). Metabolic parameters and baseline dietary self-selection behavior during sedentary (SED) housing were measured for 21 days, after which half of the animals were allowed to run on a vertical running wheel (VWR) for another 30 days. This resulted in four experimental groups (SEDCD, SEDfc-HFHSD, VWRCD, and VWRfc-HFHSD). Gene expression of opioid and dopamine neurotransmission components, which are associated with dietary self-selection, was assessed in the lateral hypothalamus (LH) and nucleus accumbens (NAc), two brain regions involved in reward-related behavior, following 51 and 30 days of diet consumption and VWR, respectively. Compared to CD controls, consumption of fc-HFHSD before and during VWR did not alter total running distances. VWR and fc-HFHSD had opposite effects on body weight gain and terminal fat mass. VWR transiently lowered caloric intake and increased and decreased terminal adrenal and thymus mass, respectively, independent of diet. VWR during fc-HFHSD consumption consistently increased CD self-selection, had an acute negative effect on fat self-selection, and a delayed negative effect on sucrose solution self-selection compared to SED controls. Gene expression of opioid and dopamine neurotransmission components in LH and NAc were unaltered by fc-HFHSD or VWR. We conclude that VWR modulates fc-HFHSD component self-selection in a time-dependent manner in male Wistar rats.

References 3 and 9 are duplicates (identical); hence, one was deleted and the references including their citations in the text were renumbered accordingly. The original article has been corrected.

Background Cardiac CT acquired during the acute stroke imaging protocol is an emerging alternative to transthoracic echocardiography (TTE) to screen for sources of cardioembolism. Currently, its diagnostic accuracy to detect patent foramen ovale (PFO) is unclear. Methods This was a substudy of Mind the Heart, a prospective cohort in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent TTE. We included patients Results Of 452 patients in Mind the Heart, 92 were younger than 60 years. Of these, 59 (64%) patients underwent both cardiac CT and cTTE and were included. Median age was 54 (IQR 49–57) years and 41/59 (70%) were male. Cardiac CT detected a PFO in 5/59 (8%) patients, 3 of which were confirmed on cTTE. cTTE detected a PFO in 12/59 (20%) patients. Sensitivity and specificity of cardiac CT were 25% (95% CI 5–57%) and 96% (95% CI 85–99%), respectively. Positive and negative predictive values were 59% (95% CI 14–95) and 84% (95% CI 71–92). Conclusion Prospective ECG-gated cardiac CT acquired during the acute stroke imaging protocol does not appear to be a suitable screening method for PFO due to its low sensitivity. Our data suggest that if cardiac CT is used as a first-line screening method for cardioembolism, additional echocardiography remains indicated in young patients with cryptogenic stroke, in whom PFO detection would have therapeutic consequences. These results need to be confirmed in larger cohorts.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Background: Leptomeningeal collateral status on baseline computed tomographic angiography (CTA) is associated with clinical outcome after acute ischemic stroke treatment. However, assessment of collateral status is not uniform. To compare 3 different CTA collateral scores (CS) and imaging techniques about their association with clinical outcome. Methods: Pooled analysis of patient-level data from the Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration. Patients with large vessel occlusion from 7 randomized controlled trials that compared endovascular thrombectomy with standard medical care were included. Three different CS (Tan CS, regional CS [rCS], and regional Alberta Stroke Program Early CT Score CS) and 2 imaging techniques (single-phase [sCTA] and multiphase/dynamic CTA) were evaluated. Functional independence (modified Rankin Scale score 0–2) at 3 months poststroke was the primary outcome. Furthermore, we assessed the effect of sCTA image acquisition time on collateral status assessment using an adjusted ordinal logistic regression model to obtain predicted values for the trichotomized rCS. Results: Among 1147 pooled patients, 948 (82.7%) had sCTA and 199 (17.3%) multiphase/dynamic CTA as baseline angiography. With all 3 collateral scales, better CSs were associated with better 3-month functional outcome. With sCTA images, the rCS (area under the curve [AUC] 0.63) and regional Alberta Stroke Program Early CT Score CS (AUC 0.62) better predicted functional outcome than the Tan CS (AUC 0.60, respectively; P P =0.02). With multiphase/dynamic CTA images, all collateral scales performed similarly in predicting functional outcome (rCS [AUC 0.61]; regional Alberta Stroke Program Early CT Score CS [AUC 0.61] versus Tan CS [AUC 0.61], respectively; P =0.93 and P =0.91). Overall, no endovascular thrombectomy treatment effect modification by collateral status (rCS) was demonstrated ( P =0.41). sCTA timing independently influenced CS assessment. On earlier timed sCTA, the predicted proportions of scans with poor collaterals was higher and vice versa. Conclusions: In this data set of highly selected patients with stroke, using a regional CS on sCTA likely allows for the most accurate prediction of functional outcome while on time-resolved CTA, the type of CS did not matter. Patients across all collateral grades benefit from endovascular thrombectomy. sCTA timing independently influenced CS assessment.

