Sepsis

[raypeatclips]

I had never really heard of sepsis before about a year ago, now every day there is someone in the news that has died of sepsis and reportedly in a day or two, and the symptoms are very similar to many other ailments.

Does anybody have any thoughts about sepsis? Specifically what causes it and how to prevent it?

 

[Sucrates]

A major cause is endotoxin, or the inflammation that occurs when large amounts get into the liver and circulation. So anything that interrupts anything in those steps could mitigate it (TNFa or TLR4 antagonists for example). I think it's often an acute stress that precedes death from sepsis. There are other known triggers like gram positive bacteria.

 

[PakPik]

Hi @raypeatclips , @Sucrates

the old concept that sepsis is a problem of excess inflammation has largely been challenged and shown to be inaccurate (as shown by papers and research from the last few years). Research shows that a big part of people who develop sepsis (and who go on to die or fare really bad) are not able to mount an effective pro-inflammatory early on when challenged with antigenic/infectious material burden. That is, they are immunosuppressed in one way or another and lack enough inflammatory, anti-infectious immunity power. In fact, trials with TLR4 antagonists and immunosuppressants (TLR blockers, etc) have been absolute disappointment: either not improve outcomes, or in fact increase in mortality:

"companies initiated many clinical trials—eg, TNF and interleukin 1 antagonists, toll receptor blockers, and endotoxin antagonists in sepsis. The results of more than 30 trials of diverse anticytokine and anti-inflammatory drugs showed no benefit or, in some cases, reduced survival rates." Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach
​

Now, excessive inflammation can certainly be dangerous, but a lack of inflammatory power can also be, if not more. They in fact have been proposing the use of immune-stimulatory, i.e pro-inflammatory agents for sepsis:

"Several small phase 2 clinical trials of immune-enhancing drugs have shown benefit, thereby substantiating the concept that immunosuppression has a central role.9,10 Findings from studies of clinically relevant animal models of sepsis that mimic the protracted nature of the disease also support the premise that boosting immunity improves survival.11 Sepsis and cancer share many immunological defects, and therefore the recent successes of several immunomodulatory drugs in cancer provide hope for and insight into potential immunostimulatory therapies in sepsis" Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach​

The observation that a bulk of these patients are immunosuppressed would explain why the outcomes are so bad in sepsis: lack of anti-infectious immunity allows the infectious -with its respective antigenic- burden to increase, spreading farther and further in the body, damaging organs and circulation in the process. Worse off, the immune system keeps failing so that it can get to the point where secondary infections are acquired/reactivated, terribly worsening the prognosis:

"However, the crucial message remains that many patients in intensive care units do not recover because there is ongoing infection. Despite broad-spectrum antibiotics and aggressive source control measures, many patients do not eradicate their infections and develop secondary hospital-acquired infections.27,28 Therefore, therapy that boosts immune competence could affect outcomes by leading to more rapid resolution of the primary infection and prevention of lethal secondary infections." Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach​

Another good paper for further reading:
http://www.sciencedirect.com/science/article/pii/S235239641400005X

A couple of quotes:

• "The association between the endotoxin tolerance signature and confirmed sepsis was strong and statistically significant in a total of 12 distinct datasets ... . These results are consistent with our hypothesis that the endotoxin tolerance signature is robustly associated with very early sepsis. The endotoxin tolerance signature was also associated with disease severity measured primarily by the development of organ dysfunction. Therefore, we propose here an updated model of sepsis pathogenesis mediated by an endotoxin tolerance-mediated immune dysfunction."

• "This is consistent with but further clarifies a recent study (Hotchkiss et al., 2013) that suggested that early sepsis was associated with coincident inflammatory and anti-inflammatory/immunosuppressive responses. It is worth mentioning that endotoxin tolerance is not an anti-inflammatory state per se but rather a cellular reprogramming (which also occurs with Gram positive bacteria) that leads to immune amnesia, disabling responses to agonists like endotoxin ..."

• "In the future, our genetic classifier could help to define a subset of patients who might benefit from immunomodulation (e.g. anti-endotoxin tolerance) and supportive therapies."

