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Background: Stroke patients with large vessel occlusions risk long-term or permanent sickness absence. We aimed to analyze the proportions and days of sickness absence and disability pension in thrombectomy-treated patients., Methods: A register-based nationwide longitudinal cohort study of stroke patients treated with mechanical thrombectomy in 2016-2021 in Sweden (identified through the Swedish Board of Health and Welfare procedural code for care interventions, KVÅ:AAL15). All thrombectomy-treated patients aged 18-63 were followed one year prior and one after stroke. Proportions (%) and number of net days of sickness absence and disability pension were calculated. Predictors for absence were calculated through multinomial regression analysis., Results: We included 672 patients, mean age was 53 years and 66 % were men. The proportion of patients on sickness absence decreased from 70.4 % at 30 days to 63.2 % at 90 days after stroke onset. Proportions of sickness absence and disability pension did not differ between women and men after treatment. Amongst predictors for having full-time absence at 90 days were: OR (95 % CI) being born in Europe (excl. Nordic countries) 2.17 (1.15-4.11), being single 1.59 (1.12-2.26), elementary education 2.08 (1.21-3.57), and living in a town or suburb 1.47 (1.01-2.14). Patients with no income 0.21 (0.13-0.35) or the lowest income level 0.36 (0.22-0.58) had low odds for full-time sickness absence and disability pension at 90 days., Conclusions: One third of thrombectomy-treated patients had no sickness absence nor disability pension at day 30 after stroke, and the proportion of patients without absence increased during follow-up. Absence proportions and predictors for full-time absence were centered around income level, educational level, birth country, and type of living area. Notably, there were no sex differences., Competing Interests: Declaration of competing interest The authors have no declarations of interest., (Copyright © 2025. Published by Elsevier Inc.)

Introduction: Mechanical thrombectomy (MT) is the standard of care in anterior circulation large vessel occlusion. A vital modifiable factor is successful reperfusion. While multiple passes improve the rates of successful reperfusion, previous studies have reported progressively diminishing returns. This study aimed to investigate the relationship between number of passes and outcomes in basilar artery occlusion (BAO)., Methods: This multicentre retrospective cohort study included patients who were treated with MT for acute BAO from eight comprehensive stroke centres between 2015 and 2020. The primary outcome was favourable functional outcome (FFO) defined as modified Rankin Scale (mRS) 0-3 measured at 90 days. Secondary outcomes included spontaneous intracranial haemorrhage and mortality. Patients were stratified according to reperfusion status and the number of passes for further analysis., Results: The adjusted odds ratio (OR) for FFO 90 days for each additional pass of a thrombectomy device was 0.56 ( P = 0.003). When ≤3 passes of the thrombectomy device were made, achieving reperfusion led to higher rates of FFOs. However, when >3 passes of the thrombectomy device were made, achieving reperfusion no longer led to higher rates of FFOs (FFO = 0% in patients who did not achieve reperfusion vs. FFO = 14.5 in patients who achieved reperfusion; P = 0.200). Notably, increasing number of passes was associated with a non-significant trend towards higher rate of parenchymal haemorrhage (OR 1.55, P = 0.055)., Conclusion: Acute BAO patients treated with up to three passes of a thrombectomy device derived improved functional outcomes from reperfusion compared to those with more than three passes. Further prospective cohort studies are necessary to validate these findings., (Copyright © 2025 Singapore Medical Journal.)

Background Symptomatic acute occlusions of the internal carotid artery (ICA) below the circle of Willis can cause a variety of stroke symptoms, even if the major intracranial cerebral arteries remain patent; however, outcome and safety data are limited. Purpose To compare treatment effects and procedural safety of endovascular treatment (EVT) and best medical treatment (BMT) in patients with symptomatic acute occlusions of the ICA below the circle of Willis. Materials and Methods This retrospective, multicenter cohort study from 22 comprehensive stroke centers in Europe and Asia includes patients treated between January 1, 2008, and December 31, 2022. Functional (modified Rankin Scale [mRS]) and clinical (National Institutes of Health Stroke Scale [NIHSS]) outcomes, safety measures (symptomatic intracerebral hemorrhage), mortality, and procedural complications were assessed. Results A total 354 patients met the inclusion criteria (median age, 72 years [IQR, 60-81 years]; median NIHSS, 13 [IQR, 7-19]). Most frequent occlusions were in the C1 segment (243 of 354; 68.6%). Of 354 patients, 82.2% (291 patients) were administered EVT. In the overall population, favorable outcomes (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage occurred in 40.6% (108 of 266 patients), 25.2% (67 of 266 patients), and 7.1% (25 of 350 patients), respectively. After adjustment, no statistically significant difference in functional outcome was observed (adjusted odds ratio [AOR], 0.82 [95% CI: 0.31, 2.12]; average treatment effect, -12.7%; P = .19) in the EVT compared with BMT group. Symptomatic intracerebral hemorrhage (average treatment effect, -0.28%; P = .95) and mortality did not differ between both groups (average treatment effect, -17.1%; P = .07). EVT resulted in complete recanalization of the occlusion in 80.9% (229 of 283) of cases. Periprocedural distal embolization occurred in 27.8% (81 of 291 patients) and was associated with poor outcomes (AOR, 0.41; 95% CI: 0.18, 0.93; P = .03). Conclusion EVT did not reveal a favorable treatment effect over BMT, and both therapies were safe. EVT had a risk for periprocedural distal embolization associated with poor outcomes. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Daou and Chaudhary in this issue.

Objective: Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs., Methods: In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study., Results: Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03-1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18-12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00-1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0-306.7, p < 0.001)., Conclusions: Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.