Background: Early and accurate detection of ankle fractures are crucial for optimizing treatment and thus reducing future complications. Radiographs are the most abundant imaging techniques for assessing fractures. Deep learning (DL) methods, through adequately trained deep convolutional neural networks (DCNNs), have been previously shown to faster and accurately analyze radiographic images without human intervention. Herein, we aimed to assess the performance of two different DCNNs in detecting ankle fractures using radiographs compared to the ground truth. Methods: In this retrospective case-control study, our DCNNs were trained using radiographs obtained from 1050 patients with ankle fracture and the same number of individuals with otherwise healthy ankles. Inception V3 and Renet-50 pretrained models were used in our algorithms. Danis-Weber classification method was used. Out of 1050, 72 individuals were labeled as occult fractures as they were not detected in the primary radiographic assessment. Single-view (anteroposterior) radiographs was compared with 3-views (anteroposterior, mortise, lateral) for training the DCNNs. Results: Our DCNNs showed a better performance using 3-views images versus single-view based on greater values for accuracy, F-score, and area under the curve (AUC). The highest sensitivity was 98.7 % and specificity was 98.6 % in detection of ankle fractures using 3-views using inception V3. This model missed only one fracture on radiographs. Conclusion: The performance of our DCNNs showed that it can be used for developing the currently used image interpretation programs or as a separate assistant solution for the clinicians to detect ankle fractures faster and more precisely. Level of evidence: III

Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target

Objectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. Methods Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R2. For patients with available thin-slice (≤ 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). Results In 332 included patients, the presence of HAS (aβ 7.8 [95% CI 3.9–11.7]) and shift towards a more proximal occlusion location (aβ 3.9 [95% CI 0.6–7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. Conclusions Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. Key Points • With hyperdense artery sign and occlusion location, 12% of variability in thrombus RBC content can be explained. • With hyperdense artery sign, occlusion location, and quantitative thrombus characteristics on thin-slice (≤ 2.5 mm) non-contrast CT and CTA, 30% of variability in thrombus RBC content can be explained. • Absolute thrombus density and thrombus length were the strongest predictors for thrombus composition.

Contains fulltext : 287508.pdf (Publisher’s version ) (Closed access) BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Background: We aimed to assess whether the effect of intravenous alteplase treatment (IVT) before endovascular treatment (EVT) on outcome is modified by first-line technique during EVT in IVT eligible patients. Methods: This was a post hoc analysis from MR CLEAN-NO IV (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands - Intravenous Treatment Followed by Intra-Arterial Treatment Versus Direct Intra-Arterial Treatment for Acute Ischemic Stroke Caused by a Proximal Intracranial Occlusion), a randomized trial of IVT followed by EVT versus EVT alone in patients presenting directly to EVT-capable centers. We included data from all patients who underwent EVT with a thrombectomy attempt. We compared patients treated with stent retriever (with or without aspiration) to aspiration alone as first-line EVT technique and assessed the interaction of first-line EVT technique with IVT treatment. Primary outcome was the 90-day modified Rankin Scale score, analyzed with mixed model ordinal regression for a shift towards better outcome. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2b–3). Results: Of 473 included patients, 102 (21.6%) were treated with aspiration alone as first-line technique. In the full population, functional outcome was similar for patients treated with stent retriever versus aspiration only (adjusted common odds ratio [acOR]‚ 1.07 [95% CI, 0.69–1.66]). We observed a significant interaction between IVT and first-line EVT technique ( P =0.03). In the aspiration-only group, patients treated with EVT alone had worse functional outcome compared to those treated with IVT and EVT (acOR, 0.44 [95% CI, 0.21–0.90]). In the stent retriever group, functional outcome did not differ between patients treated with or without IVT (acOR, 1.08 [95% CI, 0.74–1.57]). There was no statistically significant interaction for successful reperfusion. Conclusions: In MR CLEAN-NO IV, the treatment effect of IVT was modified by first-line EVT technique. Patients treated with aspiration only as first-line technique had worse clinical outcomes if they did not receive IVT. No such difference was observed in patients treated with stent retrievers. Confirmation by pooling with results from other trials is needed to confirm these findings.

