Association of a Network of Immunologic Response and Clinical Features With the Functional Recovery From Crotalinae Snakebite Envenoming.

dc.contributor.author

Gerardo, Charles J

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Silvius, Elizabeth

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Schobel, Seth

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Eppensteiner, John C

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McGowan, Lauren M

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Elster, Eric A

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Kirk, Allan D

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Limkakeng, Alexander T

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2021-10-01T14:53:09Z

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2021-10-01T14:53:09Z

dc.date.issued

2021-01

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2021-10-01T14:53:08Z

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Background

The immunologic pathways activated during snakebite envenoming (SBE) are poorly described, and their association with recovery is unclear. The immunologic response in SBE could inform a prognostic model to predict recovery. The purpose of this study was to develop pre- and post-antivenom prognostic models comprised of clinical features and immunologic cytokine data that are associated with recovery from SBE.

Materials and methods

We performed a prospective cohort study in an academic medical center emergency department. We enrolled consecutive patients with Crotalinae SBE and obtained serum samples based on previously described criteria for the Surgical Critical Care Initiative (SC2i)(ClinicalTrials.gov Identifier: NCT02182180). We assessed a standard set of clinical variables and measured 35 unique cytokines using Luminex Cytokine 35-Plex Human Panel pre- and post-antivenom administration. The Patient-Specific Functional Scale (PSFS), a well-validated patient-reported outcome of functional recovery, was assessed at 0, 7, 14, 21 and 28 days and the area under the patient curve (PSFS AUPC) determined. We performed Bayesian Belief Network (BBN) modeling to represent relationships with a diagram composed of nodes and arcs. Each node represents a cytokine or clinical feature and each arc represents a joint-probability distribution (JPD).

Results

Twenty-eight SBE patients were enrolled. Preliminary results from 24 patients with clinical data, 9 patients with pre-antivenom and 11 patients with post-antivenom cytokine data are presented. The group was mostly female (82%) with a mean age of 38.1 (SD ± 9.8) years. In the pre-antivenom model, the variables most closely associated with the PSFS AUPC are predominantly clinical features. In the post-antivenom model, cytokines are more fully incorporated into the model. The variables most closely associated with the PSFS AUPC are age, antihistamines, white blood cell count (WBC), HGF, CCL5 and VEGF. The most influential variables are age, antihistamines and EGF. Both the pre- and post-antivenom models perform well with AUCs of 0.87 and 0.90 respectively.

Discussion

Pre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.
dc.identifier.issn

1664-3224

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1664-3224

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https://hdl.handle.net/10161/23881

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eng

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Frontiers Media SA

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Frontiers in immunology

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10.3389/fimmu.2021.628113

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Animals

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Humans

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Snake Bites

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Crotalid Venoms

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Antivenins

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Cytokines

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Treatment Outcome

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Prospective Studies

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Predictive Value of Tests

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Recovery of Function

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Models, Immunological

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Time Factors

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Adult

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Aged

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Middle Aged

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Female

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Male

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Biomarkers

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Crotalinae

dc.title

Association of a Network of Immunologic Response and Clinical Features With the Functional Recovery From Crotalinae Snakebite Envenoming.

dc.type

Journal article

duke.contributor.orcid

Gerardo, Charles J|0000-0002-8265-1370

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Eppensteiner, John C|0000-0003-4450-5548

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Kirk, Allan D|0000-0003-2004-5962

duke.contributor.orcid

Limkakeng, Alexander T|0000-0002-9822-5595

pubs.begin-page

628113

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School of Medicine

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Surgery, Emergency Medicine

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Duke

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Surgery

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Clinical Science Departments

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Duke Cancer Institute

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Immunology

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Pediatrics

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Surgery, Abdominal Transplant Surgery

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Institutes and Centers

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Basic Science Departments

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Duke Global Health Institute

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University Institutes and Centers

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Institutes and Provost's Academic Units

pubs.publication-status

Published

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12

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