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Incremental Value of Adding S100B to NSE for High-Specificity Rule-in of Poor Neurological Outcome After
Seokjae Hong1,2, Seungho Lee1,2, Jung Soo Park1,2
1Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Insights
Adding S100B to neuron-specific enolase (NSE) did not improve predicting poor neurological outcomes after out-of-hospital cardiac arrest (OHCA). While the combination showed a higher rule-in yield at 48 hours, results require cautious interpretation and external validation.
Area of Science:
- Neurology
- Biomarkers
- Critical Care Medicine
Background:
- Assessing neurological outcome after out-of-hospital cardiac arrest (OHCA) is critical.
- Neuron-specific enolase (NSE) is a known biomarker for neurological injury.
- S100B is another protein marker potentially indicative of brain damage.
Purpose of the Study:
- To determine if combining S100B with NSE improves the prediction of poor neurological outcomes in OHCA survivors.
- To evaluate the diagnostic performance (discrimination and rule-in capability) of NSE alone versus NSE plus S100B.
Main Methods:
- Retrospective cohort study of 124 comatose adult OHCA survivors treated with targeted temperature management.
- NSE and S100B levels measured at 0, 24, 48, and 72 hours post-resuscitation.
- Area under the receiver operating characteristic curve (AUC) used for discrimination; 100% specificity thresholds for rule-in performance.
Main Results:
- Overall discrimination (AUC) was similar between NSE alone and the NSE + S100B combination at all time points (p > 0.3).
- At 48 hours, the combination identified 10 additional patients with poor neurological outcome compared to NSE alone (70.8% vs 55.4% rule-in).
- This improved rule-in yield at 48 hours had a wide confidence interval, indicating imprecision.
Conclusions:
- Adding S100B to NSE does not enhance the overall discrimination for poor neurological outcomes in OHCA survivors.
- The potential benefit of S100B for rule-in prediction at 48 hours needs cautious interpretation due to imprecise estimation.
- External validation is necessary before clinical application of these biomarker combinations.
Abstract:
Background: We evaluated whether adding S100B to NSE improved discrimination or high-specificity rule-in of poor neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: In this single-center retrospective cohort study, comatose adult OHCA survivors treated with targeted temperature management had NSE and S100B measured at 0, 24, 48, and 72 h after return of spontaneous circulation. At each time point, we assessed NSE alone, S100B alone, and a logistic model combining both biomarkers in paired complete cases. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Rule-in performance was evaluated using a timepoint-specific threshold that achieved 100% specificity in our cohort. Poor neurological outcome was defined as cerebral performance category 3-5 at 6 months. Results: Among 124 patients, 66 (53.2%) had poor outcomes. AUCs were similar between NSE alone and the combination across all time points (all p > 0.3). At 48 h, the combination ruled in 46/65 (70.8%) patients with poor outcome versus 36/65 (55.4%) with NSE alone, identifying 10 additional patients and a 15.4-percentage-point difference (95% confidence interval, -5.6 to 23.6). Conclusions: Adding S100B to NSE did not improve overall discrimination. The higher 48 h rule-in yield was estimated imprecisely and should be interpreted cautiously. Our findings require external validation before they can be translated to clinical settings.