Background: Numerous questions regarding procedural details of distal stroke thrombectomy remain unanswered. This study assesses the effect of anesthetic strategies on procedural, clinical and safety outcomes following thrombectomy for distal medium vessel occlusions (DMVOs)., Methods: Patients with isolated DMVO stroke from the TOPMOST registry were analyzed with regard to anesthetic strategies (ie, conscious sedation (CS), local (LA) or general anesthesia (GA)). Occlusions were in the P2/P3 or A2-A4 segments of the posterior and anterior cerebral arteries (PCA and ACA), respectively. The primary endpoint was the rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3) and the secondary endpoint was the rate of modified Rankin Scale score 0-1. Safety endpoints were the occurrence of symptomatic intracranial hemorrhage and mortality., Results: Overall, 233 patients were included. The median age was 75 years (range 64-82), 50.6% (n=118) were female, and the baseline National Institutes of Health Stroke Scale score was 8 (IQR 4-12). DMVOs were in the PCA in 59.7% (n=139) and in the ACA in 40.3% (n=94). Thrombectomy was performed under LA±CS (51.1%, n=119) and GA (48.9%, n=114). Complete reperfusion was reached in 73.9% (n=88) and 71.9% (n=82) in the LA±CS and GA groups, respectively (P=0.729). In subgroup analysis, thrombectomy for ACA DMVO favored GA over LA±CS (aOR 3.07, 95% CI 1.24 to 7.57, P=0.015). Rates of secondary and safety outcomes were similar in the LA±CS and GA groups., Conclusion: LA±CS compared with GA resulted in similar reperfusion rates after thrombectomy for DMVO stroke of the ACA and PCA. GA may facilitate achieving complete reperfusion in DMVO stroke of the ACA. Safety and functional long-term outcomes were comparable in both groups., Competing Interests: Competing interests: JF: Consulting fees from Cerenovus, Medtronic, Phenox, Penumbra, Roche, Tonbridge; participation on a Data Safety Monitoring Board of Stryker and Phenox; stock holdings for Tegus and Vastrax, Associate Editor for JNIS. RC: Consultant and/or proctor for BALT, Stryker, Microvention, Rapid Medical, Siemens Medical Systems. MM: Institutional grants: Balt, Medtronic, MicroVention, Stryker. AG: Proctor/consultant/speaker for Medtronic, Stryker and Penumbra. MM-G: Consultant for Medtronic, Stryker and Balt, Associate Editor for JNIS. FD: Grant from Cerenovus/ Johnson&Johnson, consulting fees from Cerus Endovascular, Balt, Cerenovus/Johnson&Johnson, honoraria for lectures Asahi, Cerenovus/Johnson&Johnson, Acandis, Stryker, Advisory Board Cerenovus Johnson&Johsno, Associate Editor for JNIS. JK: Grants from SAMW/Bangerter, grants from Swiss Stroke Society, and grants from Clinical Trial Unit Bern outside the submitted work. LLLY: Consultant for Stryker, SeeMode, and See-mode, Cerenovus honoraria, Jakarta Neuroupdate honorarium, Research Support from National Medical research Council (NMRC) Singapore and Ministry of Health (MOH). Stock holdings for Cereflo, SNVIS vice president. BT: Grants from ExxonMobil-NUS Research Fellowship for Clinicians. PN: Consultant/Proctor for Balt, Cerenovus, Medtronic, Penumbra, Stryker. AG: Honoraria for lectures from Stryker Neurovascular, Medtronic, Penumbra. BG: grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial; consulting fees from Air Liquide, MIVI, Medtronic, Microvention, and Penumbra. LM: Compensation as a speaker for Balt Prime. GB: Compensation as a speaker for Balt Prime., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke (AIS) from basilar artery occlusion (BAO)., Objective: To compare the clinical outcomes of MT, with and without bridging intravenous thrombolysis (IVT), in acute BAO through a systematic review and meta-analysis of the current literature., Methods: Systematic searches of Medline, EMBASE, and Cochrane Central were undertaken on August 1, 2022. Good functional outcome defined as 90-day modified Rankin Scale score 0-2 was the primary outcome measure. Secondary outcome measures were 90-day mortality, successful post-thrombectomy recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and subarachnoid hemorrhage (SAH)., Results: Three studies reporting 1096 patients with BAO AIS were included in the meta-analysis. No significant differences in good functional outcome were detected between the two groups (RR=1.28 (95% CI 0.86 to 1.92); p=0.117). However, specifically patients with large artery atherosclerosis (LAA) benefited from bridging IVT (OR=2.52 (95% CI 1.51 to 4.22); p<0.001) with better functional outcomes. There was a significantly lower 90-day mortality rate for patients who underwent bridging IVT compared with MT alone (RR=0.70 (95% CI 0.62 to 0.80); p=0.008). No significant differences were detected in rates of post-treatment recanalization (RR=1.01 (95% CI 0.35 to 2.91); p=0.954), sICH (RR=0.96 (95% CI 0.66 to 1.42); p=0.724), and SAH (RR=0.93 (95% CI 0.31 to 2.83); p=0.563)., Conclusions: In patients with AIS due to BAO, bridging IVT was associated with lower mortality rates at 90 days, compared with direct MT. There were no improved functional outcomes or increased sICH or SAH between both arms, However, patients with LAA benefited from bridging IVT, with better functional outcomes., Competing Interests: Competing interests: GA: Stryker Neurovascular, Penumbra Inc, Medtronic: payments were received by the employer for consulting and proctoring assignments., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Evidence supporting a potential benefit of thrombectomy for distal medium vessel occlusions (DMVOs) of the anterior cerebral artery (ACA) is, to the knowledge of the authors, unknown. Purpose To compare the clinical and safety outcomes between mechanical thrombectomy (MT) and best medical treatment (BMT) with or without intravenous thrombolysis for primary isolated ACA DMVOs. Materials and Methods Treatment for Primary Medium Vessel Occlusion Stroke, or TOPMOST, is an international, retrospective, multicenter, observational registry of patients treated for DMVO in daily practice. Patients treated with thrombectomy or BMT alone for primary ACA DMVO distal to the A1 segment between January 2013 and October 2021 were analyzed and compared by one-to-one propensity score matching (PSM). Early outcome was measured by the median improvement of National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours. Favorable functional outcome was defined as modified Rankin scale scores of 0-2 at 90 days. Safety was assessed by the occurrence of symptomatic intracerebral hemorrhage and mortality. Results Of 154 patients (median age, 77 years; quartile 1 [Q1] to quartile 3 [Q3], 66-84 years; 80 men; 94 patients with MT; 60 patients with BMT) who met the inclusion criteria, 110 patients (median age, 76 years; Q1-Q3, 67-83 years; 50 men; 55 patients with MT; 55 patients with BMT) were matched. DMVOs were in A2 (82 patients; 53%), A3 (69 patients; 45%), and A3 (three patients; 2%). After PSM, the median 24-hour NIHSS point decrease was -2 (Q1-Q3, -4 to 0) in the thrombectomy and -1 (Q1-Q3, -4 to 1.25) in the BMT cohort ( P = .52). Favorable functional outcome (MT vs BMT, 18 of 37 [49%] vs 19 of 39 [49%], respectively; P = .99) and mortality (MT vs BMT, eight of 37 [22%] vs 12 of 39 [31%], respectively; P = .36) were similar in both groups. Symptomatic intracranial hemorrhage occurred in three (2%) of 154 patients. Conclusion Thrombectomy appears to be a safe and technically feasible treatment option for primary isolated anterior cerebral artery occlusions in the A2 and A3 segment with clinical outcomes similar to best medical treatment with and without intravenous thrombolysis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhu and Wang in this issue.

