| 1. |
- Globisch, Maria A., et al.
(författare)
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Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation
- 2022
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 140:20, s. 2154-2169
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.
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| 2. |
- Kumsars, Indulis, et al.
(författare)
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Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch : the Nordic-Baltic Bifurcation Study IV
- 2020
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods: The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results: A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years.
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| 3. |
- Rezai Jahromi, Behnam, et al.
(författare)
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Slow-Closing Clip for the Treatment of Nonsaccular Vertebrobasilar Aneurysms : A Retrospective Case Series
- 2022
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Ingår i: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 168, s. e645-e665
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveVertebrobasilar artery nonsaccular aneurysms (VBANSAs) are associated with a 13% annual mortality. Revascularization and flow diversion are life-saving options in select cases; technical failures and rapid hemodynamic changes may contribute to unwanted outcomes. We describe a technique and report clinical outcomes of patients treated with an experimental slow-closing clip (SCC).MethodsAn experimental SCC was created to gradually close the parent artery of aneurysms. Clinical, radiographic, and outcome data from patients with VBANSAs who underwent experimental treatment with the SCC were retrospectively analyzed.ResultsAmong 10 patients (7 men; mean age, 49.5 years; range, 18–73 years), 6 presented with mass effect symptoms, 1 with ischemic stroke, 2 with subarachnoid hemorrhage, and 1 with hydrocephalus. Five patients underwent revascularization plus SCC application, and 5 were treated with SCC alone. The mean follow-up was 6.7 years. The expected mortality among patients with unruptured VBANSAs with previous treatment options in this period was 52.7%, whereas the observed rate was 20%. Four patients died within 12 months after treatment. Causes of death were brainstem ischemic stroke, poor-grade subarachnoid hemorrhage, poor clinical presentation, and unknown. Six patients were alive at last follow-up, with unchanged or improved modified Rankin Scale scores. Mortality was associated with posterior-projecting aneurysms and late-stage treatment.ConclusionsIn this small case series, use of SCC overcame the natural history of VBANSAs when treatment timing and aneurysm anatomy were suitable. The SCC potentially favors aneurysm thrombosis and collateral reactivation. More studies are necessary to better develop the SCC.
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| 4. |
- Satopää, Jarno, et al.
(författare)
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Comparison of all 19 published prognostic scores for intracerebral hemorrhage.
- 2017
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Ingår i: Journal of the neurological sciences. - : Elsevier BV. - 1878-5883 .- 0022-510X. ; 379, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the accuracy of 19 published prognostic scores to find the best tool for predicting mortality after intracerebral hemorrhage (ICH).A retrospective single-center analysis of consecutive patients with ICH (n=1013). After excluding patients with missing data (n=131), we analyzed 882 patients for 3-month (primary outcome), in-hospital, and 12-month mortality. We analyzed the strength of the individual score components and calculated the c-statistics, Youden index, sensitivity, specificity, negative and positive predictive value (NPV and PPV) for the scores. Finally, we included every score component in a multivariable model to analyze the maximum predictive value of the data elements combined.Observed in-hospital mortality was 23.6%, 3-month mortality was 31.0%, and 12-month mortality was 35.3%. For in-hospital mortality, the National Institutes of Health Stroke Scale (NIHSS) performed equally good as the best score for the other outcomes, the ICH Functional Outcome Score (ICH-FOS). The c-statistics of the scores varied from 0.6293 (95% CI 0.587-0.672) to 0.8802 (0.855-0.906). With all variables from all the scores in a multivariable regression model, the c-statistics did not improve, being 0.89 (0.867-0.913). Using the Youden index cutoff for the ICH-FOS score, the sensitivity (73%), specificity (90%), PPV (76%), and NPV (88%) for the primary outcome were good.A plethora of scores exists to help clinicians estimate the prognosis of an acute ICH patient. The NIHSS can be used to quantify the risk of in-hospital death while the ICH-FOS performed best for the other outcomes.
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| 5. |
- Satopää, Jarno, et al.
(författare)
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Treatment of intracerebellar haemorrhage: Poor outcome and high long-term mortality.
- 2017
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Ingår i: Surgical neurology international. - : Scientific Scholar. - 2229-5097 .- 2152-7806. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Intracerebellar haemorrhage constitutes around 10% of all spontaneous, non-aneurysmal intracerebral haemorrhages (ICHs) and often carries a grim prognosis. In symptomatic patients, surgical evacuation is usually regarded the standard treatment. Our objective was to compare the in-hospital mortality and functional outcome at hospital discharge in either medically or surgically treated patients, and the impact of either treatment on long-term mortality after a cerebellar ICH.An observational, retrospective, single-centre consecutive series of 114 patients with cerebellar ICH. We assessed the effect of different demographic factors on functional outcome and in-hospital mortality using logistic regression. We also divided the patients in medical and surgical treatment groups based on how they had been treated and compared the clinical and radiological parameters, in-hospital, and long-term mortality in the different groups.In our series, 38 patients (33.3%) underwent haematoma evacuation and 76 (66.7%) received medical treatment. Glasgow coma scale <8, blocked quadrigeminal cistern, and severe hydrocephalus were associated with in-hospital death or poor functional outcome at discharge (modified Rankin scale 4-6). Surgically treated patients were younger, had larger haematomas both in volume and diameter, were in a worse clinical condition, and suffered more from hydrocephalus and brainstem compression. There were no statistically significant differences in in-hospital or long-term mortality. However, the surgically treated patients remained in a poor clinical condition.Surgical treatment of cerebellar ICH can be life-saving but often leads to a poor functional outcome. New studies are needed on long-term functional outcome after a cerebellar ICH.
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