scholarly journals Genetic Markers in the EET Metabolic Pathway Are Associated with Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage

2014 ◽  
Vol 35 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Mark K Donnelly ◽  
Yvette P Conley ◽  
Elizabeth A Crago ◽  
Dianxu Ren ◽  
Paula R Sherwood ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Metabolic Pathway ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Epoxyeicosatrienoic Acids ◽  
Multiple Testing Correction ◽  
Long Term Outcomes ◽  
Fisher Grade ◽  
Csf Levels

Preclinical studies show that epoxyeicosatrienoic acids (EETs) regulate cerebrovascular tone and protect against cerebral ischemia. We investigated the relationship between polymorphic genes involved in EET biosynthesis/metabolism, cytochrome P450 (CYP) eicosanoid levels, and outcomes in 363 patients with aneurysmal subarachnoid hemorrhage (aSAH). Epoxyeicosatrienoic acids and dihydroxyeicosatetraenoic acid (DHET) cerebrospinal fluid (CSF) levels, as well as acute outcomes defined by delayed cerebral ischemia (DCI) or clinical neurologic deterioration (CND), were assessed over 14 days. Long-term outcomes were defined by Modified Rankin Scale (MRS) at 3 and 12 months. CYP2C8∗4 allele carriers had 44% and 36% lower mean EET and DHET CSF levels ( P=0.003 and P=0.007) and were 2.2- and 2.5-fold more likely to develop DCI and CND ( P=0.039 and P=0.041), respectively. EPHX2 55Arg, CYP2J2∗7, CYP2C8∗1B, and CYP2C8 g.36785A allele carriers had lower EET and DHET CSF levels. CYP2C8 g.25369T and CYP2C8 g.36755A allele carriers had higher EET levels. Patients with CYP2C8∗2C and EPHX2 404del variants had worse long-term outcomes while those with EPHX2 287Gln, CYP2J2∗7, and CYP2C9 g.816G variants had favorable outcomes. Epoxyeicosatrienoic acid levels were associated with Fisher grade and unfavorable 3-month outcomes. Dihydroxyeicosatetraenoic acids were not associated with outcomes. No associations passed Bonferroni multiple testing correction. These are the first clinical data demonstrating the association between the EET biosynthesis/metabolic pathway and the pathophysiology of aSAH.

scholarly journals Assessment of the Subarachnoid Hemorrhage International Trialists (SAHIT) Models for Dichotomized Long-Term Functional Outcome Prediction After Aneurysmal Subarachnoid Hemorrhage in a United Kingdom Multicenter Cohort Study

Neurosurgery ◽  
2020 ◽  
Author(s):  
Isabel C Hostettler ◽  
Menelaos Pavlou ◽  
Gareth Ambler ◽  
Varinder S Alg ◽  
Stephen Bonner ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Outcome ◽  
Outcome Prediction ◽  
Prediction Models ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Predictive Performance ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Fisher Grade

Abstract BACKGROUND Long-term outcome after subarachnoid hemorrhage, beyond the first few months, is difficult to predict, but has critical relevance to patients, their families, and carers. OBJECTIVE To assess the performance of the Subarachnoid Hemorrhage International Trialists (SAHIT) prediction models, which were initially designed to predict short-term (90 d) outcome, as predictors of long-term (2 yr) functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS We included 1545 patients with angiographically-proven aSAH from the Genetic and Observational Subarachnoid Haemorrhage (GOSH) study recruited at 22 hospitals between 2011 and 2014. We collected data on age, WNFS grade on admission, history of hypertension, Fisher grade, aneurysm size and location, as well as treatment modality. Functional outcome was measured by the Glasgow Outcome Scale (GOS) with GOS 1 to 3 corresponding to unfavorable and 4 to 5 to favorable functional outcome, according to the SAHIT models. The SAHIT models were assessed for long-term outcome prediction by estimating measures of calibration (calibration slope) and discrimination (area under the receiver-operating characteristic curve [AUC]) in relation to poor clinical outcome. RESULTS Follow-up was standardized to 2 yr using imputation methods. All 3 SAHIT models demonstrated acceptable predictive performance for long-term functional outcome. The estimated AUC was 0.71 (95% CI: 0.65-0.76), 0.73 (95% CI: 0.68-0.77), and 0.74 (95% CI: 0.69-0.79) for the core, neuroimaging, and full models, respectively; the calibration slopes were 0.86, 0.84, and 0.89, indicating good calibration. CONCLUSION The SAHIT prediction models, incorporating simple factors available on hospital admission, show good predictive performance for long-term functional outcome after aSAH.