Background: Endovascular thrombectomy (EVT) for ischemic stroke (IS) beyond 6 hours has been proven effective in randomized controlled trials. We present data on implementation and outcomes for EVT beyond 6 hours in Sweden., Methods: We included all cases of anterior circulation IS caused by occlusion of the intracranial carotid artery, and the M1 or M2 segment of the middle cerebral artery, registered in two nationwide quality registers for stroke in 2015-2020. Three groups were defined from onset-to-groin-puncture (OTG) time: early window (<6 hours), late window (6-24 hours) known onset, late window last seen well (LSW). Favorable outcome (modified Rankin Scale (mRS) 0-2) and all-cause mortality at 90 days were the main outcomes, and symptomatic intracerebral hemorrhage (sICH) was the safety outcome., Results: Late window EVT increased from 0.3% of all IS in 2015 to 1.8% in 2020, and from 17.4% of all anterior circulation EVTs in 2015 to 32.9% in 2020. Of 2199 patients, 76.9% (n=1690) were early window EVTs and 23.1% late window EVTs (n=509; 141 known onset, 368 LSW). Median age was 73 years, and 46.2% were female, with no differences between groups. Favorable outcome did not differ between groups (early window 42.4%, late window known onset 38.9%, late window LSW 37.3% (p=0.737)) and remained similar when adjusted for baseline differences. sICH rates did not differ (early window 4.0%, late window known onset 2.1%, late window LSW 4.9% (p=0.413))., Conclusion: Late window EVTs have increased substantially over time, and currently account for one third of anterior circulation treatments. Early and late window patients had similar outcomes., Competing Interests: Competing interests: BN has received honoraria from AstraZeneca for serving on the DSMB for the THALES trial. TU has received honoraria from AstraZeneca for an expert group assignment. JW is a shareholder for UmanSense AB. FA has received grants from Stryker and Cerenovus. MvE receive honoraria from the Committee for Clinical Therapy Research. TA received honoraria from Anaconda, Cerenovus, Stryker. TA also received honoraria for serving on the DSMB for the Excellent registry, SPERO and Solonda studies, and is a shareholder on Rapid Medical and Ceroflo. PW is a clinical adjudication member in Portico 1 and Portico IDE phase IV studies supported from Abbott., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of a combination of balloon guide catheter (BGC), aspiration catheter, and stent retriever in acute ischemic stroke thrombectomy has not been shown to be better than a stent retriever and BGC alone, but this may be due to a lack of power in these studies. We therefore performed a meta-analysis on this subject., Methods: A systematic literature search was performed on PubMed, Scopus, Embase/Ovid, and the Cochrane Library from inception to October 20, 2021. Our primary outcomes were the rate of successful final reperfusion (Treatment in Cerebral Ischemia (TICI) 2c-3) and first pass effect (FPE, defined as TICI 2c-3 in a single pass). Secondary outcomes were 3 month functional independence (modified Rankin Scale score of 0-2), mortality, procedural complications, embolic complications, and symptomatic intracranial hemorrhage (SICH). A meta-analysis was performed using RevMan 5,4, and heterogeneity was assessed using the I 2 test., Results: Of 1629 studies identified, five articles with 2091 patients were included. For the primary outcomes, FPE (44.9% vs 45.4%, OR 1.04 (95% CI 0.90 to 1.22), I 2 =57%) or final successful reperfusion (64.5% vs 68.6%, OR 0.98 (95% CI 0.81% to 1.20%), I 2 =85%) was similar between the combination technique and stent retriever only groups. However, the combination technique had significantly less rescue treatment (18.8% vs 26.9%; OR 0.70 (95% CI 0.54 to 0.91), I 2 =0%). This did not translate into significant differences in secondary outcomes in functional outcomes, mortality, emboli, complications, or SICH., Conclusion: There was no significant difference in successful reperfusion and FPE between the combined techniques and the stent retriever and BGC alone groups. Neither was there any difference in functional outcomes, complications, or mortality., Competing Interests: Competing interests: LM received compensation as a speaker for Balt., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular thrombectomy (EVT) is standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO), but data on nationwide performance in routine healthcare are sparse. The study aims were to describe EVT patients with LVO AIS, analyze mortality and functional outcome, and compare results with randomized controlled trials (RCTs)., Methods: Data from the Riksstroke and the Swedish Endovascular Treatment of Acute Stroke Registry (RSEVAS) on pre-stroke independent patients, with LVO AIS in 2017-2019, defined as occlusion of the intracranial internal carotid artery, or the M1 or M2 segments of the middle cerebral artery, and groin puncture <6 h of onset, were compared to aggregated HERMES collaboration RCT data. We assessed 90-day survival and function, defined by the modified Rankin Scale. Specific analyzes were stratified by occlusion location., Results: In all, 1011/2560 of RSEVAS patients matched RCT inclusion criteria. Compared with RCT data, patients were older (73 vs. 68), fewer received intravenous thrombolysis (63.1% vs. 83%), and M2 occlusions were more common (24.5% vs. 8%). 90-day survival in RSEVAS was 85.3%, 42.8% achieved good outcome and 5% had symptomatic intracerebral hemorrhage (sICH). Corresponding outcomes in RCT data were 84.7% survival, 46% good outcome, and 4.4% sICH. Functional outcome was most favorable following M2 occlusions., Conclusions: EVT patients from our large real-world national dataset differed from RCT patients in several baseline factors including distribution of vascular occlusion site. However, the overall outcome of EVT in our Swedish cohort appeared to well match the pivotal trial findings.

Background: The optimal endovascular strategy for reperfusing distal medium-vessel occlusions (DMVO) remains unknown. This study evaluates angiographic and clinical outcomes of thrombectomy strategies in DMVO stroke of the posterior circulation., Methods: TOPMOST (Treatment for Primary Medium Vessel Occlusion Stroke) is an international, retrospective, multicenter, observational registry of patients treated for DMVO between January 2014 and June 2020. This study analyzed endovascularly treated isolated primary DMVO of the posterior cerebral artery in the P2 and P3 segment. Technical feasibility was evaluated with the first-pass effect defined as a modified Thrombolysis in Cerebral Infarction Scale score of 3. Rates of early neurological improvement and functional modified Rankin Scale scores at 90 days were compared. Safety was assessed by the occurrence of symptomatic intracranial hemorrhage and intervention-related serious adverse events., Results: A total of 141 patients met the inclusion criteria and were treated endovascularly for primary isolated DMVO in the P2 (84.4%, 119) or P3 segment (15.6%, 22) of the posterior cerebral artery. The median age was 75 (IQR, 62-81), and 45.4% (64) were female. The initial reperfusion strategy was aspiration only in 29% (41) and stent retriever in 71% (100), both achieving similar first-pass effect rates of 53.7% (22) and 44% (44; P =0.297), respectively. There were no significant differences in early neurological improvement (aspiration: 64.7% versus stent retriever: 52.2%; P =0.933) and modified Rankin Scale rates (modified Rankin Scale score 0-1, aspiration: 60.5% versus stent retriever 68.6%; P =0.4). In multivariable logistic regression analysis, the time from groin puncture to recanalization was associated with the first-pass effect (adjusted odds ratio, 0.97 [95% CI, 0.95-0.99]; P <0.001) that in turn was associated with early neurological improvement (aOR, 3.27 [95% CI, 1.16-9.21]; P <0.025). Symptomatic intracranial hemorrhage occurred in 2.8% (4) of all cases., Conclusions: Both first-pass aspiration and stent retriever thrombectomy for primary isolated posterior circulation DMVO seem to be safe and technically feasible leading to similar favorable rates of angiographic and clinical outcome.

