Usability of serum AIM2 as a predictive biomarker of stroke-associated pneumonia and poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

Abstract

Background: Absent in melanoma 2 (AIM2) is implicated in inflammatory processes. We measured serum AIM2 with intent to unveil its predictive significance for stroke-associated pneumonia (SAP) and functional prognosis following acute intracerebral hemorrhage (ICH).

Methods: In this prospective cohort study, serum AIM2 concentrations of 163 ICH patients were gauged upon admission and 57 of them also consented for measurements at days 1, 3, 5, 7, 10 and 14. Coupled with 57 individuals without health conditions, dynamic change of serum AIM2 levels were uncovered. National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume were identified as the dual indicators of severity. Poststroke six-month modified Rankin Scale (mRS) scores ranging from 3 to 6 indicated an unfavorable outcome. SAP was observed during the first seven days after ICH. Sequential univariate and multivariate analyses were performed to discern predictors of SAP and adverse prognosis.

Results: The serum levels of AIM2 in patients exhibited a marked elevation upon admission, reaching peak levels on the third and fifth days, and remained notably elevated until day 14 compared to those of the control group. Serum AIM2 levels showed independent correlations with both NIHSS scores and the volume of hematoma. Additionally, AIM2 concentrations were independently associated with a poor prognosis and SAP at the six-month mark. Within the framework of restricted cubic spline analysis, serum AIM2 concentrations exhibited a linear correlation with the likelihood of developing SAP and experiencing a poor prognosis. In the context of receiver operating characteristic (ROC) curve analysis, serum AIM2 concentrations effectively differentiated risks of SAP and poor prognosis. By employing segmented analysis, serum AIM2 concentrations showed negligible interactions with several traditional variables, such as age, gender, smoking habits, alcohol consumption, and more. The integrated model incorporating serum AIM2, NIHSS scores, and the volume of hematoma was depicted by employing a nomogram and demonstrated strong predictive performance for poor prognosis or SAP across various evaluation metrics, including ROC curve analysis, calibration curve analysis, and decision curve analysis.

Conclusion: Serum AIM2 levels show a marked increase shortly after intracerebral hemorrhage (ICH), which may accurately reflect stroke severity, and effectively predict SAP and poor neurological outcomes, and therefore serum AIM2 stands out as an encouraging predictive indicator for ICH.

Keywords: Absent in melanoma 2; Biomarkers; Intracerebral hemorrhage; Prognosis; Severity; Stroke-associated pneumonia.

Fig. 1

Flowchart depicting the selection process for eligible patients with acute intracerebral hemorrhage. A group of consecutively enrolled 217 individuals with acute intracerebral hemorrhage were assessed, leading to a final group of 163 participants chosen for clinical examination. From this pool, 57 patients agreed with multiple-time-point blood-drawings, 43 had development of stroke-associated pneumonia and 77 suffered from adverse outcomes six months post the onset of stroke. ICH indicates intracerebral hemorrhage.

Fig. 2

Longitudinal change of serum absent in melanoma 2 levels subsequent to acute intracerebral hemorrhage. Patients afflicted by acute intracerebral hemorrhage, in contrast to individuals without any known neurological disorders, displayed substantially rising serum absent in melanoma 2 levels during fourteen days after stroke. The levels peaked on day 3 and plateaued on day 5 following the onset of stroke (P < 0.001). ICH stands for intracerebral hemorrhage; AIM2, absent in melanoma 2.

Fig. 3

Serum absent in melanoma 2 in relation to modified Rankin Scale scores at six months post-acute intracerebral hemorrhage. Serum absent in melanoma 2 concentrations were markedly reduced in individuals with a Modified Rankin Scale score of 0 at six months, progressively increasing across scores 1 to 5, and peaking among those with a score of 6 (P < 0.001). mRS indicates modified Rankin Scale; AIM2, absent in melanoma 2.

Fig. 4

Serum absent in melanoma 2 levels and modified Rankin Scale scores at six months post-acute intracerebral hemorrhage. Serum absent in melanoma 2 levels exhibited a strong correlation with six months modified Rankin Scale scores following stroke (P < 0.001). mRS indicates modified Rankin Scale; AIM2, absent in melanoma 2.

Fig. 5

Restricted cubic spline illustrating the linear association between serum absent in melanoma 2 concentrations and the likelihood of adverse outcomes at six months post-acute intracerebral hemorrhage. Serum absent in melanoma 2 concentrations exhibited a linear correlation with the risk of poor prognosis at six months following stroke. AIM2 denotes absent in melanoma 2; OR, odds ratio; 95 % CI, 95 % confidence interval.

Fig. 6

Predictive capacity for prognosis of serum absent in melanoma 2 levels after acute intracerebral hemorrhage evaluated by receiver operating characteristic curve. Serum absent in melanoma 2 concentrations effectively differentiated the likelihood of adverse outcomes at the six-month mark after hemorrhagic stroke. Employing the Youden approach, the threshold value of serum absent in melanoma 2 concentrations was selected, which anticipated unfavorable prognostic outcomes with the corresponding sensitivity and specificity. AUC means area under curve; 95 % CI, 95 % confidence interval.

Fig. 7

Nomogram assessing the predictive model for prognosis in individuals with acute intracerebral hemorrhage. Serum absent in melanoma 2, hematoma size and National Institutes of Health Stroke Scale scores were combined to differentiate the likelihood of an unfavorable prognosis six months after acute intracerebral hemorrhage. NIHSS denotes National Institutes of Health Stroke Scale; AIM2, absent in melanoma 2.

Fig. 8

Calibration plot assessing the reliability of the nomogram in predicting the likelihood of an adverse prognosis six months after stroke. The constructed framework remained consistent in forecasting an unfavorable outcome six months following the onset of acute intracerebral hemorrhage.

Fig. 9

The decision curve assessed the clinical applicability of the model in identifying the likelihood of an adverse outcome six months after stroke. The developed model demonstrated clinical utility in forecasting adverse outcomes six months following intracerebral hemorrhage.

Fig. 10

Receiver operating characteristic curve evaluating prognostic capacity of serum absent in melanoma 2 concentrations and combined model for adverse outcomes six months following acute intracerebral hemorrhage. Serum absent in melanoma 2 levels had similar prognosis predictive ability, as compared to National Institutes of Health Stroke Scale scores and the volume of hematoma. Combination of National Institutes of Health Stroke Scale scores with hematoma volume and serum absent in melanoma 2 showed significantly higher prognosis predictive ability, as opposed to other variables. AIM2 means absent in melanoma 2; NIHSS, National Institutes of Health Stroke Scale; ns, non-significant. *P < 0.05, **P < 0.01.

Fig. 11

Restricted cubic spline indicating the direct relationship between serum absent in melanoma 2 concentrations and the likelihood of stroke-associated pneumonia following acute intracerebral hemorrhage. Serum levels of absent in melanoma 2 displayed a linear correlation with the likelihood of stroke-associated pneumonia following intracerebral hemorrhage. AIM2 denotes absent in melanoma 2; OR, odds ratio; 95 % CI, 95 % confidence interval.

Fig. 12

Receiver operating characteristic plot assessing stroke-associated pneumonia predictive ability of serum absent in melanoma 2 levels after acute intracerebral hemorrhage. Serum absent in melanoma 2 concentrations efficiently discriminated risk of stroke-associated pneumonia after hemorrhagic stroke. Employing the Youden approach, the threshold value of serum absent in melanoma 2 levels was chosen, which predicted stroke-associated pneumonia along with its associated sensitivity and specificity. AUC means area under curve; 95 % CI, 95 % confidence interval.

Fig. 13

Nomogram evaluating the stroke-associated pneumonia prediction model of individuals experiencing acute intracerebral hemorrhage. Serum absent in melanoma 2, hematoma volume and National Institutes of Health Stroke Scale scores were merged to discriminate risk of stroke-associated pneumonia subsequent to acute intracerebral hemorrhage. NIHSS denotes National Institutes of Health Stroke Scale; AIM2, absent in melanoma 2.

Fig. 14

Graph assessing the reliability of a nomogram in distinguishing the likelihood of stroke-associated pneumonia following acute intracerebral hemorrhage. The confirmed framework maintained a consistent level of reliability in forecasting pneumonia linked with stroke subsequent to sudden intracerebral bleeding.

Fig. 15

Assessment graph confirming the practical applicability of the model in identifying the likelihood of stroke-associated pneumonia. The built model was clinically fit for predicting stroke-associated pneumonia after intracerebral hemorrhage.

Fig. 16

Plotting the receiver operating characteristic curve to evaluate the predictive capacity of serum absent in melanoma 2 concentrations and a combined model for stroke-associated pneumonia following sudden intracerebral bleeding. Serum absent in melanoma 2 concentrations had similar stroke-associated pneumonia predictive ability, as compared to National Institutes of Health Stroke Scale scores and the volume of hematoma. Combination of National Institutes of Health Stroke Scale scores with the volume of hematoma and serum absent in melanoma 2 showed significantly higher stroke-associated pneumonia predictive ability, as opposed to serum absent in melanoma 2 levels. AIM2 means absent in melanoma 2; NIHSS, National Institutes of Health Stroke Scale; ns, non-significant. *P < 0.05.