Endovascular Treatment for Acute Ischemic Stroke : Towards Personalized Treatment in Clinical Practice

The main objective of this thesis was to improve personalized endovascular treatment (EVT) for acute ischemic stroke in clinical practice. Chapter 2 focuses on the effect of EVT in certain patient subgroups. We used MR CLEAN trial data to perform three subgroup analyses. We showed that endovascular treatment is effective and safe for patients with acute ischemic stroke caused by proximal anterior vessel occlusion irrespective of antiplatelet medication, prior intravenous alteplase treatment and blood pressure. Chapter 3 focuses on improving patient selection for EVT. In this chapter a clinical decision that predicts EVT benefit for individual patients at the emergency department, was developed and validated. The tool emphasizes the wide variety of treatment benefit in individual patients and the importance of combining multiple characteristics simultaneously. This decision tool is the first step towards individualized selection of patients for EVT. Finally chapter 4 is focused on EVT in clinical practice. Data of the MR CLEAN Registry were used. This chapter shows that in routine clinical practice, endovascular treat

Use of diagnostic subtraction angiography for ischemic stroke (US DUTCH study) <i>Regional variation and time-trend among medicare beneficiaries</i>

Introduction: There are no guideline recommendations for DSA in the ischemic stroke work-up. We studied the rate of DSA in ischemic stroke, the recent time-trend, hospital variation and associated factors. Methods: This is a retrospective cross-sectional study among Medicare fee-for-service beneficiaries with ischemic stroke admitted between 2016 and 2020 in the United States. ICD-10 codes were used to determine ischemic stroke diagnosis and procedure codes for thrombectomy and DSA. Hospital trends and factors associated with DSA performance were analyzed in hospitals with DSA capacity. Results: 7.373 (0.7 %) of the 1,085,644 ischemic stroke patients, had a DSA for diagnostic purposes. In the patients that were admitted to a hospital with DSA facility, the following factors showed the strongest association with DSA: younger age (aOR=0.81 [95 % confidence interval (CI):0.81-0.83]), thrombectomy rate in that hospital (aOR=2549 [95 %CI:610-10663]), transfer (aOR=1.41[95 %CI:1.34-1.50]) and carotid disease (aOR=5.8 [95 %CI:5.6-6.1]). There was large variation in the hospital DSA rate, varying from 0.07 % to 11.1 %. Of the variance of DSA rates, 15 % was attributed to the residual effect hospital propensity to perform DSA. The top decile of hospitals with the highest DSA rate, performed DSA's in &gt;2.3 % of patients, compared to the 0.6 % median. There was no change in DSA rates over time. Conclusion: DSA is used infrequently in acute ischemic stroke patients and did not change between 2016 to 2020. Hospital variation in DSA use was however large, and not solely explained by patient and facility factors.</p

Endovascular treatment for acute ischaemic stroke in routine clinical practice:prospective, observational cohort study (MR CLEAN Registry)

OBJECTIVETo determine outcomes and safety of endovascular treatment for acute ischaemic stroke, due to proximal intracranial vessel occlusion in the anterior circulation, in routine clinical practice.DESIGNOngoing, prospective, observational cohort study.SETTING16 centres that perform endovascular treatment in the Netherlands.PARTICIPANTS1488 patients included in the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) Registry who had received endovascular treatment, including stent retriever thrombectomy, aspiration, and all alternative methods for acute ischaemic stroke within 6.5 hours from onset of symptoms between March 2014 and June 2016.MAIN OUTCOME MEASURESThe primary outcome was the modified Rankin Scale (mRS) score, ranging from 0 (no symptoms) to 6 (death) at 90 days after the onset of symptoms. Secondary outcomes were excellent functional outcome (mRS score 0-1), good functional outcome (mRS score 0-2), and favourable functional outcome (mRS score 0-3) at 90 days; score on the extended thrombolysis in cerebral infarction scale at the end of the intervention procedure; National Institutes of Health Stroke Scale score 24-48 hours after intervention; and complications that occurred during intervention, hospital admission, or three months' follow up period. Outcomes and safety variables in the MR CLEAN Registry were compared with the MR CLEAN trial intervention and control arms.RESULTSA statistically significant shift was observed towards better functional outcome in patients in the MR CLEAN Registry compared with the MR CLEAN trial intervention arm (adjusted common odds ratio 1.30, 95% confidence interval 1.02 to 1.67) and the MR CLEAN trial control arm (1.85, 1.46 to 2.34). The reperfusion rate, with successful reperfusion defined as a score of 2B-3 on the extended thrombolysis in cerebral infarction score, was 58.7%, the same as for patients in the MR CLEAN trial. Duration from onset of stroke to start of endovascular treatment and from onset of stroke to successful reperfusion or last contrast bolus was one hour shorter for patients in the MR CLEAN Registry. Symptomatic intracranial haemorrhage occurred in 5.8% of patients in the MR CLEAN Registry compared with 7.7% in the MR CLEAN trial intervention arm and 6.4% in the MR CLEAN trial control arm.CONCLUSIONIn routine clinical practice, endovascular treatment for patients with acute ischaemic stroke is at least as effective and safe as in the setting of a randomised controlled trial.</p