Background: Endovascular thrombectomy (EVT) in large vessel occlusion (LVO) in anterior circulation acute ischaemic stroke (AIS) results in good functional outcomes in only approximately 60% of the patients. Internal cerebral veins (ICVs) are easily visible, with a consistent midline location, and are linked to stroke outcomes. We hypothesize that ICV asymmetry on multiphasic CT angiogram (mCTA) can be an adjunctive predictor for poor functional outcomes., Methods: We studied consecutive AIS patients from 2017 to 2019 with anterior circulation LVO treated with EVT regardless of intravenous thrombolysis. Asymmetrical ICV was defined as the presence of hypodensity (less opacification) on the ipsilateral occlusion side as compared with the contralateral side. The primary outcome was modified Rankin Score (mRS) score at 3 months. Secondary outcomes were good recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3), symptomatic hemorrhage, and mortality., Results: A total of 185 patients were included with a median age of 70 years (IQR 59-77); 87 patients (47%) were female. 82 patients (44.3%) achieved good functional outcomes (mRS 0-2) at 3 months. On multivariate analysis, National Institutes of Health Stroke Scale (NIHSS) (OR 1.076, 95% CI 1.015 to 1.140; p<0.013), poor collateral score (OR 0.285, 95% CI 0.162 to 0.501; p<0.001), asymmetrical ICV on the peak venous phase (OR 2.47, 95% CI 1.115 to 5.471; p<0.026), and late venous phase of the mCTA (OR 2.642, 95% CI 1.161 to 6.016; p<0.021) were independent risks factors of poor outcomes., Conclusion: ICV asymmetry is a novel radiological sign which is independently associated with poor functional outcomes in EVT, even after correction for collateral circulation. Further studies are needed to validate this finding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered., Objective: To investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO)., Methods: TOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events., Results: Among 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71)., Conclusion: Thrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment., Competing Interests: Competing interests: JF: research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus. PP: consultant for Penumbra and Ab Medica. AG: has served as proctor/consultant/speaker for Medtronic, Stryker, and Penumbra M. MM-G: consultant of Medtronic, Stryker, and Balt. FD: research support from Cerenovus; consultant for Cerus Endovascular, AB Medica, and Phenox; speaker honorary from Acandis, Cerenovus. JK reports grants from SAMW/Bangerter, grants from Swiss Stroke Society, and grants from Clinical Trial Unit Bern outside the submitted work. LLLY: consultant for Stryker and SeeMode; research support from National Medical Research Council (NMRC) Singapore and Ministry of Health (MOH); stock holdings for Cereflo. PBS: consultant/proctor for Balt, Acandis, Microvention. RC: consultant and/or proctor for BALT, Stryker, Microvention, Rapid Medical, Siemens Medical Systems. PN: consultant/proctor for Balt, Stryker, and Penumbra. KZ: support under the Operational Programme Integrated Infrastructure for the project: TENSION – complementary project, IMTS: 313011W875, co-financed by the European Regional Development Fund., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1-2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited., Objectives: To characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy., Methods: One-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected., Results: We identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich ( n = 3), adipocyte-like pattern-rich ( n = 2), collagen-rich ( n = 2) and myxomatous ( n = 1) thrombi were also identified and are discussed with regard to pathogenesis and clinical and intervention characteristics. Finally, a thrombus with parts of a vascular wall is described. Suggestions for future studies are made and clinical and technical aspects of the management for these rare but important patients are discussed., Conclusion: In our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aspegren, Staessens, Vandelanotte, Desender, Cordonnier, Puy, Bricout, De Meyer, Andersson and Arnberg.)

Acute ischemic stroke caused by large vessel occlusion is treated with endovascular thrombectomy, but treatment failure may occur when clot composition and thrombectomy technique mismatch. In this proof-of-concept study, diffuse reflectance spectroscopy (DRS) is evaluated for identification of clot composition ex vivo. DRS spectra and histology were acquired from 45 clot units retrieved from 29 stroke patients. DRS spectra correlated to clot RBC content, R= 81, p < .001, and could discriminate between RBC-rich and fibrin-rich clots, p < 0.001. Sensitivity and specificity for detection of RBC-rich clots were 0.722 and 0.846 respectively. Applied in an intravascular device, DRS could potentially provide intraprocedural information on clot composition that could increase endovascular thrombectomy efficiency., Competing Interests: T.A. holds equity for Ceroflo and is a consultant for Amnis Therapeutics, Anaconda, Cerenovus-Neuravi, Medtronic, Rapid Medical and Stryker. None of the authors who are affiliated with clinical institutions or universities (S.S, G.B, E.E, O.A, A.E.-T, F.A, T.A.) have financial interests in the subject matter, materials, or equipment or with any competing materials and did not receive any payments from Philips. Karolinska University hospital and Philips have a major collaboration agreement. The authors affiliated with Philips Research (M.M, G.L.) have financial interests in the subject matter, materials, and equipment, in the sense that they are employees of Philips. Philips provided support in the form of salaries but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors without conflicts of interest had full control of all data labelling, data analysis and information submitted for publication and over all conclusions drawn in the manuscript., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

The objective of the study was to investigate the safety profile of high-risk micro-endomyocardial biopsy (micro-EMB) compared to conventional EMB in a large animal model. Twenty pigs were subjected to a maximum of 30 consecutive biopsies, including sampling from the free ventricular wall, with either micro-EMB (n = 10) or conventional EMB (n = 10). There were no major complications in the micro-EMB group (0/10), compared to six major complications in the EMB group (6/10; p = 0.003). Survival analysis further highlighted these differences (p = 0.004). There were significantly higher volumes of pericardial effusion in the EMB group (p = 0.01). The study shows a safety advantage of micro-EMB compared to standard EMB in the experimental high-risk circumstances investigated in this animal study. These results indicate enhanced possibilities to collect samples from sensitive areas by using the micro-EMB technique instead of standard EMB., (© 2021. The Author(s).)

Introduction: Outcomes after mechanical thrombectomy (MT) in young stroke patients remain elusive due to small patient cohorts. We sought to determine outcomes after MT in stroke patients between ages 18 and 64 years and compare with outcomes in older patients in a large national stroke cohort., Patients and Methods: We used the Swedish National Stroke Registry and the Swedish National Endovascular Thrombectomy Registry to identify all patients treated with MT for anterior circulation occlusions. We examined outcome measures in terms of functional independence at 90 days (modified Rankin Scale score of 0-2), symptomatic intracerebral hemorrhage (sICH), and mortality at 90 days with multivariable logistic regression analysis., Results: Of 2143 patients, 565 were between 18 and 64 years (26.4%) and 1179 (55.0%) were males. Analysis showed that patient aged 18-64 achieved higher rate of functional independence at 90 days (46.2% vs 28.4%, p < .001), had less often sICH (5.5% vs 6.8%, p = .008), and lower 90-day mortality rate (6.9% vs 17.7%, p < .001). Increasing age was associated with a lesser probability of functional independence at 90 days (adjusted odds ratio (aOR), 0.94; [95% confidence intervals (CIs) 0.93-0.95]), higher odds of mortality at 90 days (aOR, 1.05; [95% CIs 1.03-1.06]), and of sICH (aOR 1.03; [95% CIs 1.01-1.05])., Conclusion: Patients aged 18-64 years demonstrated better outcome after thrombectomy regarding functional independence, sICH, and mortality at 90 days when compared to older ages., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TA is a consultant for Amnis Therapeutics, Anaconda, Cerenovus - Neuravi, Rapid Medical and Stryker., (© European Stroke Organisation 2022.)

