Longitudinal change of serum AIM2 levels after aneurysmal subarachnoid hemorrhage and its prognostic significance: a two-center prospective cohort study.

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.

The association between hematologic traits and aneurysm-related subarachnoid hemorrhage: a two-sample mendelian randomization study.

Several hematologic traits have been suggested to potentially contribute to the formation and rupture of intracranial aneurysms (IA). The purpose of this study is to explore the causal association between hematologic traits and the risk of IA. To explore the causal association between hematologic traits and the risk of IA, we employed two-sample Mendelian randomization (MR) analysis. Two independent summary-level GWAS data were used for preliminary and replicated MR analyses. The inverse variance weighted (IVW) method was employed as the primary method in the MR analyses. The stabilities of the results were further confirmed by a meta-analysis. In the preliminary MR analysis, hematocrit, hemoglobin concentration (p = 0.0047), basophil count (p = 0.0219) had a suggestive inverse causal relationship with the risk of aneurysm-associated subarachnoid hemorrhage (aSAH). The monocyte percentage of white cells (p = 0.00956) was suggestively positively causally correlated with the risk of aSAH. In the replicated MR analysis, only the monocyte percentage of white cells (p = 0.00297) remained consistent with the MR results in the preliminary analysis. The hematocrit, hemoglobin concentration, and basophil count no longer showed significant causal relationship (p > 0.05). Meta-analysis results further confirmed that only the MR result of monocyte percentage of white cells reached significance in the random effect model and fixed effect model. None of the 25 hematologic traits was causally associated with the risk of unruptured intracranial aneurysms (uIA). This study revealed a suggestive positive association between the monocyte percentage of white cells and the risk of aSAH. This finding contributes to a better understanding that monocytes/macrophages could participate in the risk of aSAH.

Hematocrit drift and outcomes in surgical patients with aneurysmal subarachnoid hemorrhage.

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.

Serum C-reactive protein value on day 14 as a possible prognostic factor of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Serum C-reactive protein (CRP), as a reflection of early brain injury at onset, is a prognostic factor in aneurysmal subarachnoid hemorrhage (aSAH). However, in some severe cases, patients exhibit a good prognosis despite their elevated serum CRP level. Therefore, we examined the relationship between serum CRP transitions in the acute phase of aSAH and the prognosis. METHODS: We recruited 63 patients with aSAH and retrospectively analyzed the relationships between the serum CRP transitions during the acute phase and the prognosis, patient background, and clinical course. RESULTS: Serum CRP values on days 1, 3, and 14 were significantly lower in the good prognosis group than those in the poor prognosis group. Moreover, serum CRP values on days 1 and 14 significantly affected the prognosis in the multiple regression analysis. CONCLUSIONS: A low serum CRP value on day 14, in addition to that on day 1 as reported previously, is associated with a good prognosis of aSAH. Furthermore, a good prognosis of aSAH is determined not only by absence of early brain injury at onset but also by appropriate management to obtain a low serum CRP value on day 14.

Triglyceride Glucose Index and Prognosis of Patients with Subarachnoid Hemorrhage.

OBJECTIVE: The triglyceride glucose (TyG) index is regarded as a reliable alternative indicator for measuring insulin resistance. We investigated the association between the prognosis of patients with subarachnoid hemorrhage (SAH)and the TyG index, explored the potential of the TyG index as a new biomarker for forecasting the outcomes of SAH patients, and explored independent risk factors for predicting the condition of SAH patients. METHODS: A retrospective analysis was performed of patients who were admitted to a single center due to SAH. Differences in clinical data and correlation between laboratory indexes, disease severity score on admission, and prognosis score were compared between the 2 groups. The study employed multivariate logistic regression analysis to examine the independent influencing aspects of Glasgow Outcome Scale score. The receiver operating characteristic curve was drawn and the area under the curve (AUC) calculated to predict the best cutoff value of the degree of neurological impairment in patients with SAH. RESULTS: Univariate analysis showed that Glasgow Coma Scale score (86.3% vs. 12.0%, P < 0.001), Hunt-Hess grade (88.2% vs. 15.7%, P < 0.001), white blood cell count (11.20 [7.9, 15.2] vs. 9.1 [7.0, 12.2], P = 0.027), and TyG index (1.49 [1.40, 1.59] vs. 1.16 [1.06, 1.27], P < 0.001) were statistically significantly different. Multivariate analysis showed that TyG index, Hunt-Hess grade, and GCS score were independent risk factors for poor prognosis. CONCLUSIONS: Patients with SAH may benefit from using the TyG index as a predictive method. In our clinical practice, the TyG index is beneficial for managing diseases and making decisions. More research is required to determine if improved TyG index control would lead to better clinical results in the future.

