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.

Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage.

BACKGROUND: A20 may be a neuroprotective factor. Herein, we aimed to investigate whether serum A20 levels were associated with disease severity, delayed cerebral ischemia (DCI), and outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective cohort study containing 112 aSAH patients and 112 controls, serum A20 levels were quantified. At 90 d poststroke, Modified Rankin Scale (MRS) scores ≥3 were defined as a poor outcome. All correlations and associations were assessed using multivariate analysis. RESULTS: Compared with controls, there was a significant elevation of serum A20 levels in patients (median 123.7 pg/mL vs. 25.8 pg/mL; P<0.001). Serum A20 levels were independently correlated with Hunt-Hess scores (ß 9.854; 95% confidence interval [95% CI] 2.481-17.227, P=0.009) and modified Fisher scores (ß 10.349, 95% CI 1.273-19.424, P=0.026). Independent associations were found between serum A20 levels and poor outcome (odds ratio [OR] 1.015, 95% CI 1.000-1.031, P=0.047) and DCI (OR 1.018, 95% CI 1.001-1.035, P=0.042). Areas under the curve for predicting poor outcome and DCI were 0.771 (95% CI 0.682-0.845) and 0.777 (95% CI 0.688-0.850), respectively. Serum A20 levels ≥128.15 pg/mL predicted poor outcome, with a sensitivity of 73.9% and specificity of 74.2%, and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with 65.5% sensitivity and 89.2% specificity. Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores (both P>0.05). CONCLUSION: Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH, implying that serum A20 may be a potential prognostic biomarker for aSAH.

Prognostic significance of plasma S1P in acute intracerebral hemorrhage: A prospective cohort study.

OBJECTIVE: Sphingosine-1-phosphate (S1P) may regulate neuroinflammatory immunity and blood-brain barrier integrity. This study was designed to assess the prognostic role of plasma S1P in intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, plasma S1P levels were measured in 51 controls, at admission in 114 ICH patients and at days 1, 3, 5 and 7 in 51 of all patients. Univariate analysis and multivariate analysis were sequentially used to investigate severity correlation and prognosis association. RESULTS: Plasma S1P levels were significantly elevated at admission, peaked at day 5, and declined at day 7, which were significantly higher during 7 days than those of controls (all P < 0.001). Areas under receiver operating characteristic curve (AUCs) of plasma S1P levels insignificant differed among all time points (all P > 0.05). Admission plasma S1P levels, in close correlation with National Institutes of Health Stroke Scale (NIHSS) scores [ß, 7.661; 95 % confidence interval (CI), 4.893-10.399; P < 0.001] and hematoma volume (ß, 1.285; 95 % CI, 0.348-2.230; P < 0.001), independently predicted 3-month poor prognosis (modified Rankin Scale scores of 3-6) (odds ratio, 3.184; 95 % CI, 1.057-9.597; P = 0.040). Admission plasma S1P levels had AUC of 0.799 (95 % CI, 0.713-0.868) for prognosis prediction. The levels > 240.4 ng/ml distinguished risk of poor prognosis with the maximum Youden index of 0.518. Prediction model integrating NIHSS scores, hematoma volume and admission plasma S1P levels had substantially higher prognostic predictive ability than NIHSS scores (P = 0.023), but not than hematoma volume (P = 0.061). CONCLUSION: There is a significant elevation of plasma S1P levels during early period after ICH, which were independently related to severity and poor prognosis. Thus, plasma S1P may be a potential prognostic biomarker of ICH.