This review describes the evolution of endovascular treatment for acute ischemic stroke, current state of the art, and the challenges for the next decade. The rapid development of endovascular thrombectomy (EVT), from the first attempts into standard of care on a global scale, is one of the major achievements in modern medicine. It was possible thanks to the establishment of a scientific framework for patient selection, assessment of stroke severity and outcome, technical development by dedicated physicians and the MedTech industry, including noninvasive imaging for patient selection, and radiological outcome evaluation. A series of randomized controlled trials on EVT in addition to intravenous thrombolytics, with overwhelmingly positive results for anterior circulation stroke within 6 h of onset regardless of patient characteristics with a number needed to treat of less than 3 for any positive shift in outcome, paved the way for a rapid introduction of EVT into clinical practice. Within the "extended" time window of 6-24 h, the effect has been even greater for patients with salvageable brain tissue according to perfusion imaging with a number needed to treat below 2. Even so, EVT is only available for a small portion of stroke patients, and successfully recanalized EVT patients do not always achieve excellent functional outcome. The major challenges in the years to come include rapid prehospital detection of stroke symptoms, adequate clinical and radiological diagnosis of severe ischemic stroke cases, enabling effective recanalization by EVT in dedicated angiosuites, followed by personalized post-EVT stroke care., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Endovascular thrombectomy has revolutionized the management of acute ischemic stroke and proven superior to stand-alone intravenous thrombolysis for large vessel occlusions. However, failed or delayed revascularization may occur as a result of a mismatch between removal technique and clot composition. Determination of clot composition before thrombectomy provides the possibility to adapt the technique to improve clot removal efficacy. We evaluated the application of diffuse reflectance spectroscopy (DRS) for intravascular determination of clot composition in vivo., Methods: Three clot types, enriched in red blood cells or fibrin or with a mixed content, were prepared from porcine blood and injected into the external carotids of a domestic pig. A guidewire-like DRS probe was used to investigate the optical spectra of clots, blood and vessel wall. Measurement positions were confirmed with angiography. Spectra were analyzed by fitting an optical model to derive physiological parameters. To evaluate the method's accuracy, photon scattering and blood and methemoglobin contents were included in a decision tree model and a random forest classification., Results: DRS could differentiate between the three different clot types, blood and vessel wall in vivo (p<0.0001). The sensitivity and specificity for detection was 73.8% and 98.8% for red blood cell clots, 80.6% and 97.8% for fibrin clots, and 100% and 100% for mixed clots, respectively., Conclusion: Intravascular DRS applied via a custom guidewire can be used for reliable determination of clot composition in vivo. This novel approach has the potential to increase efficacy of thrombectomy procedures in ischemic stroke., Competing Interests: Competing interests: TA holds equity for Ceroflo and is a consultant for Amnis Therapeutics, Anaconda, Cerenovus-Neuravi, Medtronic, Rapid Medical and Stryker. None of the authors who are affiliated with clinical institutions or universities (SS, GB, EE, OA, AE-T, FA, TA) have financial interests in the subject matter, materials, or equipment or with any competing materials and did not receive any payments from Philips. Karolinska University hospital and Philips Healthcare have a major collaboration agreement. The authors affiliated with Philips Research and Philips Healthcare (MM, GL) have financial interests in the subject matter, materials, and equipment, in the sense that they are employees of Philips. Philips provided support in the form of salaries but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Authors without conflicts of interest had full control of all data labeling, data analysis and information submitted for publication and over all conclusions drawn in the manuscript., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The vasodilatory response to inhaled CO 2 occurs in the acute stroke ischemic penumbra and may be a potential therapeutic modality., Methods: Twenty-two Sprague-Dawley rats were subjected to 90-min occlusion of the M2 segment of the middle cerebral artery (M2CAO) by endovascular technique. The animals were administered different C02 concentrations and scanned serially with 9.4 T MRI. Infarct tissue was determined by diffusion-weighted imaging (DWI) and hypoperfused tissue was determined by arterial spin labeling (PWI)., Results: 4 animals were administered room air (RA)+ 6% CO 2 (group 1), 6 animals RA+12% CO 2 (Group 2) and 4 animals only RA (group 3). In the rats with CO 2 administered (groups 1 and 2), the DWI lesion to cerebral hypoperfusion volume ratio (SD) at pre-CO 2 administration, was 0.145(0.168), which increased to 0.708(0.731) during CO 2 administration and reduced to 0.533(0.527) post-CO 2 administration. In 9 of 10 rats the hypoperfused volume decreased when CO 2 was administered. When CO 2 was stopped the hypoperfused volume became larger again. Administration of RA+12% CO 2 (Group 2) decreased the volume of CBF hypoperfusion significantly compared to the control group (95%CI: 0.084 ± 0.0213, p = 0.004)., Conclusion: Inhaled CO 2 appears to reduce the size of the hypoperfused tissue volume during acute stroke and may be a potential modality for treatment of acute ischemic stroke. These findings will nonetheless need to be validated in a larger cohort in other centers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yeo, Arnberg, Chireh, Sharma, Tan, Gontu, Little and Holmin.)

Introduction: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO., Methods: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH)., Results: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups., Conclusion: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background and Purpose: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT., Methods: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH)., Results: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013)., Conclusions: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

Endovascular thrombectomy (EVT) has been validated in several randomized controlled trials in recent years for its efficacy in the treatment of acute ischemic strokes (AIS) and is now the standard of care according to international guidelines. However, in about 20% of EVT procedures, recanalization is not achieved, and over 50% of patients who undergo EVT still do not have good functional outcome. In this article, we provide an extensive review of the latest evidence and developments in the field of EVT, with particular focus on the factors that improve patient outcomes. These factors include new and adjunctive techniques such as combination of direct aspiration and stent retriever, intra-arterial urokinase or 2b/3a inhibitors, rescue stenting, as well as novel devices including balloon guide catheters and the newer generations of aspiration catheters and stent retrievers. We also examined the latest notion of using first-pass effect (FPE) as the target to achieve during EVT, which has been associated with an improved functional outcome. While the field of EVT has been rapidly evolving, further research is required in specific AIS patient populations such as those with large ischemic core, late presentation beyond 24 h, posterior circulation strokes, and with distal medium vessel occlusion or tandem lesions to better assess its efficacy and safety., Competing Interests: TA is a consultant for Ablynx, Amnis Therapeutics, Medtronic, Cerenovus/J&J, Rapid Medical and Anaconda. AG is a consultant for Stryker, Medtronic, Penumbra and has received educational grants from Abbott. PB is consultant for Phenox. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yeo, Jing, Bhogal, Tu, Gopinathan, Yang, Tan, Arnberg, Sia, Holmin and Andersson.)

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT., (© 2021 European Academy of Neurology.)

Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints., Competing Interests: AC, RG, MS, and SH are board members of Microcardix AB, which holds pending patents for the micro-EMB device (Patent Cooperation Treaty application no. WO2020089422A1). RG, JL, and SH own shares in SmartCella Holding AB, whose subsidiaries have interests in catheter technology and regenerative cardiology. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse., Objective: To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice., Design, Setting, and Participants: This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching., Interventions: Mechanical thrombectomy or standard medical treatment with or without IVT., Main Outcomes and Measures: Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up., Results: Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P = .06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P = .04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P = .005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort., Conclusions and Relevance: This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.

PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [ 18 F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [ 64 Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [ 18 F]FMISO ( n  = 12) or [ 64 Cu]CuATSM ( n  = 6) examinations. [ 64 Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [ 18 F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [ 18 F]FMISO uptake in the M2CAO cortex. No increase in [ 64 Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [ 18 F]FMISO is superior to [ 64 Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [ 18 F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [ 64 Cu]CuATSM in experimental AIS.

