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Busch LM, Sun J, Cui X, et al. Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis. Intensive Care Med Exp. 2020;8(1):7doi: 10.1186/s40635-019-0290-x.
Busch, L. M., Sun, J., Cui, X., Eichacker, P. Q., & Torabi-Parizi, P. (2020). Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis. Intensive care medicine experimental, 8(1), 7. https://doi.org/10.1186/s40635-019-0290-x
Busch, Lindsay M, et al. "Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis." Intensive care medicine experimental vol. 8,1 (2020): 7. doi: https://doi.org/10.1186/s40635-019-0290-x
Busch LM, Sun J, Cui X, Eichacker PQ, Torabi-Parizi P. Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis. Intensive Care Med Exp. 2020 Feb 04;8(1):7. doi: 10.1186/s40635-019-0290-x. PMID: 32020483; PMCID: PMC7000606.
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Intensive Care Med Exp. 2020 Feb 04;8(1):7. doi: 10.1186/s40635-019-0290-x.

Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis.

Intensive care medicine experimental

Lindsay M Busch, Junfeng Sun, Xizhong Cui, Peter Q Eichacker, Parizad Torabi-Parizi

Affiliations

  1. Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, USA. [email protected].
  2. Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, USA.

PMID: 32020483 PMCID: PMC7000606 DOI: 10.1186/s40635-019-0290-x

Abstract

BACKGROUND: Animal studies reporting immune checkpoint inhibitors (CPIs) improved host defense and survival during bacterial sepsis provided one basis for phase I CPI sepsis trials. We performed a systematic review and meta-analysis examining the benefit of CPI therapy in preclinical studies, and whether variables potentially altering this clinical benefit were investigated. Studies were analyzed that compared survival following bacteria or lipopolysaccharide challenge in animals treated with inhibitors to programmed death-1 (PD-1), PD-ligand1 (PD-L1), cytotoxic T lymphocyte-associated protein-4 (CTLA-4), or B- and T-lymphocyte attenuator (BTLA) versus control.

RESULTS: Nineteen experiments from 11 studies (n = 709) were included. All experiments were in mice, and 10 of the 19 were published from a single research group. Sample size calculations and randomization were not reported in any studies, and blinding procedures were reported in just 1. Across all 19 experiments, CPIs increased the odds ratio for survival (OR, 95% CI) [3.37(1. 55, 7.31)] but with heterogeneity (I

CONCLUSIONS: Preclinical studies showing that CPIs add benefit to antibiotic therapy for the common bacterial infections causing sepsis clinically are needed to support this therapeutic approach. Studies should be reproducible across multiple laboratories and include procedures to reduce the risk of bias.

Keywords: Bacterial infection; Checkpoint inhibitor; Checkpoint molecule; Preclinical model; Sepsis; Treatment

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