scholarly journals 20-HETE is Associated with Unfavorable Outcomes in Subarachnoid Hemorrhage Patients

2015 ◽  
Vol 35 (9) ◽  
pp. 1515-1522 ◽  
Author(s):  
Mark K Donnelly ◽  
Elizabeth A Crago ◽  
Yvette P Conley ◽  
Jeffery R Balzer ◽  
Dianxu Ren ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Medical Center ◽  
Delayed Cerebral Ischemia ◽  
University Of Pittsburgh ◽  
Potential Contributor ◽  
Csf Levels ◽  
Novel Target ◽  
Poor Outcomes

Emerging evidence has suggested that patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) develop vascular dysregulation as a potential contributor to poor outcomes. Preclinical studies have implicated the novel microvascular constrictor, 20-hydroxyeicosatetraenoic acid (20-HETE) in aSAH pathogenesis, yet the translational relevance of 20-HETE in patients with aSAH is largely unknown. The goal of this research was to determine the relationship between 20-HETE cerebrospinal fluid (CSF) levels, gene variants in 20-HETE synthesis, and acute/long-term aSAH outcomes. In all, 363 adult patients (age 18 to 75) with aSAH were prospectively recruited from the University of Pittsburgh Medical Center neurovascular Intensive Care Unit. Patients were genotyped for polymorphic variants and cytochrome P450 (CYP)-eicosanoid CSF levels were measured over 14 days. Outcomes included delayed cerebral ischemia (DCI), clinical neurologic deterioration (CND), and modified Rankin Scores (MRS) at 3 and 12 months. Patients with CND and unfavorable 3-month MRS had 2.2- and 2.7-fold higher mean 20-HETE CSF levels, respectively. Patients in high/moderate 20-HETE trajectory groups (35.7%) were 2.5-, 2.1-, 3.1-, 3.3-, and 2.1-fold more likely to have unfavorable MRS at 3 months, unfavorable MRS at 12 months, mortality at 3 months, mortality at 12 months, and CND, respectively. These results showed that 20-HETE is associated with acute and long-term outcomes and suggest that 20-HETE may be a novel target in aSAH.

scholarly journals Long-term outcomes among octogenarians with aneurysmal subarachnoid hemorrhage

2019 ◽  
Vol 131 (2) ◽  
pp. 426-434 ◽  
Author(s):  
Hormuzdiyar Dasenbrock ◽  
William B. Gormley ◽  
Yoojin Lee ◽  
Vincent Mor ◽  
Susan L. Mitchell ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Treatment Modality ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Long Term Outcomes ◽  
Data Set ◽  
Term Survival ◽  
Microsurgical Clipping ◽  
Male Sex ◽  
National Analysis

OBJECTIVEData evaluating the long-term outcomes, particularly with regard to treatment modality, of aneurysmal subarachnoid hemorrhage (SAH) in octogenarians are limited. The primary objectives were to evaluate the disposition (living at home vs institutional settings) and analyze the predictors of long-term survival and return to home for octogenarians after SAH.METHODSData pertaining to patients age 80 and older who underwent microsurgical clipping or endovascular coiling for SAH were extracted from 100% nationwide Medicare inpatient claims and linked with the Minimum Data Set (2008–2011). Patient disposition was tracked for 2 years after index SAH admission. Multivariable logistic regression stratified by aneurysm treatment modality, and adjusted for patient factors including SAH severity, evaluated predictors of return to home at 60 and 365 days after SAH. Survival 365 days after SAH was analyzed with a multivariable Cox proportional hazards model.RESULTSA total of 1298 cases were included in the analysis. One year following SAH, 56% of the patients had died or were in hospice care, 8% were in an institutional post–acute care setting, and 36% had returned home. Open microsurgical clipping (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.54–0.81), male sex (aHR 0.70, 95% CI 0.57–0.87), tracheostomy (aHR 0.63, 95% CI 0.47–0.85), gastrostomy (aHR 0.60, 95% CI 0.48–0.76), and worse SAH severity (aHR 0.94, 95% CI 0.92–0.97) were associated with reduced likelihood of patients ever returning home. Older age (aHR 1.09, 95% CI 1.05–1.13), tracheostomy (aHR 2.06, 95% CI 1.46–2.91), gastrostomy (aHR 1.55, 95% CI 1.14–2.10), male sex (aHR 1.66, 95% CI 1.20–2.23), and worse SAH severity 1.51 (95% CI 1.04–2.18) were associated with reduced survival.CONCLUSIONSIn this national analysis, 56% of octogenarians with SAH died, and 36% returned home within 1 year of SAH. Coil embolization predicted returning to home, which may suggest a benefit to endovascular treatment in this patient population.

Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling

Neurosurgery ◽  
2021 ◽  
Vol 89 (Supplement_2) ◽  
pp. S7-S7
Author(s):  
Jinjin Liu ◽  
Ye Xiong ◽  
Ming Zhong ◽  
Yunjun Yang ◽  
Xianzhong Guo ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Decision Tree ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Long Term Outcomes ◽  
Poor Grade ◽  
Tree Modeling

scholarly journals Clinical prediction of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage

2019 ◽  
Vol 130 (6) ◽  
pp. 1914-1921 ◽  
Author(s):  
Hubert Lee ◽  
Jeffrey J. Perry ◽  
Shane W. English ◽  
Fahad Alkherayf ◽  
Joanne Joseph ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Characteristic Curve ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Delayed Cerebral Ischemia ◽  
Clinical Prediction ◽  
Anterior Circulation ◽  
Fisher Grade

OBJECTIVEThe aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients.METHODSPatients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses.RESULTSOf 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67–0.78] vs 0.66 [95% CI 0.60–0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40–59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm.CONCLUSIONSAmong patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk.

Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling

Neurosurgery ◽  
2020 ◽  
Vol 87 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Jinjin Liu ◽  
Ye Xiong ◽  
Ming Zhong ◽  
Yunjun Yang ◽  
Xianzhong Guo ◽  
...  
Keyword(s):  
Decision Tree ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Unfavorable Outcome ◽  
Long Term Outcomes ◽  
Tree Model ◽  
Poor Grade ◽  
Fisher Grade ◽  
Tree Modeling ◽  
Pupillary Reactivity

Abstract BACKGROUND Despite advances in the treatment of poor-grade aneurysmal subarachnoid hemorrhage (aSAH), predicting the long-term outcome of aSAH remains challenging, although essential. OBJECTIVE To predict long-term outcomes after poor-grade aSAH using decision tree modeling. METHODS This was a retrospective analysis of a prospective multicenter observational registry of patients with poor-grade aSAH with a World Federation of Neurosurgical Societies (WFNS) grade IV or V. Outcome was assessed by the modified Rankin Scale (mRS) at 12 mo, and an unfavorable outcome was defined as an mRS of 4 or 5 or death. Long-term prognostic models were developed using multivariate logistic regression and decision tree algorithms. An additional independent testing dataset was collected for external validation. Overall accuracy, sensitivity, specificity, and area under receiver operating characteristic curves (AUC) were used to assess model performance. RESULTS Of the 266 patients, 139 (52.3%) had an unfavorable outcome. Older age, absence of pupillary reactivity, lower Glasgow coma score (GCS), and higher modified Fisher grade were independent predictors of unfavorable outcome. Modified Fisher grade, pupillary reactivity, GCS, and age were used in the decision tree model, which achieved an overall accuracy of 0.833, sensitivity of 0.821, specificity of 0.846, and AUC of 0.88 in the internal test. There was similar predictive performance between the logistic regression and decision tree models. Both models achieved a high overall accuracy of 0.895 in the external test. CONCLUSION Decision tree model is a simple tool for predicting long-term outcomes after poor-grade aSAH and may be considered for treatment decision-making.

Long-Term Outcomes of Elderly Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage

2020 ◽  
Vol 144 ◽  
pp. e743-e749
Author(s):  
Shinichiro Yoshikawa ◽  
Tomoya Kamide ◽  
Yuichiro Kikkawa ◽  
Kaima Suzuki ◽  
Toshiki Ikeda ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Elderly Patients ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Long Term Outcomes ◽  
Poor Grade

Assessment of lipoprotein-associated phospholipase A2 level and its changes in the early stages as predictors of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 132 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Chen-Yu Ding ◽  
Han-Pei Cai ◽  
Hong-Liang Ge ◽  
Liang-Hong Yu ◽  
Yuan-Xiang Lin ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Phospholipase A2 ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Poor Grade ◽  
Early Stages ◽  
Fisher Grade ◽  
The Relationship

OBJECTIVEThe relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.METHODSThe authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.RESULTSForty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).CONCLUSIONSThe serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

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