Background: Albumin is commonly used as a carrier platform for drugs to extend their circulatory half-lives and influence their uptake into tissues that have altered permeability to the plasma protein. The albumin-binding domain (ABD) protein, which binds in vivo to serum albumin with high affinity, has proven to be a versatile scaffold for engineering biopharmaceuticals with a range of binding capabilities. In this study, the ABD protein equipped with a mal-DOTA chelator (denoted ABY-028) was radiolabeled with gallium-68 ( 68 Ga). This novel radiotracer was then used together with positron emission tomography (PET) imaging to examine variations in the uptake of the ABD-albumin conjugate with variations in endothelial permeability., Results: ABY-028, produced by peptide synthesis in excellent purity and stored at - 20 °C, was stable for 24 months (end of study). [ 68 Ga]ABY-028 could be obtained with labeling yields of > 80% and approximately 95% radiochemical purity. [ 68 Ga]ABY-028 distributed in vivo with the plasma pool, with highest radioactivity in the heart ventricles and major vessels of the body, a gradual transport over time from the circulatory system into tissues and elimination via the kidneys. Early [ 68 Ga]ABY-028 uptake differed in xenografts with different vascular properties: mean standard uptake values (SUV mean ) were initially 5 times larger in FaDu than in A431 xenografts, but the difference decreased to 3 after 1 h. Cutaneously administered, vasoactive nitroglycerin increased radioactivity in the A431 xenografts. Heterogeneity in the levels and rates of increases of radioactivity uptake was observed in sub-regions of individual MMTV-PyMT mammary tumors and in FaDu xenografts. Higher uptake early after tracer administration could be observed in lower metabolic regions. Fluctuations in the increased permeability for the tracer across the blood-brain-barrier (BBB) direct after experimentally induced stroke were monitored by PET and the increased uptake was confirmed by ex vivo phosphorimaging., Conclusions: [ 68 Ga]ABY-028 is a promising new tracer for visualization of changes in albumin uptake due to disease- and pharmacologically altered vascular permeability and their potential effects on the passive uptake of targeting therapeutics based on the ABD protein technology.

Endomyocardial biopsy is a valuable tool in cardiac diagnostics but is limited by low diagnostic yield and significant complication risks. Meanwhile, recent developments in transcriptomic and proteomic technologies promise a wealth of biological data from minimal tissue samples. To take advantage of the minimal tissue amount needed for molecular analyses, we have developed a sub-millimeter endovascular biopsy device, considerably smaller than current clinical equipment, and devised a low-input RNA-sequencing protocol for analyzing small tissue samples. In in vivo evaluation in swine, 81% of biopsy attempts (n = 157) were successful. High quality RNA-sequencing data was generated from 91% of the sequenced cardiac micro-biopsy samples (n = 32). Gene expression signatures of samples taken with the novel device were comparable with a conventional device. No major complications were detected either during procedures or during 7 days' follow-up, despite acquiring a relatively large number of biopsies (median 30) in each animal. In conclusion, the novel device coupled with RNA-sequencing provides a feasible method to obtain molecular data from the myocardium. The method is less traumatic and has a higher flexibility compared to conventional methods, enabling safer and more targeted sampling from different parts of the myocardium.

Placenta-derived decidua stromal cells (DSCs) are being investigated as an alternative to other sources of mesenchymal stromal cells (MSCs) for cellular therapy. DSCs are more effective in treating acute inflammatory diseases in human and this is our preclinical safety study of human DSCs in Sprague-Dawley rats and Balb/c mice. Human DSCs were cultured and expanded from fetal membranes obtained from placentas following cesarean section. In rats, 0.5 × 10 6 cells/kg were injected intravenously ( n = 4) or intra-aortal ( n = 4). In mice, DSCs were given intravenously at doses ranging from 4-40 × 10 6 cells/kg (total of n = 120 mice). In vivo tracking of human cells in mice was performed by using transduced DSC with luciferin gene, and in rats by using 18 F-FDG PET. Clotting parameters were determined in vitro and in vivo . All intra-arterially DSC-treated rats had normal motility and behavior and histological examination was normal for liver, spleen kidneys and thigh muscles. Mice treated with DSCs showed no immediate or long-term side effects. None of the mice died or showed acute toxicity or adverse reactions 3 and 30 days after DSC infusion. Murine blood biochemistry profiles related to liver, kidney, heart, and inflammatory indices was not influenced by DSC infusion and complete blood counts were normal. In vivo tracking of infused DSCs detected a signal in the lungs for up to 4 days post infusion. Compared to bone marrow derived MSCs, the DSCs had better viability, smaller size, but stronger clotting in human blood and plasma. Both MSC- and DSC-induced coagulation and complement activation markers, thrombin-anti-thrombin complex (TAT) and C3a, and in vitro clotting parameters were decreased by heparin supplementation. In conclusion, DSCs are safe with almost no side effects even with doses 40 times higher than are used clinically, particularly when supplemented with low-dose heparin., (Copyright © 2019 Sadeghi, Moretti, Arnberg, Samén, Kohein, Catar, Kamhieh-Milz, Geissler, Moll, Holmin and Ringdén.)

Purpose: In mechanical thrombectomy (MT) for ischemic stroke, endothelial cells (ECs) from intracranial blood vessels adhere to the stent retriever device and can be harvested. However, understanding the molecular biology and the role of the endothelium in different pathological conditions remains insufficient. The purpose of the study was to characterize and analyze the molecular aspect of harvested ECs using cell culture and transcriptomic techniques in an MT swine model relevant to clinical ischemic stroke., Methods: In swine, preformed thrombi were injected into the external carotid and subclavian arteries to occlude their branches. MT was performed according to clinical routine. The stent retriever device and thrombus were treated with cell dissociation buffer. The resulting cell suspension was analyzed by immunohistochemistry and was cultured. Cultured cells were analyzed using single-cell RNA sequencing (scRNA-seq) after fluorescence-activated cell sorting (FACS)., Results: A total number of 37 samples were obtained containing CD31-positive cells. Cell culture was successful in 90% of samples, and the cells expressed multiple typical EC protein markers. Eighty-nine percent of the sorted cells yielded high-quality transcriptomes, and single-cell transcriptomes from cultured cells showed that they expressed typical endothelial gene patterns. Gene expression analysis of ECs from an occluded artery did not show distinctive clustering into subtypes., Conclusion: ECs harvested during MT can be cultured and analyzed using single-cell transcriptomic techniques. This analysis can be implemented in clinical practice to study the EC gene expression of comorbidities, such as hypertension, diabetes mellitus, and metabolic syndrome, in patients suffering from acute ischemic stroke.

Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury., Competing Interests: The authors have declare that no competing interests exist.

Adequate estimation of neuroinflammatory processes following ischemic stroke is essential for better understanding of disease mechanisms, and for the development of treatment strategies. With the TSPO (18 kDa translocator protein) positron emission tomography (PET) radioligand [(11)C]PBR28, we monitored longitudinally the inflammatory response post-transient cerebral ischemia in rats, using a recently developed rat stroke model that produces isolated focal cortical infarcts with clinical relevance in size and pathophysiology. Six Sprague-Dawley rats were subjected to 90 min transient endovascular occlusion of the M2 segment of the middle cerebral artery (M2CAO). Animals were imaged with a nanoScan(®) PET/MRI system at 1, 4, 7 and 14 days after M2CAO with a bolus injection of [(11)C]PBR28. In the infarct region, we found a significantly increased uptake of [(11)C]PBR28 on day 4, 7 and 14 compared to day 1 as well as compared to the contralateral cortex. No significant increase was detected in the contralateral cortex during the 14 days of imaging. The activation in the infarct region gradually decreased between day 4 and day 14. In an additional group of animals (n = 26), immunofluorescence studies were performed with antibodies for activated microglia/monocytes (Cd11b), phagocytes (Cd68), astrocytes (glial fibrillary acidic protein) and TSPO. The TSPO immunofluorescence signal indicated reactive microgliosis post injury, corresponding to PET findings. The present clinically relevant animal model and TSPO PET ligand appear to be well suited for studies on neuroinflammation after ischemic stroke.

