Development of a Nomogram for Predicting the Occurrence of Symptomatic Intracranial Haemorrhage after Thrombectomy: A Single-Center Retrospective Observational Study

Background Symptomatic intracranial haemorrhage (SICH) is a severe and deadly complication in patients with large vessel occlusion (LVO) who receive endovascular treatment (EVT). Recent studies have indicated that many risk factors, including pretreatment scores and the operation process, may be associated with the occurrence of SICH after thrombectomy. This study aims to identify independent risk factors and establish a novel nomogram-based model for patients with anterior LVO to predict the occurrence of SICH after direct thrombectomy or bridge therapy (thrombectomy based on intravenous thrombolysis). Methods Patients with acute ischaemic stroke after EVT to recanalize the blocked artery in anterior circulation were consecutively recruited from November 2017 to March 2019. Baseline information was collected from each patient. These data were subsequently analysed by R Project for Statistical Computing. Results A total of 127 patients with complete data were classified into the training set, among whom 37 patients (29.1%) fulfilled the criteria for SICH. The results of the multivariate analyses showed that NIHSS (P=0.024), ASPECT (P<0.001) and ASITN (P=0.017) scores were independently associated with the occurrence of SICH after thrombectomy. Ultimately, three independent pretreatment predictors were included in the NIHSS/ASPECT/ASITN (NAA) prediction model, and the receiver operating characteristic analysis results showed an area under the curve (AUC) of 0.845 (95% CI=0.763–0.928). The calibration plots showed that the actual observations were consistent with the measured and predicted results of the nomogram. Conclusions In this study, a novel model based on NAA for predicting the occurrence of SICH after thrombectomy in patients with anterior LVO was established and validated internally. The results suggest that this model can help improve perioperative evaluations and individualized treatment strategies.

156 Rivaroxaban in very elderly patients with atrial fibrillation

Aims The incidence of atrial fibrillation (AF) increases with age. The risk of stroke is increased 4- to 5-fold in old patients with AF. In the Framingham Study, 23.5% of strokes in patients aged 80 and older were attributable to AF. Advanced age is also associated with a progressive increase in the risk of major bleeding in subjects ≥85 years, particularly if treated by oral anticoagulants (OAC). Only 20% of patients &gt;75 years were included in randomized controlled trials (RCTs) involving OACs in AF, due to the high risk of falls and bleeding, especially intracranial haemorrhage (ICH). The management of anticoagulation in the very elderly represents a challenging issue because they are at high thromboembolic risk, and also at high haemorrhagic risk. The aim of our study was to describe the use and tolerability of rivaroxaban in very old patients with heart failure with reduced ejection fraction. The average age of enrolled patients is 76.0 ± 8.4 years with a significant prevalence of the elderly (16.0% with age ≥85 years with a slight male prevalence). Methods We analysed retrospective data from 50 patients from June 2016 to June 2018 and taking rivaroxaban 20 mg. The average age of enrolled patients was 76 ± 8.2 years and 40% were females. The inclusion criteria were patients with at least one episode of documented AF of any duration in the preceding 12 months. The average CHA2DS2-VASc of these subjects is 3.2 ± 1.4, while the haemorrhagic risk expressed by the HAS-BLED appears more contained (2.7 ± 1.1). The risk profile of these patients was complex as documented by an older age, by a CHA2DS2-VASc higher and by the prevalence of comorbidities such as heart failure, valvular disease, peripheral vasculopathy and diabetes mellitus. Follow-up, characterized by clinical examination and blood analysis, was performed at 3, 6, and 12 months. The AF patients were followed for the effectiveness outcome of thromboembolism (ischaemic stroke and/or systemic embolism) and bleeding outcomes (composite of major bleeding, gastrointestinal bleeding, and intracranial Haemorrhage), as well as bleeding requiring hospitalization. A secondary safety endpoint was total minor bleedings. Standard two-dimensional transthoracic echocardiographic examination was performed. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction (LVEF) were measured using the modified Simpson’s rule from the apical view. Results During follow-up, we observed no major bleedings, strokes, or cardiovascular deaths. Only two minor haemorrhages (one epistaxis and one haematuria, none of which required blood transfusion or hospital admission) observed with no differences observed in LVEF or left atrial dimension at echocardiography, body mass index, and the thrombotic and haemorrhagic risk profile. Conclusions Such data confirm that the new oral anticoagulants, and in particular rivaroxaban, are considered safe even in the most population frail and above all elderly, allowing for enlargement the use of anticoagulant therapy. Results are expected of long-term follow-up to confirm the benefits of that therapeutic choice.

Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study

Background and objectivesThe risks of postoperative risk of epilepsy after a craniotomy is widely believed to be raised. A study is warranted to quantify the risks for any neurosurgical indication. In this unselected register-based nationwide cohort study with virtually complete follow-up, the short-term and long-term cumulative risks of postoperative de novo epilepsy for all major neurosurgical indications were estimated.MethodsThe study was based on 8948 first-time craniotomy patients in Denmark 1 January 2005 to 31 December 2015 with follow-up until 31 December 2016. The patients were classified according to their underlying neurosurgical pathology. Patients with preoperative epilepsy were excluded. The postcraniotomy risks of de novo epilepsy were estimated using the Aalen-Johansen estimator in a multistate model.ResultsThe overall cumulative 1-year risk of postcraniotomy de novo epilepsy was 13.9% (95% CI 13.2 to 14.6). For patients with intracranial tumour the cumulative 1-year risk was 15.4% (95% CI 14.4 to 16.5), for spontaneous intracranial haemorrhage 11.3% (95% CI 10.1 to 12.6), for traumatic intracranial haemorrhage 11.1% (95% CI 9.6 to 12.9), for cerebral abscess 27.6% (95% CI 22.8 to 33.5) and for congenital malformations 3.8% (95% CI 1.3 to 11.7). The 6-month, 1-year and 5-year risks for all major indications by specific subtypes are provided.ConclusionsThe cumulative risk of de novo epilepsy following craniotomy is high for patients with any indication for craniotomy, as compared with the background population. The results provide comprehensive data to support future recommendations regarding prophylactic antiepileptic treatment and driving restrictions.

Association between systolic blood pressure course and outcomes after stroke thrombectomy

BackgroundSystolic blood pressure (SBP) after endovascular thrombectomy (EVT) for large artery occlusive stroke is dynamic, requiring adaptable early prediction tools for improving outcomes. We investigated if post-EVT SBP course was associated with outcomes.MethodsEVT-treated patients who had a stroke at Karolinska University Hospital, Stockholm, Sweden, were included in the study during 12 February 2018–11 February 2020. SBP was recorded during the first 24 hours after EVT. Primary outcome was functional independence defined by a Modified Rankin Scale score of 0–2 at 3 months. Secondary outcomes were death by 3 months, symptomatic intracranial haemorrhage and any intracranial haemorrhage. Patients with favourable outcomes were used as a reference SBP course in mixed linear effects models and compared with SBP courses of patients with unfavourable outcomes using the empirical best linear unbiased predictor, measuring deviations from the reference SBP course using the random effects. We tested model predictive stability for SBP measurements of only 18, 12 or 6 hours after EVT.Results374 patients were registered, with mean age 71, median NIHSS score of 15, and 53.2% men. Deviating from a linear SBP course starting at 130 mm Hg and decreasing to 123 mm Hg at 24 hours after EVT was associated with lower chances of functional independence (adjusted OR 0.53, 95% CI 0.29 to 0.88, for reaching either 99 or 147 mm Hg at 24 hours after EVT). All SBP course models for the remaining outcomes did not show statistical significance. Functional independence models showed stable predictive values for all time periods.ConclusionDeviating from a linear SBP course was associated with lower chances of 3-month functional independence.

Paediatric Trauma Score as a non-imaging tool for predicting intracranial haemorrhage in patients with traumatic brain injury

To identify a useful non-imaging tool to screen paediatric patients with traumatic brain injury for intracranial haemorrhage (ICH). We retrospectively analysed patients aged < 15 years who visited the emergency department with head trauma between January 2015 and September 2020. We divided patients into two groups (ICH and non-ICH) and compared their demographic and clinical factors. Among 85 patients, 21 and 64 were in the ICH and non-ICH groups, respectively. Age (p = 0.002), Pediatric trauma score (PTS; p < 0.001), seizure (p = 0.042), and fracture (p < 0.001) differed significantly between the two groups. Factors differing significantly between the groups were as follows: age (odds ratio, 0.84, p = 0.004), seizure (4.83, p = 0.013), PTS (0.15, p < 0.001), and fracture (69.3, p < 0.001). Factors with meaningful cut-off values were age (cut-off [sensitivity, specificity], 6.5 [0.688, 0.714], p = 0.003) and PTS [10.5 (0.906, 0.81), p < 0.001]. Based on the previously known value for critical injury (≤ 8 points) and the cut-off value of the PTS identified in this study (≤ 10 points), we divided patients into low-risk, medium-risk, and high-risk groups; their probabilities of ICH (95% confidence intervals) were 0.16–12.74%, 35.86–89.14%, and 100%, respectively. PTS was the only factor that differed significantly between mild and severe ICH cases (p = 0.012). PTS is a useful screening tool with a high predictability for ICH and can help reduce radiation exposure when used to screen patient groups before performing imaging studies.

