- 1Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, China
- 2Department
of Neurosurgery, Linping Campus, The Second Affiliated Hospital of
Zhejiang University School of Medicine, Hangzhou, China - 3Department
of Critical Care Medicine, Linping Campus, The Second Affiliated
Hospital of Zhejiang University School of Medicine, Hangzhou, China - 4Emergency Department, Linping Campus, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
Background: A20 is an endogenous protective
protein. We quantified serum A20 levels following acute intracerebral
hemorrhage (ICH) and assessed their association with the severity of
illness and clinical outcomes of patients.
Methods: In total, 243 patients with acute
supratentorial ICH and 76 controls were included in this prospective
cohort study. Serum A20 levels were measured at admission in all
patients, at study entry in all controls, and on post-ICH days 1, 3, 5,
7, 10, and 14 in 76 patients. The National Institutes of Health Stroke
Scale (NIHSS) scores and hematoma volume were used to estimate the
severity. Stroke-associated pneumonia (SAP), early neurological
deterioration (END), and post-ICH 6-month poor prognosis (modified
Rankin Scale scores: 3–6) were considered as the three outcome variables
of interest.
Results: Patients, as opposed to controls,
exhibited significantly heightened serum A20 levels from admission until
14 days following ICH, with a peak value at day 3. Serum A20 levels at
all-time points after ICH, which were significantly correlated with
NIHSS scores and hematoma volume, were significantly higher in patients
with END, SAP, or poor prognosis than in those without the corresponding
one. Serum A20 levels at admission possessed similar predictive ability
of these clinical outcomes to those at other time points. Serum A20
levels at admission, along with initial NIHSS scores and hematoma
volume, remained independent predictors of clinical outcomes among
patients. As confirmed by numerous statistical approaches, their
conjunctions comprised three prediction models: satisfactory stability,
clinical validity, and discrimination efficiency.
Conclusion: Serum A20 levels were significantly
increased following ICH and may accurately reflect hemorrhagic severity
and effectively predict END, SAP, and poor neurological prognosis,
suggesting that serum A20 may be a promising prognostic biomarker for
ICH.(Biomarkers don’t get you recovered, do they? So why the fuck are you researching biomarkers?)
1 Introduction
Spontaneous intracerebral hemorrhage (ICH) is one of the
most common cerebrovascular diseases and seriously threatens human life
and health (1). Etiologies of primary ICH principally are age, hypertension, diabetes mellitus, cigarette smoking, and alcohol drinking (2). The pathophysiological mechanisms of ICH occurrence mainly encompass vascular atherosclerosis and amyloidosis (3).
Bleeding into the brain parenchyma activates an array of cascading
molecular reactions, such as inflammation, oxidative stress, and
cellular apoptosis, thereby resulting in neurological impairments (4).
Clinically, the National Institutes of Health Stroke Scale (NIHSS)
score and hematoma volume are widely used for severity estimation (5). The modified Rankin Scale (mRS) is an assessment tool of neurological outcomes in ICH (6).
Early neurological deterioration (END) and stroke-associated pneumonia
(SAP) are the two common complications of ICH and are highly connected
with the poor prognosis of patients (7, 8). Therefore, the accurate prediction of END, SAP, and neurological outcomes is equally important during ICH management (9).
Considering the easy availability of blood in clinical practice, blood
biomarkers have gained great attention with respect to their clinical
prospects in severity evaluation and outcome anticipation of ICH (10–13).
Neuroinflammation is a pivotal process among secondary brain injury subsequent to ICH (14). Nuclear factor-kappa B (NF-κB) is a key factor for driving various inflammatory pathways in the central nervous system (15). A20 is known as the tumor necrosis factor α-inducible
protein 3, and as a central inhibitor of NF-κB, it can potently reduce
the tumor necrosis factor receptor-associated factor 6/NF-κB signaling
pathway (16). It is abundantly localized in neurons and astrocytes (16, 17).
In response to experimental ischemic, traumatic, or hemorrhagic brain
injury, A20 expressions were significantly promoted in lesion borders
and held endogenous brain-protective properties (18–21).
Recently, serum A20 levels were reported to be independently associated
with delayed cerebral ischemia and poor prognosis following aneurysmal
subarachnoid hemorrhage (22).
Thus, these features could imply serum A20 as a biomarker of brain
injury. Here, serum A20 levels were quantified so as to investigate
their temporal alteration following ICH and their predictive effects on
END, SAP, and poor prognosis of patients.
More at link.
