Purpose: Pre-clinical animal studies precede the majority of clinical trials. While the clinical sepsis definitions and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May, 2017. The conference goal was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models.

Methods: 31 experts from 13 countries participated and were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013).

Results: Overall, the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9 at "consideration" (C) strength. This Executive Summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2 and 3).

Conclusions: We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" that should be implemented for animal sepsis models. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182493PMC
http://dx.doi.org/10.1007/s15010-018-1183-8DOI Listing

Publication Analysis

Top Keywords

pre-clinical sepsis
16
sepsis models
12
sepsis
10
quality threshold
8
pre-clinical
8
threshold pre-clinical
8
pre-clinical models
8
models sepsis
8
models
5
minimum quality
4

Similar Publications

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

View Article and Find Full Text PDF

Intestinal epithelial-specific occludin deletion worsens gut permeability and survival following sepsis.

Shock

December 2024

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

Article Synopsis
  • - Sepsis leads to increased intestinal permeability, which is linked to higher mortality rates; occludin, a tight junction protein, is crucial for maintaining the intestinal barrier.
  • - Research comparing occludin knockout mice and wild-type controls demonstrated that occludin KOIEC mice experienced significantly increased intestinal permeability only under septic conditions, without changes in other permeability pathways.
  • - The occludin-deficient mice showed elevated inflammatory cytokines and higher mortality rates after sepsis, highlighting occludin's essential role in gut barrier function and survival, suggesting potential therapeutic approaches to enhance occludin function in sepsis treatment.
View Article and Find Full Text PDF
Article Synopsis
  • Researchers created a non-human primate model of septic shock to better study the disease and test new treatments under conditions similar to modern intensive care.
  • The study analyzed how different doses of a bacteria impacted the animals, noting significant effects on heart rate, blood pressure, and organ function.
  • The model showed key immunological and pathological responses similar to human sepsis, revealing potential for its use in understanding disease mechanisms and developing effective therapies.
View Article and Find Full Text PDF

Systematic review of microRNAs in human acute kidney injury.

Ren Fail

December 2024

Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.

Introduction: Early diagnosis of acute kidney injury (AKI) is limited with current tools. MicroRNAs (miRNAs) are implicated in AKI pathogenesis in preclinical models, but less is known about their role in humans. We conducted a systematic review to identify dysregulated miRNAs in humans with AKI.

View Article and Find Full Text PDF

Targeting AMP-activated protein kinase in sepsis.

Front Endocrinol (Lausanne)

October 2024

Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States.

Sepsis is a global health challenge marked by limited clinical options and high mortality rates. AMP-activated protein kinase (AMPK) is a cellular energy sensor that mediates multiple crucial metabolic pathways that may be an attractive therapeutic target in sepsis. Pre-clinical experimental studies have demonstrated that pharmacological activation of AMPK can offer multiple potential benefits during sepsis, including anti-inflammatory effects, induction of autophagy, promotion of mitochondrial biogenesis, enhanced phagocytosis, antimicrobial properties, and regulation of tight junction assembly.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!