Selective administration of mesenchymal stromal cells to the mesenteric arteries is a potential technique to overcome pulmonary trapping and increase the density of transplanted cells in extensive mural inflammation of the intestine, such as in inflammatory bowel disease and graft-versus-host disease. We injected 5 × 10(6) (111)In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit superior mesenteric artery (SMA) using clinical routine catheters guided by an angiographical system under sterile conditions. We used longitudinal single-photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking and distribution of DSCs. We used digital subtraction angiography, computed tomography, and hematoxylin and eosin stainings to determine biodistribution of cells and to assess safety end points. We found that selective injection of human DSCs to the rabbit SMA does not result in acute embolic complications. Furthermore, we found that IV administration resulted in extensive retention of the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary trapping. In sharp contrast, selective injections to the SMA resulted in uptake distributed in the intestine supplied by the SMA and in the liver, indicating that this approach could significantly increase the fraction of injected DSCs reaching the target tissue.

Background and Purpose: Ischemic stroke has been shown to cause hypermetabolism of glucose in the ischemic penumbra. Experimental and clinical data indicate that infarct-related systemic hyperglycemia is a potential therapeutic target in acute stroke. However, clinical studies aiming for glucose control in acute stroke have neither improved functional outcome nor reduced mortality. Thus, further studies on glucose metabolism in the ischemic brain are warranted., Methods: We used a rat model of stroke that preserves collateral flow. The animals were analyzed by [2-(18)F]-2-fluoro-2-deoxy-d-glucose positron emission tomography or magnetic resonance imaging during 90-minute occlusion of the middle cerebral artery and during 60 minutes after reperfusion. Results were correlated to magnetic resonance imaging of cerebral blood flow, diffusion of water, lactate formation, and histological data on cell death and blood-brain barrier breakdown., Results: We detected an increased [2-(18)F]-2-fluoro-2-deoxy-d-glucose uptake within ischemic regions succumbing to infarction and in the peri-infarct region. Magnetic resonance imaging revealed impairment of blood flow to ischemic levels in the infarct and a reduction of cerebral blood flow in the peri-infarct region. Magnetic resonance spectroscopy revealed lactate in the ischemic region and absence of lactate in the peri-infarct region. Immunohistochemical analyses revealed apoptosis and blood-brain barrier breakdown within the infarct., Conclusions: The increased uptake of [2-(18)F]-2-fluoro-2-deoxy-d-glucose in cerebral ischemia most likely reflects hypermetabolism of glucose meeting increased energy needs of ischemic and hypoperfused brain tissue, and it occurs under both anaerobic and aerobic conditions measured by local lactate production. Infarct-related systemic hyperglycemia could serve to facilitate glucose supply to the ischemic brain. Glycemic control by insulin treatment could negatively influence this mechanism., (© 2015 American Heart Association, Inc.)

Introduction: The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery., Methods: All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG)., Results: Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of (18)F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue., Conclusion: Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers.

Prothrombin complex concentrates (PCC) can rapidly normalise prolonged prothrombin time, induced by vitamin K antagonists (VKA). We conducted a multicentre retrospective study to investigate whether reversal of VKA coagulopathy with 4-factor PCC improves the survival of patients with VKA-related intracerebral haemorrhage as compared to plasma.We included 135 consecutive patients with VKA-related intracerebral haemorrhage treated either with plasma (mainly in Canada) or 4-factor PCC (The Netherlands and Sweden) for the reversal of VKA. Data on characteristics of the patients and the haemorrhage were collected. The volume of intracerebral haematoma was calculated from the first computed tomography (CT) scan. The unadjusted and adjusted odds ratio (OR) for 30-day all-cause mortality in both treatment groups was compared using logistic regression. Patients who received plasma (n=35, median 4 units) more often had diabetes, antiplatelet therapy, and intraventricular haemorrhage on the initial CT scans than patients who received PCC (n=100, median 22.5 IU/kg [interquartile range 20-26 IU], median of total dose 1,700 IU). The volume of intracerebral haematoma was larger in the plasma-treated group compared to the PCC-treated group (haematoma, mean 64.5 vs 36.0 cm³; p=0.021). The unadjusted OR for all-cause 30-day mortality in the PCC group was 0.40 (95% confidence interval, 0.18-0.87; p=0.021) compared to the plasma group. After adjusting for the haematoma volume, bleeding localisation and age, the effect of PCC on mortality became non-significant. In conclusion, treatment with 4-factor PCC for VKA reversal in patients with intracerebral haemorrhage does not seem to reduce the 30-day all-cause mortality compared to plasma.

Unlabelled: Several tracers have been evaluated as probes for noninvasive epidermal growth factor receptor (EGFR) quantification with PET. One of the most promising candidates is the (11)C-labeled analog of the EGFR tyrosine kinase inhibitor PD153035. However, previous in vitro studies indicated extensive metabolism of the tracer, which could be disadvantageous for the assessment of receptor density in vivo. The aim of this study was to investigate the in vivo metabolism of [(11)C]PD153035 to determine whether alterations in metabolite formation are accompanied by changes in biodistribution and tumor uptake., Methods: EGFR-overexpressing human epidermoid carcinoma xenografts in rats were used in all examinations of tumor uptake. Cytochrome P450 enzymes of subfamilies CYP2D and CYP3A were inhibited before intravenous injection of [(11)C]PD153035 into healthy and tumor-bearing male rats. Samples were taken from arterial blood and urine, and the occurrence of radioactive metabolites was assessed with radio-high-performance liquid chromatography. Dynamic PET examinations of healthy and tumor-bearing animals were performed. In 1 rat, the effect of local intraarterial administration was examined., Results: [(11)C]PD153035 labeled at position 6 was metabolized extensively in vivo in male rats, resulting in very low levels of the intact tracer in plasma only minutes after injection. The major identified radiolabeled metabolites found were the N-oxide and metabolites arising from O demethylation at position 7. They were reduced by inhibition of CYP2D and CYP3A enzymes. PET revealed enzyme activity-dependent changes in the radioactivity distribution in the liver and tumors. Local administration of [(11)C]PD153035 greatly increased radioactivity levels in the adjacent tumor compared with levels typically found after intravenous administration. The highest tumor-to-muscle ratio at 60 min after intravenous injection was found in the untreated animals, whereas the overall highest ratio was found in the tumor near the intraarterial administration site., Conclusion: We suggest that the metabolism of [(11)C]PD153035 should be taken into consideration when this tracer is used to quantify EGFR expression, as our results indicated that the distribution of radioactivity to EGFR-overexpressing tumors was affected by the rate of metabolism and the route of administration.