Acute-Phase Plasma Pigment Epithelium-Derived Factor Predicting Outcomes after Aneurysmal Subarachnoid Hemorrhage in the Elderly.

Aneurysmal subarachnoid hemorrhage (SAH) has increased with the aging of the population, but the outcome for elderly SAH patients is very poor. Therefore, predicting the outcome is important for determining whether to pursue aggressive treatment. Pigment epithelium-derived factor (PEDF) is a matricellular protein that is induced in the brain, and the plasma levels could be used as a biomarker for the severity of metabolic diseases. This study investigated whether acute-phase plasma PEDF levels could predict outcomes after aneurysmal SAH in the elderly. Plasma samples and clinical variables were collected over 1-3 days, post-SAH, from 56 consecutive elderly SAH patients ≥75 years of age registered in nine regional stroke centers in Japan between September 2013 and December 2016. The samples and variables were analyzed in terms of 3-month outcomes. Acute-phase plasma PEDF levels were significantly elevated in patients with ultimately poor outcomes, and the cutoff value of 12.6 µg/mL differentiated 3-month outcomes with high sensitivity (75.6%) and specificity (80.0%). Acute-phase plasma PEDF levels of ≥12.6 µg/mL were an independent and possibly better predictor of poor outcome than previously reported clinical variables. Acute-phase plasma PEDF levels may serve as the first biomarker to predict 3-month outcomes and to select elderly SAH patients who should be actively treated.

Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.

We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Subarachnoid Hemorrhage and Extracorporeal Blood Purification with HA-380 and High-Volume Hemofiltration: A New Therapeutic Challenge at the Neurocritical Care Unit? A Case Report.

We present the case of a patient with subarachnoid hemorrhage (SAH) secondary to a ruptured cerebral aneurysm and a refractory shock with high doses of vasopressors without a proven source of infection. This patient received therapy with high-volume hemofiltration plus adsorption, resolving the hemodynamic deterioration and with good neurological evolution. Our clinical case proposes that extracorporeal therapies may have a feasibility role in the management of complications of SAH.

Sodium Variability and Probability of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm. MATERIALS AND METHODS: A single-center retrospective analysis from 2007-2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes. RESULTS: A total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality. CONCLUSIONS: Serum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit.

Predictive effects of admission white blood cell counts and hounsfield unit values on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Neuroinflammatory response is deemed the primary pathogenesis of delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). Both white blood cell (WBC) count and Hounsfield Unit (HU) are gradually considered can reflect inflammation in DCI. This study aims to identify the relationship between WBC count and HU value and investigate the effects of both indicators in predicting DCI after aSAH. METHODS: We enrolled 109 patients with aSAH admitted within 24 h of onset in our study. A multivariate logistic regression analysis was used to evaluate the admission WBC count, HU value, and combined WBC-HU associated with DCI. The receiver operating characteristic curve and area under the curve (AUC) were used to determine thresholds and detect the predictive ability of these predictors. These indicators were also compared with the established inflammation markers. RESULTS: Thirty-six (33%) patients developed DCI. Both WBC count and HU value were strongly associated with the admission glucose level (ρ = .303, p = .001; ρ = .273, p = .004), World Federation of Neurosurgical Societies grade (ρ = .452, p < .001; ρ = .578; p < .001), Hunt-Hess grade (ρ = .450, p < .001; ρ = .510, p < .001), and modified Fisher scale score (ρ = .357, p < .001; ρ = .330, p < .001). After controlling these public variables, WBC count (ρ = .300, p = .002) positively correlated with HU value. An early elevated WBC (odds ratio [OR] 1.449, 95% confidence interval [CI]: 1.183-1.774, p < .001) count and HU value (OR 1.304, 95%CI: 1.149-1.479, p < .001) could independently predict the occurrence of DCI. However, only these patients with both WBC count and HU value exceeding the cut-off points (OR 36.89, 95%CI: 5.606-242.78, p < .001) were strongly correlated with DCI. Compared with a single WBC count (AUC 0.811, 95%CI: 0.729-0.892, p < .001) or HU value (AUC 0.869, 95%CI: 0.803-0.936, p < .001), the combined WBC-HU (AUC 0.898, 95%CI: 0.839-0.957, p < .001) demonstrated a better ability to predict the occurrence of DCI. Inspiringly, the prediction performance of these indicators outperformed the established inflammatory markers. CONCLUSION: An early elevated WBC count and HU value could independently predict DCI occurrence between 4 and 30 days after aSAH. Furthermore, WBC count was positively correlated with HU value, and the combined WBC-HU demonstrated a superior prediction ability for DCI development compared with the individual indicator.

