Sepsis treatment that looks one step ahead of evidence

– Crosstalk between basics and clinical practice –

Abstract

 The evidence regarding the pathology and treatment of sepsis is insufficient, and there are many treatments that require further investigation. Based on this background, we conducted basic and clinical research conducted to control PAMPs (pathogen-associated molecular patterns), typified by endotoxin, and DAMPs (damage-associated molecular patterns), which are produced as a result of excessive innate immune responses associated with infectious diseases.

 First, we focused on the anti-inflammatory effects of recombinant thrombomodulin (rhTM), which has an anticoagulant effect, and investigated the relationship between histone H3, a DAMPs, and organ damage using a rat peritonitis sepsis model. The results revealed that rhTM neutralizes histone H3 and reduces renal damage. Then, using clinical data to examine the relationship between rhTM administration and renal damage, it was shown that rhTM significantly lowers blood purification dependence rate and improves renal prognosis. This was a corroborating result.

 Next, we focused on the fact that sepsis may be accompanied by hypogammaglobulinemia due to consumption or increased vascular permeability.

 There is still no unified opinion regarding the management of sepsis associated with hypogammaglobulinemia. Intravenous immunenoglobulin therapy (IVIG) is one of the treatment options, but it is not recommended in the guidelines due to insufficient evidence level. Therefore, when we conducted the study about the prognosis of hypogammaglobulinemia using data on patients with sepsis in the ICU, we found that the 28-day mortality rate increased. Furthermore, when we investigated the effectiveness of IVIG therapy for sepsis patients with low IgG level, we found that it improved the prognosis and was associated with an increase in renal replacement therapy-free days.