Search

Background and Objectives: The incidence of stroke among young adults was rising globally, but the death burden of stroke in young adults in China is lacking. We aimed to examine the temporal trends in mortality and years of life lost (YLLs) caused by stroke among young adults from 2005 to 2020 across China., Methods: Based on the data from the National Mortality Surveillance System in China, we estimated the number and age-standardized rate of mortality and YLLs due to stroke and its subtypes among young adults aged 15-49 years during 2005-2020, for both China and its 31 mainland provinces., Results: During 2005-2020, the age-standardized mortality rate of stroke among young adults aged 15-49 years in China decreased by 21.0%, from 5.9/100,000 to 4.7/100,000, and the YLL rate decreased from 286.9/100,000 to 229.5/100,000. The age-standardized mortality rate among young adults due to intracerebral hemorrhage (ICH) showed a significant downward trend with a decrease of 26.3% while that of ischemic stroke (IS) and subarachnoid hemorrhage (SAH) decreased by 4.5% and 0.6%, respectively. In 2020, the mortality rate of ICH was 3.5 times higher than that of IS (3.3/100,000 vs 0.9/100,000) among young adults in China. The male/female ratio of age-standardized mortality rate of stroke in young adults increased from 2.0 in 2005 to 3.1 in 2020. The age-standardized mortality rate of IS and SAH in young men increased by 11.0% and 2.5%, respectively. In 2020, Tibet (18.4/100,000), Jilin (10.4/100,000), and Qinghai (8.3/100,000) were the top 3 provinces holding the highest age-standardized mortality rate due to stroke among young adults. Tibet was found to have the highest mortality rate due to ICH and SAH while that of IS was higher in northeast China., Discussion: In China, the death burden caused by ICH among young adults was substantially higher than that of IS. The increasing death burden of IS and SAH among young men requires special attention. Evidence-based intervention strategies are needed to improve the outcomes of stroke and alleviate the death burden due to stroke among young adults in Chinese population.

Background: To date, inconsistent evidence exists on the role of hypernatremia in patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent surgical clipping. We aimed to investigate the association between serum sodium and mortality in these patients., Methods: A cohort study was performed to include adult patients with aSAH who underwent surgical clipping in a university hospital. The primary outcome was follow-up mortality. Propensity score matching (PSM) was used for matching patients' baseline characteristics. Net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess and compare the reclassification and discrimination capacity of different models. Trends in serum sodium over time were detected by the ordinary least squares model., Results: Of 618 aSAH patients with surgical clipping during the study period, normal serum sodium was observed in 467 patients (75.6 %), and admission hypernatremia was noted in 151 patients (24.4 %). After adjustment with multivariate regression analysis, patients with hypernatremia had significantly higher odds for follow-up mortality (aOR: 2.86, 95 % CI: 1.54 to 5.30; P = 0.001). PSM analysis observed similar results (aOR: 2.38, 95 % CI: 1.29 to 4.55; P = 0.009). The incorporation of serum sodium during hospitalization markedly enhanced the IDI (P < 0.001) and NRI (P < 0.001) for the prediction of mortality., Conclusions: In conclusion, the findings from this cohort study of aSAH patients with surgical clipping indicated that serum sodium can be an independent predictive factor of all-cause mortality, and inferior sequelae in aSAH patients. These findings endorsed the importance of managing hypernatremia and monitoring serum sodium in patients with aSAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients., Methods: Data of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed., Results: Among 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17-2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36-2.85), compared to ePWV < 10.12. The receiver operator characteristic (ROC) curves showed that compared to single SOFA score, ePWV combined with SOFA score had a relative superior predictive performance on both 30-day mortality and 1-year mortality, with the area under the curves (AUCs) of 0.740 vs. 0.664 and 0.754 vs. 0.658. This positive relationship between ePWV and mortality risk was also found in age ≥ 65 years old, SOFA score < 2, non-surgery, non-hepatic diseases, non-COPD, non-hypertension, non-DM, and sepsis subgroups., Conclusion: Baseline ePWV level may have potential prediction value on short- and long-term mortality in SAH patients. However, the application of ePWV in SAH prognosis needs further clarification., (© 2024. The Author(s).)

Background: Treatment outcomes of octogenarians with aneurysmal subarachnoid hemorrhage (aSAH) are often considered poor. With ongoing advancements and experience in endovascular technology, we sought to evaluate the outcomes of octogenarians treated for aSAH in the second post-International Subarachnoid Aneurysm Trial (ISAT)/Barrow Ruptured Aneurysm Trial (BRAT) decade., Method: A single-center database of aSAH was reviewed to identify patients aged 80 years or above undergoing aneurysm treatment. Mortality and favorable neurologic outcome (defined as modified Rankin Scale score <3) were assessed among the series and compared across several subgroups., Results: Octogenarian patients constituted 6% of the aSAH cohort (38 of 619) over the reviewed period. Twenty-one percent were high grade (Hunt-Hess grade 4-5). Endovascular treatment was the first-line modality in 90% of patients. During a median follow-up of 17 months, the overall mortality was 39%. Higher mortality was associated with poor Hunt-Hess grade (100% for grade 5, 47% for III-IV, 13% for 1-2, P = 0.004) and non-independent baseline function status (100% mortality for non-independent vs. 28% for independent group, P = 0.002). At last follow-up, 53% of patients achieved a favorable neurologic outcome. The stratified rate was 80% in Hunt-Hess grade I-II and over 60% in patients with premorbid independent function status or less than 5 frailty components (P ≤ 0.02 vs. poorer counterparts)., Conclusions: Neurologic outcomes of octogenarian patients with aSAH are improving in the second post-trial decade, particularly given the preponderance of endovascular treatment. Baseline functional status and comorbidities of octogenarians should be considered in addition to the Hunt-Hess grade in prognostication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To study associations of clinical characteristics and treatment choice with functional outcome, mortality, and time to death in a national sample of aneurysmal subarachnoidal hemorrhage patients., Methods: Data were extracted from a prospective nationwide multicenter study performed in September 2014 to March 2018. Glasgow Outcome Scale Extended (GOSE) grade, 1-year mortality, and survival probability were assessed at one year after ictus. Logistic univariate, multivariate, and Cox regression analyses were used to study the variables' associations with the outcomes., Results: Unfavorable dichotomized GOSE (dGOSE; grades 1-4) was observed in 35.4% of patients. Microsurgery was preferred for middle cerebral artery aneurysms and Fisher grade 4. Treatment modality was not associated with any outcome measure. Dichotomized World Federation of Neurosurgical Societies (dWFNS), age, and delayed ischemic neurological deficit (DIND) showed significant correlations with dGOSE and 1-year mortality in multivariate regression analyses. Pupil dilatation was associated with a 1-year mortality outcome. Cox regression analysis showed lower survival probability for pupil dilatation (hazard ratio [HR]: 3.546), poor dWFNS (HR: 3.688), higher age (HR: 1.051), and DIND occurrence (HR: 2.214)., Conclusions: The patient selection in Sweden after aneurysmal subarachnoidal hemorrhage showed similar values for dGOSE, 1-year mortality, and survival probability between patients treated with microsurgery or endovascular technique. Poor dWFNS, higher age, and DIND were significantly associated with unfavorable dGOSE, mortality, and survival probability. Pupil dilatation was significantly associated with mortality and survival probability., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The mortality risk is exceptionally high in non-traumatic subarachnoid hemorrhage (SAH). Elevated blood urea nitrogen (BUN) levels and hypokalemia are prevalent issues in patients with non-traumatic SAH. To explore the correlation between the blood urea nitrogen-to-potassium ratio (BPR) and 30-day all-cause mortality in non-traumatic SAH patients., Methods: We systematically extracted specific clinical data from the Medical Information Mart for Intensive IV (MIMIC-IV) database. To assess the prognostic relevance of the BPR, we categorized patients into those experiencing in-hospital mortality within 30 days and those surviving, subjecting them to both univariate and multivariate Cox regression analyses. The optimal BPR cut-off value was identified using Receiver Operating Characteristic (ROC) curve analysis, employing the maximum Youden index to predict survival status. Furthermore, we employed Kaplan-Meier (K-M) analysis to illustrate survival curves., Results: A cohort comprising 608 patients with non-traumatic SAH was enrolled in the investigation. Multivariate Cox regression analysis identified the BPR as an independent predictor of all-cause mortality within 30 days of admission for patients with non-traumatic SAH (Hazard Ratio [HR], 1.13; 95 % Confidence Interval [CI], 1.04---1.23; P<0.05). Further refinement resulted in the establishment of an optimized prediction model (AUC=83.61 %, 95 % CI: 79.73 % - 87.49 %) for forecasting all-cause mortality at 30 days post-hospital admission in patients with non-traumatic SAH., Conclusion: The BPR emerges as an independent prognostic indicator for all-cause mortality within the initial 30 days of admission among non-traumatic SAH patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Subarachnoid hemorrhage (SAH) is defined as sudden bleeding into the subarachnoid space. Although its incidence is low, mortality remains high. The most frequent cause of spontaneous SAH is aneurysm rupture. Cerebral CT scans are highly sensitive in ruling out SAH within the first 6 hours. Due to the recent improvement in imaging resolution, only a strong clinical suspicion can justify a cerebrospinal fluid analysis if the CT scan is normal after 6 hours. Cerebral MRI is also highly sensitive in both the acute and sub-acute phases. This article reviews the various clinical and paraclinical elements of the diagnostic approach, the main etiologies and the risk factors associated with SAH., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Delayed cerebral ischemia(DCI) is one of the most significant complications of subarachnoid hemorrhage. Despite significant evolution in understanding DCI pathophysiology, vasospasm affecting cerebral vessels of large and moderate diameters remain the only clinically measurable component of DCI and is therefore the primary target for intervention in the postoperative management of subarachnoid hemorrhage. In Japan, fasudil hydrochloride and ozagrel sodium are widely used to prevent vasospasms; however, their effects are sometimes insufficient. Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage. This was demonstrated in a recent randomized phase 3 trial, leading to the approval of clazosentan by the Pharmaceuticals and Medical Devices Agency in Japan. Recent advances in our understanding of subarachnoid hemorrhage will facilitate improved management to reduce the incidence of DCI.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease with high mortality and morbidity. Patients with aSAH in Sweden are cared for at one of six neuro intensive care units (NICU) or at a general intensive care unit (ICU).This study aimed to describe the incidence, length of stay, time in ventilator and mortality for these patients., Methods: This is a retrospective, descriptive study of patients with aSAH, registered in the Swedish Intensive care Registry between 2017 and 2019. The cohort was divided in sub-cohorts (NICU and general ICU) and regions. Mortality was analysed with logistic regression., Results: A total of 1520 patients with aSAH from five regions were included in the study. Mean age of the patients were 60.6 years and 58% were female. Mortality within 180 days of admission was 30% (n = 456) of which 17% (n = 258) died during intensive care. A majority of the patients were treated at one hospital and in one ICU (70%, n = 1062). More than half of the patients (59%, n = 897) had their first intensive care admission at a hospital with a NICU. Patients in the North region had the lowest median GCS (10) and the highest SAPS3 score (60) when admitted to NICU. Treatment with invasive mechanical ventilation differed significantly between regions; 91% (n = 80) in the region with highest proportion versus 56% (n = 94) in the region with the lowest proportion, as did mortality; 16% (n = 44) versus 8% (n = 23). No differences between regions were found regarding age, sex and length of stay., Conclusions: Patients with aSAH treated in a NICU or in an ICU in Sweden differs in characteristics. The study further showed some differences between regions which might be reduced if there were national consensus and treatment guidelines implemented., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: A previous systematic review of population-based studies from 1973 to 2002 found a decrease in case fatality for spontaneous subarachnoid haemorrhage, but could not find a sufficient number of studies to assess changes in functional outcome. Since then, treatment has advanced distinctly. We assessed whether case fatality has decreased further and whether functional outcome has improved., Patients and Methods: We searched PubMed and Web of Science for new population-based studies using the same criteria as in our previous systematic review. We assessed changes in case fatality and functional outcome over time using linear regression., Results: We included 24 new studies with 827 patients and analysed 9542 patients described in 62 study periods between 1973 and 2017. Case fatality decreased by 0.3% (95% CI: -0.7 to 0.1) per year. In a sensitivity analysis excluding studies that did not provide 1-month outcome and outliers, the age and sex-adjusted decrease was 0.1% per year (95% CI: -0.9 to 0.6). The mean case fatality rate decreased from 47% (95% CI: 31-63) in the 1970s to 35% (95% CI: 30-39) in the 1990s, and remained stable in the 2000s (34%; 95% CI: 27-41) and 2010s (38%; 95% CI: 15-60). In 15 studies, the mean proportion of patients living independently increased by 0.2% per year (95%CI: -0.7 to 1.1) and the mean was 45% (95% CI: 39-50) in six studies that reported outcome after 12 months., Discussion and Conclusion: From 1973 to 2017, the case-fatality rate of spontaneous subarachnoid haemorrhage declined overall by 13.5%, but remained stable over the last two decades. The data on time trends in functional outcome were inconclusive., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Subarachnoid hemorrhage (SAH) from spontaneous aneurysm rupture is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in SAH patients., Materials and Methods: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28., Results: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89 %) had a comorbid diagnosis of AKI. SAH patients with AKI were older (p < 0.01) and more often obese (p < 0.01) compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p < 0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities., Conclusions: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to improve their chances of recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The serum calcium plays a role as a cofactor in critical steps such as cardiac contractility, vascular tone, and the coagulation cascade. This study aimed to determine if the level of ionized calcium can predict outcomes in patients with spontaneous subarachnoid hemorrhage (SAH) in the emergency department., Methods: The study was a retrospective cross-sectional case series. Patients aged 18 and over diagnosed with spontaneous SAH in the emergency department were included in the study. Patients' demographic characteristics, comorbidities, vital signs, laboratory parameters, World Federation of Neurosurgical Societies score, SAH grading according to the Fisher scale, needs of mechanical ventilation and inotropic treatment, administered treatments, complications, Rankin scores at discharge, and outcome were recorded in a standard data form., Results: A total of 267 patients were studied, with a mean age of 55.5 ± 13.4 years, and 53.9% (n = 144) were female. Hydrocephalus was present in 16.5% of patients. The average hospital stay was 20.4 ± 19.8 days. Mortality rate was 34.8% (n = 93). Mortality was significantly higher in patients with low calcium levels upon admission (P = 0.024). Ionized calcium levels during complication development independently predicted mortality (OR: 0.945, 95% CI: 0.898-0.996, P = 0.034). Patients with poor neurologic outcomes (Rankin: 3-6) had significantly lower initial ionized calcium levels (P = 0.002)., Conclusions: The ionized calcium level is a readily accessible blood gas parameter that assists clinicians in predicting functional independence and mortality at discharge in patients presenting to the emergency department with spontaneous SAH., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The prevalence of stroke disability associated with high BMI has significantly increased over the past three decades. However, it remains uncertain whether high body-mass index (BMI) exerts a similar impact on the disease burden of different stroke subtypes. The aim of this study is to assess the long-term trends of stroke and subtypes mortality attributable to high BMI in China between 1990 and 2019., Methods: Data on stroke and subtypes mortality attributable to high BMI in China was extracted in the Global Burden of Disease (GBD) 2019. The trends of age-standardized mortality rate (ASMR) were calculated using the linear regression and age-period-cohort framework., Results: The changing trend of ASMR on stroke attributable to high BMI in China differed among subtypes, with an estimated annual percentage change (EAPC) and 95%CI of 2.04 (1.86 to 2.21) for ischemic stroke (IS), 0.36 (-0.03 to 0.75) for intracerebral hemorrhage (ICH), and - 4.62 (-5.44 to -3.78) for subarachnoid hemorrhage (SAH). Net and local drift analyses revealed a gradual increase in the proportion of older people with IS and a gradual increase in the proportion of younger people with hemorrhagic strokes. The cohort and period rate ratios varied by subtype, showing an increasing trend for IS and ICH but a decreasing trend for SAH. The stroke mortality attributable to high BMI increased significantly with age for IS and ICH, peaking between ages 50-70 for SAH. Notably, males had higher ASMR related to stroke but exhibited slighter declines or higher growth compared to females in China. Moreover, the population affected by fatal strokes tended to be older among females but more evenly distributed across a wider age range encompassing both younger and older individuals., Conclusion: The research findings indicate a rising trend in the ASMR of stroke and subtypes attributable to high BMI in China from 1990 to 2019, with different patterns of change for different subtypes, genders and ages. Consequently, it is imperative for public health authorities in China to formulate guidelines for specific stroke subtypes, genders and ages to prevent the burden of stroke attributable to high BMI., (© 2024. The Author(s).)

Background and Objectives: Aneurysmal subarachnoid hemorrhage (ASAH) is defined as bleeding in the subarachnoid space caused by the rupture of a cerebral aneurysm. About 11% of people who develop ASAH die before receiving medical treatment, and 40% of patients die within four weeks of being admitted to hospital. There are limited data on single-center experiences analyzing intrahospital mortality in ASAH patients treated with an endovascular approach. Given that, we wanted to share our experience and explore the risk factors that influence intrahospital mortality in patients with ruptured intracranial aneurysms treated with endovascular coil embolization. Materials and Methods: Our study was designed as a clinical, observational, retrospective cross-sectional study. It was performed at the Department for Radiology, University Clinical Center Kragujevac in Kragujevac, Serbia. The study inclusion criteria were ≥18 years, admitted within 24 h of symptoms onset, acute SAH diagnosed on CT, aneurysm on DSA, and treated by endovascular coil embolization from January 2014 to December 2018 at our institution. Results: A total of 66 patients were included in the study-48 (72.7%) women and 18 (27.3%) men, and 19.7% of the patients died during hospitalization. After adjustment, the following factors were associated with in-hospital mortality: a delayed ischemic neurological deficit, the presence of blood in the fourth cerebral ventricle, and an elevated urea value after endovascular intervention, increasing the chances of mortality by 16.3, 12, and 12.6 times. Conclusions: Delayed cerebral ischemia and intraventricular hemorrhage on initial head CT scan are strong predictors of intrahospital mortality in ASAH patients. Also, it is important to monitor kidney function and urea levels in ASAH patients, considering that elevated urea values after endovascular aneurysm embolization have been shown to be a significant risk factor for intrahospital mortality.

It has been shown that living alone is one of the risk factors for unfavorable outcomes in ischemic stroke patients, mostly due to delay in receiving appropriate treatment. A single-center retrospective observational study was conducted to evaluate whether living alone was associated with unfavorable outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. Among 451 SAH patients admitted to our institution between January 2013 and December 2022, 43 patients who lived alone had sustained SAH at home (group A) and 329 patients who lived with family had sustained SAH at home (group F). The mortality rate (46.5% vs. 29.8%, p = 0.04) and a tendency for having unfavorable outcomes were higher in group A than in group F. The incidence of concomitant hydrocephalus was significantly higher in the former (37.2% vs. 21.3%, p = 0.03). Group A was further classified to the Able to Call (n = 15, group AC) and Unable to Call (n = 28, group UC) subgroups based on their ability to call for help by themselves. Group AC tended to have favorable outcomes (27% vs. 4%, p = 0.04). Treatment to obliterate a ruptured aneurysm had particularly been challenging in group UC, in which the accurate time of onset often remained unidentifiable: Their overall mortality was as high as 57% and their capability to undergo surgical/interventional treatment was only 67%. Perioperative complications resulting from delayed presentation had been common. Considering the present finding that most of those who lived alone could not call for help, further effort is warranted to facilitate early detection of those patients.

This study aimed to assess the current status and changing trends of the disease burden of stroke and its subtypes due to low dietary fiber intake in China from 1990 to 2019. In cases of stroke and its subtypes attributable to low dietary fiber, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMR), age-standardized DALYs rates (ASDR), and percentage change were used to assess disease burden. Data were obtained from the 2019 global burden of disease study. Trends were assessed using Joinpoint regression and age-period-cohort analysis. Between 1990 and 2019, there was a declining trend in stroke and its subtypes, ASDR and ASMR, as well as the corresponding number of deaths and DALYs, due to low dietary fiber intake in China. Subarachnoid hemorrhage (SH) showed the greatest decrease, followed by intracerebral hemorrhage (IH) and ischemic stroke (IS). Local drift curves showed a U-shaped distribution of stroke, IS, and IH DALYs across the whole group and sex-based groups. For mortality, the overall and male trends were similar to those for DALYs, whereas female stroke, IH, and IS showed an upward trend. The DALYs for stroke and IH showed a clear bimodal distribution, IS showed an increasing risk with age. For mortality, the SH subtype showed a decreasing trend, whereas other subtypes showed an increasing risk with age. Both the period and cohort rates of stroke DALYs and motality due to low dietary fiber have declined. Males had a higher risk of DALYs and mortality associated with low fiber levels. The burden of stroke and its subtypes associated with a low-fiber diet in China has been declining over the past 30 years, with different patterns of change for different stroke subtypes and a higher burden for males, highlighting the differential impact of fiber intake on stroke and its subtypes., (© 2024. The Author(s).)

Purpose: We explored the relationships between electrocardiographic (ECG) abnormalities and the clinical outcomes and mortality of patients with non-traumatic aneurysmal subarachnoid hemorrhages (SAHs)., Methods: This retrospective cohort study enrolled consecutive adult patients who presented to emergency departments with non-traumatic aneurysmal SAHs. We recorded their demographics, clinical characteristics, and ECG findings, and explored the relationships between ECG abnormalities, on the one hand, and 28-day mortality and prognosis, on the other., Results: We enrolled 158 patients, 76 females (48.10%) and 82 males (51.90%) of average age 54.70 ± 7.07 years. A total of 107 patients (67.72%) exhibited at least one ECG abnormality, most commonly a T-wave change (n = 54, 34.18%). Such patients evidenced significantly higher Hunt-Hess and Fisher scale scores than those without abnormalities (both p < 0.001). Patients with abnormal ECG findings experienced more unfavorable outcomes and higher mortality than others (both p < 0.001). ECG abnormalities, including PR prolongation, pathological Q waves, QRS widening, left bundle branch blocks, premature ventricular contractions, ST segment changes, and T-wave changes, were more common in non-survivors and patients with Hunt-Hess scores of 4-5 compared to survivors and those with Hunt-Hess scores <4, respectively. Moreover, increased age and presence of abnormal ECG findings were independent predictors of mortality in aneurysmal SAHs., Conclusions: Patients with abnormal ECG findings exhibited unfavorable clinical outcomes and increased mortality rates. Abnormal ECG findings combined with higher Hunt-Hess or Fischer grade scores usefully predict adverse clinical outcomes in and mortality of SAH patients., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The association between patient age and cerebral arterial vasospasm (CVS) and delayed cerebral ischemia (DCI) risk following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. This study aims to assess the role of age on aSAH-related complications., Methods: Single-center retrospective study comprising aSAH patients treated between January 2009 and March 2023. Age was analyzed as continuous and categorical variables (<60 yrs vs. ≥60 yrs and by decade). Outcomes of interest included radiographic CVS, DCI, cerebral infarction, in-hospital mortality, length-of-stay (LOS), ventriculoperitoneal shunt placement, and modified Rankin Scale (mRS) scores at discharge and 3-month follow-up., Results: Nine hundred and twenty-five aSAH patients were included. Most (n = 598; 64.6%) were <60 yrs old (46 ± 9.1 yrs). CVS likelihood was lower in the older cohort (aOR = 0.56 [0.38-0.82]). Patients ≥60 yrs had higher mortality rates (aOR = 2.24 [1.12-4.47]) and worse mRS scores at discharge (aOR = 2.66 [1.91-3.72]) and 3-month follow-up (aOR = 2.19 [1.44-3.32]). Advanced age did not have a significant effect on DCI or cerebral infarction risk. Higher in-hospital mortality was documented with increasing age (P < 0.001). A significant interaction between CVS and age for the outcome of DCI was documented, with a stronger positive effect on poor outcomes (i.e., higher odds of DCI) among patients aged <60 years compared to those aged ≥60., Conclusions: There is an inverse relationship between patient age and CVS incidence following aSAH. Nonetheless, patients ≥60 yrs had comparable DCI rates, higher in-hospital mortality, and worse functional outcomes than their younger counterparts. Routine screening and reliance on radiographic CVS as primary marker for aSAH-related complications should be reconsidered, particularly in older patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality., Methods: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model., Results: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW., Conclusion: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Aneurysmal subarachnoid hemorrhage (SAH) is catastrophic, and microsurgery for ruptured intracranial aneurysms is one of the preventive modalities for rebleeding. However, patients remain at high risk of medical morbidities after surgery, one of the most important of which is health care-associated infections (HAIs). We analyzed the incidence and risk factors of HAIs, as well as their association with the outcomes after surgical treatment of ruptured aneurysms., Methods: We retrospectively enrolled 607 patients with SAH who had undergone surgery for intracranial aneurysms. Information was retrieved from the database using codes of the International Classification of Diseases, Ninth Revision, Clinical Modification., Results: Of the 607 patients, 203 were male and 404 were female. HAIs occurred in 113 patients, accounting for 18.6 % of the population. The independent risk factors for HAIs included age ((p = 0.035), hypertension ((p = 0.042), convulsion ((p = 0.023), external ventricular drain ((p = 0.035), ventricular shunt ((p = 0.033), and blood transfusion ((p = 0.001). The mean length of hospital stay was 25.3 ± 18.2 and 18.8 ± 15.3 days for patients with and without HAIs, respectively ((p = 0.001). The in-hospital mortality rates were 11.5 % in the HAIs group, and 14.0 % in the non-HAIs group ((p = 0.490)., Conclusion: HAIs are a frequent complication in patients with SAH who underwent surgery for ruptured intracranial aneurysms. The length of hospital stay is remarkably longer for patients with HAIs, and to recognize and reduce the modifiable risks should be implemented to improve the quality of patient care., Competing Interests: Declaration of competing interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Ischemic and hemorrhagic stroke incidence tends to be higher among minority racial and ethnic groups. The effect of race and ethnicity following an aneurysmal subarachnoid hemorrhage (aSAH) remains poorly understood. Thus, we aimed to explore the association between race and ethnicity and aSAH outcomes., Methods: Single-center retrospective review of patients with aSAH from January 2009 to March 2023. Primary outcome was in-hospital mortality. Secondary outcomes included delayed cerebral ischemia, cerebral infarction, radiographic and symptomatic vasospasm, pulmonary complications, epileptic seizures, external ventricular drain placement, and modified Rankin Scale score at discharge and 3-month follow-up. Associations between race and ethnicity and outcomes were assessed using binary and ordinal regression models, with multivariable models adjusted for significant covariates., Results: A total of 1325 patients with subarachnoid hemorrhage presented to our center. Among them, 443 cases were excluded, and data from 882 patients with radiographically confirmed aSAH were analyzed. Distribution by race and ethnicity was 40.8% (n=360) White, 31.4% (n=277) Hispanic, 22.1% (n=195) Black, and 5.7% (n=50) Asian. Based on Hunt-Hess and modified Fisher grade, aSAH severity was similar among groups ( P =0.269 and P =0.469, respectively). In-hospital mortality rates were highest for Asian (14.0%) and Hispanic (11.2%) patients; however, after adjusting for patient sex, age, health insurance, smoking history, alcohol and substance abuse, and aneurysm treatment, the overall likelihood was comparable to White patients. Hispanic patients had higher risks of developing cerebral infarction (adjusted odds ratio, 2.17 [1.20-3.91]) and symptomatic vasospasm (adjusted odds ratio, 1.64 [1.05-2.56]) than White patients and significantly worse discharge modified Rankin Scale scores (adjusted odds ratio, 1.44 [1.05-1.99]). Non-White patients also demonstrated a lower likelihood of 0 to 2 discharge modified Rankin Scale scores (adjusted odds ratio, 0.71 [0.50-0.98]). No significant interactions between race and ethnicity and age or sex were found for in-hospital mortality and functional outcomes., Conclusions: Our study identified significant differences in cerebral infarction and symptomatic vasospasm risk between Hispanic and White patients following aSAH. A higher likelihood of worse functional outcomes at discharge was found among non-White patients. These findings emphasize the need to better understand predisposing risk factors that may influence aSAH outcomes. Efforts toward risk stratification and patient-centered management should be pursued., Competing Interests: Disclosures Dr Becerril-Gaitan receives research funding through the National Institutes of Health (NIH; 1U01NS102289 and 1UF1NS120871). Dr Chen receives research funding through NIH (1U01NS102289 and 1UF1NS120871). The other authors report no conflicts.

Background: Whether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH)., Methods: We conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. The primary outcome was adjusted for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were neurologic and cardiopulmonary dysfunction events., Results: Among 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64 % were female, and 41 (53 %) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95 % CI, 0.14-0.80; P = 0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22 % vs. 39 %, P = 0.16); cardiac dysfunction (0 % vs. 11 %; P = 0.10); and pulmonary edema (15 % vs. 8 %; P = 0.59)., Conclusions: The risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients., Competing Interests: Declaration of competing interest Isaac Abecassis has the following disclosures: 1) Remedy Robotics: Consultant, Equity. 2) IschemaView Inc/Rapid AI: Clinical consultant. 3) Rapid Medical: Consultant. 4) Balt: Consultant. 5) CNS Foundation: Grant Research Support., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations., Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed., Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division ( D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic ( D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p  < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p  = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p  < 0. 001) ( p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p  < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p  < 0.001) ( p  < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p  < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p  < 0.001) ( p  = 0.029)., Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kabangu, Fry, Bhargav, De Stefano, Bah, Hernandez, Rouse, Peterson, Ebersole, Camarata and Eden.)

Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3-6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH., (© 2024. The Author(s).)

Background: There is a paucity of conclusive evidence regarding the impact of downward drift in hematocrit levels among patients who have undergone surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH). This study endeavors to explore the potential association between hematocrit drift and mortality in this specific patient population., Methods: A cohort study was conducted, encompassing adult patients diagnosed with aSAH at a university hospital. The primary endpoint was follow-up mortality. Propensity score matching was employed to align patients based on their baseline characteristics. Discrimination capacity across various models was assessed and compared using net reclassification improvement (NRI)., Results: Among the 671 patients with aSAH in the study period, 118 patients (17.6%) experienced an in-hospital hematocrit drift of more than 25%. Following adjustment with multivariate regression analysis, patients with elevated hematocrit drift demonstrated significantly increased odds of mortality (aOR: 2.12, 95% CI: 1.14 to 3.97; P = 0.019). Matching analysis yielded similar results (aOR: 2.07, 95% CI: 1.05 to 4.10; P = 0.036). The inclusion of hematocrit drift significantly improved the NRI (P < 0.0001) for mortality prediction. When in-hospital hematocrit drift was served as a continuous variable, each 10% increase in hematocrit drift corresponded to an adjusted odds ratio of 1.31 (95% CI 1.08-1.61; P = 0.008) for mortality., Conclusions: In conclusion, the findings from this comprehensive cohort study indicate that a downward hematocrit drift exceeding 25% independently predicts mortality in surgical patients with aSAH. These findings underscore the significance of monitoring hematocrit and managing anemia in this patient population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The relationship between early spontaneous hypothermia and adverse clinical outcomes in patients with subarachnoid hemorrhage (SAH) has not been paid much attention. We designed this retrospective cohort study to determine this relationship by analyzing the association between the lowest body temperature (T-lowest) on the first day of ICU admission and in-hospital mortality. In this study, 550 participants with non-traumatic SAH were chosen from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Multivariate Cox regression analysis showed that T-lowest was nonlinearity correlated with in-hospital mortality (HR = 0.72, 95% CI: 0.59-0.86, p < 0.001). We divided the T-lowest into quartile groups. In comparison to reference group Q1 (31.30-36.06 ℃), group Q3 (36.56-36.72 ℃) had a 50% lower risk of death in the hospital (HR: 0.5, 95% CI: 0.28-0.87, p = 0.014). We further confirmed the curve-like relationship between T-lowest and in-hospital mortality using restricted cubic splines. The mortality is lowest when the T-lowest is close to 36.5 °C, and the risk of death is increased when the temperature is lower or higher than that. Our study demonstrates that in-hospital mortality is associated with T-lowest. Patients with non-traumatic SAH are at increased risk of death if their body temperature on the first day of ICU admission is too low., (© 2024. The Author(s).)

Objective: COVID-19 had massive effects on the healthcare system and multifactorial implications for the management of intensive care unit and cerebrovascular patients. This study aimed to assess the effect of COVID-19 on the outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH)., Methods: The National Inpatient Sample (NIS) was used to identify patients with nontraumatic SAH (ICD-10 code I60.x). Patients with nonaneurysmal cerebrovascular malformations or traumatic intracranial injuries were excluded. Only patients managed from April to December 2020 were included in the study given the availability of an ICD-10 code for COVID-19. Data on sociodemographic factors, hospital characteristics, comorbidities, NIS SAH Severity Score (NIS-SSS), surgical treatment, and death were acquired. Multivariable analysis was used to assess predictors of both surgical intervention and in-hospital mortality., Results: In total, 6984 patients met the study criteria, 359 (5.1%) of whom had COVID-19. Those with COVID-19 were more likely to be younger and male and had a higher All Patient Refined Diagnosis-Related Groups illness severity subclass, and NIS-SSS. Moreover, patients with COVID-19 were less likely to undergo surgery (10.0% vs 23.6%, OR 0.35, p < 0.0001) and had significantly higher mortality rates (48.2% vs 22.7%, p < 0.0001). When controlling for other variables, COVID-19 was an independent predictor of death (OR 1.67, p = 0.0002). Aneurysm surgery was performed in 1597 patients (317 open and 1280 endovascular procedures). There was no difference between the cohorts positive and negative for COVID-19 in terms of time to surgery or type of surgery., Conclusions: COVID-19 had significant impacts on patients with nontraumatic SAH. Specifically, patients with COVID-19 were significantly less likely to undergo surgery and had higher in-hospital mortality rates; however, for patients who did undergo procedural intervention, there was no significant difference in the type of intervention. Multiple factors, from medical acuity to healthcare system limitations, may contribute to these findings. Further retrospective research is needed to identify both specific causes of lower intervention rates and other potential nonaneurysmal causes of SAH in patients with COVID-19.

Objective: The relationships between immediate bleeding severity, postoperative complications, and long-term functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH) remain uncertain. Here, the authors apply their recently developed automated deep learning technique to quantify total bleeding volume (TBV) in patients with aSAH and investigate associations between quantitative TBV and secondary complications, adverse long-term functional outcomes, and death., Methods: Electronic health record data were extracted for adult patients admitted to a single institution within 72 hours of aSAH onset between 2018 and 2021. An automatic deep learning model was used to fully segment and quantify TBV on admission noncontrast head CT images. Patients were subgrouped by TBV quartile, and multivariable logistic regression, restricted cubic splines, and subgroup analysis were used to explore the relationships between TBV and each clinical outcome., Results: A total of 819 patients were included in the study. Sixty-six (8.1%) patients developed hydrocephalus, while 43 (5.3%) experienced rebleeding, 141 (17.2%) had delayed cerebral ischemia, 88 (10.7%) died in the 12 months after discharge, and 208 (25.7%) had a modified Rankin Scale score ≥ 3 12 months after discharge. On multivariable analysis, patients in the highest TBV quartile (> 37.94 ml) had an increased risk of hydrocephalus (adjusted OR [aOR] 4.38, 95% CI 1.61-11.87; p = 0.004), rebleeding (aOR 3.26, 95% CI 1.03-10.33; p = 0.045), death (aOR 6.92, 95% CI 1.89-25.37; p = 0.004), and 12-month disability (aOR 3.30, 95% CI 1.62-6.72; p = 0.001) compared with the lowest TBV quantile (< 8.34 ml). The risks of hydrocephalus (nonlinear, p = 0.025), rebleeding, death, and disability (linear, p > 0.05) were positively associated with TBV by restricted cubic splines. In subgroup analysis, TBV had a stronger effect on 12-month outcome in female than male patients (p for interaction = 0.0499) and on rebleeding prevalence in patients with endovascular coiling than those with surgical clipping (p for interaction = 0.008)., Conclusions: Elevated TBV is associated with a greater risk of hydrocephalus, rebleeding, death, and poor prognosis.

Aim: To determine the risk factors affecting the mortality rate and outcomes of patients with subarachnoid hemorrhage (SAH)., Material and Methods: The records of patients who underwent aneurysm treatment and intensive care unit (ICU) followup in our hospital between 2013-2021 were reviewed retrospectively. Demographics of the patients, aneurysm characteristics, complications in the ICU, the Hunt Hess score, Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II score (APACHE II), sepsis status, and mechanical ventilation (MV) needed during ICU admission were collected. The generalized linear mixed modeling method was used to determine independent risk factors affecting mortality., Results: The records of 91 patients who met the inclusion criteria were analyzed. The age of the patients ranged from 21 to 86 years, and the female-to-male ratio was 6 / 7, with a mean age of 49.9 ± 13.06 years. The aneurysm treatment modality was surgical in 79 patients (86.8%) and endovascular in 12 patients (13.2%). The length of the ICU stay was mean 10.96 ± 13.66 days. While 64.8% (n=59) of the patients were discharged, 7.7% (n=7) were referred to palliative care units, and 25% (n=25) died. A one-unit increase in the APACHE II score was determined to increase the risk of vasospasm 1.154 times (p < 0.001). Analysis showed that a one-day increase in the MV day increased the mortality risk 1.838 times (p < 0.001), and vasospasm increased the mortality risk 32.151 times (p=0.004) CONCLUSION: The length of hospital stay, the day of MV, and the presence of vasospasm were determined as independent risk factors affecting mortality. Early diagnosis and rapid treatment of vasospasm, which increases mortality during ICU follow-up, positively impact patient outcomes.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death., Methods: Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified., Results: Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects., Conclusion: The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Early fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH., Materials and Methods: A total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association., Results: Of 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients., Conclusions: Elevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients., Competing Interests: Declaration of Competing Interest The authors have no personal, financial, or institutional interest in any of the materials or methods used in this study or the findings specified in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) survivors is concerning. The goal of this study was to investigate and demonstrate the relationship between the neutrophil-to-albumin ratio (NAR) and long-term mortality of aSAH survivors., Methods: A retrospective observational cohort study was conducted at Sichuan University West China Hospital between January 2009 and June 2019. The investigation of relationship between NAR and long-term mortality was conducted using univariable and multivariable Cox regression models. To demonstrate the predictive performance of different biomarkers over time, time-dependent receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were created., Results: In total, 3173 aSAH patients were included in this study. There was a strong and continuous relationship between NAR levels and long-term mortality (HR 3.23 95% CI 2.75-3.79, p < 0.001). After adjustment, the result was still significant (adjusted HR 1.78 95% CI 1.49-2.12). Compared with patients with the lowest quartile (< 0.15) of NAR levels, the risk of long-term mortality in the other groups was higher (0.15-0.20: adjusted HR 1.30 95% CI 0.97-1.73; 0.20-0.28: adjusted HR 1.37 95% CI 1.03-1.82; >0.28: adjusted HR 1.74 95% CI 1.30-2.32). Results in survivors were found to be still robust. Moreover, out of all the inflammatory markers studied, NAR demonstrated the highest correlation with long-term mortality., Conclusions: A high level of NAR was associated with increased long-term mortality among patients with aSAH. NAR was a promising inflammatory marker for long-term mortality of aSAH., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Importance: Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited., Objective: To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery., Design, Setting, and Participants: This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021., Exposures: Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records., Main Outcomes and Measures: Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models., Results: Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective df = 3.83 in the generalized additive model, χ2 test P = .002 for the 4-df cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test: df = 3, deviance = 9.57, χ2 test P = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications., Conclusions and Relevance: This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.

Background: There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types., Methods: We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints., Results: Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year., Conclusion: Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes., Competing Interests: Conflict of interest The Authors declare no conflict of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

Background: It is known that patients suffering poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have a dismal prognosis. The importance of early intervention is well established in the pertinent literature. Our aim was to assess the functional outcome and overall survival of these patients undergoing surgical clipping., Material and Methods: In the current retrospective study we included all consecutive poor-grade patients after spontaneous SAH who presented at our institution over an eight-year period. All participants suffering SAH underwent brain CT angiography (CTA) to identify the source of hemorrhage. We assessed the severity of hemorrhage according to the Fisher grade classification scale. All patients were surgically treated. The functional outcome was evaluated six months after the onset with the Glasgow Outcome Scale. Finally, we performed logistic and Cox regression analyses to identify potential prognostic risk factors., Results: Our study included twenty-three patients with a mean age of 53 years. Five (22%) patients presented with Hunt and Hess grade IV, and eighteen (78%) with grade V. The mean follow-up was 15.8 months, while the overall mortality rate was 48%. The six-month functional outcome was favorable in 6 (26%) patients. The vast majority of our patients died between the 15 th and the 60 th post-ictal days. We did not identify any statistically significant prognostic factors related to the patient's outcome and/or survival., Conclusions: Poor-grade aSAH patients may have a favorable outcome with proper surgical management. Large-scale studies are necessary for accurately outlining the prognosis of this entity, and identifying parameters that could be predictive of outcome.

Abstract: Studies on the relationship between hospital annualized case volume and in-hospital mortality in patients with subarachnoid hemorrhage (SAH) have shown conflicting results. Therefore, we performed a meta-analysis to further examine this relationship.The authors searched the PubMed and Embase databases from inception through July 2020 to identify studies that assessed the relationship between hospital annualized SAH case volume and in-hospital SAH mortality. Studies that reported in-hospital mortality in SAH patients and an adjusted odds ratio (OR) comparing mortality between low-volume and high-volume hospitals or provided core data to calculate an adjusted OR were eligible for inclusion. No language or human subject restrictions were imposed.Five retrospective cohort studies with 46,186 patients were included for analysis. The pooled estimate revealed an inverse relationship between annualized case volume and in-hospital mortality (OR, 0.53; 95% confidence interval, 0.42-0.68, P < .0001). This relationship was consistent in almost all subgroup analyses and was robust in sensitivity analyses.This meta-analysis confirms an inverse relationship between hospital annualized SAH case volume and in-hospital SAH mortality. Higher annualized case volume was associated with lower in-hospital mortality., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The efficacy of tranexamic acid for subarachnoid hemorrhage remains controversial. Thus, we conduct this meta-analysis to explore the efficacy of tranexamic acid for subarachnoid hemorrhage., Methods: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model., Results: Five RCTs and 2359 patients were included in the meta-analysis. Overall, compared with control intervention for subarachnoid hemorrhage, tranexamic acid was associated with significantly reduced risk of rebleeding (Odd ratio [OR] =0.62; 95% confidence interval [CI] =0.41 to 0.93; P = 0.02), but had no influence on mortality (OR = 0.94; 95% CI = 0.75 to 1.18; P = 0.61), poor outcome (OR = 0.95; 95% CI = 0.61 to 1.48; P = 0.82), hydrocephalus (OR = 1.17; 95% CI = 0.94 to 1.46; P = 0.17) or delayed cerebral ischemia (OR = 1.26; 95% CI = 0.78 to 2.04; P = 0.34)., Conclusions: Tranexamic acid may be effective to reduce the risk of rebleeding in patients with subarachnoid hemorrhage., (Copyright © 2021. Published by Elsevier Inc.)

Cerebral vasospasm (CVS) is a common complication of subarachnoid hemorrhage (SAH) with high deformity rates and cerebral vascular smooth muscle cells (VSMCs) phenotypic switch is considered to be involved in the regulation of CVS. However, to the best of the authors' knowledge, its underlying molecular mechanism remains to be elucidated. Peroxisome proliferator‑activated receptor β/δ (PPARβ/δ) has been demonstrated to be involved in the modulation of vascular cells proliferation and maintains the autoregulation function of blood vessels. The present study investigated the potential effect of PPARβ/δ on CVS following SAH. A model of SAH was established by endovascular perforation on male adult Sprague‑Dawley rats, and the adenovirus PPARβ/δ (Ad‑PPARβ/δ) was injected via intracerebroventricular administration prior to SAH. The expression levels of phenotypic markers α‑smooth muscle actin and embryonic smooth muscle myosin heavy chain were measured via western blotting or immunofluorescence staining. The basilar artery diameter and vessel wall thickness were evaluated under fluorescence microscopy. SAH grade, neurological scores, brain water content and brain swelling were measured to study the mechanisms of PPARβ/δ on vascular smooth muscle phenotypic transformation. It was revealed that the expression levels of synthetic proteins were upregulated in rats with SAH and this was accompanied by CVS. Activation of PPARβ/δ using Ad‑PPARβ/δ markedly upregulated the contractile proteins elevation, restrained the synthetic proteins expression and attenuated SAH‑induced CVS by regulating the phenotypic switch in VSMCs at 72 h following SAH. Furthermore, the preliminary study demonstrated that PPARβ/δ downregulated ERK activity and decreased the expression of phosphorylated (p‑)ETS domain‑containing protein Elk‑1 and p‑p90 ribosomal S6 kinase, which have been demonstrated to serve an important role in VSMC phenotypic change. Additionally, it was revealed that Ad‑PPARβ/δ could positively improve CVS by ameliorating the diameter of the basilar artery and mitigating the thickness of the vascular wall. Furthermore, subsequent experiments demonstrated that Ad‑PPARβ/δ markedly reduced the brain water content and brain swelling and improved the neurological outcome. Taken together, the present study identified PPARβ/δ as a useful regulator for the VSMCs phenotypic switch and attenuating CVS following SAH, thereby providing novel insights into the therapeutic strategies of delayed cerebral ischemia.

Objective: To visualise the non-linear correlation between age and poor outcome at discharge in patients with aneurysmal subarachnoid haemorrhage (SAH) while adjusting for covariates, and to address the heterogeneity of this correlation depending on disease severity by a registry-based design., Methods: We extracted data from the Japanese Stroke Databank registry for patients with SAH treated via surgical clipping or endovascular coiling within 3 days of SAH onset between 2000 and 2017. Poor outcome was defined as a modified Rankin Scale Score ≥3 at discharge. Variable importance was calculated using machine learning (random forest) model. Correlations between age and poor outcome while adjusting for covariates were determined using generalised additive models in which spline-transformed age was fit to each neurological grade of World Federation of Neurological Societies (WFNS) and treatment., Results: In total, 4149 patients were included in the analysis. WFNS grade and age had the largest and second largest variable importance in predicting the outcome. The non-linear correlation between age and poor outcome was visualised after adjusting for other covariates. For grades I-III, the risk slope for unit age was relatively smaller at younger ages and larger at older ages; for grade IV, the slope was steep even in younger ages; while for grade V, it was relatively smooth, but with high risk even at younger ages., Conclusions: The clear visualisation of the non-linear correlation between age and poor outcome in this study can aid clinical decision making and help inform patients with aneurysmal SAH and their families better., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.

