Intracranial Hemorrhage Research Articles

POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large‐Vessel Occlusion Stroke): Study Protocol of a Multicenter, Prospective, Randomized, Open‐Label, Blinded‐End Point Trial

BACKGROUND Intra‐arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy was regarded as a promising strategy to promote outcomes of patients with stroke. Given the characteristics of urokinase as an affordable, available, and widely applied medication, especially in Eastern countries, this trial aims to assess the safety and efficacy of intra‐arterial urokinase as adjunct to endovascular thrombectomy in improving outcomes among patients with anterior large‐vessel occlusion stroke after excellent to complete reperfusion. METHODS The POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large Vessel Occlusion Stroke) trial is a multicenter, prospective, randomized, open‐label, blinded‐end point trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large‐vessel occlusion stroke and achieving excellent to complete reperfusion by endovascular thrombectomy are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra‐arterial urokinase) or to standard of care. RESULTS The primary outcome is a freedom from disability (modified Rankin Scale score of 0–1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. CONCLUSION The POST‐UK trial will provide valuable insight of efficacy and safety of intra‐arterial urokinase in patients with large‐vessel occlusion stroke after achieving excellent to complete reperfusion by endovascular thrombectomy.

Outcomes of different anesthesia techniques in nonagenarians treated with mechanical thrombectomy for anterior circulation large vessel occlusion: An inverse probability weighting analysis.

There is a lack of evidence for the optimal type of anesthesia technique in patients ⩾ 90 years with acute ischemic stroke undergoing mechanical thrombectomy (MT) as this subgroup of patients was often excluded or under-represented in previous trials. We aimed to compare outcomes between general anesthesia (GA) and non-GA techniques in patients ⩾ 90 years with large vessel occlusion (LVO) undergoing MT. Our study included patients ⩾ 90 years with anterior circulation LVO, NIHSS ⩾ 6, ASPECTS ⩾ 5 consecutively treated with MT within 6 h after stroke onset in three thrombectomy capable centers between January 1st, 2016 and March 30th, 2023. Inverse probability weighting (IPW) was used to reduce bias by indication of the anesthesia type on study outcomes. We used a weighted ordinal robust logistic regression analysis to explore the primary outcome of modified Rankin Scale (mRS) shift at 90 days in GA versus non-GA treated patients. Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH) and TICI score of 2b, 2c, or 3. We included 139 patients ⩾ 90 years treated with MT, 62 were in GA group and 77 in non-GA group. There was a significant shift for worse mRS scores at 90-day in non-GA treated patients (cOR 3.65, 95% CI 1.77-7.77, p = 0.001). The weighted logistic regression showed that non-GA technique was an independent predictor of 90-day mortality (OR 7.49, 95% CI 2.00-28.09; p = 0.003). Our study indicated that nonagenarians with acute ischemic stroke treated with MT without GA have a worse prognosis than their counterparts undergoing MT with GA. Further studies in larger cohorts are warranted to evaluate the optimal type of anesthesia in this patient population.

Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial.

There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; P=0.04) with LBMT vs CDT and less postprocedural ICU utilization (P<0.001), including admissions (41.6% vs 98.6%) and stays >24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies, nor in a secondary WR endpoint including the first 4 components (WR 1.34 [95% CI: 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs 20.1±5.1; P<0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs 26.4%; P<0.001), NYHA classifications (16.3% vs 27.4%; P=0.002), and RV dysfunction (42.1% vs 57.9%; P=0.004). RV/LV ratio reduction was similar (0.32±0.24 vs 0.30±0.26; P=0.55). LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% vs 7.9%; P=0.03), while 30-day mortality was similar (0.4% vs 0.8%; P=0.62). PEERLESS met its primary endpoint in favor of LBMT vs CDT in treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding.

Impacts of Hospital Volume and Patient-Hospital Distances on Outcomes of Older Adults Receiving Percutaneous Microaxial Ventricular Assist Devices for Cardiogenic Shock.

Background: Percutaneous microaxial ventricular assist devices (pVAD) have the potential to reduce mortality of patients with cardiogenic shock (CS). However, the association between the distribution of pVAD-performing centers and outcomes of CS has not been explored. Methods: This observational study included Medicare fee-for-service beneficiaries aged 65-99 years treated with pVAD for CS from 2016 to 2020 and examined the associations between patient outcomes and two exposure variables: hospitals' procedure volumes of pVAD and patient-hospital distances (in quintiles [Qn]). We developed Cox proportional hazard regression for 180-day mortality and heart failure (HF) readmission rates and multivariable logistic regression for in-hospital outcomes, adjusting for patient demographics, comorbidities, concomitant treatments, and hospital characteristics, including CS volume, teaching status, and the ability to perform extracorporeal membrane oxygenation. Results: A total of 6,637 patients with CS underwent pVAD at 1,041 hospitals, with the annualized hospital volume ranging widely from 0.3 to 55.6 cases/year. Patients treated at higher-volume centers experienced lower 180-day mortality compared with patients treated at lower-volume centers (Qn1=reference; Qn2: adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.79-0.97; Qn3: aHR, 0.88; 95% CI, 0.79-0.98; Qn4: aHR, 0.88; 95% CI, 0.78-0.99; Qn5: aHR, 0.84; 95% CI, 0.74-0.95; p-for-trend, 0.026), while we found no evidence that patient-hospital distances were associated with mortality (Qn1=reference; Qn2: adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.89-1.09; Qn3: aHR, 0.94; 95% CI, 0.85-1.04; Qn4: aHR, 1.01; 95% CI, 0.92-1.11; Qn5: aHR, 0.91; 95% CI, 0.82-1.01; p-for-trend, 0.160). We found no evidence that the hospital volume and patient-hospital distances were associated with in-hospital bleeding, intracranial hemorrhage, or renal replacement therapy initiation. Conclusions: Hospital volume was more strongly associated with mortality than patient-hospital distances, suggesting that rational distribution of pVAD-performing centers while ensuring adequate procedure volumes may optimize patient mortality.

Evaluating the Risk of Traumatic Brain Injury in Adults Following a Fall With Concomitant Use of Anti-Coagulation: A Retrospective Cohort Study.

Introduction Falls and fractures are major health challenges for older adults in England. Despite the advantages of anticoagulants, their use in the elderly is often restricted due to concerns about fall-related injuries. However, there is a lack of clear data on the risk of discontinuing anticoagulation therapy solely due to fall risk. NICE guidelines (2021) advise that anticoagulation should not be withheld solely based on age or fall risk. This study aims to assess the incidence of significant brain injuries or intracranial haemorrhages in patients on anticoagulant therapy, also comparing the independent risk factors for traumatic brain injury. Objective This study aims to assess the incidence of TBI following falls in patients on anticoagulant therapy, comparing outcomes between those using DOACs and Vitamin K antagonists. Methods A retrospective cohort study was conducted at Queen Alexandra Hospital, University Hospitals Portsmouth NHS Trust, from November 2023 to May 2024. Data were collected from 3,468 CT head scans performed on patients with a history of falls, including 801 on anticoagulation therapy. Results Of the 801 patients on anticoagulation, 763 (95.2%) were aged 65 or older, with a mean age of 83.1 years. Acute hemorrhage was detected in 3.1% (25/801) of patients. Patients on Warfarin and Dabigatran had significantly higher TBI risk compared to those on Apixaban (6.7%, p=0.02; and 7.6%, p=0.01, respectively), while Edoxaban and Rivaroxaban showed no significant difference. Also, older age (≥65 years) and higher frailty scores (CFS 6 and 7) were associated with increased TBI risk (p<0.05). All patients with acute hemorrhage received conservative management, and two patients experienced mortality within six months. Discussion The study indicates that the risk of TBI following falls in anticoagulated patients is 3.1% relatively low, aligning with existing literature. This underscores the need for careful consideration before discontinuing anticoagulation therapy solely based on fall risk. Hence, discontinuation of anticoagulation should be a patient-specific decision that carefully considers the balance between the risk of traumatic brain injury (TBI) and the benefits of anticoagulation therapy. Factors such as age, frailty, and the type of anticoagulant should all be taken into account. Clinical judgment and selective CT imaging can help balance patient safety with healthcare costs. Conclusion The incidence of adverse outcomes following head injury in patients on anticoagulant therapy is 3.1% and relatively low. Careful decision-making regarding the discontinuation of anticoagulation therapy, informed by patient background and presentation and selective CT imaging, is essential to manage risks effectively and optimize healthcare resource utilization.

