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Premise for Standardized Sepsis Models

Remick, Daniel G.*; Ayala, Alfred; Chaudry, Irshad H.; Coopersmith, Craig M.§; Deutschman, Clifford||; Hellman, Judith; Moldawer, Lyle**; Osuchowski, Marcin F.††

doi: 10.1097/SHK.0000000000001164
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ABSTRACT Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity, and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step toward creating standardized models, we suggest standardizing the technical standards of the widely used cecal ligation and puncture model and creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

*Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts

Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Alpert School of Medicine at Brown University, Providence, Rhode Island

Department of Surgery and Center for Surgical Research, University of Alabama at Birmingham, Birmingham, Alabama

§Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia

||Department of Pediatrics and the Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York

Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, San Francisco, California

**Department of Surgery, University of Florida College of Medicine, Gainesville, Florida

††Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria

Address reprint requests to Daniel G. Remick, MD, 670 Albany Street, Boston, MA 02118. E-mail:

Received 14 August, 2017

Revised 17 October, 2017

Accepted 11 April, 2018

Supported by T32GM86308 (DGR), R21AI112887 (DGR), R01 GM 117519 (DGR) R35 GM118097 (AA), DoD Contract #W911QY-15-C-0134 (IC), R01GM072808 (CMC), T32GM095442 (CMC), R01GM104323 (CMC), R01GM109779 (CMC), R01GM113228 (CMC), R01GM121102 (CSD), T32 GM008440 (JH), International Anesthesia Research Society FARA (JH), R01 GM-040586 (LM), P50 GM-111152 (LM), FWF Grant T707-B13 (MFO).

The authors report no conflicts of interest.

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