# Practicability of Activating Transcription Factor 3 as a Serological Marker for Severity Appraisal and Outcome Anticipation in Acute Supratentorial Intracerebral Hemorrhage: A Two‐center Observational Analytical Study

## TL;DR

This study shows that higher levels of a protein called ATF3 in the blood are linked to more severe brain bleeding and worse outcomes in patients, suggesting it could help predict recovery chances.

## Contribution

The study identifies serum ATF3 as a novel prognostic marker for acute intracerebral hemorrhage severity and outcomes.

## Key findings

- Serum ATF3 levels peak within three days of ICH and remain elevated compared to controls.
- Admission ATF3 levels correlate with neurological deterioration, pneumonia, and poor prognosis.
- ATF3's predictive ability is comparable to established metrics like NIHSS and hematoma volume.

## Abstract

Activating transcription factor 3 (ATF3) is a neuroprotective factor and participates in acute brain injury. Here, we intend to determine whether serum ATF3 levels are associated with the severity and clinical outcomes of acute intracerebral hemorrhage (ICH).

In this two‐center observational analytic study of 236 patients with supratentorial ICH and 114 controls, serum ATF3 levels were quantified at the admission of all patients, at study entry of all controls, and at serial time‐points of 114 patients from all patients. The Admission National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and the modified Rankin Scale (mRS) at post‐ICH six months were recorded. Outcome variables were stroke‐associated pneumonia (SAP), early neurological deterioration (END), and post‐ICH 6‐month neurological status. Associations were appraised via multifactorial analyses.

Serum ATF3 levels of patients consenting for serial sampling swiftly increased since admission, peaked until post‐ICH day 3, then slowly declined up to day 14, and were significantly higher even on day 14 than those of controls. Dynamic serum ATF3 levels of patients consenting for serial sampling were firmly related to NIHSS scores, hematoma volume, SAP, END, continuous and ordinal mRS scores, and poor prognosis (mRS scores of 3–6). Even adjusting for possible confounding factors, associations of admission serum ATF3 levels with the preceding parameters still existed among all patients. Alternatively, admission serum ATF3 levels were linearly correlated with SAP, END, and poor prognosis under restricted cubic spline, and did not interact with age, sex, alcohol consumption and others via subgroup analysis. The associations were robust in sensitivity analysis. Through receiver operating characteristic (ROC) curve analysis, admission serum ATF3 levels had predictive ability comparable to that of NIHSS scores and hematoma volume.

Elevated serum ATF3 levels following ICH are intimately correlated with disease severity and effectively predict END, SAP, and poor prognosis, solidifying serum ATF3 as a prognostic candidate of ICH.Elevated serum ATF3 levels following ICH are closely correlated with disease severity and effectively predict END, SAP, and poor prognosis, reinforcing serum ATF3 as a prognostic surrogate of ICH.

Elevated serum ATF3 levels following intracerebral hemorrhage are closely correlated with disease severity and effectively predict early neurological deterioration, stroke‐associated pneumonia and poor prognosis, reinforcing serum ATF3 as a prognostic surrogate of intracerebral hemorrhage.