Endovascular therapy in patients with acute intracranial non-terminal internal carotid artery occlusion (ICA-I).

Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions. A large international multicentre cohort was searched for patients with intracranial ICA occlusion treated with EVT between 2014 and 2023. Patients were stratified by ICA occlusion pattern, differentiating ICA-I and ICA-L/-T occlusions. Baseline factors, technical (modified thrombolysis in cerebral infarction (mTICI) scale) and functional outcomes (modified Rankin scale [mRS] at 3 months) as well as rates of (symptomatic) intracranial hemorrhage ([s]ICH) were analyzed. Of 13,453 patients, 1825 (13.6%) had isolated ICA occlusion. ICA-occlusion pattern was ICA-I in 559 (4.2%) and ICA-L/-T in 1266 (9.4%) patients. Age (years: 74 vs 73), sex (female: 45.8% vs 49.0%) and pre-stroke functional independency (pre-mRS ⩽ 2: 89.9% vs 92.2%) did not differ between the groups. Stroke severity was lower in ICA-I patients (NIHSS at admission: 14 [7-19] vs 17 [13-21] points). EVT was similarly successful with respect to technical (mTICI2b/3: 76.1% (ICA-I) vs 76.6% (ICA-L/-T); aOR 1.01 [0.76-1.35]) and functional outcome (mRS ordinal shift cOR 1.01 [0.83-1.23] in adjusted analyses. Rates of ICH (18.9% vs 34.5%; aOR 0.47 [0.36-0.62] and sICH (4.7% vs 7.3%; aOR 0.58 [0.35-0.97] were lower in ICA-I patients. EVT might be performed safely and similarly successful in patients with ICA-I occlusions as in patients with ICA-L/-T occlusions.

Head injuries in prehospital and Emergency Department settings: a prospective multicenter cross-sectional study in France

BackgroundHead injuries are the leading cause of trauma in Emergency Departments (EDs). Recent studies have shown epidemiological changes in patients consulting ED for head injuries. The main objective of this study was to describe the profile of head injury patients consulting in the EDs in France and assess i) head injury severity across age groups; ii) the delay between the occurrence of head injury and ED arrival; iii) factors associated with traumatic intracranial hemorrhage (ICH).MethodsThis cross-sectional study collected patient data over a three-day period in March 2023. All adult patients (≥ 18 years old) admitted to the ED with a head injury (defined as a trauma to the head) were included. TBI severity was classified according to patients’ initial Glasgow Coma Scale score in the ED: severe (3–8); moderate (9 -12); mild (13–15); and simple head trauma in the absence of transient or persistent neurological symptoms.ResultsAmong the 71 participating EDs, 26,008 patients visited EDs and a total of 1070 patients (4.1%, IC 95 3.9—4.4) presented a head injury were included in the study, with a median age of 68.5 [37–85] years old. Most of the patients (66.7%) were referred to ED after a call to the Emergency Medical Dispatcher (EMD). The median time from head injury to ED visit was 2 h [1.0 – 5.5]. Ground-level falls were the leading cause of head injury (60.3%). Most of patient presented a simple head trauma (n = 715, 66.8%) followed by mild TBI (n = 337, 31.5%). CT head scans were performed for 636 patients (59.6%), of which 58 were positive. Traumatic ICH prevalence was 5.4% (95% CI: 4.1–6.9) and three patients (0.3%) required an urgent neurosurgical intervention. Neither preinjury anticoagulant (p = 0.97) nor antiplatelet (p = 0.93) use was associated with an increased risk of traumatic ICH.ConclusionsOne head injury patient out of two presenting in the ED is aged over 65 years. Patients referred by EMD were more likely to visit ED promptly. The majority of older patients underwent a head CT scan and preinjury anticoagulant use was not associated with increased risk of traumatic ICH.