Background: Delayed cerebral ischemia (DCI) is a cause of morbidity associated with aneurysmal subarachnoid hemorrhage (aSAH). Neuroinflammation contributes to the development of DCI. Melatonin is a sleep-promoting hormone known to have cerebral anti-inflammatory properties. We hypothesized that synthetic melatonin (or the selective melatonin receptor agonist ramelteon) incidentally prescribed to improve sleep may lower the incidence of DCI among hospitalized aSAH patients., Methods: Subjects with a Hunt and Hess Grade I-III were identified from a data registry involving all aSAH patients admitted to our hospital between January 2015 and September 1, 2018. A cohort of patients who received either melatonin or ramelteon during their hospitalization was compared to a matched cohort that did not receive these drugs. The primary endpoint was incidence of DCI. Secondary outcomes included modified Rankin score (mRS) at discharge, discharge destination, and mortality at 6 weeks from discharge. The two groups were compared using univariate analysis. P < 0.05 was considered significant., Results: There was no significant difference in the incidence of DCI (15.8% vs. 16.9%, p = 1), discharge mRS (mRS 0-3: 51.3% vs. 45.1%, p = 0.59), discharge disposition (Home: 43.6% vs. 44.4, p = 0.47), or mortality (0% vs. 9.2%; p = 0.074) between the melatonin/ramelteon and non-melatonin groups., Conclusion: The use melatonin had no effect on DCI but may improve mortality in aSAH subjects. Prospective studies using a larger cohort are warranted to validate these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Endosaccular treatment is the backbone of endovascular treatment for acutely ruptured aneurysms. Stent-assisted coiling is a niche technique in this context. Data on X-stenting or Y-stenting (dual crossing stenting, DCS) in the acute phase after subarachnoid hemorrhage (aSAH) are scarce, and the impact of stent properties on the outcome is unknown. We retrospectively evaluated the clinical and imaging results of DCS in patients treated for aSAH., Methods: Patients with aSAH treated with DCS were evaluated retrospectively. Patient and procedural characteristics were evaluated to determine clinical outcomes, associated complications, and follow-up imaging findings., Results: Sixteen procedures (16 patients; 10 women, mean age 55.8) were performed within 3.2 ± 2.6 days (range 1-10 days) of aSAH. Only the latest generation of intracranial stents (dual Neuroform Atlas-12 cases, dual Leo Baby-2 cases, Neuroform Atlas with Acclino Flex, or Leo Baby-2 cases) were used. Technical success rate was 100%; however, 25% of the procedures were complicated, leading to adverse events in 3 procedures (18.8%; 2 stent thrombosis, 1aneurysm rupture). Procedure-related morbidity and mortality and overall permanent morbidity and mortality were 6.3%, none, 6.3%, and 12.5%, respectively. No additional neurologic events were noted on a mean clinical follow-up of 160 ± 156 (range: 1-540) days., Conclusions: Our findings and the patient-by-patient data we extracted from the literature suggest that DCS can be performed with new-generation, low-profile stents in aSAH if a definite procedural risk is acceptable for a specific patient. New-generation open-cell stent combinations appear as a viable choice for DCS in aSAH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels., Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level., Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0])., Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests V Feigin reports support for the present manuscript from PreventS web app and free Stroke Riskometer app, which are owned and copyrighted by Auckland University of Technology, New Zealand. V Feigin reports grants received from the Brain Research New Zealand Centre of Research Excellence (16/STH/36), National Health & Medical Research Council (NHMRC, Australia APP1182071) and World Stroke Organization to their institution; leadership or fiduciary role in board, society, committee or advocacy group, paid or unpaid with World Stroke Organization as Executive Committee member, New Zealand Stroke Education (charitable) Trust as CEO, Stroke Central New Zealand as Honorary Medical Director, all of which are honorary unpaid roles; all outside the submitted work. O Adebayo reports grants or contracts from Merck Foundation; support for attending meetings and/or travel from Novartis; all outside the submitted work. R Akinyemi reports grants or contracts from NIH (U01HG010273), and GCRF (GCRFNGR6\1498), all outside the submitted work. R Ancuceanu consulting fees from AbbVie and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Sandoz, and B. Braun; support for attending meetings and/or travel from AbbVie and AstraZeneca; all outside the submitted work. J Ärnlöv reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca and Novartis; participation on a Data Safety Monitoring Board or Advisory Board with AstraZeneca and Boehringer Ingelheim; all outside the submitted work. Z Aryan reports support for the present manuscript from American Heart Association as funding to their institution, and from Brigham and Women's Hospital as an employee. M Ausloos reports grants or contracts from [Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI project number PN-III-P4-ID-PCCF-2016-0084, research grant (Oct 2018–Sept 2022), grant title “Understanding and modelling time-space patterns of psychology-related inequalities and polarization” outside the submitted work. T Bärnighausen reports grants or contracts from Research grants from the European Union (Horizon 2020 and EIT Health), German Research Foundation (DFG), US National Institutes of Health, German Ministry of Education Research, Alexander von Humboldt Foundation, Else-Kröner-Fresenius-Foundation, Wellcome Trust, Bill & Melinda Gates Foundation, KfW, UNAIDS, and WHO; consulting fees from KfW on the OSCAR initiative in Vietnam; participation on a Data Safety Monitoring Board or Advisory Board with the NIH-funded study “Healthy Options” (PIs: Smith Fawzi, Kaaya), Chair of the Data Safety and Monitoring Board (DSMB), German National Committee on the “Future of Public Health Research and Education”, Chair of the scientific advisory board to the EDCTP Evaluation, Member of the UNAIDS Evaluation Expert Advisory Committee, National Institutes of Health Study Section Member on Population and Public Health Approaches to HIV/AIDS (PPAH), US National Academies of Sciences, Engineering, and Medicine's Committee for the “Evaluation of Human Resources for Health in the Republic of Rwanda under the President's Emergency Plan for AIDS Relief (PEPFAR)”, and University of Pennsylvania (UPenn) Population Aging Research Center (PARC) External Advisory Board Member; leadership or fiduciary role in board, society, committee or advocacy group, paid or unpaid as the co-chair of the Global Health Hub Germany (which was initiated by the German Ministry of Health); all outside the submitted work. E Beghi reports grants or contracts from Italian Health Ministry, American ALS Association, and SOBI Pharmaceutical Company made to their institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from University of Rochester; support for attending meetings and/or travel from ILAE; participation on a Data Safety Monitoring Board or Advisory Board with Arvelle Therapeutics; all outside the submitted work. Y Béjot reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medtronic, Boehringer-Ingelheim, Pfizer, BMS, Servier, and Amgen; support for attending meetings and/or travel from Servier; all outside the submitted work. A Catapano reports grants or contracts from Sanofi, Eli Lilly, Mylan, Sanofi Regeneron, Menarini, and Amgen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Akcea, Amgen, AstraZeneca, Aegerion, Amryt, Daiichi, Sankyo, Esperion, Kowa, Ionis Pharmaceuticals, Mylan, Merck, Menarini, Novartis, Recordati, Regeneron, Sandoz, and Sanofi; all outside the submitted work. S Costanzo reports grants or contracts from ERAB (the European Foundation for Alcohol Research; id. EA1767; 2018–2020 and Italian Ministry of Health (grant RF-2018-12367074, CoPI), both paid to their institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from as a member of the Organizing Committee and speaker for the 9th European Beer and Health Symposium (Bruxelles 2019) and for given lecture at the 13th European Nutrition Conference FENS 2019 (Dublin), sponsored by the Beer and Health Initiative (The Dutch Beer Institute foundation—The Brewers of Europe); all outside the submitted work. M Endres reports grants or contracts from Bayer as an unrestricted grant to Charité for MonDAFIS study and Berlin AFib registry; consulting fees from Bayer paid to their institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Boehringer Ingelheim, Pfizer, Amgen, GSK, Sanofi, and Novartis, all paid to their institution; participation on a Data Safety Monitoring Board or Advisory Board with BMS as a Country PI for Axiomatic-SSP, Bayer as Country PO for NAVIGATE-ESUS, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Covidien, with all fees paid to their institution; leadership or fiduciary role in board, society, committee or advocacy group, paid or unpaid with EAN as part of the Board of Directors, DGN, ISCBFM, AHA/ASA, ESO, WSO, DZHK (German Centre of Cardiovascular Research) as a PI, all of which are unpaid positions, and with DZNE (German Center of Neurodegenerative Diseases) as a paid PI; receipt of PCSK9 inhibitors for mouse studies from Amgen; all outside the submitted work. I Filip reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Avicenna Medical and Clinical Research Institute, outside the submitted work. A Gialluisi reports grants or contracts from Italian Ministry of Economic Development (PLATONE project, bando “Agenda Digitale” PON I&C 2014–2020; Prog. n. F/080032/01-03/X35) paid to their institution, outside the submitted work. C Herteliu reports grants or contracts from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI project number PN-III-P4-ID-PCCF-2016-0084 research grant (Oct 2018–Sept 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2.1-SOL-2020-2-0351 research grant (June–Oct, 2021) “Approaches within public health management in the context of COVID-19 pandemic,” and from the Ministry of Labour and Social Justice, Romania, project number 30/PSCD/2018 research grant (Sept 2018–June 2019) “Agenda for skills Romania 2020–2025;” all outside the submitted work. S Islam reports grants or contracts from National Heart Foundation Vanguard grant, Postdoctoral Fellowship and NHMRC Emerging Leadership Fellowship, outside the submitted work. Y Kalkonde reports grants or contracts from DBT/Wellcome Trust India Alliance as a DBT/Wellcome Trust India Alliance fellow in Public Health (grant number IA/CPHI/14/1/501514). M Kivimäki reports support for the present manuscript from The Wellcome Trust (221854/Z/20/Z) and Medical Research Council (MR/S011676/1), as research grants paid to their institute. K Krishnan reports non-financial support from UGC Centre of Advanced Study, Phase II, Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. P Lavados reports grants or contracts from Boehringer Ingelheim as grant support to their institute for RECCA stroke registry, and from ANID as personal grant support for ADDSPISE trial; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim as personal honoraria for lectures; support for attending meetings and/or travel from Boehringer Ingelheim as support for attending Global Stroke Netowrk meeting in 2020; all outside the submitted work. W Lo reports grants or contracts from 1U01NS106655-01A1 (MPI: S Ramey, Lo), 5U24NS1072050-02 (PI: Kolb), and 1P2CHD101912-01 (PD: S. Ramey), all outside the submitted work. S Lorkowski reports grants or contracts from Akcea Therapeutics Germany as payments made to their institution; consulting fees from Danone, Swedish Orphan Biovitrum (SOBI), and Upfield; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Akcea Therapeutics Germany, AMARIN Germany, Amedes Holding, AMGEN, Berlin-Chemie, Boehringer Ingelheim Pharma, Daiichi Sankyo Deutschland, Danone, Hubert Burda Media Holding, Lilly Deutschland, Novo Nordisk Pharma, Roche Pharma, Sanofi-Aventis, and SYNLAB Holding Deutschland & SYNLAB Akademie as personal payments; support for attending meetings and/or travel from Amgen as personal payments; participation on a Data Safety Monitoring Board or Advisory Board with Akcea Therapeutics Germany, Amgen, Daiichi Sankyo Deutschland, and Sanofi-Aventis as personal payments; all outside the submitted work. N Manafi reports support for the present manuscript from BMGF as funding to IHME for this project. B Norrving reports consulting fees from AstraZeneca and Bayer as personal payments outside the submitted work. O Odukoya reports grants or contracts from the Fogarty International Center of the National Institutes of Health as protected time towards the research reported in this publication was supported under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A Pana reports grants or contracts from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI project number PN-III-P4-ID-PCCF-2016-0084 research grant (Oct 2018–Sept 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2·1-SOL-2020-2-0351 research grant (June–Oct 2021) “Approaches within public health management in the context of COVID-19 pandemic,” all outside the submitted work. M Postma reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with the UK's JCVI as an unpaid member, outside the current manuscript. A Radfar reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Avicenna Medical and Clinical Research Institute. S Sacco reports grants or contracts from Novartis and Allergan-AbbVie; consulting fees from Allergan-AbbVie, Novartis, Eli Lilly, AstraZeneca, and Novo Nordisk; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Allergan-AbbVie, Novartis, Eli Lilly, TEVA, Abbott, Medscape, and Olgology; support for attending meetings and/or travel from Allergan, Eli Lilly, Abbott, Novartis, and Teva; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with Guideline Board European Stroke Organization as Co-chair, and with the European Headache Federation as a board member; all outside the submitted work. A Schutte reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Sanofi, Takeda, Abbott, Servier, and Omron Healthcare as honoraria for lectures during educational events; support for attending meetings and/or travel from Takeda and Omron; all outside the submitted work. J Singh reports consulting fees from Crealta/Horizon, Medisys, Fidia, Two labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Simply Speaking; support for attending meetings and/or travel from OMERACT, an international organization that develops measures for clinical trials and receives arm's length funding from 12 pharmaceutical companies, when traveling to OMERACT meetings; participation on a Data Safety Monitoring Board or Advisory Board as a member of the FDA Arthritis Advisory Committee; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with OMERACT as a member of the steering committee, with the Veterans Affairs Rheumatology Field Advisory Committee as a member, and with the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis as a director and editor; stock or stock options in TPT Global Tech, Vaxart pharmaceuticals, Charlotte's Web Holdings and previously owned stock options in Amarin, Viking, and Moderna pharmaceuticals; all outside the submitted work. S Stortecky reports grants or contracts from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific as grants made to their institution; consulting fees from Boston Scientific/BTG Teleflex; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boston Scientific; all outside the submitted work. M Woodward reports consulting fees from Amgen as personal payment. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Systemic inflammation is recognized as a hallmark of stroke. We aimed to evaluate the prognostic value of various inflammatory factors using blood at admission in patients with aneurysmal subarachnoid hemorrhage., Methods: In a multicenter observational study of patients with aneurysmal subarachnoid hemorrhage, the counts of neutrophil, platelet, and lymphocyte were collected on admission. Patients were stratified based on neutrophil counts with propensity score matching to minimize confounding. We calculated the adjusted odds ratios with 95% CIs for the primary outcome of in-hospital mortality and hospital-acquired infections., Results: A total of 6041 patients were included in this study and 344(5.7%) of them died in hospital. Propensity score matching analyses indicated that compared with the lower neutrophil counts, higher neutrophil counts were associated with increased risk of in-hospital mortality (odds ratio, 1.53 [95% CI, 1.14–2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38–1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09–1.97]). Moreover, out of all the inflammatory factors studied, neutrophil counts demonstrated the highest correlation with in-hospital mortality and hospital-acquired infections., Conclusions: Among patients with aneurysmal subarachnoid hemorrhage, high neutrophil counts at admission were associated with increased mortality and hospital-acquired infections. The neutrophil count is a simple, useful marker with prognostic value in patients with aneurysmal subarachnoid hemorrhage.

Background and Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown., Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019. The primary outcome was in-hospital all-cause mortality., Results: This study included 6228 cases of aSAH, 489 (7.9%) of whom also had CLD. In a propensity-matched analysis, CLD was associated with increased mortality in patients with aSAH compared with non-CLD (odds ratio, 2.04 [95% CI, 1.43–2.92]). In aSAH patients with CLD, a high Model for End-Stage Liver Disease score was still associated with an increased odds of mortality., Conclusions: Among aSAH patients, CLD was associated with increased mortality compared with non-CLD. Among aSAH patients with CLD, a higher Model for End-Stage Liver Disease score was associated with an increased odds of mortality.

Background: The prevalence of risk factors for poor outcomes from aneurysmal subarachnoid hemorrhage (SAH) varies widely and has not been fully elucidated to date in Vietnam. Understanding the risk and prognosis of aneurysmal SAH is important to reduce poor outcomes in Vietnam. The aim of this study, therefore, was to investigate the rate of poor outcome at 90 days of ictus and associated factors from aneurysmal SAH in the country., Methods: We performed a multicenter prospective cohort study of patients (≥18 years) presenting with aneurysmal SAH to three central hospitals in Hanoi, Vietnam, from August 2019 to August 2020. We collected data on the characteristics, management, and outcomes of patients with aneurysmal SAH and compared these data between good (defined as modified Rankin Scale (mRS) of 0 to 3) and poor (mRS, 4-6) outcomes at 90 days of ictus. We assessed factors associated with poor outcomes using logistic regression analysis., Results: Of 168 patients with aneurysmal SAH, 77/168 (45.8%) were men, and the median age was 57 years (IQR: 48-67). Up to 57/168 (33.9%) of these patients had poor outcomes at 90 days of ictus. Most patients underwent sudden-onset and severe headache (87.5%; 147/168) and were transferred from local to participating central hospitals (80.4%, 135/168), over half (57.1%, 92/161) of whom arrived in central hospitals after 24 hours of ictus, and the initial median World Federation of Neurological Surgeons (WFNS) grading score was 2 (IQR: 1-4). Nearly half of the patients (47.0%; 79/168) were treated with endovascular coiling, 37.5% (63/168) were treated with surgical clipping, the remaining patients (15.5%; 26/168) did not receive aneurysm repair, and late rebleeding and delayed cerebral ischemia (DCI) occurred in 6.1% (10/164) and 10.4% (17/163) of patients, respectively. An initial WFNS grade of IV (odds ratio, OR: 15.285; 95% confidence interval, CI: 3.096-75.466) and a grade of V (OR: 162.965; 95% CI: 9.975-2662.318) were independently associated with poor outcomes. Additionally, both endovascular coiling (OR: 0.033; 95% CI: 0.005-0.235) and surgical clipping (OR: 0.046; 95% CI: 0.006-0.370) were inversely and independently associated with poor outcome. Late rebleeding (OR: 97.624; 95% CI: 5.653-1686.010) and DCI (OR: 15.209; 95% CI: 2.321-99.673) were also independently associated with poor outcome., Conclusions: Improvements are needed in the management of aneurysmal SAH in Vietnam, such as increasing the number of aneurysm repairs, performing earlier aneurysm treatment by surgical clipping or endovascular coiling, and improving both aneurysm repairs and neurocritical care., Competing Interests: The authors have declared that no competing interests exist.

Background Previous studies of patients with nontraumatic subarachnoid hemorrhage (SAH) suggest better outcomes at hospitals with higher case and procedural volumes, but the shape of the volume-outcome curve has not been defined. We sought to establish minimum volume criteria for SAH and aneurysm obliteration procedures that could be used for comprehensive stroke center certification. Methods and Results Data from 8512 discharges in the National Inpatient Sample (NIS) from 2010 to 2011 were analyzed using logistic regression models to evaluate the association between clinical outcomes (in-hospital mortality and the NIS-SAH Outcome Measure [NIS-SOM]) and measures of hospital annual case volume (nontraumatic SAH discharges, coiling, and clipping procedures). Sensitivity and specificity analyses for the association of desirable outcomes with different volume thresholds were performed. During 8512 SAH hospitalizations, 28.7% of cases underwent clipping and 20.1% underwent coiling with rates of 21.2% for in-hospital mortality and 38.6% for poor outcome on the NIS-SOM. The mean (range) of SAH, coiling, and clipping annual case volumes were 30.9 (1-195), 8.7 (0-94), and 6.1 (0-69), respectively. Logistic regression demonstrated improved outcomes with increasing annual case volumes of SAH discharges and procedures for aneurysm obliteration, with attenuation of the benefit beyond 35 SAH cases/year. Analysis of sensitivity and specificity using different volume thresholds confirmed these results. Analysis of previously proposed volume thresholds, including those utilized as minimum standards for comprehensive stroke center certification, showed that hospitals with more than 35 SAH cases annually had consistently superior outcomes compared with hospitals with fewer cases, although some hospitals below this threshold had similar outcomes. The adjusted odds ratio demonstrating lower risk of poor outcomes with SAH annual case volume ≥35 compared with 20 to 34 was 0.82 for the NIS-SOM (95% CI, 0.71-094; P =0.0054) and 0.80 (95% CI, 0.68-0.93; P =0.0055) for in-hospital mortality. Conclusions Outcomes for patients with SAH improve with increasing hospital case volumes and procedure volumes, with consistently better outcomes for hospitals with more than 35 SAH cases per year.

Aim: Although radiological methods are sufficient for the diagnosis of spontaneous subarachnoid hemorrhage (SAH), additional biomarkers are needed to predict prognosis. The aim of this study was to investigate the effects of serum S100B protein, Glial Fibrillary Acidic Protein (GFAP) levels and, Optic Nerve Sheath Diameter (ONSD) on mortality and clinical severity in patients with spontaneous SAH., Materials and Methods: Fifty-six patients who were diagnosed with SAH after first evaluation in the emergency department (ED) were included in the study group; Forty-six patients who were admitted to the ED with headache of non-intracranial etiology, were included as the control group. Cerebral computed tomography (CT) images and peripheral blood samples were obtained from all patients; at the time of diagnosis and 24 h after diagnosis. Serum S100B protein and GFAP levels were measured from the blood samples and ONSD was measured on CT., Results: Serum S100B protein and GFAP levels and, ONSDs at the time of diagnosis and 24 h after diagnosis were significantly higher in the study group (p < 0.05). Both GFAP levels and ONSD at the time of diagnosis and 24 h after the diagnosis were found to be related with increased mortality (p < 0.05). A similar association was found for serum S100B protein levels 24 h after the diagnosis, but not at the time of diagnosis (p = 0.540)., Conclusion: Serum S100B protein and GFAP levels and, ONSD were increased in patients with spontaneous SAH. All parameters were found to be associated with increased mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Cerebral vasospasm (CVS) and delayed ischemic neurological deficits (DIND) are a common cause of morbidity following aneurysmal subarachnoid hemorrhage (SAH). Statins have been shown to decrease CVS. The objective of this article was to ascertain the effect of statins on functional outcome and mortality following aneurysmal SAH by performing meta-analysis., Methods: A comprehensive search of different databases was performed to retrieve randomized controlled trials. Meta-analysis with subgroup analysis and metaregression was done. Trial sequential analysis (TSA) was performed to determine if the cumulative sample size was appropriately powered for the obtained pooled effect values and to avoid random error., Results: Twelve articles were selected for meta-analysis. Pooled OR for the change in favorable outcome, mortality, CVS, DIND and elevated transaminases was 1.07 (p = 0.55), 0.78 (p = 0.17), 0.58 (p = 0.0004), 0.54 (p = 0.0293) and 0.68 (p = 0.1774) respectively. Further, subgroup analysis and metaregression showed that the use of different statin or dose did not result in significant variation in results in the parameters studied. TSA showed that more trials and patients are required to reach to a definitive conclusion regarding any effect on statins on functional outcome and mortality as the current studies neither reached the level of confidence nor crossed the futility boundary., Conclusion: Use of statins in patients with aneurysmal SAH resulted in marginal but non-significant favorable impact on functional outcome and mortality. TSA showed that more studies are required to get conclusive evidence in this regard., (Copyright © 2021. Published by Elsevier B.V.)