Ultrasound-accelerated thrombolysis in high-risk perioperative pulmonary embolism: two case reports and review of literature

Introduction Treatment of high-risk pulmonary embolism (PE) in perioperative patients remains challenging. Systemic thrombolysis is associated with a high risk of major bleedings and intracranial haemorrhage. High mortality rates are reported for open pulmonary embolectomy. Therefore, postoperative surgical patients may benefit substantially from catheter-directed ultrasound-accelerated thrombolysis (USAT). Case presentation We report two cases of high-risk perioperative PE. Both patients developed severe haemodynamic instability leading to cardiac arrest. After the implantation of a veno-arterial extracorporeal membrane oxygenation (ECMO), they were both successfully treated with USAT. Adequate improvement of right ventricular function was achieved; thus, ECMO could be successfully weaned after 3 and 4 days, respectively. Both patients showed favourable outcomes and could be discharged to rehabilitation. Conclusion Current guidelines on treatment of PE offer no specific therapies for perioperative patients with high-risk PE. However, systemic thrombolysis is often excluded due to the perioperative setting and the risk of major bleeding. Catheter-directed thrombolysis was shown to utilise less thrombolytic agent while obtaining comparable thrombolytic effects. The risk for major bleeding (including intracranial haemorrhage) is also significantly lowered. Until further trials determining the value of adopted treatment strategies of high-risk PE in perioperative patients are available, USAT should be considered in similar cases.

Low rate of worsening renal function after 2 years of treatment with edoxaban in patients from the ETNA-AF-Europe study

Background Use of vitamin K antagonists (VKAs) is associated with a crude event rate of 23% per year for worsening renal function (WRF). Although non-vitamin K antagonist oral anticoagulants (NOACs) have been associated with a lower risk of longitudinal decline in renal function compared with VKAs, available evidence on renal function decline in patients using NOACs is still limited. Furthermore, renal function is a dose reduction criterion for NOACs, which poses an important question about how physicians should treat patients whose renal function worsens over time. Purpose To evaluate the degree of renal function decline in AF patients treated with edoxaban after 2 years of follow-up, and to investigate clinical outcomes of patients with vs without WRF in the ETNA-AF-Europe study. Methods ETNA-AF-Europe is a multinational, multicentre, observational, post-authorisation safety study conducted in 825 sites in 10 European countries. Results are based on a data snapshot taken on 26th October 2020 which include data up to 2 years of follow-up. Patients were excluded from the analysis population if data to calculate estimated glomerular filtration rate [eGFR] were not available for at least one of the follow-up time-points of 1-year and 2-year. We categorised patients (n=9084) into two subgroups: 1) those with WRF (i.e. ≥25% decline in eGFR from baseline; n=918), and 2) those without WRF (n=8166). eGFR was estimated using the Cockcroft-Gault formula. Baseline characteristics and annualised event rates including 95% confidence intervals were analysed using descriptive analyses. Results Of the 13,417 patients in ETNA-AF-Europe who were included in the 2-year follow-up analysis, 9084 were included in this subgroup analysis, of whom 56.2% were male. Baseline eGFR were similar between patients with and without WRF when comparing across the different renal function categories (Table 1). The majority of the edoxaban-treated patients did not experience WRF (89.9%) during the 2 years of follow-up. The proportion of patients with WRF (10.1%) were older, more often frail and had higher rates of underlying comorbidities, such as diabetes, hypertension and heart failure (Table 1). Patients with WRF had higher annualised event rates of all-cause and cardiovascular death than those without (3.78% vs 1.90% and 2.06% vs 0.92%, respectively). Major bleeding and stroke rates were low, but numerically higher in patients with renal worsening compared to those without WRF (Figure 1). Intracranial haemorrhage rates remained low (0.17% vs 0.19%; Figure 1) in both subgroups. Conclusions This subgroup analysis provides real-world evidence for a low risk of WRF in AF patients treated with edoxaban over a 2-year period. Patients with WRF had higher mortality than those without, as well as numerically higher major bleeding and stroke rates. Importantly, intracranial haemorrhage rates remained low irrespective of WRF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH /