Association between neutrophil-to-albumin ratio and long-term mortality of aneurysmal subarachnoid hemorrhage.

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.

Um cirurgião sob o olhar de Deus

Objetivo A síndrome de Terson (ST), também conhecida como hemorragia vítrea, é relatada em pacientes com hemorragia subaracnóide causada por um aneurisma rompido. Este estudo tem como objetivo avaliar a presença de hemorragia ocular nesses pacientes, buscando identificar aqueles que poderiam se beneficiar do tratamento específico para a recuperação do déficit visual. Métodos Estudo prospectivo de 53 pacientes com hemorragia subaracnóide espontânea (SSAH) por aneurisma rompido. Os pacientes foram avaliados quanto à hemorragia vítrea por fundoscopia indireta com 6 a 12 meses de seguimento. Resultados A idade dos pacientes variou de 17 a 79 anos (média de 45,9 ± 11,7); 39 pacientes eram do sexo feminino (73%) e 14 do sexo masculino (27%). Seis pacientes (11%) apresentaram ST e 83,3% apresentaram perda transitória de consciência durante a ictus. Conclusões Uma avaliação oftalmológica deve ser realizada rotineiramente em pacientes com hemorragia subaracnóide, especialmente naqueles com pior grau neurológico. Além disso, o prognóstico foi ruim em pacientes com ST.

Association of Onset-to-Treatment Time With Discharge Destination, Mortality, and Complications Among Patients With Aneurysmal Subarachnoid Hemorrhage.

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.

Case-Fatality and Functional Outcome after Subarachnoid Hemorrhage (SAH) in INternational STRoke oUtComes sTudy (INSTRUCT).

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.

Intermediate surgical outcome in patients suffering poor-grade aneurysmal subarachnoid hemorrhage. A single center experience.

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 15th and the 60th 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.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

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.

Tranexamic acid for subarachnoid hemorrhage: A systematic review and meta-analysis.

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.

Melatonin and risk of mortality in subjects with aneurysmal subarachnoid hemorrhage.

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.

Peroxisome proliferator­activated receptor ß/δ regulates cerebral vasospasm after subarachnoid hemorrhage via modulating vascular smooth muscle cells phenotypic conversion.

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 proliferator­activated receptor ß/δ (PPARß/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 PPARß/δ on CVS following SAH. A model of SAH was established by endovascular perforation on male adult Sprague­Dawley rats, and the adenovirus PPARß/δ (Ad­PPARß/δ) was injected via intracerebroventricular administration prior to SAH. The expression levels of phenotypic markers α­smooth 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 PPARß/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 PPARß/δ using Ad­PPARß/δ markedly upregulated the contractile proteins elevation, restrained the synthetic proteins expression and attenuated SAH­induced CVS by regulating the phenotypic switch in VSMCs at 72 h following SAH. Furthermore, the preliminary study demonstrated that PPARß/δ downregulated ERK activity and decreased the expression of phosphorylated (p­)ETS domain­containing protein Elk­1 and p­p90 ribosomal S6 kinase, which have been demonstrated to serve an important role in VSMC phenotypic change. Additionally, it was revealed that Ad­PPARß/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 Ad­PPARß/δ markedly reduced the brain water content and brain swelling and improved the neurological outcome. Taken together, the present study identified PPARß/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.

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

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.

Terson Syndrome: Assessment of 53 Patients with Subarachnoid Hemorrhage by a Ruptured Aneurysm

Objective Terson syndrome (TS), also known as vitreous hemorrhage, is reported in patients with subarachnoid hemorrhage caused by a ruptured aneurysm. This study aims to evaluate the presence of ocular hemorrhage in such patients, trying to identify those who could benefit from the specific treatment for visual deficit recovery. Methods Prospective study of 53 patients with spontaneous subarachnoid hemorrhage (SSAH) due to ruptured aneurysm. The patients were evaluated for vitreous hemorrhage through indirect fundoscopy with 6 to 12 months of follow-up. Results The ages of the patients ranged from 17 to 79 years-old (mean age, 45.9 11.7); 39 patients were female (73%) and 14 were male (27%). Six patients (11%) presented TS, and 83.3% had a transient loss of consciousness during ictus. Conclusions An ophthalmologic evaluation must be routinely performed in subarachnoid hemorrhage patients, especially in those with worse neurological grade. Moreover, prognosis was bad in TS patients.

Clinical characteristics and factors relating to poor outcome in patients with aneurysmal subarachnoid hemorrhage in Vietnam: A multicenter prospective cohort study.

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.

The Effect of Biomarkers and Optic Nerve Sheath Diameter in Determining Mortality in non-Traumatic Subarachnoid Hemorrhage.

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.

Effect of statins on functional outcome and mortality following aneurysmal subarachnoid hemorrhage - Results of a meta-analysis, metaregression and trial sequential analysis.

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.

Dual Stenting with New-Generation Stents for Aneurysm Embolization in Acute Subarachnoid Hemorrhage.

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.

Association of Chronic Liver Disease and Mortality 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, 1.43­2.92]). 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.

Association Between Hospital Volumes and Clinical Outcomes for Patients With Nontraumatic Subarachnoid Hemorrhage.

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.

Neutrophil Counts as Promising Marker for Predicting In-Hospital Mortality in Aneurysmal Subarachnoid Hemorrhage.

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, 1.14­2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38­1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09­1.97]). 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.

Visualisation of the non-linear correlation between age and poor outcome in patients with aneurysmal subarachnoid haemorrhage.

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.

Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage.

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.