Objectives Enlarged lateral lymph nodes (LLNs) are associated with increased (lateral) local recurrence rates. Size and anatomical location should therefore always be reported by radiologists and discussed during multidisciplinary meetings. The objective was to investigate how often LLNs are mentioned in MRI reports in a tertiary referral centre. Methods A single - centre, retrospective study of 202 patients treated for primary rectal cancer between 2012 and 2020, with at least a T2 tumour located within 12cm of the anorectal junction. The radiology reports were written by 30–40 consultant radiologists. MRI scans were independently re-assessed by an expert radiologist. The primary outcome was how often the presence or absence of LLNs was mentioned in the initial report. Results Primary MRI reports explicitly mentioned the presence or absence of LLNs in 89 (44%) cases. Of the 43 reports with present LLNs, only one (1%) reported on all features such as size, location or malignant features. Expert review revealed 17 LLNs which were ≥ 7 mm (short-axis); two of these were not mentioned in the original reports. In 14/43 (33%) cases, LLNs were discussed during the primary multidisciplinary meeting, while 17/43 (40%) restaging MRI reports failed to report on the previously visible LLN. Reporting LLNs increased significantly with higher N-stage (p = .010) and over time (p = .042). Conclusions Though improving with time, there is still limited consistency in reporting LLNs. Only 44% of primary MRI reports mentioned LLNs and relevant features of those LLNs were seldomly reported. Given the importance of this information for subsequent treatment; increased awareness, proper training and the use of templates are needed. Key Points • Comprehensive reporting of lateral lymph nodes in primary MRI reports was limited to less than 50%. • Lateral lymph nodes are not always discussed during primary multidisciplinary meetings or mentioned in restaging reports. • Improvements in the awareness and knowledge of lateral lymph nodes are needed to ensure adequate multidisciplinary treatment decisions.

Background and ObjectivesGuidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE).MethodsWe performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations.ResultsBetween May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5–7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28–16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%).DiscussionCardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans.MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient.RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59 mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions.CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.

In-transit metastases (ITM) are defined as metastatic lymph nodes or deposits occurring between the primary tumor and proximal draining lymph node basin. In extremity rhabdomyosarcoma (RMS), they have rarely been reported. This study evaluates the frequency, staging and survival of patients with ITM in distal extremity RMS. Methods: Patients with extremity RMS distal to the elbow or knee, enrolled in the EpSSG RMS 2005 trial between 2005 and 2016 were eligible for this study. Results: One hundred and nine distal extremity RMS patients, with a median age of 6.2 years (range 0–21 years) were included. Thirty seven of 109 (34%) had lymph node metastases at diagnosis, 19 of them (51%) had ITM, especially in lower extremity RMS. 18F-FDG-PET/CT detected involved lymph nodes in 47% of patients. In patients not undergoing 18F-FDG-PET/CT lymph node involvement was detected in 22%. The 5-yr EFS of patients with ITM vs proximal lymph nodes vs combined proximal and ITM was 88.9% vs 21.4% vs 20%, respectively (p = 0.01) and 5-yr OS was 100% vs 25.2% vs 15%, respectively (p = 0.003). Conclusion: Our study showed that in-transit metastases constituted more than 50% of all lymph node metastases in distal extremity RMS. 18F-FDG-PET/CT improved nodal staging by detecting more regional and in-transit metastases. Popliteal and epitrochlear nodes should be considered as true (distal) regional nodes, instead of in-transit metastases. Biopsy of these nodes is recommended especially in distal extremity RMS of the lower limb. Patients with proximal (axillary or inguinal) lymph node involvement have a worse prognosis.

Foot ulcers are a frequent and costly problem in people with diabetes mellitus and can lead to amputations. Prevention of these ulcers is therefore of paramount importance. Claw/hammer toe deformities are commonly seen in people with diabetes. These deformities increase the risk of ulcer development specifically at the (tip of) the toe. Percutaneous needle tenotomy of the tendon of the m. flexor digitorum longus (tendon tenotomy) can be used to reduce the severity of claw/hammer toe deformity with the goal to prevent ulcer recurrence. The main objective of this randomized controlled trial is to assess the efficacy of flexor tenotomy to prevent recurrence of toe ulcers in people with diabetes and a history of toe (pre-)ulcers. Additionally, we aim to assess interphalangeal joints (IPJ) and metatarsophalangeal joint (MTPJ) angles in a weight-bearing and non-weight-bearing position, barefoot plantar pressure during walking, cost-effectiveness and quality of life before and after the intervention and compare intervention and control study groups. Sixty-six subjects with diabetes and claw/hammer toe deformity and a recent history of (pre-)ulceration on the tip of the toe will be included and randomized between flexor tenotomy of claw/hammer toes (intervention) versus standard of care including orthosis and shoe offloading (controls) in a mono-center randomized controlled trial. Clinicaltrials.gov registration: NCT05228340.