Early-stage serum Stanniocalcin 1 as a predictor of outcome in patients with aneurysmal subarachnoid hemorrhage.

ABSTRACT: Stanniocalcin-1 (STC1) takes part in anti-inflammatory and anti-oxidative processes, thus demonstrating neuroprotective properties. Early brain injuries associated with initial subarachnoid hemorrhage typically led to secondary cerebral infarction and poor outcomes. This retrospective study aimed to clarify the clinical significance of serum STC1 level in patients with subarachnoid hemorrhage.We collected demographic information, comorbidities, neurological status in detail. All blood samples were collected on admission. Enzyme-linked immunosorbent assay kits were used to detect the serum level of STC1. Spearman analysis was used to explore the relationship between STC1 and clinical severity. Multivariate logistic regression was used to investigate the prognostic role of STC1 in patients with aneurysmal subarachnoid hemorrhage (aSAH). Receiver operating characteristic curve was performed to investigate the power of STC1 in predicting outcome in aSAH patients.Serum STC1 concentration was significantly higher in aSAH patients than in healthy individuals. Serum concentration of STC1 positively correlated with Hunt-Hess grade (r = 0.62, P < .01) and Fisher grade (r = 0.48, P < .01), and negatively correlated with Glasgow Coma Scale on admission (r = -0.45, P < .01). Patients with delayed cerebral ischemia (DCI) had higher level of serum STC1 than those without DCI (13.12 ±â€Š1.44 vs 8.56 ±â€Š0.31, P < .01). Moreover, patients with poor outcome had higher concentration of STC1 than patients with good outcome (11.82 ±â€Š0.62 vs 8.21 ±â€Š0.35,P < 0.01). Results of univariate and multivariate logistic analysis revealed that Hunt-hess III-IV, DCI, and high STC1 level were independent risk factors associated with poor outcome of patients with aSAH. Further analysis revealed that combination of STC1 with Hunt-hess grade was more superior to 2 indicators alone in predicting clinical outcome of aSAH patients.STC1 can be used as a novel biomarker in predicting outcome of patients with aSAH, especially when combined with Hunt-hess grade.

Relation between brain natriuretic peptide and delayed cerebral ischemia in patients with aneurysmalsubarachnoid hemorrhage.

BACKGROUND: Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted. RESULTS: Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p = 0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632). CONCLUSION: Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.

TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage.

Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1ß, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH.

PaCO2-management in the neuro-critical care of patients with subarachnoid hemorrhage.

The partial pressure of carbon dioxide (PaCO2) in the arterial blood is a strong vasomodulator affecting cerebral blood flow and the risk of cerebral edema and ischemia after acute brain injury. In turn, both complications are related to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to analyze the effect of PaCO2 levels on the course and outcome of aSAH. All patients of a single institution treated for aSAH over 13.5 years were included (n = 633). Daily PaCO2 values from arterial blood gas measurements were recorded for up to 2 weeks after ictus. The study endpoints were: delayed cerebral ischemia (DCI), need for decompressive craniectomy due to increased intracranial pressure > 20 mmHg refractory to conservative treatment and poor outcome at 6-months follow-up (modified Rankin scale > 2). By correlations with the study endpoints, clinically relevant cutoffs for the 14-days mean values for the lowest and highest daily PaCO2 levels were defined by receiver operating characteristic curve analysis. Association with the study endpoints for the identifies subgroups was analyzed using multivariate analysis. The optimal range for PaCO2 values was identified between 30 and 38 mmHg. ASAH patients with poor initial condition (WFNS 4/5) were less likely to show PaCO2 values within the range of 30-38 mmHg (p < 0.001, OR = 0.44). In the multivariate analysis, PaCO2 values between 30 and 38 mmHg were associated with a lower risk for decompressive craniectomy (p = 0.042, aOR = 0.27), DCI occurrence (p = 0.035; aOR = 0.50), and poor patient outcome (p = 0.004; aOR = 0.42). The data from this study shows an independent positive association between low normal mean PaCO2 values during the acute phase of aSAH and patients' outcome. This effect might be attributed to the reduction of intracranial hypertension and alterations in the cerebral blood flow.