Early antiplatelet therapy after intravenous thrombolysis for acute ischemic stroke: a systematic review and meta-analysis.

Early neurological deterioration (END) and recurrence of vessel blockage frequently complicate intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Several studies have indicated the potential effectiveness of the early initiation (within < 24 h) of antiplatelet therapy (APT) after IVT. However, conflicting results have been reported by other studies. We aimed to offer a thorough overview of the current literature through a systematic review and meta-analysis. Our systematic review and meta-analysis were prospectively registered on PROSPERO (ID: CRD42023488173) following the PRISMA guidelines. We systematically searched Web of Science, SCOPUS, PubMed, and Cochrane Library until May 5, 2024. Rayyan. ai facilitated the screening process. The R statistical programming language was used to calculate the odds ratios and conduct a meta-analysis. Our primary outcomes were excellent functional recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage (sICH), and mortality. Eight studies involving 2,134 participants were included in the meta-analysis. Early APT showed statistically significant increased odds of excellent functional recovery (mRS 0-1) compared to the standard APT group (OR, 1.81; [95% CI: 1.10, 2.98], p = 0.02). However, we found no differences between the early and standard APT groups regarding sICH (OR, 1.74; [95% CI: 0.91, 3.33], p = 0.10) and mortality (OR, 0.88; [95% CI: 0.62, 1.24]; p = 0.47). Early APT within 24 h of IVT in stroke patients is safe, with no increase in bleeding risk, and has a positive effect on excellent functional recovery. However, there was a statistically insignificant trend of increased sICH with early APT, and the current evidence is based on highly heterogeneous studies. Further large-scale RCTs are warranted.

Safety and efficacy of intravenous thrombolytic therapy in the extended window up to 24 hours: A systematic review and meta-analysis.

About 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS. Using PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0-1 and mRS 0-2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta-analyses were conducted employing random-effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection. Eight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0-1: RR 1.21 95% CI 1.1-1.34, p < 0.001, and mRS 0-2: RR 1.11 95% CI 1.03-1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93-1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53-5.6, p = 0.001. Subgroup analysis showed higher mRS 0-1 among patients who were selected based on perfusion imaging (p < 0.05). The use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection.

Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF

Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH

Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample

Abstract Background Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase. Purpose To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample. Methods The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P&amp;lt;0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P&amp;lt;0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P&amp;lt;0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P&amp;lt;0.001), acute kidney injury (OR 3.60 [3.09-4.18], P&amp;lt;0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P&amp;lt;0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P&amp;lt;0.001; multivariable OR: 6.16 [5.64-6.72], P&amp;lt;0.001). Conclusions In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.

Long-term cardiovascular outcomes of patients experiencing intra-cranial hemorrhage with or without acute cardiovascular events

