Association of serum A20 levels with stroke-associated pneumonia, early neurological deterioration, and poor neurological prognosis following acute supratentorial intracerebral hemorrhage: a prospective cohort study

 

So you found an association. WHAT THE FUCK NEEDS TO BE DONE TO PREVENT THE PROBLEMS? That is what good stroke research should be doing. This is useless for stroke recovery or mortality! I'd have the mentors and senior researchers fired for such crapola!

Association of serum A20 levels with stroke-associated pneumonia, early neurological deterioration, and poor neurological prognosis following acute supratentorial intracerebral hemorrhage: a prospective cohort study

Chao Tang^1,2Wei Li^1,2*Suijun Zhu^1,2Min Zhang^1,2Gaofeng Xiong³Yijuan Lin⁴

• 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.

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