• "Sepsis has been traditionally classified as an early stage excessive inflammatory state followed by a transition to a late stage anti-inflammatory/immunosuppressive state (e.g. endotoxin tolerance) ... . However, a model of concurrent immunosuppression and hyperinflammation has been recently hypothesised to explain the complex pathogenesis of sepsis at various timepoints (Hotchkiss et al., 2013). The current study indicates that immunosuppression is being driven by endotoxin tolerance that occurs at a much earlier stage of clinical disease than previously appreciated, consistent with the failure of immunosuppressive treatments in more than 30 clinical trials (Lyle et al., 2014). In agreement with the concurrent inflammation/immunosuppression model, we observed significant enrichment of both the endotoxin tolerance and inflammatory signatures at all early-stages of disease, although the endotoxin tolerance signature dominated."

Of course, there's still no perfectly clear rule in sepsis (and every person tends to have their own set of factors and characteristics), but the old notions have had to be reconsidered and slowly being replaced with a more complex one, integrating the findings such as I've shared above. It seems that for a lot of people high inflammation is not the root nor even the main problem -quite the contrary, inability to mount effective pro-inflammatory, antiinfectious immune responses seems to be the signature of the problem-.

Sharing with @Sheila !

 

[paymanz]

Limiting pufa intake lowers sepsis risk.

And thiamine is very important for sepsis treatment.

 

[ddjd]

https://x.com/MakisMD/status/1704391725526196515?s=20

 

[Rinse & rePeat]

I had never really heard of sepsis before about a year ago, now every day there is someone in the news that has died of sepsis and reportedly in a day or two, and the symptoms are very similar to many other ailments.

Does anybody have any thoughts about sepsis? Specifically what causes it and how to prevent it?

My husband got sepsis quickly and died within days too. I documented his demise in the threads below. Looking back there was a lot of medical errors, and it all started with his tetanus vaccine and then x-rays and prescribed drugs….

TETANUS Vaccine & Health Decline Reports (Post Here)

My husband got a tetanus vaccine in August of 2020, and his health immediately declined afterwards. He now deals with crippling back pain and has horrible reactions to foods that he had no trouble with before. The back pain is so debilitating that coughing brings him to his knees. He has been to...

raypeatforum.com

A 3rd Opinion - What does this blood test mean?

My husband had this blood test taken under stressful conditions from a spinal compression fracture, that originally happened from a golf swing. He thought it was just a pulled muscle and went about his business in pain, hoping for it to heal. When it didn't after two months he went to a highly...

raypeatforum.com

“But not much research exists to explain why our bodies develop sepsis, which is when the immune system overreacts to a serious infection, attacking more than just the infection itself and damaging tissue and vital organs if not treated early.

Sepsis kills more than 270,000 adults in the U.S. each year, according to the Sepsis Alliance.Emergency rooms are where most sepsis patients are seen, and until now, there hasn’t been a timely “gold standard” test for sepsis, leading to the possible misallocation of medical resources and the overuse of antibiotics in an already high-pressure environment.

This January, the medical diagnostic company Cytovale got FDA approval for its IntelliSep test, which examines blood samples taken from patients as they enter the emergency room and — within 10 minutes — determines their likelihood of developing sepsis.”

https://health.fmolhs.org/about-us/sepsis-leading-cause-of-death-in-hospitals-and-how-we-are-helping-stop-it/#:~:text=Sepsis%20kills%20more%20than%20270%2C000,according%20to%20the%20Sepsis%20Alliance.

 

[Rinse & rePeat]

IS THIS THE REAL CAUSE OF COVID DEATHS C. DIFF INFECTIONS?

I have been reading about Clostridium Difficile because my husband has been diagnosed with it today. It is a "super bug" bacterial infection with a high mortality rate. The doctor said he got it from his last hospital visit for a spinal compression fracture. This is some scary stuff, but it is...

raypeatforum.com

 

[Rinse & rePeat]

COVID-19 And Sepsis

COVID-19 causes sepsis: "Now that more scientific data are available on COVID-19, the Global Sepsis Alliance can more definitively state that COVID-19 does indeed cause sepsis. Sepsis is “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” In the case of...

raypeatforum.com

 

[Rinse & rePeat]

Limiting pufa intake lowers sepsis risk.

And thiamine is very important for sepsis treatment.

My husband and I have been low PUFA for many years and he succumbed to sepsis. It is the immune suppressing medical procedures, vaccines and drugs, and stress, that increases one’s risk.