Abstract Background Acute cardiovascular (CV) events would happen during the acute stage of ischemic stroke or intra-cranial hemorrhage (ICH), so called "Stroke-Heart Syndrome". However, long-term outcomes of patients who experienced acute CV events during the acute stage of ICH were unclear. In the present study, we aimed to report and compare long-term prognosis of patients with or without acute CV events after ICH. Methods A total of 104,955 patients who experienced ICH and survived longer than 90 days without past history of acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and ventricular arrhythmia (VA) were identified from the Taiwan National Health Insurance Research Database. Among them, 1,888 patients experienced CV events (AMI, HF, AF or VA) within 90 days after ICH, while 103,067 did not. Results Compared to patients without acute CV events, patients with acute CV events were older (73.53 vs 62.46 years, p&amp;lt;0.001), less males (57.89% vs 61.83%, p&amp;lt;0.001) and had more comorbidities , such as hypertension (77.17% vs 61.58%), diabetes mellitus (35.81% vs 26.54%), vascular diseases (3.5% vs 2.02%) and chronic obstructive pulmonary disease (15.57% vs 9.88%), all p&amp;lt;0.001. Compared to patients without acute CV events, those experiencing acute CV events had a higher adjusted risk of ischemic stroke (adjusted hazard ratio [aHR] 1.564), recurrent ICH (aHR 1.266), HF (aHR 4.693), AF (aHR 19.116), VA (aHR 3.485), AMI (aHR 2.463), sudden cardiac death (aHR 1.609) and mortality (aHR 1.855)(Figure). Conclusions Acute CV events occurring during acute stage of ICH were not a benign course simply related to acute stress and were associated with a poor long-term outcome. How to improve long-term clinical outcomes of these patients deserves more attentions, efforts and studies involving both cardiologists and neurologists.

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.

Direct oral anticoagulants exhibit lower risks of mortality and bleeding compared to vitamin-k antagonists in atrial fibrillation patients on chronic hemodialysis: a meta-analysis

Abstract Background Atrial fibrillation (AF) is a common arrhythmia in patients with chronic kidney disease (CKD). Although direct oral anticoagulants (DOACs) are equally or more effective than vitamin K antagonists (VKAs) in patients with moderate CKD, evidence claiming the benefits of DOACs over VKAs in patients on hemodialysis (HD) is scarce. Purpose This meta-analysis aimed to assess the outcomes of patients with AF on chronic HD by comparing the clinical outcomes of DOACs versus VKAs. Methods A systematic literature search was conducted across various databases to retrieve studies focusing on efficacy and safety outcomes in patients with AF on chronic hemodialysis comparing DOACs and VKAs. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel random-effects model in Review Manager 5.4. Statistical significance was set at p &amp;lt;0.05. Results Nine studies with 39, 831 patients were included. The risk of all-cause mortality [RR: 0.73; 95% CI: 0.60, 0.88; p=0.001], major bleeding [RR: 0.63; 95% CI: 0.52, 0.76; p&amp;lt;0.00001], gastrointestinal bleeding [RR: 0.67; 95% CI: 0.53, 0.85; p=0.0009], intracranial hemorrhage [RR: 0.57; 95% CI: 0.38, 0.84; p=0.004], all-cause stroke [RR: 0.64; 95% CI: 0.51, 0.81; p=0.0001], and ischemic stroke [RR: 0.53; 95% CI: 0.29, 0.96; p=0.04] were lower in the DOAC group than in the VKA group. The risk of cardiovascular-related death [RR: 1.34; 95% CI: 0.69, 2.60; p=0.39], and clinically relevant non-major bleeding [RR: 0.90; 95% CI: 0.75, 1.08; p=0.26] showed no significant differences. Conclusion The risks of all-cause stroke, ischemic stroke, all-cause mortality, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage in the patients with AF undergoing chronic HD were lower in the DOAC group than in the VKA group. Further large-scale RCTs are needed to generate more robust evidence through adequately powered studies, leading to conclusive results that are applicable to real-world scenarios.

The real-world safety of ticagrelor among older adults (above 75 years): a pharmacovigilance study from the FDA data

