Contents lists available at ScienceDirect Resuscitation journal homepage: www.elsevier.com/locate/resuscitation Short paper Low serum Kallistatin level was associated with poor neurological outcome of out-of-hospital cardiac arrest survivors: Proteomics study Yoon Sun Jung a , Woon Yong Kwon a,b, ⁎ , Gil Joon Suh a,b , Sungyoon Moon c , Mi-Hee Han c , Je-In Youn c,d , Sang-Uk Seo c,d , Kyung Su Kim a , Seung-Yong Seong c,d,e a Department of Emergency Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea b Department of Emergency Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea c Wide River Institute of Immunology, Seoul National University College of Medicine, Gangwon-do 25159, Republic of Korea d Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea e Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea ARTICLE INFO Keywords: Heart arrest Proteomics Kallistatin Hypothermia Induced ABSTRACT Aim of the study: To identify proteins of which depletion are associated with the poor 6-month neurological outcome of out-of-hospital cardiac arrest survivors. Methods: Seven healthy volunteers and 34 out-of-hospital cardiac arrest survivors admitted to the intensive care unit (ICU) and underwent targeted-temperature management were enrolled. According to the 6-month cerebral performance category (CPC) scale, patients were divided into the good (CPC 1–2) and poor (CPC 3–5) outcome groups. Blood samples were obtained at 0, 24, and 72 h after admission to the ICU. Results: With proteomic approaches, we found 23 proteins that showed group-differences between the sera pooled from 7 study groups: healthy volunteers, the good outcome groups (0, 24, and 72 h), and the poor outcome groups (0, 24, and 72 h). We selected 7 candidate proteins of which intensities were different between the good and poor outcome groups (> 2-fold change) and excluded 5 proteins related to haemolysis or re- maining high abundant proteins. To confirm the 2 identified proteins: retinal dehydrogenase 1 and Kallistatin, we performed enzyme-linked immunosorbent assay with individual serum. Finally, old age (odds ratio = 1.055; 95% confidence interval, 1.002–1.112; p = 0.043) and low serum kallistatin level at 0 h (odds ratio = 0.784; 95% confidence interval, 0.618–0.995; p = 0.046) were independently associated with the poor 6-month neu- rological outcome. Conclusion: The depletion of serum kallistatin at admission to the ICU was associated with the poor neurological outcome of out-of-hospital cardiac arrest survivors. Introduction Cardiac arrest frequently results in neurological disability [1,2]. However, no pharmacological agents are available to improve neuro- logical outcomes of cardiac arrest survivors [3]. During the past dec- ades, many biomarkers have been developed. Most of them, such as neuron specific enolase and S-100 protein, are overexpressed in patients with poor neurological outcome [4–6]. They are only markers for re- cent or present neuronal injuries, and thus, their elimination or in- hibitor use have not been considered as therapeutic strategies [4–6]. For the development of pharmacological agents, candidate proteins of which depletion is significantly associated with poor neurological out- come and their supplement may improve neurological outcome should be identified [7,8]. Proteomics is a peptide screening method to identify candidate proteins associated with pathological conditions by investigating all of the integrated proteins rather than an individual protein [9,10]. Therefore, we hypothesized that with proteomic approaches, we could compare the changes in serum proteome profiles between cardiac arrest survivors with good and poor neurological outcomes and could identify candidate proteins of which depletion are significantly associated with poor neurological outcome. Our aim was to identify proteins of which depletion was associated with the poor 6-month neurological outcomes of cardiac arrest survi- vors. https://doi.org/10.1016/j.resuscitation.2018.04.025 Received 22 January 2018; Received in revised form 2 April 2018; Accepted 19 April 2018 ⁎ Corresponding author at: Department of Emergency Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-gu, Seoul, 03080, Republic of Korea. E-mail address: kwy711@hanmail.net (W.Y. Kwon). Resuscitation 128 (2018) 6–10 0300-9572/ © 2018 Elsevier B.V. All rights reserved. T