Purpose: To develop a deep learning-based metal artifact reduction technique (DL-MAR) and quantitatively compare metal artifacts on DL-MAR-corrected CT-images, orthopedic metal artifact reduction (O-MAR)-corrected CT-images and uncorrected CT-images after sacroiliac (SI) joint fusion. Methods: DL-MAR was trained on CT-images with simulated metal artifacts. Pre-surgery CT-images and uncorrected, O-MAR-corrected and DL-MAR-corrected post-surgery CT-images of twenty-five patients undergoing SI joint fusion were retrospectively obtained. Image registration was applied to align pre-surgery with post-surgery CT-images within each patient, allowing placement of regions of interest (ROIs) on the same anatomical locations. Six ROIs were placed on the metal implant and the contralateral side in bone lateral of the SI joint, the gluteus medius muscle and the iliacus muscle. Metal artifacts were quantified as the difference in Hounsfield units (HU) between pre- and post-surgery CT-values within the ROIs on the uncorrected, O-MAR-corrected and DL-MAR-corrected images. Noise was quantified as standard deviation in HU within the ROIs. Metal artifacts and noise in the post-surgery CT-images were compared using linear multilevel regression models. Results: Metal artifacts were significantly reduced by O-MAR and DL-MAR in bone (p < 0.001), contralateral bone (O-MAR: p = 0.009; DL-MAR: p < 0.001), gluteus medius (p < 0.001), contralateral gluteus medius (p < 0.001), iliacus (p < 0.001) and contralateral iliacus (O-MAR: p = 0.024; DL-MAR: p < 0.001) compared to uncorrected images. Images corrected with DL-MAR resulted in stronger artifact reduction than images corrected with O-MAR in contralateral bone (p < 0.001), gluteus medius (p = 0.006), contralateral gluteus medius (p < 0.001), iliacus (p = 0.017), and contralateral iliacus (p < 0.001). Noise was reduced by O-MAR in bone (p = 0.009) and gluteus medius (p < 0.001) while noise was reduced by DL-MAR in all ROIs (p < 0.001) in comparison to uncorrected images. Conclusion: DL-MAR showed superior metal artifact reduction compared to O-MAR in CT-images with SI joint fusion implants.

Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between‐hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between‐hospital variation in outcomes was assessed using the variance of random hospital effects (tau 2 ). In addition, we estimated the correlation between hospitals' EVT‐patient volume and (case‐mix–adjusted) outcomes. Both early outcomes and case‐mix characteristics varied significantly across hospitals. Between‐hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case‐mix adjustment (tau 2 =0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case‐mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT‐patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores ( r =0.48) and weakly with lower NIHSS score at 24 to 48 hours ( r =0.15). Conclusions Between‐hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case‐mix but not by patient volume. In contrast, between‐hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT‐patient volume but not by case‐mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case‐mix is applied for NIHSS score.

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71–0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16–0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24–0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50–0.89]; P =0.005; adjusted cOR, 0.74 [95% CI, 0.55–1.0]; P =0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.

Purpose To gain insight into how patients with primary brain tumors experience MRI, follow-up protocols, and gadolinium-based contrast agent (GBCA) use. Methods Primary brain tumor patients answered a survey after their MRI exam. Questions were analyzed to determine trends in patients’ experience regarding the scan itself, follow-up frequency, and the use of GBCAs. Subgroup analysis was performed on sex, lesion grade, age, and the number of scans. Subgroup comparison was made using the Pearson chi-square test and the Mann–Whitney U-test for categorical and ordinal questions, respectively. Results Of the 100 patients, 93 had a histopathologically confirmed diagnosis, and seven were considered to have a slow-growing low-grade tumor after multidisciplinary assessment and follow-up. 61/100 patients were male, with a mean age ± standard deviation of 44 ± 14 years and 46 ± 13 years for the females. Fifty-nine patients had low-grade tumors. Patients consistently underestimated the number of their previous scans. 92% of primary brain tumor patients did not experience the MRI as bothering and 78% would not change the number of follow-up MRIs. 63% of the patients would prefer GBCA-free MRI scans if diagnostically equally accurate. Women found the MRI and receiving intravenous cannulas significantly more uncomfortable than men (p = 0.003). Age, diagnosis, and the number of previous scans had no relevant impact on the patient experience. Conclusion Patients with primary brain tumors experienced current neuro-oncological MRI practice as positive. Especially women would, however, prefer GBCA-free imaging if diagnostically equally accurate. Patient knowledge of GBCAs was limited, indicating improvable patient information.