InterPro in 2011: new developments in the family and domain prediction database

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interface

Measurement of the forward Z boson production cross-section in pp collisions at s=13\sqrt{s} = 13 TeV

A measurement of the production cross-section of Z bosons in pp collisions at $\sqrt{s} = 13$ TeV is presented using dimuon and dielectron final states in LHCb data. The cross-section is measured for leptons with pseudorapidities in the range $2.0 \eta 4.5$, transverse momenta $p_\text{T} 20$ GeV and dilepton invariant mass in the range $60 m(\ell\ell) 120$ GeV. The integrated cross-section from averaging the two final states is \begin{equation*}\sigma_{\text{Z}}^{\ell\ell} = 194.3 \pm 0.9 \pm 3.3 \pm 7.6\text{ pb,}\end{equation*} where the first uncertainty is statistical, the second is due to systematic effects, and the third is due to the luminosity determination. In addition, differential cross-sections are measured as functions of the Z boson rapidity, transverse momentum and the angular variable $\phi^*_\eta$

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Improving quality of stroke care through benchmarking center performance:why focusing on outcomes is not enough.

Background: Between-center variation in outcome may offer opportunities to identify variation in quality of care. By intervening on these quality differences, patient outcomes may be improved. However, whether observed differences in outcome reflect the true quality improvement potential is not known for many diseases. Therefore, we aimed to analyze the effect of differences in performance on structure and processes of care, and case-mix on between-center differences in outcome after endovascular treatment (EVT) for ischemic stroke. Methods: In this observational cohort study, ischemic stroke patients who received EVT between 2014 and 2017 in all 17 Dutch EVT-centers were included. Primary outcome was the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death), at 90 days. We used random effect proportional odds regression modelling, to analyze the effect of differences in structure indicators (center volume and year of admission), process indicators (time to treatment and use of general anesthesia) and case-mix, by tracking changes in tau2, which represents the amount of between-center variation in outcome. Results: Three thousand two hundred seventy-nine patients were included. Performance on structure and process indicators varied significantly between EVT-centers (P < 0.001). Predicted probability of good functional outcome (modified Rankin Scale 0–2 at 90 days), which can be interpreted as an overall measure of a center’s case-mix, varied significantly between 17 and 50% across centers. The amount of between-center variation (tau2) was estimated at 0.040 in a model only accounting for random variation. This estimate more than doubled after adding case-mix variables (tau2: 0.086) to the model, while a small amount of between-center variation was explained by variation in performance on structure and process indicators (tau2: 0.081 and 0.089, respectively). This indicates that variation in case-mix affects the differences in outcome to a much larger extent. Conclusions: Between-center variation in outcome of ischemic stroke patients mostly reflects differences in case-mix, rather than differences in structure or process of care. Since the latter two capture the real quality improvement potential, these should be used as indicators for comparing center performance. Especially when a strong association exists between those indicators and outcome, as is the case for time to treatment in ischemic stroke

Endovascular treatment for isolated posterior cerebral artery occlusion stroke in the MR CLEAN registry

BACKGROUND: Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) occlusions are limited, although PCA occlusions can cause severe neurological deficit.OBJECTIVE: To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions.METHODS: We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (ΔNIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications.RESULTS: Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median ΔNIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred.CONCLUSIONS: EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study.</p