Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Background: Sepsis is a life-threatening disorder that leads to the induction of inflammatory responses and organ failure. Phage therapy is a new approach to controlling infections resistant to common treatments, including sepsis. Several studies have shown the effect of lytic bacteriophages on infection control by reducing the bacterial load. ⋯ Results According to the in vitro results, 10 9 PFU/mL of bacteriophage M13 was not toxic and did not affect the level of cytokine, nitric oxide, and reactive oxygen species production by splenocytes, but it reduced the inflammatory response of splenocytes in responses to LPS. In vivo studies indicated that the amount of proinflammatory cytokines, liver enzymes, bacterial load, and organ failure were decreased in the CLP + M13 group compared with CLP + NS, whereas the survival rate was increased. Conclusions These experiments demonstrated that bacteriophage M13 could lessen the consequences related to sepsis in CLP mice and can be considered a therapeutic approach in sepsis.
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The COVID-19 pandemic has been a challenge to propose efficient therapies. Because severe SARS-CoV2 infection is a viral sepsis eventually followed by an immunological autoinflammatory phenomenon, many approaches have been inspired by the previous attempts made in bacterial sepsis, while specific antiviral strategies (use of interferon or specific drugs) have been additionally investigated. We summarize our current thinking on the use of SARS-CoV-2 antivirals, corticosteroids, anti-IL-1, anti-IL-6, anti-C5a, as well as stem cell therapy in severe COVID-19. Patient stratification and appropriate time window will be important to be defined to guide successful treatment.
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The unacceptable high mortality of severe infections and sepsis led over the years to understand the need for adjunctive immunotherapy to modulate the dysregulated host response of the host. However, not all patients should receive the same type of treatment. The immune function may largely differ from one patient to the other. ⋯ ImmunoSep is a first-in-class paradigm of precision medicine for sepsis. Other approaches need to consider classification by sepsis endotypes, targeting T cell and application of stem cells. Basic principle for any trial to be successful is the delivery of appropriate antimicrobial therapy as standard-of-care taking into consideration not just the likelihood for resistant pathogens but also the pharmacokinetic/pharmacodynamic mode of action of the administered antimicrobial.
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Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. ⋯ In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.
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Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg per hour) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery pressure and pulmonary vascular resistance index. ⋯ Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50-min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.