Whether endovascular thrombectomy (EVT) improves functional outcome in patients with large-vessel occlusion (LVO) stroke that do not comply with inclusion criteria of randomized controlled trials (RCTs) but that are considered for EVT in clinical practice is uncertain. We aimed to systematically identify patients with LVO stroke underrepresented in RCTs who might benefit from EVT. Following the premises that (i) patients without reperfusion after EVT represent a non-treated control group and (ii) the level of reperfusion affects outcome in patients with benefit from EVT but not in patients without treatment benefit, we systematically assessed the importance of reperfusion level on functional outcome prediction using machine learning in patients with LVO stroke treated with EVT in clinical practice (N = 5235, German-Stroke-Registry) and in patients treated with EVT or best medical management from RCTs (N = 1488, Virtual-International-Stroke-Trials-Archive). The importance of reperfusion level on outcome prediction in an RCT-like real-world cohort equaled the importance of EVT treatment allocation for outcome prediction in RCT data and was higher compared to an unselected real-world population. The importance of reperfusion level was magnified in patient groups underrepresented in RCTs, including patients with lower NIHSS scores (0–10), M2 occlusions, and lower ASPECTS (0–5 and 6–8). Reperfusion level was equally important in patients with vertebrobasilar as with anterior LVO stroke. The importance of reperfusion level for outcome prediction identifies patient target groups who likely benefit from EVT, including vertebrobasilar stroke patients and among patients underrepresented in RCT patients with low NIHSS scores, low ASPECTS, and M2 occlusions.

Background: Knowledge on the role of synovial signal intensity (SI) grading on static contrast-enhanced (CE) MRI of the knee for assessment of disease activity in juvenile idiopathic arthritis (JIA) is lacking. Objectives: To assess the value of synovial SI on static CE-MRI of the knee for evaluation of disease activity in children with JIA. Materials and methods: Children with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for potential time-dependent post-contrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated. Results: We included 427 JIA patients (clinically inactive JIA: 150 [35,1%]; clinically active JIA: 277 [64.9%]), 65.3% female, with a mean age of 13.3 ± 3.2 years. Mean SI synovium-to-muscle ratio was 2.1 ± 0.7 in patients with clinically inactive JIA versus 2.2 ± 0.8 in patients with clinically active JIA. Subgroup analysis showed no significant difference in SI synovium-to-muscle ratio between JIA patients with clinically inactive disease and JIA patients with clinically active disease (p-value 0.22). Conclusions: Evaluation of the brightness of the synovium on static CE-MRI of the knee for assessment of JIA disease activity should be avoided, as this might lead to incorrect clinical conclusions.

Context Sodium-glucose cotransporter-2 inhibitors (SGLT2i) cause less weight loss than expected based on urinary calorie excretion. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists are associated with reduced appetite and body weight, mediated by direct and indirect central nervous system (CNS) effects. Objective We investigated the separate and combined effects of dapagliflozin and exenatide on the CNS in participants with obesity and type 2 diabetes. Methods This was a 16-week, double-blind, randomized, placebo-controlled trial. Obese participants with type 2 diabetes (n = 64, age 63.5 ± 0.9 years, BMI 31.7 ± 0.6 kg/m2) were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice daily 10 µg with dapagliflozin-matched placebo, dapagliflozin and exenatide, or double placebo. Using functional MRI, the effects of treatments on CNS responses to viewing food pictures were assessed after 10 days and 16 weeks of treatment. Results After 10 days, dapagliflozin increased, whereas exenatide decreased CNS activation in the left putamen. Combination therapy had no effect on responses to food pictures. After 16 weeks, no changes in CNS activation were observed with dapagliflozin, but CNS activation was reduced with dapagliflozin-exenatide in right amygdala. Conclusion The early increase in CNS activation with dapagliflozin may contribute to the discrepancy between observed and expected weight loss. In combination therapy, exenatide blunted the increased CNS activation observed with dapagliflozin. These findings provide further insights into the weight-lowering mechanisms of SGLT2i and GLP-1 receptor agonists.

Imaging of dopaminergic transmission in neurodegenerative disorders such as Parkinson disease (PD) or dementia with Lewy bodies plays a major role in clinical practice and in clinical research. We here review the role of imaging of the nigrostriatal pathway, as well as of striatal receptors and dopamine release, in common neurodegenerative disorders in clinical practice and research. Imaging of the nigrostriatal pathway has a high diagnostic accuracy to detect nigrostriatal degeneration in disorders characterized by nigrostriatal degeneration, such as PD and dementia with Lewy bodies, and disorders of more clinical importance, namely in patients with clinically uncertain parkinsonism. Imaging of striatal dopamine D2/3 receptors is not recommended for the differential diagnosis of parkinsonian disorders in clinical practice anymore. Regarding research, recently the European Medicines Agency has qualified dopamine transporter imaging as an enrichment biomarker for clinical trials in early PD, which underlines the high diagnostic accuracy of this imaging tool and will be implemented in future trials. Also, imaging of the presynaptic dopaminergic system plays a major role in, for example, examining the extent of nigrostriatal degeneration in preclinical and premotor phases of neurodegenerative disorders and to examine subtypes of PD. Also, imaging of postsynaptic dopamine D2/3 receptors plays a role in studying, for example, the neuronal substrate of impulse control disorders in PD, as well as in measuring endogenous dopamine release to examine, for example, motor complications in the treatment of PD. Finally, novel MRI sequences as neuromelanin-sensitive MRI are promising new tools to study nigrostriatal degeneration in vivo.