Abstract Introduction Potent P2Y12 inhibitors are recommended in conjunction with Aspirin for the treatment of acute coronary syndrome. Since Prasugrel is relatively contraindicated in patients older than 75 years, Ticagrelor remains the primary potent P2Y12 inhibitor option for this age group. However, its safety profile among older adults has not been adequately examined. Purpose To examine Ticagrelor safety profile among older adults (≥75 years) patients Methods We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database. We employed disproportionality analysis comparing Ticagrelor to Clopidogrel. We evaluated the reporting of predefined adverse events (dyspnea, bradyarrhythmia, complete AV block [CAVB], intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury [AKI], and gout) in adults (&amp;lt;75 years) and older adults (≥75 years). For each group, we calculated reporting odds ratio (ROR) and its 95% confidence interval and compared them by calculating P for interaction. Results The FAERS database encompassed 6,476 adverse event reports for Ticagrelor; 4,795 (74%) adults and 1,681 (26%) older adults. Among older adults and compared to Clopidogrel, Ticagrelor was not associated with an increased reporting for dyspnea (ROR 3.3 [2.7-3.9] vs. 3.9 [3.5-4.5]), bradyarrhythmia (ROR 4.1 [2.5 – 6.7] vs 5.4 [3.9 – 7.6]) intracranial hemorrhage (ROR 1.1 [0.7-1.7] vs. 1.1[0.8-1.5]), CAVB (ROR 11.5 [3.1–42.4] vs. ROR 27.8 [6.7-116.3]), and gout (ROR 3.8 [0.5-27] vs. 3.9 [2-7.5]). AKI was reported more frequently among older adults (ROR 2.3 [1.5-3.6] vs. 0.6 [0.4-0.9]). Ticagrelor was not associated with an increased reporting of GI hemorrhage. Conclusion According to the FAERS, Ticagrelor is generally safe for use in older adults (≥75 years) with no significant increase in the reporting of major adverse events compared to adults (&amp;lt;75 years), except for a higher reporting of AKI.

Mechanical thrombectomy is associated with worse outcomes in infective endocarditis: a retrospective cohort study

Abstract Background Acute Ischaemic stroke (AIS) is a common complication in infective endocarditis (IE) and associated is with high mortality. There is a paucity of data evaluating mechanical thrombectomy (MT) in patients with AIS secondary to IE. Our retrospective cohort study aimed to quantify the efficacy and safety of MT in this patient population. Methods The National Inpatient Sample (NIS) was utilised. We obtained data from 2004 – 2019. We included all patients who had AIS and IE. We excluded patients who received thrombolysis. Those who received mechanical thrombectomy were compared to those who did not. Odds ratios were calculated using logistic regressions. We adjusted for multiple confounders. Outcomes included inpatient mortality, long length of stay (&amp;gt; 4 days), discharge status (normal vs ‘other’) and intracranial haemorrhage. Results The sample population consisted of 22,6390 patients (mean age 69, 52.3% female). ME was performed on 496 (2.2%). Patients with IE who received MT had a greater odds of death compared to those who did not (OR 1.91 95% CI 1.00 – 3.67). In addition, they had a greater odds of intracranial bleeding (OR 4.47 95% CI 2.78 – 7.20). Length of stay and neurological outcome did the significantly differ. We performed a sub-analysis, which included patients who had received thrombolysis in addition to MT. This did not modify the results for mortality and intracranial bleeding outcomes. Conclusion Mechanical thrombectomy was associated with increased mortality and intracranial bleeding in patients who have AIS associated with IE. While acknowledging the limitations of observational data, we therefore advise caution when considering mechanical thrombectomy in this patient population.

Ependymal cell lineage reprogramming as a potential therapeutic intervention for hydrocephalus

Hydrocephalus is a common neurological condition, characterized by the excessive accumulation of cerebrospinal fluid in the cerebral ventricles. Primary treatments for hydrocephalus mainly involve neurosurgical cerebrospinal fluid diversion, which hold high morbidity and failure rates, highlighting the necessity for the discovery of novel therapeutic approaches. Although the pathophysiology of hydrocephalus is highly multifactorial, impaired function of the brain ependymal cells plays a fundamental role in hydrocephalus. Here we show that GemC1 and McIdas, key regulators of multiciliated ependymal cell fate determination, induce direct cellular reprogramming towards ependyma. Our study reveals that ectopic expression of GemC1 and McIdas reprograms cortical astrocytes and programs mouse embryonic stem cells into ependyma. McIdas is sufficient to establish functional activity in the reprogrammed astrocytes. Furthermore, we show that McIdas’ expression promotes ependymal cell regeneration in two different postnatal hydrocephalus mouse models: an intracranial hemorrhage and a genetic form of hydrocephalus and ameliorates the cytoarchitecture of the neurogenic niche. Our study provides evidence on the restoration of ependyma in animal models mimicking hydrocephalus that could be exploited towards future therapeutic interventions.