Background and Purpose: Experimental models are essential for research on ischemic stroke, the second most common cause of death worldwide. The failure of clinical trials on neuroprotective treatment may be due in part to poor animal models. To push the translation of new therapies, we describe a new rat model that captures key elements of human brain ischemia. The model includes imaging and neurointerventional tools that represent the near future of clinical diagnosis and treatment of stroke., Methods: Using Sprague-Dawley rats (n=26), we navigated a microwire with fluoroscopy and MRI guidance from the ventral tail artery to 2 different positions in the middle cerebral artery to establish local occlusion. Animals were scanned with 9.4-T MRI before occlusion, during ischemia, and after reperfusion., Results: We detected stroke lesions, corresponding to the level of occlusion, in all animals by diffusion-weighted and T2 images. We measured lesion volume (mm(3)±SD) on T2 scans at 24 hours to be 23.2±29.8 in the somatosensory cortex group and 107.9±80 in the striatum group., Conclusions: We present a new rat model for focal stroke with the possibility to cause lesions in different regions of the brain under fluoroscopic and MRI control. The model will be highly useful for extended studies on the ischemic penumbra, alterations in neural connectivity, and for investigating neurotransmitter-mediated events and biochemical changes in the hyperacute phase of brain ischemia. Also, the model uses clinical routine microcatheters facilitating superselective administration of therapeutics directly to the cerebral circulation.

Background: The effects, and thereby possible benefit, of inhibiting nitric oxide synthases (NOS) after brain injury are not fully understood. Nitric oxide (NO) has both neuroprotective and damaging features, and its effect on the cellular proliferation and differentiation that occurs in response to traumatic brain injury (TBI) is largely unknown. This study was undertaken to investigate the effects of the selective inducible NOS-inhibitor, L-N-iminoethyl-lysine (L-NIL), on proliferating cell populations in rat brain areas with self-renewing capacity., Methods: A brain contusion was produced using a weight-drop model in rats. Animals received treatment with L-NIL or saline, and were killed after 6 days. Brain sections were stained with a cell marker of proliferation, Ki67, to detect dividing cells in the hippocampus, perilesional zone and the subventricular zone (SVZ)., Results: A significant decrease of proliferating cells was seen in the SVZ bilaterally in L-NIL-treated animals compared to controls. Hippocampal proliferation showed a tendency to decrease in L-NIL-treated animals that did not reach statistical significance. Perilesional proliferation was equal in the treatment group and controls. The percentage of proliferating GFAP expressing cells was, however, lower in L-NIL-treated animals. The proliferating cell populations were predominantly immunoreactive for GFAP, while a smaller population was immunoreactive for Nestin. The inhibition of inducible NOS with L-NIL attenuated the level of cellular proliferation and influenced the differentiation of astrocytes at 6 days after experimental brain contusion., Conclusions: Our results confirmed that reactive glial cells dominated the proliferating cell population after TBI and suggested that NO-regulated mechanisms are relevant for post-traumatic cellular proliferation and differentiation, since NO inhibition decreased the number of proliferating cells in the SVZ and the proportion of proliferating cells expressing GFAP, a marker of glial proliferation.

Background: Our aim was to design a practical algorithm for management of an increasing number of incidental findings of thyroid lesions identified by (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT)., Methods: The reports of 3641 patients examined by FDG-PET/CT for evaluation of nonthyroid cancer were reviewed. The anatomic locations and standardized uptake values (SUV) of any focally increased thyroid FDG uptake were reanalyzed and related to surrounding normal thyroid ((T)SUV(max)/(thy)SUV(mean) ratio) and liver ((T)SUV(max)/(liver)SUV(mean))., Results: Focal FDG uptakes in the thyroid were reported in 37 cases (1%; 26 women). Neoplastic thyroid lesions were diagnosed in 16 patients: papillary thyroid cancer in 9, follicular neoplasia in 5, and metastatic lesions (lung cancer and squamous cell carcinoma) in 2. Benign lesions were diagnosed in 11 patients. Ten patients with malignancy elsewhere did not undergo thyroid examination. In all, 11 patients underwent thyroid surgery (8 with papillary cancer, 3 with follicular adenoma); the median tumor size was 12 mm (8-40 mm). The (T)SUV(max)/(thy)SUV(mean) ratio was higher for the malignant lesions [median 5.53 (2.75-30.81) vs. 3.70 (1.82-31.70); P < 0.05], albeit with a considerable overlap between individual patients. The (T)SUV(max) and (T)SUV(max)/(liver)SUV(mean) did not differ between groups. The (T)SUV(max)/(thy)SUV(mean) and / (thy)SUV(mean) ratios correlated with the tumor size (r = 0.64 and r = 0.66; P < 0.05)., Conclusions: An incidental finding of focal uptake of FDG in the thyroid is associated with a significant risk of thyroid cancer. If the patient would benefit from thyroidectomy if a malignancy were identified, further diagnostic workup with ultrasonography-guided fine-needle aspiration and cytology is recommended.

Background: Currarino syndrome (CS) is a triad consisting of partial sacral agenesis, presacral mass, and anorectal malformations, typically anal stenosis but the phenotype varies. The main cause of this monogenic disorder is mutations in the motor neuron and pancreas homeobox 1 gene. We describe the clinical and genetic findings in 4 unrelated Swedish cases with CS and their relatives., Methods: We performed mutation analysis of the motor neuron and pancreas homeobox 1 gene in 4 cases with CS by DNA sequence analysis as well as multiplex ligation-dependent probe amplification. In addition, array comparative genome hybridization was performed in 2 cases. Including relatives, totally, 14 individuals were analyzed., Results: We found 2 previously described mutations, 1 de novo nonsense mutation (p.Gln212X) and 1 maternally inherited frameshift mutation (p.Pro18ProfsX38). In the family with the frameshift mutation, we also detected the same maternally inherited mutation in 3 of the proband's 4 brothers, who displayed varying symptoms. All mutation carriers had presacral tumors, although 2 were asymptomatic., Conclusion: Our findings emphasize the need for genetic counseling and mutation analysis in patients with CS to detect tumors early. It shows the importance of evaluation of the sacrum and the presacral region in patients with anal stenosis with or without funnel anus. Family members of index cases should be considered for evaluation even if they are asymptomatic., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Traumatic brain damage is dependent on energy transfer to the brain at impact. Different injury mechanisms may cause different types of brain injury. It is, however, unknown if the relative distribution between apoptotic cell-death and necrotic cell- death in different populations of brain cells varies depending on energy transfer., Method: Experimental contusions were produced with a modified weight drop onto the exposed dura of rats. Animals were divided into two groups. They received a weight drop from two different heights to vary energy transfer to be higher or lower. Animals were sacrificed at 24 hours post injury (1 DPI) or 6 days (6 DPI); brains were frozen and processed for TUNEL (TdT mediated dUTP nick end labelling), light microscopy and immunochemistry., Findings: The total number of TUNEL positive cells was higher in the higher energy group on the first day after the injury. At the same time point, relatively fewer cells were apoptotic than necrotic, while relatively more glial cells than neurons were TUNEL-positive in higher energy trauma. At 6 day after the injury fewer cells were TUNEL positive and there were no longer significant differences between the high and low energy groups., Conclusions: Increasing energy transfer in a model for brain contusion demonstrated qualitative and quantitative changes in the pattern of cell death. This complexity must be considered when evaluating brain-protection as treatment results may vary depending on which cellular population and which mechanism of cell death is treated under the exact experimental and clinical conditions.