Background: Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications such as diagnosis, characterization, and treatment planning and monitoring in glioma patients. While APT-CEST has demonstrated high potential, reproducibility remains underexplored. Purpose: To investigate whether cerebral APT-CEST with clinically feasible scan time is reproducible in healthy tissue and glioma for clinical use at 3 T. Study Type: Prospective, longitudinal. Subjects: Twenty-one healthy volunteers (11 females; mean age ± SD: 39 ± 11 years) and 6 glioma patients (3 females; 50 ± 17 years: 4 glioblastomas, 1 oligodendroglioma, 1 radiologically suspected low-grade glioma). Field Strength/Sequence: 3 T, Turbo Spin Echo - ampling perfection with application optimized contrasts using different flip angle evolution - chemical exchange saturation transfer (TSE SPACE-CEST). Assessment: APT-CEST measurement reproducibility was assessed within-session (glioma patients, scan session 1; healthy volunteers scan sessions 1, 2, and 3), between-sessions (healthy volunteers scan sessions 1 and 2), and between-days (healthy volunteers, scan sessions 1 and 3). The mean APT CEST values and standard deviation of the within-subject difference (SD diff) were calculated in whole tumor enclosed by regions of interest (ROIs) in patients, and eight ROIs in healthy volunteers—whole-brain, cortical gray matter, putamen, thalami, orbitofrontal gyri, occipital lobes, central brain—and compared. Statistical Tests: Brown-Forsythe tests and variance component analysis (VCA) were used to assess the reproducibility of ROIs for the three time intervals. Significance was set at P < 0.003 after Bonferroni correction. Results: Intratumoral mean APT CEST was significantly higher than APT CEST in healthy-appearing tissue in patients (0.5 ± 0.46%). The average within-session, between-sessions, and between-days SD diff of healthy control brains was 0.2% and did not differ significantly with each other (0.76 > P > 0.22). The within-session SD diff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. VCA showed that within-session factors were the most important (60%) for scanning variance. Data Conclusion: Cerebral APT-CEST imaging may show good scan–rescan reproducibility in healthy tissue and tumors with clinically feasible scan times at 3 T. Short-term measurement effects may be the dominant components for reproducibility. Level of Evidence: 2. Technical Efficacy: Stage 2.

Introduction Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and thought to be caused by a mismatch between oxygen delivery and consumption. The mechanism underlying insufficient oxygen utilization is related to severity of anemia, and paradoxically, to the elevated cerebral blood flow (CBF) observed in SCD patients. CBF is elevated as a compensatory mechanism to maintain oxygen delivery, but high CBF levels can result in rapid transit of blood through the brain capillaries, limiting offloading of oxygen to the tissue; a process called arteriovenous shunting. One way to assess functional arteriovenous shunting is to use noncontrast perfusion MRI techniques in which we can assess the signal intensity of an endogenous blood tracer when it reaches the sagittal sinus. This venous signal (VS) reflects the amount of labeled blood that has not exchanged with the brain parenchyma. Under normal physiological conditions, the VS intensity will increase approximately proportionally with CBF as we expect only some of the water to exchange with tissue as it flows by. However, it is unknown whether functional shunting scales with CBF only, or whether other hemodynamic processes play a role in patients with SCD. We hypothesize that, under pathophysiological conditions such as in SCD patients, more labeled blood may pass unexchanged through the capillaries, which results in higher VS. In the present study, we investigated functional shunting by quantifying VS and assessed its association with hemodynamic, demographic and laboratory parameters in both pediatric and adult SCD patients, and controls. In addition, VS-CBF relationship was studied by further increasing CBF after a vasodilatory challenge. Methods We included 28 children (mean age 12.7 ± 2.3, 9 F) and 38 adults (mean age 32.1 ± 11.2, 14 F) with SCD (HbSS and HbS), and 10 healthy race-matched adult controls (mean age 36.4 ± 15.9, 4 F). For the CBF and VS measurements, pseudo-continuous arterial spin labelling (pCASL) data were acquired using 3T MRI. We segmented the ASL blood pool in the sagittal sinus to determine a common region of interest for each group. We used these images as masks to calculate average VS. Notably, for the comparison between children and adults the ratio between VS to gray matter CBF was used (VGR) instead of the VS, to take into account higher CBF in children. To get more insight into the oxygen utilization, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2) were calculated. In adult participants acetazolamide (ACZ) was used as a vasodilatory challenge. The hematologic laboratory parameters hemoglobin (Hb) and LDH were used as markers of anemia and hemolysis, respectively. Results VS as a marker of cerebral shunting was higher in both adult and pediatric patients with SCD as compared to controls (p Conclusion Our results show that the VS in the sagittal sinus on ASL images can be used to assess functional arteriovenous shunting in the brain. Given its negative association with CMRO 2 in combination with the negative association with hemoglobin and positive correlation with LDH, this functional shunting seems to reflect pathophysiologic shunting related to higher disease severity. Future studies will focus on the relation between functional shunting and the prevalence of SCI, investigating its link to aberrant capillary oxygen exchange in SCD. Figure 1 Figure 1. Disclosures Vaclavu: Philips Healthcare: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Sanquin: Research Funding.