Delirium and risk of incident cardiovascular events in elderly: data from a global health research network

Abstract Introduction Delirium is a common complication of acute medical disorders. A strong association between cardiovascular events and the occurrence of delirium has been recorded. Thus far, no data are available regarding the risk of incident cardiovascular events after delirium onset in older adults. Methods Using data from TriNetX, a global health federated research network, we performed a propensity score matched (PSM) analysis of older adults (age ≥65 years) admitted to the emergency department (ED) reporting delirium within two weeks, who were compared with those without delirium. We evaluated the occurrence of a composite outcome of cardiovascular events (myocardial infarction, ischemic stroke, heart failure, intracranial haemorrhage, ventricular arrhythmias, takotsubo syndrome, and atrial fibrillation) at 30 days and 1 and 3 years of follow-up. Results 4,480,229 patients were retrieved for the analysis, and 82,693 (1.8%) reported delirium. Before PSM, patients reporting delirium were older, with more prevalent comorbidities. After PSM, a total of 165,386 patients were included in the analysis (mean (SD) age 76.6 (9.0) years, 51.1% females). Throughout the entire follow-up period, the cumulative composite cardiovascular events outcome was significantly higher in patients which reported delirium [Red Line, Figure 1]. Delirium was associated with cardiovascular events at 30 days (HR 1.96, 95% CI 1.92-2.00) ,1 year (HR 1.75, 95% CI 1.72-1.78) and 3 years (HR 1.67, 95% CI 1.64-1.69) of follow-up, as well as for each of its components (Table 1). The presence of delirium was also associated with a higher risk of all-cause death and hospital access (Table 1), evaluated as secondary outcomes. In patients with delirium associated with the occurrence of incident cardiovascular events, there was a higher risk of recurrent cardiovascular events at 1 year (HR 3.11, 95% CI 2.92-3.31) and 3 years (HR 2.84, 95% CI 2.67-3.01) of follow-up. Conclusions In a large, unselected cohort of older adults admitted to ED, occurrence of delirium was associated with a higher risk of cardiovascular events, both in the short and long-term follow-up.Figure 1:Delirium and CV EventsTable 1:Cox Regression Analysis

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P&amp;lt;0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P&amp;lt;0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P&amp;lt;0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

Intraoperative transfontanelle ultrasonography for pediatric patients.

Cerebral blood flow (CBF) plays a vital role in delivering cerebral oxygen, and the accurate assessment of CBF is crucial for the intraoperative management of critically ill infants. Although the direct measurement of CBF is challenging, CBF velocity (CBFV) can be assessed using transcranial Doppler. Recent advances in point-of-care ultrasound have introduced brain ultrasound as a feasible intraoperative option, in which transfontanelle ultrasonography (TFU) has been applied to measure the CBFV through the anterior fontanelle. However, the intraoperative application of TFU in pediatric patients remains limited. The present review highlights the procedural aspects and clinical applications of TFU for anesthetic and intensive care management in pediatric patients. TFU facilitates the visualization of cerebral vessels and allows a noninvasive assessment of cerebral hemodynamics. The clinical significance of TFU involves its usefulness in various clinical scenarios, including monitoring CBF during cardiac surgery, assessing fluid responsiveness, and estimating intracranial pressure. TFU also enables the detection of cerebral emboli and the evaluation of anatomical abnormalities such as hydrocephalus or intracranial hemorrhage. TFU has demonstrated potential as an invaluable tool in pediatric care, despite limited familiarity among anesthesiologists. Additional research is needed to explore the associations between CBF and clinical outcomes, focusing on autoregulation, the impact of physiological changes, the associations of TFU findings with other brain monitoring tools such as electroencephalography, cerebral oximetry, and the implications of microemboli. TFU is a significant advancement and valuable tool for noninvasively assessing cerebral hemodynamics and CBF in pediatric patients with open fontanelles.