Tag: sepsis

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Sepsis Leaves a Dangerous Imprint in Immune System

On By ModernMedia
E. Coli bacteria. Image by Gerd Altmann from Pixabay

New research suggests that sepsis can cause alterations in the functioning of defence cells that persist even after the patient is discharged from hospital.

This cellular reprogramming creates a disorder the authors term ‘post-sepsis syndrome’, symptoms of which include frequent reinfections, cardiovascular alterations, cognitive disabilities, declining physical functions, and poor quality of life.This explains why so many patients who survive sepsis die sooner after hospital discharge than patients with other diseases or suffer from post-sepsis syndrome, immunosuppression and chronic inflammation.

The article reviews studies done to investigate cases of septic patients who died up to five years after hospital discharge.

Sepsis is one of the main causes of death in intensive care units, sepsis is a life-threatening systemic organ dysfunction triggered by the body’s dysregulated response to a pathogen, usually a bacterium or fungus. While fighting the pathogen, the defence system injures the body’s own tissues and organs.

If not caught and treated in time, the condition can lead to septic shock and multiple organ failure. Patients with severe COVID and other infectious diseases have an increased risk of developing and dying from sepsis.

Worldwide, new sepsis cases are estimated to reach some 49 million per year. Hospital mortality from septic shock exceeds 40% globally, up to 55% in Brazil, according to the Sepsis Prevalence Assessment Database (SPREAD) study, conducted with support from FAPESP.

“The massive infection and the accompanying intense immune response with a cytokine outpouring during sepsis may promote irreversible cell metabolic reprogramming. Cell reprogramming is unlikely to occur in leukocytes or bone marrow only. This might happen in several tissues and cells that prompt systemic organ dysfunctions […] Bacteria can transfer genetic material to host cell DNA as eukaryotic cells develop tools to protect themselves against the microorganism invasion. The latter may induce cell biology and metabolic reprogramming that remains even after the infection’s elimination,” the investigators wrote in the article.

According to Raquel Bragante Gritte, joint first author with Talita Souza-Siqueira, one of the hypotheses was that metabolic reprogramming begins in the bone marrow, whose cells acquire a pro-inflammatory profile.

“Our analysis of blood samples from patients even three years after ICU discharge showed that monocytes [a type of defense cell] were activated and ready for battle. They should have been neutral. Monocytes are normally activated only when they are ‘recruited’ to the tissue,” Gritte told Agência FAPESP. Both Gritte and Souza-Siqueira are researchers at Cruzeiro do Sul University (UNICSUL) in the state of São Paulo, Brazil.

The researchers conducted a follow-up study of 62 patients for three years after discharge from the ICU at USP’s University Hospital, analysing alterations in monocytes, neutrophils and lymphocytes, as well as microRNAs, in order to identify prognostic markers and factors associated with post-sepsis syndrome.

“Our hypothesis is that white blood cells conserve a memory of sepsis, which helps explain why patients remain sick after they leave hospital,” said co-author Rui Curi, Professor at UNICSUL, and Director of Butantan Institute.

The investigators suggest that sepsis may create a specific macrophage phenotype that stays active even after hospital discharge. “Cell metabolism reprogramming is also involved in the functions and even generation of the different lymphocyte subsets. Several stimuli and conditions change lymphocyte metabolism, including microenvironment nutrient availability,” they wrote.

The next stage of research will be bone marrow studies to understand how cells are reprogrammed by sepsis. “We think the key to this alteration is in bone marrow,” she said. “However, another possibility is that activation occurs in the blood. We’ll need to do more in-depth research to find answers.”

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions Hospitals PaediatricsTags :

Children with Sepsis Respond Better to ‘Relaxed’ Care Bundle

On By ModernMedia

Following a ‘relaxed care bundle’ was linked to lower 30-day mortality and shorter hospital stays among children with sepsis, according to preliminary data from the Improving Pediatric Sepsis Outcomes (IPSO) FACTO trial.

The study findings were presented virtually at the Society of Critical Care Medicine’s Critical Care Congress.

Sepsis is the leading cause of death in children, with an estimated 7.5 million deaths a year. Childhood sepsis includes severe pneumonia, severe diarrhoea, severe malaria, and severe measles. Some 25-40% of children who recover from sepsis still have long-term consequences.

The ‘relaxed’ sepsis bundle is based on a group of best evidence-based interventions. It involves an initial fluid bolus delivery within 60 minutes, as opposed to 20 minutes; and antibiotic delivery within 180 instead of 60 minutes. Accepted sepsis recognition protocols (screen, huddle, or care order) were also involved with the bundle.

This trial data came from about 40 000 patients with sepsis or suspected sepsis at a range of children’s hospitals across the US, from 2017 to 2019. Raina M Paul, MD, of Advocate Children’s Hospital, Illinois, USA reported the data, saying that the relaxed bundle saw better outcomes than the more original bundle which was more time-restrictive. 
Sepsis-attributable mortality fell by 48.9% among the relaxed bolus-compliant versus non-compliant group (3.1% vs 3.5%), and by 13.7% in original bundle-compliant vs non-compliant cases. Following all aspects of the relaxed bundle was associated with a reduction in median days in hospital from 9 to 6 days.

In a separate presentation, Kayla Bronder Phelps, MD, of CS Mott Children’s Hospital in Michigan, USA, reported the results of a study that showed children hospitalised for severe sepsis were likely to have longer hospital stays if they were from lower-income neighbourhoods. Using a national database, she identified 10 130 cases of children with severe sepsis. Severe sepsis hospitalisations were also highest among the lowest-income quartile, reflecting the fact that there were more children living in low-income neighbourhoods.

Overall, 8.4% of children in the cohort died of sepsis during hospitalisation, with no association between mortality rates and income level. However, children in the lowest-income areas spent a median 9 days in the hospital, while children from the highest-income areas spent 8 days.

Bronder Phelps noted that the study is among the first to examine the impact of poverty on paediatric sepsis outcomes. Poverty is a known risk factor for a wide range of paediatric diseases, such as neonatal bacterial infection, asthma, and migraine, and in adults, poverty is associated with poorer outcomes including higher mortality rates.

Source: MedPage Today

Presentation information 1: Paul R, et al “Improving pediatric sepsis outcomes for all children together (IPSO FACTO): Interim results” SCCM 2021; Abstract 32.

Presentation information 2: Phelps K, et al “The association of socioeconomic status and pediatric sepsis outcomes” SCCM 2021; Abstract 37.