Background: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0–6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. Methods: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. Results: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0–2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82–1.33], adjusted odds ratio, 1.04, [95% CI, 0.80–1.35]). Conclusions: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.

Understanding the neural mechanisms of emotional reactivity in Attention-Deficit/Hyperactivity Disorder (ADHD) may help develop more effective treatments that target emotion dysregulation. In adult ADHD, emotion regulation problems cover a range of dimensions, including emotional reactivity (ER). One important process that could underlie an impaired ER in ADHD might be impaired working memory (WM) processing. We recently demonstrated that taxing WM prior to the exposure of emotionally salient stimuli reduced physiological and subjective reactivity to such cues in heavy drinkers, suggesting lasting effects of WM activation on ER. Here, we investigated neural mechanisms that could underlie the interaction between WM and ER in adult ADHD participants. We included 30 male ADHD participants and 30 matched controls. Participants performed a novel functional magnetic resonance imaging paradigm in which active WM-blocks were alternated with passive blocks of negative and neutral images. We demonstrated group-independent significant main effects of negative emotional images on amygdala activation, and WM-load on paracingulate gyrus and dorsolateral prefrontal cortex activation. Contrary to earlier reports in adolescent ADHD, no impairments were found in neural correlates of WM or ER. Moreover, taxing WM did not alter the neural correlates of ER in either ADHD or control participants. While we did find effects on the amygdala, paCG, and dlPFC activation, we did not find interactions between WM and ER, possibly due to the relatively unimpaired ADHD population and a well-matched control group. Whether targeting WM might be effective in participants with ADHD with severe ER impairments remains to be investigated.

Background: Symptomatic intracranial hemorrhage (sICH) is a severe complication of reperfusion therapy for ischemic stroke. Multiple models have been developed to predict sICH or intracranial hemorrhage (ICH) after reperfusion therapy. We provide an overview of published models and validate their ability to predict sICH in patients treated with endovascular treatment in daily clinical practice. Methods: We conducted a systematic search to identify models either developed or validated to predict sICH or ICH after reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) for ischemic stroke. Models were externally validated in the MR CLEAN Registry (n=3180; Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was sICH according to the Heidelberg Bleeding Classification. Model performance was evaluated with discrimination (c-statistic, ideally 1; a c-statistic below 0.7 is considered poor in discrimination) and calibration (slope, ideally 1, and intercept, ideally 0). Results: We included 39 studies describing 40 models. The most frequently used predictors were baseline National Institutes of Health Stroke Scale (NIHSS; n=35), age (n=22), and glucose level (n=22). In the MR CLEAN Registry, sICH occurred in 188/3180 (5.9%) patients. Discrimination ranged from 0.51 (SPAN-100 [Stroke Prognostication Using Age and National Institutes of Health Stroke Scale]) to 0.61 (SITS-SICH [Safe Implementation of Treatments in Stroke Symptomatic Intracerebral Hemorrhage] and STARTING-SICH [STARTING Symptomatic Intracerebral Hemorrhage]). Best calibrated models were IST-3 (intercept, −0.15 [95% CI, −0.01 to −0.31]; slope, 0.80 [95% CI, 0.50−1.09]), SITS−SICH (intercept, 0.15 [95% CI, −0.01 to 0.30]; slope, 0.62 [95% CI, 0.38−0.87]), and STARTING−SICH (intercept, −0.03 [95% CI, −0.19 to 0.12]; slope, 0.56 [95% CI, 0.35−0.76]). Conclusions: The investigated models to predict sICH or ICH discriminate poorly between patients with a low and high risk of sICH after endovascular treatment in daily clinical practice and are, therefore, not clinically useful for this patient population.