Identifying critical genes associated with aneurysmal subarachnoid hemorrhage by weighted gene co-expression network analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening medical condition with a high mortality and disability rate. aSAH has an unclear pathogenesis, and limited treatment options are available. Here, we aimed to identify critical genes involved in aSAH pathogenesis using peripheral blood gene expression data of 43 patients with aSAH due to ruptured intracranial aneurysms and 18 controls with headache, downloaded from Gene Expression Omnibus. These data were used to construct a co-expression network using weighted gene co-expression network analysis (WGCNA). The biological functions of the hub genes were explored, and critical genes were selected by combining with differentially expressed genes analysis. Fourteen modules were identified by WGCNA. Among those modules, red, blue, brown and cyan modules were closely associated with aSAH. Moreover, 364 hub genes in the significant modules were found to play important roles in aSAH. Biological function analysis suggested that protein biosynthesis-related processes and inflammatory responses-related processes were involved in the pathology of aSAH pathology. Combined with differentially expressed genes analysis and validation in 35 clinical samples, seven gene (CD27, ANXA3, ACSL1, PGLYRP1, ALPL, ARG1, and TPST1) were identified as potential biomarkers for aSAH, and three genes (ANXA3, ALPL, and ARG1) were changed with disease development, that may provide new insights into potential molecular mechanisms for aSAH.

Neutrophil Count on Admission Predicts Acute Symptomatic Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To investigate the association between immunologic counts on admission and acute symptomatic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We conducted a retrospective analysis of 143 consecutive patients with aSAH. Patient demographics, clinical parameters, laboratory values, and radiographic imaging were obtained. Univariate and multivariate logistic regression analyses were performed to investigate parameters independently associated with acute symptomatic hydrocephalus. Receiver operating characteristic (ROC) curve analysis determined the best threshold value of neutrophil count to differentiate patients with and without hydrocephalus. RESULTS: Overall, acute symptomatic hydrocephalus developed in 39.16% of patients. In an adjusted multivariate logistic regression model, Hunt and Hess grade 4-5 (odds ratio [OR]: 16.052, 95% confidence interval [CI]: 1.188-216.983; P = 0.037), modified Fisher score 3-4 (OR: 10.107, 95% CI: 1.715-59.572; P = 0.011), intraventricular hemorrhage (OR: 4.578, 95% CI: 1.417-14.788; P = 0.011), neutrophil count (OR: 1.183, 95% CI: 1.033-1.354; P = 0.015), and prior ischemic stroke (OR: 7.003, 95% CI: 1.293-37.929; P = 0.024) were significantly associated with hydrocephalus. ROC analysis for neutrophil count confirmed an acceptable area under the curve (AUC 0.780, 95% CI: 0.701-0.859; P < 0.001). The best threshold value of neutrophil count to predict hydrocephalus was ≥9.80 × 103/mL. Overall, 81.25% of patients who developed shunt dependence had a neutrophil count ≥9.80 × 103/mL on admission (P = 0.003). CONCLUSIONS: Neutrophil count ≥9.80 × 103/mL on admission predicts acute symptomatic hydrocephalus after aSAH in an adjusted multivariate logistic regression model. Moreover, shunt dependence was associated with higher neutrophil counts.

Copeptin and insulin-like growth factor-1 predict long-term outcomes after aneurysmal subarachnoid hemorrhage: A large prospective cohort study.

OBJECTIVE: The predictive roles of copeptin and insulin-like growth factor-1 (IGF-1) in aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. We aimed to define the relationship between copeptin and IGF-1 levels and functional outcome as well as quality of life (QoL) after aSAH. METHODS: Patients with aSAH were prospectively enrolled in a tertiary university hospital. Controls were sex- and age-matched healthy subjects. Plasma concentrations of copeptin and IGF-1 were measured on admission. Demographics and clinical, radiological and laboratory characteristics of the patients were collected. Favorable functional outcome was defined as modified Rankins≤2, and QoL was evaluated by the 36-Item Short Form Health Survey (SF-36) 1 year after aSAH. Uni- and multivariable analyses were performed. RESULTS: One hundred eighteen patients were eligible, with 122 healthy controls were included in this study. Plasma copeptin levels were significantly higher and plasma IGF-1 was lower in patients than in controls. Both copeptin (adjusted HR 4.143 [1.120-15.328], p = 0.033) and IGF-1 levels (adjusted HR 0.089 [0.013-0.602], p = 0.013) were positively associated with 1-year mortality, while only single copeptin and IGF-1 concentrations were independent predictors of poor functional outcome and QoL, respectively. CONCLUSIONS: Plasma copeptin and IGF-1 levels are abnormal in patients with acute aSAH, and this may reliably predict long-term mortality, functional outcome and QoL.

Association of Troponin T levels and functional outcome 3 months after subarachnoid hemorrhage.

TroponinT levels are frequently elevated after subarachnoid hemorrhage (SAH). However, their clinical impact on long term outcomes still remains unclear. This study evaluates the association of TroponinT and functional outcomes 3 months after SAH. Data were obtained in the frame of a randomized controlled trial exploring the association of Goal-directed hemodynamic therapy and outcomes after SAH (NCT01832389). TroponinT was measured daily for the first 14 days after admission or until discharge from the ICU. Outcome was assessed using Glasgow Outcome Scale (GOS) 3 months after discharge. Logistic regression was used to explore the association between initial TroponinT values stratified by tertiles and admission as well as outcome parameters. TroponinT measurements were analyzed in 105 patients. TroponinT values at admission were associated with outcome assessed by GOS in a univariate analysis. TroponinT was not predictive of vasospasm or delayed cerebral ischemia, but an association with pulmonary and cardiac complications was observed. After adjustment for age, history of arterial hypertension and World Federation of Neurosurgical Societies (WFNS) grade, TroponinT levels at admission were not independently associated with worse outcome (GOS 1-3) or death at 3 months. In summary, TroponinT levels at admission are associated with 3 months-GOS but have limited ability to independently predict outcome after SAH.

Fatty Acid-Binding Protein 3 and CXC-Chemokine Ligand 16 are Associated with Unfavorable Outcome in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with activation of the inflammatory cascade contributing to unfavorable outcome and secondary complications, such as delayed cerebral ischemia (DCI). Both fatty acid-binding protein 3 (FABP3) and CXC-chemokine ligand 16 (CXCL-16) have been linked to vascular inflammation and cellular death. The authors aimed to assess the 30-day prognostic value of serum levels of FABP3 and CXCL-16 and explore their associations with DCI in aSAH patients. METHODS: A total of 60 patients with aSAH were prospectively enrolled. Sampling for markers was done at 24 hours after the index event. FABP3 and CXCL-16 serum concentrations were determined by MilliPlex multiplex immunoassay method. The primary endpoint was unfavorable outcome at Day 30 based on the modified Rankin Scale. RESULTS: Both FABP3 and CXCL-16 levels were significantly elevated in patients with unfavorable outcome compared to those with favorable outcome after aSAH (FABP3: 2133 pg/mL, IQR: 1053-4567 vs. 3773, 3295-13116; p<0.003 and CXCL-16: 384 pg/mL, 313-502 vs. 498, 456-62, p<0.001). The area under the curve (AUC) for serum CXCL-16 levels as a predictor of unfavorable outcome at Day 30 was 0.747 (95% CI =0.622-0.871; p<0.001). Based on binary logistic regression analysis, serum CXCL-16 with a cut-off level >446.7 ng/L independently predicted Day 30 unfavorable outcome with a sensitivity of 81% and a specificity of 62%. Neither CXCL-16 nor FABP3 showed a significant correlation with DCI. CONCLUSION: Early FABP3 and CXCL-16 levels are significantly associated with poor 30-day outcome in patients with aSAH.

Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - Preliminary findings from an observational cohort study.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH. MATERIALS AND METHODS: Daytime (from 11:00 am to 05:00 pm) melatonin levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 30 patients on the day of aSAH onset (d0) and in five pre-defined time intervals during the early (d1-4), critical (d5-8, d9-12, d13-15) and late (d16-21) phase. Perioperative daytime melatonin levels determined in 30 patients who underwent elective open aortic surgery served as a control for the acute effects of surgical treatment on melatonin homeostasis. RESULTS: There was no difference between serum melatonin levels measured in the control patients and on the day of aSAH onset (p = 0.664). However, aSAH was associated with a sustained up-regulation that started during the critical phase (d9-12) and progressed to the late phase (d16-21), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d5-8 in patients with a poor clinical status on admission (p = 0.031), patients with anterior communicating artery aneurysms (p = 0.040) and patients without an external ventricular drain (p = 0.018), possibly pointing to a role of hypothalamic dysfunction. CONCLUSION: Our observations in a small cohort of patients provide first evidence for a delayed up-regulation of circulatory daytime melatonin levels after aSAH and a role of aneurysm location for higher levels during the critical phase. These findings are discussed in terms of previous results about stress-induced melatonin production and the role of hypothalamic and brainstem involvement for melatonin levels after aSAH.