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Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients

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Abstract

Background

The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables.

Methods

This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1–4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome.

Results

One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1–1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied.

Conclusions

In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

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Funding

This work was supported by a public grant from the Fondo de Investigación Sanitaria to Dr Jon Pérez-Bárcena (FIS-PI16/00737).

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Contributions

Jon Pérez-Bárcena wrote the first draft, conceptualization, data collection, data analysis, funding, wrote the submitted version. Javier Rodríguez Pilar collected data, performed the 6-month GOSE evaluations and critical review, and gave final approval. Osman Salazar performed the initial and 24-h CT scans analysis and critical review and gave final approval. Catalina Crespí performed laboratory experiments and critical review and gave final approval. Guillem Frontera performed the statistical analysis and critical review and gave final approval. Mariana Andrea Novo performed data collection and critical review and gave final approval. María Begoña Guardiola performed data collection and critical review and gave final approval. Juan Antonio Llompart-Pou performed data collection and critical review and gave final approval. Javier Ibáñez performed conceptualization and critical review and gave final approval. Juan Pablo de Rivero Vaccari performed conceptualization and critical review and gave final approval.

Corresponding author

Correspondence to Jon Pérez-Bárcena.

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Conflicts of interest

JPdRV is a co-founder and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. JPdRV is Scientific Advisory Board Members of ZyVersa Therapeutics. No financial disclosure is reported for the rest of the authors.

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Pérez-Bárcena, J., Rodríguez Pilar, J., Salazar, O. et al. Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients. Neurocrit Care 36, 527–535 (2022). https://doi.org/10.1007/s12028-021-01340-y

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  • DOI: https://doi.org/10.1007/s12028-021-01340-y

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