Release date: 2018-03-13
Globally, millions of people die each year from sepsis, which is a common cause of death in patients who have been hospitalized. Despite the high incidence of sepsis, the standard treatment currently available to patients is antibiotic treatment. Since the clinical trial of a sepsis treatment 30 years ago ended with a high failure rate, no new treatments have been developed.
Animal models often used in preclinical trials for drug evaluation often come from mice or sputum, but they are not a good reference model for sepsis because these animals are often able to respond to human sepsis. Fight against these pathogens. Pigs have become a more appropriate option because 80% of their immune systems have the same mechanisms as humans, blood clotting is similar, and their vital signs are easily monitored due to their larger size.
Although there are such more sufficient reasons, in actual operation, it still faces various difficulties. In the study of pigs, it is often limited by the lack of suitable equipment, personnel and clinical facilities.
To overcome this problem, researchers from the Harvard University's Weiss Institute collaborated with Boston Children's Hospital to create a new clinical monitoring method to monitor pigs' physiological response to sepsis. Analysis of the multiple physiological characterization of these pigs in organ failure can provide accurate predictions of the effects of preclinical sepsis drugs on the human body. The study was published in the recent Advances in Critical Care Medicine.
The human sepsis assessment is based on a 2016 guideline called Sepsis-3, which uses a sequential organ failure assessment (SOFA) scoring standard that combines measurements of heart, kidney, liver, lung, brain, and coagulation. , classification of sepsis based on severity. Sepsis can lead to multiple organ failure. In general, animal models are assessed based on whether the animal has died from illness, and the exact cause is determined only at autopsy. Inspired by the clinical evaluation of sepsis-3, the researchers pioneered a guideline for pig-specific sepsis-3 (ss-Sepsis-3) and a scoring standard for pig-specific-SOFA (ss-SOFA) so that the researchers Assessment of sepsis can be performed in infected pigs in vivo, in a human clinical assessment.
“Our system goes beyond simply measuring the effects of pathogen infection on inflammation and animal survival. Because it mimics the life-threatening organ failure that can be observed in human patients, it can also be a manifestation of sepsis treatment in humans. Provide a good prediction," said Dr. Mike Super, co-author of the Senior Senior Scientist at the Weiss Institute.
The team in this study, in which they injected E. coli into eight young Yorkshire pigs, evaluated their real-time response to multiple organs according to the guidelines. Six pigs were consciously injected with bacteria, while six were injected with bacteria under anesthesia, and six were not injected with E. coli but received the same procedure (4 of them only had consciousness and 2 were anesthetized). ). Scientists have found an increase in the total ss-SOFA score in both conscious and anesthetized pigs, a large part of which is due to kidney and coagulation failure, and two conscious animals develop further into acute renal failure.
Three anesthetized animals were defined as having septic shock (the highest severity in the ss-SOFA system), which was caused by a combination of failure of these organs, which caused heart failure and did not cause fever due to a decrease in body temperature. These results indicate that the effects of anesthesia need to be considered when assessing sepsis.
The researchers established this new model and evaluation system that quantifies the severity of sepsis and is used to evaluate long-term studies, different types of pathogens, and antibiotic treatment and complications. Real-time monitoring of conscious or anesthetized animals requires a large amount of personnel and time commitment, but it can be more closely replicated and studied in response to human sepsis, which is of great significance for drug development and testing of the disease. of.
Source: Health New Vision
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