Cellular metabolism is important for determining cell function and shaping immune responses. Studies have shown a crucial role for stromal cells in steering proper immune responses in the lymph node microenvironment. These lymph node stromal cells (LNSCs) tightly regulate immune tolerance. We hypothesize that malfunctioning LNSCs create a microenvironment in which normal immune responses are not properly controlled, possibly leading to the development of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we set out to determine their metabolic profile during health and systemic autoimmunity. We included autoantibody positive individuals at risk of developing RA (RA-risk individuals), RA patients and healthy volunteers. All study subjects underwent lymph node biopsy sampling. Mitochondrial function in cultured LNSCs was assessed by quantitative PCR, flow cytometry, Seahorse and oleate oxidation assays. Overall, mitochondrial respiration was lower in RA(-risk) LNSCs compared with healthy LNSCs, while metabolic potential was only lower in RA LNSCs. To maintain basal mitochondrial respiration, all LNSCs were mostly dependent on fatty acid oxidation. However, RA(-risk) LNSCs were also dependent on glutamine oxidation. Finally, we showed that RA LNSCs have impaired metabolic flexibility. Our results show that the metabolic landscape of LNSCs is not only altered during established disease, but partly already in individuals at risk of developing RA. Future studies are needed to investigate the impact of restoring metabolic capacity in LNSC-mediated immunomodulation and disease progression.

Purpose As bone formation is associated with psoriatic arthritis (PsA), positron emission tomography (PET) using a 18F-Fluoride tracer may enable sensitive detection of disease activity. Our primary aim was to determine the feasibility of whole-body 18F-sodium fluoride PET-CT in clinically active PsA patients to depict new bone formation (as a reflection of disease activity) at peripheral joints and entheses. Our secondary aim was to describe 18F-sodium fluoride findings in the axial skeleton. Methods Sixteen patients (female 10/16, age 50.6 ± 8.9 years) with PsA fulfilling CASPAR criteria or with a clinical diagnosis of PsA according to the treating rheumatologist and with ≥ 1 clinically active enthesitis site were included. Of each patient, a whole-body 18F-sodium fluoride PET-CT scan was performed. All scans were scored for PET-positive lesions at peripheral joints, enthesis sites and the spine. Clinical disease activity was assessed by swollen/tender joint count 44, enthesitis according to MASES and SPARCC scores. Results Out of 1088 evaluated joints, 109 joints showed PET enhancement, mainly in the interphalangeal and metatarsal joints of the feet (14/109, 12.9%) and the distal interphalangeal joints of the hands (14/109, 12.9%). PET positivity was found at 44/464 enthesis sites, mainly at the patella tendon insertion (11/44, 25%) and quadriceps tendon insertion (10/44, 22.7%). Of the PET-positive joints and enthesis sites, respectively 18.2% and 29.5% were clinically positive; 81.8% and 70.5% of the PET-positive joints and entheses respectively were clinically asymptomatic. In 11 patients, ≥ 1 axial PET-positive lesion was observed, mainly in the cervical spine. Conclusions New molecular bone formation was observed on 18F-sodium fluoride PET-CT scans, in all domains in which PsA disease activity can be observed, with a substantial part showing no clinical symptoms. Clinical trial registration EudraCT: 2017-004,850-40, registered on 13 December 2017.

Objectives To compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps. Methods Patients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods—a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability. Results A total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference [interquartile range] in mL between the estimated and follow-up infarct volume was 29/23/23 [52/50/52] (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 [31/25/30] (ISP/bSVD/NLR) for the probabilistic classification. Conclusions Multivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions. Key Points • Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions. • Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis. • A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.

Purpose 2-[18F]FDG PET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and SCLC). This topic has been addressed in guidelines composed by experts within the field of radiation oncology. However, up to present, there is no procedural guideline on this subject, with involvement of the nuclear medicine societies. Methods A literature review was performed, followed by a discussion between a multidisciplinary team of experts in the different fields involved in the RT planning of lung cancer, in order to guide clinical management. The project was led by experts of the two nuclear medicine societies (EANM and SNMMI) and radiation oncology (ESTRO). Results and conclusion This guideline results from a joint and dynamic collaboration between the relevant disciplines for this topic. It provides a worldwide, state of the art, and multidisciplinary guide to 2-[18F]FDG PET/CT RT planning in NSCLC and SCLC. These practical recommendations describe applicable updates for existing clinical practices, highlight potential flaws, and provide solutions to overcome these as well. Finally, the recent developments considered for future application are also reviewed.

Background and Purpose: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers. Methods: We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis. Results: We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0–3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 [95% CI, 0.5–1.2]). Conclusions: Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS.