The hyperdense sign is a marker of thrombus in non-contrast computed tomography (NCCT) datasets. The aim of this work was to determine optimal Hounsfield unit (HU) thresholds for thrombus ...segmentation in thin-slice non-contrast CT (NCCT) and use these thresholds to generate 3D thrombus models. Patients with thin-slice baseline NCCT (≤2.5 mm) and MCA-M1 occlusions were included. CTA was registered to NCCT, and three regions of interest (ROIs) were placed in the NCCT, including: the thrombus, contralateral brain tissue, and contralateral patent MCA-M1 artery. Optimal HU thresholds differentiating the thrombus from non-thrombus tissue voxels were calculated using receiver operating characteristic analysis. Linear regression analysis was used to predict the optimal HU threshold for discriminating the clot only based on the average contralateral vessel HU or contralateral parenchyma HU. Three-dimensional models from 70 participants using standard (45 HU) and patient-specific thresholds were generated and compared to CTA clot characteristics. The optimal HU threshold discriminating thrombus in NCCT from other structures varied with a median of 51 (IQR: 49–55). Experts chose 3D models derived using patient-specific HU models as corresponding better to the thrombus seen in CTA in 83.8% (31/37) of cases. Patient-specific HU thresholds for segmenting the thrombus in NCCT can be derived using normal parenchyma. Thrombus segmentation using patient-specific HU thresholds is superior to conventional 45 HU thresholds.
Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to demyelination and axonal damage in the CNS. Autoimmunity plays a central role in MS pathogenesis. Per definition, ...monoclonal antibodies are recombinant biological compounds with a well defined target, thus carrying the promise of targeting pathogenic cells or molecules with high specificity, avoiding undesired off-target effects. Natalizumab was the first monoclonal antibody to be approved for the treatment of MS. Several other monoclonal antibodies are in development and have demonstrated promising efficacy in phase II studies. They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab Ly-2127399, secukinumab AIN457). In this review, we discuss the specific molecular targets, clinical efficacy and safety of these compounds and discuss criteria to anticipate the position of monoclonal antibodies in the diversifying armamentarium of MS therapy in the coming years.
Reply Gensicke, Henrik; Bonati, Leo H
Journal of the American College of Cardiology,
07/2015, Letnik:
66, Številka:
4
Journal Article
Recenzirano
...in the long-term follow-up analysis of the ICSS-MRI substudy (2), we observed a signal of an increased risk of recurrent clinical cerebrovascular events after the post-treatment magnetic resonance ...imaging scan among patients treated with open-cell stents compared with patients treated with closed-cell stents; 15 patients in the former group and 3 patients in the latter group experienced a stroke or a transient ischemic attack up until the end of available follow-up (hazard ratio: 3.09; 95% confidence interval: 0.89 to 10.7; p = 0.075).
It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary ...prevention should be managed.
We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists VKA or direct oral anticoagulants DOAC) prior to index event (OAC
) with those without prior oral anticoagulation (OAC
). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC
) with those who continued the same anticoagulation as secondary prevention (OAC
). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
We included 5,413 patients (median age = 78 years interquartile range (IQR) = 71-84 years; 5,136 96.7% had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 IQR = 2-12). The median CHA
DS
-Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC
(n = 1,195) and OAC
(n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC
was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC
(n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC
(n = 585).
Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA
DS
-Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
Treatment with endovascular therapy in the extended time window for acute ischaemic stroke with large vessel occlusion involves stringent selection criteria based on the two landmark studies DAWN and ...DEFUSE3. Current protocols typically include the requirement of advanced perfusion imaging which may exclude a substantial proportion of patients from receiving a potentially effective therapy. Efforts to offer endovascular reperfusion therapies to all appropriate candidates may be facilitated by the use of simplified imaging selection paradigms with widely available basic imaging techniques, such as non-contrast CT and CT angiography. Currently available evidence from our literature review suggests that patients meeting simplified imaging selection criteria may benefit as much as those patients selected using advanced imaging techniques (CT perfusion or MRI) from endovascular therapy in the extended time window. A comprehensive understanding of the role of imaging in patient selection is critical to optimising access to endovascular therapy in the extended time window and improving outcomes in acute stroke. This article provides an overview on current developments and future directions in this emerging area.
To compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits.
This was a ...retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale mRS score 0-1) at 3 months. Secondary outcomes were independence (mRS score 0-2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4-5). Safety endpoints were mortality and symptomatic hemorrhage.
Of 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51-1.72;
= 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (
= 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (
= 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%;
= 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%;
= 0.997).
In acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT.
This study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.
To derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS).
The derivation cohort consisted of patients with ...AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6.
Overall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval CI 0.787-0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72-78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32-60).
The biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin.
NCT00390962 (derivation cohort) and NCT00878813 (validation cohort).
Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes.
Admission hyponatremia is associated with worse clinical outcome in stroke ...patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination.
This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values.
We analyzed data of hospitalized patients treated at University Hospital of Basel.
Stroke patients whose data and informed consent were available.
Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records.
Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio OR 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization.
In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.
To examine the import of prior cervical trauma (PCT) in patients with cervical artery dissection (CeAD).
In this observational study, the presence of and the type of PCT were systematically ...ascertained in CeAD patients using 2 different populations for comparisons: 1) age- and sex-matched patients with ischemic stroke attributable to a cause other than CeAD (non-CeAD-IS), and 2) healthy subjects participating in the Cervical Artery Dissection and Ischemic Stroke Patients Study. The presence of PCT within 1 month was assessed using a standardized questionnaire. Crude odds ratios (ORs) with 95% confidence intervals (CIs) and ORs adjusted for age, sex, and center were calculated.
We analyzed 1,897 participants (n = 966 with CeAD, n = 651 with non-CeAD-IS, n = 280 healthy subjects). CeAD patients had PCT in 40.5% (38.2%-44.5%) of cases, with 88% (344 of 392) classified as mild. PCT was more common in CeAD patients than in non-CeAD-IS patients (ORcrude 5.6 95% CI 4.20-7.37, p < 0.001; ORadjusted 7.6 95% CI 5.60-10.20, p < 0.001) or healthy subjects (ORcrude 2.8 95% CI 2.03-3.68, p < 0.001; ORadjusted 3.7 95% CI 2.40-5.56, p < 0.001). CeAD patients with PCT were younger and presented more often with neck pain and less often with stroke than CeAD patients without PCT. PCT was not associated with functional 3-month outcome after adjustment for age, sex, and stroke severity.
PCT seems to be an important environmental determinant of CeAD, but was not an independent outcome predictor. Because of the characteristics of most PCTs, the term mechanical trigger event rather than trauma may be more appropriate.
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